Efficacy of Schwann Cell (SC) transplantation for spinal cord repair is improved with combinatorial strategies

Abstract

When cells (including Schwann cells, SCs) of the PNS could be purified and expanded in number in tissue culture, Richard Bunge in 1975 envisioned that the SCs could be introduced to repair the CNS, as SCs enable axons to regenerate after PNS injury. Importantly, autologous human SCs could be transplanted into injured human spinal cord. Availability of the new culture systems to study interactions between sensory neurons, SCs and fibroblasts increased our knowledge of SC biology in the 70 s and 80 s. Joining the Miami Project to Cure Paralysis in 1989 brought the opportunity to use this knowledge to initiate spinal cord repair studies. Development of a rat complete spinal cord transection/SC bridge model allowed the demonstration that axons regenerate into the SC bridge. Together with study of contused rat spinal cord, it was concluded that implanted SCs reduce cavitation, protect tissue around the lesion, support axon regeneration, and form myelin. SC transplantation efficacy was improved when combined with neurotrophins, elevation of cyclic AMP levels, olfactory ensheathing cells, a steroid or chondroitinase. Increased efficacy meant higher numbers of axons, particularly from the brainstem, and more SC-myelinated axons in the implants and improvement in hindlimb movements. Human SCs support axon regeneration as do rat SCs. Astrocytes at the SC bridge/host spinal cord interfaces play a key role in determining whether axons enter the SC milieu. The SC work described here contributed to gaining approval from the FDA for an initial autologous human SC clinical trial (at the Miami Project) that has been completed and found to be safe.

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Acid-sensing ion channel 1a induces AMPA receptor plasticity: a link between acidotoxicity and excitotoxicity in hippocampal CA1 neurons

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Context-dependent use of muscle spindles for human position sense

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Partial posterior vitreous detachment as a classification

Kaya A

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Accurate and Phenol Free DNA Sexing of Day 30 Porcine Embryos by PCR

This protocol describes an accurate, inexpensive, rapid and non-toxic method to determine the sex of Day 30 porcine embryo using PCR method after grinding an embryo into powder without phenol chloroform extraction and DNA column purification.

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The static evolution of the new Italian code of medical ethics

Eight years since the last revision, in May 2014 the Italian code of medical ethics has been updated. Here, the Authors examine the reform in the light of the increasing difficulties of the medical profession arising from the severity of the Italian law Courts.
The most significant aspects of this new code are firstly, the patient's freedom of self-determination and secondly, risk prevention through the disclosure of errors and adverse events. However, in both areas the reform seems to be less effective if we compare the ethical codes of France, the United Kingdom and the United States.
In particular, the non-taking into consideration of the said code quality standards and scientific evidence which should guide doctors in their clinical practice is to say the least questionable.
Since these are the most significant changes in the new code, it seems inevitable to conclude that the 2014 edition is essentially in line with previous versions.
Now more than ever it is necessary that medical ethics acknowledges that medicine, society and medical jurisprudence have changed and doctors must be given new rules in order to protect both patients' rights and dignity of the profession. The physician's right to refuse to perform treatment at odds with his own clinical beliefs cannot be the only mean to safeguard the dignity of the profession. A clear boundary must also be established between medicine and professionalism as well as the criteria in determining the scientific evidences that physicians must follow. This has not been done in the Italian code of ethics, despite all the controversy caused by the Stamina case.

L'articolo The static evolution of the new Italian code of medical ethics sembra essere il primo su European Review.

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Pregabalin administered as an anxiolytic agent in ultrasound-guided infraclavicular block: a controlled, double-blind, dose-ranging trial

OBJECTIVE: Adjuvant agents, given with local anesthetics or via venous, oral, or rectal routes for peripheral nerve blocking, have been in use for a long time. Literature studies about pregabalin usage in peripheral nerve blocking are limited in number. In this study, we aimed to reveal the blocking quality of pregabalin administered orally in various doses as an anxiolytic agent and its effective dose range.

PATIENTS AND METHODS: Eighty patients who underwent upper extremity bone surgery were included in the study. The cases were divided into 4 randomized groups of 20 patients. The group that did not receive any medication before the surgery was named the Control Group (Group C), the group that received 75 mg pregabalin per os was named Group P75, the group that received 150 mg pregabalin per os was named Group P150, and the group that received 300 mg pregabalin per os was named Group P300. The study had a controlled and double-blind design. Before, during and after routine peripheral nerve blocking, vital signs, Ramsey Sedation Scale, Patient Satisfaction, Visual Analog Scale, and termination durations of sensorial and motor blocks were recorded.

RESULTS: Motor block initiation durations of all groups given pregabalin were significantly shorter than those of Group C. Sensorial block termination durations were similar in Group P150 and Group P300, and both were significantly longer than those in Group C and Group P75. First analgesic requirement time for Group P150 and Group P300 were significantly longer than that of Group P75. Although there was no significant difference between postoperative patient satisfaction and VAS values, first analgesic requirement times of the pregabalin administered groups were longer than those of the control group.

CONCLUSIONS: The patients, who are about to undergo surgery, generally develop anxiety about death, not waking up from anesthesia, disability, pain and loss of ability to work. Pregabalin is an anti-epileptic, analgesic and anxiolytic agent. With these characteristics, it can be used to reduce pre-operative anxiety, for prophylaxis against convulsions and post-operative analgesia.
One hundred fifty mg of pregabalin provides sufficient and effective analgesia, and this dose positively affects the quality of the block.

L'articolo Pregabalin administered as an anxiolytic agent in ultrasound-guided infraclavicular block: a controlled, double-blind, dose-ranging trial sembra essere il primo su European Review.

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Comparison of the treatment effects of methoxamine and combining methoxamine with atropine infusion to maintain blood pressure during spinal anesthesia for cesarean delivery: a double blind randomized trial

OBJECTIVE: Hypotension is a common complication of spinal anesthesia for cesarean delivery. Atropine is a vagus nerve blocker that can antagonize vagus excitation to mitigate the reflex bradycardia. We aimed to assess the effect of methoxamine-atropine therapy in treating spinal anesthesia hypotension for cesarean section.

PATIENTS AND METHODS: This is a double-blind randomized controlled study. Women under spinal anesthesia for elective caesarean delivery received boluses of methoxamine 2 mg alone (Group M, n = 40), or with addition of atropine 0.1 mg (Group MA1, n = 40), atropine 0.2 mg (Group MA2, n = 40) or atropine 0.3 mg (Group MA3, n = 40) upon a maternal systolic pressure ≤ 80% of baseline. The primary endpoint was systolic blood pressure and the secondary endpoints were maternal heart rates, instant neonatal heart rates, umbilical artery pH and umbilical artery base excess.

RESULTS: Changes in systolic blood pressure were similar among the four groups. The incidences of bradycardia in groups M and MA1 were significantly higher than those in group MA2 and MA3. The fetal heart rates after delivery in groups MA2 and MA3 were higher than those in group M and MA1 but within the normal range. The acid-base status had no difference in the four groups.

CONCLUSIONS: Methoxamine-atropine combination has a similar efficacy to methoxamine alone but has an increased hemodynamic stability and a less adverse effect occurrence.

L'articolo Comparison of the treatment effects of methoxamine and combining methoxamine with atropine infusion to maintain blood pressure during spinal anesthesia for cesarean delivery: a double blind randomized trial sembra essere il primo su European Review.

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Docking-based preliminary study on the interactions of bile acids with drugs at the transporter level in intestinal bacteria

OBJECTIVE: The aim of this study was to estimate the binding-affinities of different bile acids towards drug transporters in Lactobacillus acidophilus and Bifidobacterium longum in order to predict the influence of bile acids and probiotics interactions on drug pharmacokinetics.

MATERIALS AND METHODS: In order to study interactions of bile acids with transporters of intestinal bacteria, molecular-docking step was performed, using SwissDock web-service. For the purpose of comparison, two natural bile acids, cholic acid (CA) and deoxycholic acid (DCA), and one semi-synthetic bile acid, 12-monoketocholic acid (MKC), were studied in parallel. The free-binding energy was used as the main criterion for ranking ligands.

RESULTS: Studied bile acids exhibited different binding affinities towards bacterial transporters with MKC showing the most prominent effect. For the majority of studied transporters, the estimated affinities of bile acids decreased in the following order: MKC–CA–DCA. Namely, 38.7% of examined transport proteins gave the lowest free-binding energy with MKC. The weak inverse relationship between number of hydrogen bonds and estimated free-binding energies was revealed.

CONCLUSIONS: The predominant effect of MKC for the majority of studied transport proteins suggests that keto group at carbon 12 of the steroid core has a significant influence on the properties of MKC and consequently, on interactions with membrane transporters. Present findings might have a role in the prediction of potential influence of bile acids and probiotics on drug pharmacokinetics.

L'articolo Docking-based preliminary study on the interactions of bile acids with drugs at the transporter level in intestinal bacteria sembra essere il primo su European Review.

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Negative symptoms as key features of depression among cannabis users: a preliminary report

OBJECTIVE: Cannabis use is frequent among depressed patients and may lead to the so-called "amotivational syndrome", that combines symptoms of affective flattening and loss of emotional reactivity (i.e. the so-called "negative" symptomatology). The aim of this study was to investigate the negative symptomatology in depressed patients with concomitant cannabis use disorders (CUDs) in comparison with depressed patients without CUDs.

PATIENTS AND METHODS: Fifty-one patients with a diagnosis of Major Depressive Disorder (MDD) and concomitant CUD and fifty-one MDD patients were enrolled in the study. The 21-Item Hamilton Depression Rating Scale (HDRS) and the negative symptoms subscales of the Positive and Negative Syndrome Scale (PANSS) were used to assess depressive and negative symptomatology.

RESULTS: Patients with cannabis use disorders presented significantly more severe negative symptoms in comparison with patients without cannabis use (15.18 ± 2.25 vs 13.75 ± 2.44; t100 = 3.25 p = 0.002).

DISCUSSION: A deeper knowledge of the "negative" psychopathological profile of MDD patients who use cannabis may lead to novel etiopathogenetic models of MDD and to more appropriate treatment approaches.

L'articolo Negative symptoms as key features of depression among cannabis users: a preliminary report sembra essere il primo su European Review.

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Metabolomic approach for the identification of therapeutic targets of erythropoietin against sepsis in rat models

OBJECTIVE: Owing to a lack of effective treatment approaches, sepsis is considered a life-threatening clinical syndrome worldwide. Many therapeutic interventions combating sepsis have been evaluated in animal models and clinical cases over the past few decades. Due to the pleiotropic characteristics of EPO, many studies have shown that erythropoietin (EPO) would be used to alleviate sepsis-induced tissue injury beyond the hemoglobin elevation effect. Nevertheless, the organ protective activity of EPO could not be supported by all of the results. In order to address the unanswered questions, a new methodical approach is necessary to be considered. The latest progress in metabolomics could be helpful to interpret the underlying mechanisms of EPO on sepsis, via metabolite profiling, to bring in some potent predictable fact for clinical application.

MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were divided into 3 groups of 7 rats each. Sepsis was induced by cecal ligation and puncture (CLP). Rats in the sepsis group were injected with equal volume of saline post-CLP. Rats from the EPO group were treated twice with EPO (immediately and 24 hours after CLP, 3750 IU/kg). The rats in the sham group were subjected to a sham surgery and injected with saline at the same time as the sepsis group. Serum samples were collected for biochemical and metabolomic analysis 72 hours post-CLP.

RESULTS: Biochemistry analysis revealed that erythropoietin improved the condition of multiple organs damaged by sepsis. Fifty-eight serum metabolites, including amino acids and fatty acids, displayed significant differences between the sepsis and sham groups. EPO treatment was found to attenuate the metabolic imbalances induced by CLP.

CONCLUSIONS: This study indicated that the metabolomic approach provided a comprehensive insight towards the metabolic targets of EPO treatment of sepsis.

L'articolo Metabolomic approach for the identification of therapeutic targets of erythropoietin against sepsis in rat models sembra essere il primo su European Review.

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Sivelestat sodium hydrate attenuates acute lung injury by decreasing systemic inflammation in a rat model of severe burns

OBJECTIVE: Patients with severe burns often develop acute lung injury (ALI), systemic inflammatory response syndrome (SIRS) often complicates with ALI. Sivelestat sodium hydrate is an effective drug against ALI. However, the mechanisms of this beneficial effect are still poorly understood. In the current study, we evaluate the effects of sivelestat sodium hydrate on systemic and local inflammatory parameters (neutrophil elastase [NE], interleukin [IL]-8, matrix metalloproteinase [MMP] 2 and 9) in a rat model of severe burns and ALI. And to analyze the correlations between expression of NE and IL-8 and acute lung injury.

MATERIALS AND METHODS: 48 Sprague-Dawley (SD) rats were divided into 3 groups: normal control group, severe burns injury group and severe burns treated with sivelestat sodium hydrate group (SSI). The lung water content and PaO2 were detected in each group. Pathological manifestations in each group were observed for pathology scoring in SD rats with acute lung injury. ELISA was used for detecting expression of NE and IL-8 in serum and BAL specimens of SD rats in each group. RT-PCR was used to detect mRNA expression of NE and IL-8 in lung tissues of each group. Western blotting was used for detecting protein expression of MMP-2 and MMP-9 in lung tissues of each group. SPSS 18.0 was used for statistical analysis.

RESULTS: The PaO2 was significantly increased after sivelestat sodium hydrate intravenous injection. Pathological score and water content of lung tissue were significantly decreased in SSI group compared with severe burns injury group, slightly higher than that normal control group. NE and IL-8 levels significantly decreased in serum, BAL and lung tissue specimens after sivelestat sodium hydrate intravenous injection; Expression of MMP-2 and MMP-9 were significantly up-regulated in severe burns group and showed no significantly changed after sivelestat sodium hydrate intravenous injection.

CONCLUSIONS: In a rat model of severe burns and ALI, administration of sivelestat sodium hydrate improved symptoms of ALI and significantly decreased inflammatory parameters NE and IL-8.

L'articolo Sivelestat sodium hydrate attenuates acute lung injury by decreasing systemic inflammation in a rat model of severe burns sembra essere il primo su European Review.

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Effect of sildenafil on intestinal adaptation parameters in a rat model of short bowel syndrome

OBJECTIVE: We aimed to evaluate the effect of sildenafil on the intestinal adaptation in short bowel syndrome (SBS).

MATERIALS AND METHODS: Forty-eight male Wistar-albino rats (weight, 231-390 g) were randomly divided into four groups with 12 rats in each. Group TA had only ileal transection+anastomosis, Group TA+S was given sildenafil after ileal transection+anastomosis, Group RA had a resection of 75% of the small bowel+anastomosis, Group RA+S was given sildenafil after small bowel resection+anastomosis. Sildenafil was injected subcutaneously at 60 mg/kg/day dose throughout 3–21 days postoperatively. Bowel and mucosal weights, villus height, crypt depth, DNA and protein concentrations were determined.

RESULTS: Jejunal bowel weight was lower in TA and TA+S groups than RA and RA+S groups (p < 0.05). RA+S group had higher ileal and jejunal mucosal weights than RA and TA+S groups (p < 0.05). Villus height was highest in RA+S group both in ileum and jejunum (466.1 ± 38.6 μm and 648.1 ± 65.7 μm, respectively). Jejunal crypt depth was highest in RA+S group (255.1 ± 21.9 μm) compared to other groups (p < 0.05). There was no significant difference in ileal and jejunal protein concentration between TA and TA+S groups and in ileal protein concentration between RA ve RA+S groups (p > 0.05). Ileal DNA concentration was higher in TA+S group, and jejunal DNA concentration was higher in RA and RA+S groups than TA and TA+S groups (p < 0.05).

CONCLUSIONS: Sildenafil has a positive effect on intestinal adaptation parameters, particularly in jejunum in a rat SBS model. Thus, its role in the treatment of SBS should be further investigated with clinical studies.

L'articolo Effect of sildenafil on intestinal adaptation parameters in a rat model of short bowel syndrome sembra essere il primo su European Review.

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Role of methylprednisolone in the prevention of postpericardiotomy syndrome after cardiac surgery

OBJECTIVE: Postpericardiotomy syndrome (PPS) occurs in 10-40% of patients after cardiac operations. Pericardial effusions and tamponade occurring > 7 days after surgery are usually related to PPS and remain an important cause of cardiac surgery-related morbidity and mortality; therefore, preventing PPS is important. Colchicine affords safe and efficacious protection against PPS and related complications. However, the roles of corticosteroids and nonsteroidal anti-inflammatory drugs in PPS prevention remains unclear. This study aimed to determine whether the intraoperative use of single-dose methylprednisolone can effectively prevent PPS.

PATIENTS AND METHODS: This retrospective study included 100 patients undergoing elective coronary artery bypass grafting (CABG) who received a single intraoperative dose of 1 mg/kg methylprednisolone. A further 100 patients undergoing CABG, who were not given methylprednisolone, comprised the control group. The presence and severity of pericardial effusion was determined by echocardiography, with chest X-ray used to assess pleural effusion.

RESULTS: PPS occurrence and pericardial effusion occurrence were significantly lower in patients who received methylprednisolone (p = 0.02 and p = 0.007 respectively). Although the differences were not statistically significant, pericardial and pleural effusions were more severe in the control group than in the methylprednisolone group. Logistic regression analysis demonstrated that methylprednisolone administration was independently associated with prevention of PPS (OR 0.8, 95% CI 0.25-0.91, p <  0.026).

CONCLUSIONS: Intraoperative, single-dose methylprednisolone may confer protection against PPS in patients undergoing CABG.

L'articolo Role of methylprednisolone in the prevention of postpericardiotomy syndrome after cardiac surgery sembra essere il primo su European Review.

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Autologous peripheral blood stem cell transplantation to treat thromboangiitis obliterans: preliminary results

OBJECTIVE: To investigate the efficiency of autologous peripheral blood stem cell transplantation (APBSCT) to treat severe the lower limbs ischemia caused by thromboangiitis obliterans (TAO).

PATIENTS AND METHODS: From April 2007 to December 2014, a total of 64 patients with TAO (80 affected limbs) received APBSCT at our hospital. The treatment effect was evaluated by subjective indicators including pains and cold sensation of the affected limbs, combined with objective indicators including claudication distance, ankle brachial index (ABI), transcutaneous oxygen pressure (TcPO2) and skin temperature.

RESULTS: Five patients (with 5 affected limbs) suffered from necrosis below the middle of the leg 4 weeks after transplantation and received amputation. For the remaining 59 patients (75 affected limbs), pain and cold sensation of the affected limbs were improved with varying extent 3 months after transplantation; there were statistically significant differences in pain score and cold sensation score of the affected limbs before and after APBSCT (p<0.05). Claudication distance, ABI, TcPO2 and skin temperature were also improved. Claudication distance increased from 85.69 m±43.48 m to 36.5±9.88 mmHg, and the skin temperature of the lower limbs increased from 27.70°C±0.53°C to 33.49°C±0.60°C. All four indicators were considerably improved after APBSCT (p<0.05). Arteriography was performed for 75 affected limbs in 59 patients 6 months after transplantation and found that new collateral vessels were formed in the affected limbs. No patients were complicated by retinal hyperplasia, malignant tumors, myocardial infarction and cerebral infarction during the follow-up examinations; no patients underwent symptom aggravation during 9-48 month follow-up (average, 28.5 months).

CONCLUSIONS: APBSCT is an easy, safe and reliable treatment for ischemia of lower limbs, especially for those with poor distal arterial outflow tract in the lower limbs that do not permit bridging.

L'articolo Autologous peripheral blood stem cell transplantation to treat thromboangiitis obliterans: preliminary results sembra essere il primo su European Review.

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Motif-Based Text Mining of Microbial Metagenome Redundancy Profiling Data for Disease Classification

Background. Text data of 16S rRNA are informative for classifications of microbiota-associated diseases. However, the raw text data need to be systematically processed so that features for classification can be defined/extracted; moreover, the high-dimension feature spaces generated by the text data also pose an additional difficulty. Results. Here we present a Phylogenetic Tree-Based Motif Finding algorithm (PMF) to analyze 16S rRNA text data. By integrating phylogenetic rules and other statistical indexes for classification, we can effectively reduce the dimension of the large feature spaces generated by the text datasets. Using the retrieved motifs in combination with common classification methods, we can discriminate different samples of both pneumonia and dental caries better than other existing methods. Conclusions. We extend the phylogenetic approaches to perform supervised learning on microbiota text data to discriminate the pathological states for pneumonia and dental caries. The results have shown that PMF may enhance the efficiency and reliability in analyzing high-dimension text data.

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Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis

The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms.

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Plant Responses to High Frequency Electromagnetic Fields

High frequency nonionizing electromagnetic fields (HF-EMF) that are increasingly present in the environment constitute a genuine environmental stimulus able to evoke specific responses in plants that share many similarities with those observed after a stressful treatment. Plants constitute an outstanding model to study such interactions since their architecture (high surface area to volume ratio) optimizes their interaction with the environment. In the present review, after identifying the main exposure devices (transverse and gigahertz electromagnetic cells, wave guide, and mode stirred reverberating chamber) and general physics laws that govern EMF interactions with plants, we illustrate some of the observed responses after exposure to HF-EMF at the cellular, molecular, and whole plant scale. Indeed, numerous metabolic activities (reactive oxygen species metabolism, α- and β-amylase, Krebs cycle, pentose phosphate pathway, chlorophyll content, terpene emission, etc.) are modified, gene expression altered (calmodulin, calcium-dependent protein kinase, and proteinase inhibitor), and growth reduced (stem elongation and dry weight) after low power (i.e., nonthermal) HF-EMF exposure. These changes occur not only in the tissues directly exposed but also systemically in distant tissues. While the long-term impact of these metabolic changes remains largely unknown, we propose to consider nonionizing HF-EMF radiation as a noninjurious, genuine environmental factor that readily evokes changes in plant metabolism.

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Formation and Biopharmaceutical Characterization of Electrospun PVP Mats with Propolis and Silver Nanoparticles for Fast Releasing Wound Dressing

Antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory, and anticancer activities of propolis and its ability to stimulate the immune system and promote wound healing make it a proper component for wound dressing materials. Silver nanoparticles are recognized to demonstrate strong antiseptic and antimicrobial activity; thus, it also could be considered in the development of products for wound healing. Combining propolis and silver nanoparticles can result in improved characteristics of products designed for wound healing and care. The aim of this study was to formulate electrospun fast dissolving mats for wound dressing containing propolis ethanolic extract and silver nanoparticles. Produced electrospun nano/microfiber mats were evaluated studying their structure, dissolution rate, release of propolis phenolic compounds and silver nanoparticles, and antimicrobial activity. Biopharmaceutical characterization of electrospun mats demonstrated fast release of propolis phenolic compounds and silver nanoparticles. Evaluation of antimicrobial activity on Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Bacillus cereus, and Candida albicans strains confirmed the ability of electrospun mats to inhibit the growth of the tested microorganisms.

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New Claims for Wild Carrot (Daucus carota subsp. carota) Essential Oil

The essential oil of Daucus carota subsp. carota from Portugal, with high amounts of geranyl acetate (29.0%), α-pinene (27.2%), and 11αH-himachal-4-en-1β-ol (9.2%), was assessed for its biological potential. The antimicrobial activity was evaluated against several Gram-positive and Gram-negative bacteria, yeasts, dermatophytes, and Aspergillus strains. The minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were evaluated showing a significant activity towards Gram-positive bacteria (MIC = 0.32–0.64 μL/mL), Cryptococcus neoformans (0.16 μL/mL), and dermatophytes (0.32–0.64 μL/mL). The inhibition of the germ tube formation and the effect of the oil on Candida albicans biofilms were also unveiled. The oil inhibited more than 50% of filamentation at concentrations as low as 0.04 μL/mL (MIC/128) and decreased both biofilm mass and cell viability. The antioxidant capacity of the oil, as assessed by two in chemico methods, was not relevant. Still, it seems to exhibit some anti-inflammatory potential by decreasing nitric oxide production around 20% in LPS-stimulated macrophages, without decreasing macrophages viability. Moreover, the oils safety profile was assessed on keratinocytes, alveolar epithelial cells, macrophages, and hepatocytes. Overall, the oil demonstrated a safety profile at concentrations below 0.64 μL/mL. The present work highlights the bioactive potential of D. carota subsp. carota suggesting its industrial exploitation.

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Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples -test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: "dependency on others," "loss of power over decision making," and "daily living disruption." Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways.

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Optimized Biotransformation of Icariin into Icariside II by β-Glucosidase from Trichoderma viride Using Central Composite Design Method

A crude -glucosidase has been produced from Trichoderma viride and used to explore a simple method to prepare icariside II from icariin. The crude enzyme has been studied by zymography method and used for hydrolysis of ICA. To achieve a high conversion rate of ICA, various factors have been studied including pH, reaction time, temperature, initial concentration of enzyme, and initial concentration of ICA through central composite design experiments. In the condition of the optimum hydrolysis parameters with pH 4.0, 41°C, 1.0 mg/mL ICA, and 9.8 U/mL crude -glucosidase, the conversion rate of ICA reached 95.03% at 1 h. Moreover, the cytotoxicity test showed that ICA II performed inhibition effects on proliferation of A549 cell, while ICA has no cytotoxicity. It indicated that the hydrolysis transformation study of ICA is valuable for exploration of active new drugs.

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Could In-Home Sensors Surpass Human Observation of People with Parkinson’s at High Risk of Falling? An Ethnographic Study

Self-report underpins our understanding of falls among people with Parkinson's (PwP) as they largely happen unwitnessed at home. In this qualitative study, we used an ethnographic approach to investigate which in-home sensors, in which locations, could gather useful data about fall risk. Over six weeks, we observed five independently mobile PwP at high risk of falling, at home. We made field notes about falls (prior events and concerns) and recorded movement with video, Kinect, and wearable sensors. The three women and two men (aged 71 to 79 years) having moderate or severe Parkinson's were dependent on others and highly sedentary. We most commonly noted balance protection, loss, and restoration during chair transfers, walks across open spaces and through gaps, turns, steps up and down, and tasks in standing (all evident walking between chair and stairs, e.g.). Our unobtrusive sensors were acceptable to participants: they could detect instability during everyday activity at home and potentially guide intervention. Monitoring the route between chair and stairs is likely to give information without invading the privacy of people at high risk of falling, with very limited mobility, who spend most of the day in their sitting rooms.

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Recent Advances and Perspective of Studies on Phlegm Syndrome in Chinese Medicine

This review paper summarized the current situation of studies on the essence of phlegm syndrome and relation between phlegm syndrome, diseases, and therapeutics based on published English articles. In studies on the essence of phlegm syndrome, omic technologies were used to explore the molecular basis of phlegm syndrome; in studies on relation between phlegm syndrome and diseases, discovery of markers of phlegm syndrome in diseases becomes a hotspot; the distribution of phlegm syndromes in some common chronic diseases was found; in the therapy of phlegm syndrome, two therapeutic models, treatment with CM formula and treatment with a combination of CM formula and Western medicine, were used most frequently. It is certainly that using one omic technology is not able to deal with the complexity of phlegm syndrome and that the use of a combination of multiple omic methods will be a trend in future studies. Meanwhile, for rapidly increasing clinical research quality of phlegm syndrome, a series of agreed criteria, such as syndrome diagnostic criteria and efficacy criteria clinical studies of phlegm syndrome, needed to be established urgently, and there was an urgent need of standardizing syndrome names in English.

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The Efficacy of Shen Shuaining Capsule on Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Objective. To evaluate the efficacy of Shen shuaining capsule on treating chronic kidney disease (CKD). Methods. All randomized controlled trials (RCTs) of Shen shuaining capsule in treating CKD were collected from CBM, CNKI, VIP, Wanfang, EMBASE, MEDLINE, PubMed, and Cochrane library clinical controlled trials database. Two reviewers independently performed analysis of the included trials according to the inclusion and exclusion criteria. The risk of bias tool was from the Cochrane Handbook version 5.1.0. The Review Manager 5.2 software was employed for data analysis. Funnel plot and Egger's test were applied to evaluate publication bias. Results. 20 studies including 1606 participants met the inclusion criteria, most of which were of low quality. Meta-analysis indicated that Shen shuaining capsule was effective for CKD in terms of SCR, BUN, Hb, and response rate and with less adverse effects, of which SCR and BUN decreased significantly (MD = −84.72, 95% CI: −107.36, −62.07, ) (MD = −4.30, 95% CI: −5.71, −2.89, ); Hb and response rate increased significantly (MD = 9.94, 95% CI: 9.24, 10.64, ) (OR = 4.25, 95% CI (3.32, 5.42), ). Conclusion. Shen shuaining capsule significantly reduced SCR and BUN, increased HB, and improved total efficiency of the symptoms and signs in patients with CKD. Subgroup analysis found that Shen shuaining capsule group was better than control group. Due to low quality of the methodology of included studies, further high-quality researches were needed to study its efficacy and safety.

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Laryngeal squamous cell carcinoma progression is associated with the NFκB signaling pathway regulated by IκB kinase β

OBJECTIVE: We aimed to analyze the association of NFκB signaling pathway with the carcinogenesis of laryngeal squamous cell carcinoma (LSCC).

PATIENTS AND METHODS: Protein array was used to identify the differentially expressed proteins involved in NFκB signaling pathway between LSCC cells and normal throat mucosa. Correlation analysis between significantly expressed proteins and clinical characteristics (differentiation, clinical stage, and node metastasis) was performed. The expression of IκB kinase-β (IKK-β) in Hep-2 cells transfected with IKK-β-siRNA or pcDNA3.1-IKK-β was detected both by real-time polymerase chain reaction and western blot. Besides, a tetrazolium-based colorimetric assay (MTT), flow cytometer, and transwell assay were used to examine the proliferation, apoptosis, and migration rate of Hep-2 cells, respectively.

RESULTS: Three differentially expressed proteins were identified. Among them, tumor necrosis factor receptor 1 (TNFR1) and IKK-β were significantly up-regulated (p < 0.01) and Fas-associated via death domain (FADD) was significantly down-regulated (p < 0.01). The correlation analysis showed that IKK-β expression had a significant association with differentiation, clinical stage, and node metastasis (p < 0.05). Besides, high expressed IKK-β resulted in significantly increased proliferation and migration rate (p < 0.05). Reversely, Hep-2 cells transfected with IKK-β-siRNA showed significantly lower proliferation and migration rate (p < 0.05) and significantly higher apoptosis rate (p < 0.05) than normal cells.

CONCLUSIONS: The NFκB signaling pathway involved TNFR1, IKK-β, and FADD is significantly associated with the development of LSCC. Over-expressed IKK-β efficiently inhibits cell apoptosis and has positive effects on cell proliferation and migration.

L'articolo Laryngeal squamous cell carcinoma progression is associated with the NFκB signaling pathway regulated by IκB kinase β sembra essere il primo su European Review.

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Cerebrospinal fluid IgG against TB-SA for diagnosis of tuberculous meningitis

OBJECTIVE: A commercial enzyme linked immunosorbent assay (ELISA) detecting cerebrospinal fluid (CSF) IgG against TB-SA (CYPCO TB (IgG) ELISA assay) for diagnosing tuberculous meningitis (TBM) was evaluated retrospectively. Meanwhile, Pandy test was introduced to grade patients, improving its role in the detection of TBM.

PATIENTS AND METHODS: 187 consecutive cases with determined diagnosis were enrolled and divided into TBM group and Non-TBM group. CSFs were collected and sent for Pandy test, cytology, routine biochemistry tests, acid-fast smear and mycobacterial culture. The diagnostic parameters of the ELISA assay were evaluated. Differences in sensitivity between groups were estimated using a McNemar's test.

RESULTS: The overall sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the ELISA assay were 31.6% (95% CI: 21.0-44.5%), 97.7% (95% CI: 93.4-99.2%), 85.8, 76.5, 13.7 and 0.7, respectively. McNemar's test showed the sensitivity of CYPCO TB (IgG) ELISA assay significantly positively correlated with the results of Pandy test (p < 0.05). The ten Pandy test "3+" patients were all TBM. Therefore, patients with "3+" Pandy test are highly suspected of TBM.

CONCLUSIONS: The commercial CYPCO TB (IgG) ELISA assay is able to rapidly confirm a diagnosis of TBM. The sensitivity of the ELISA assay is significantly positively correlated with the results of Pandy test. Patients with "3+" Pandy test are highly suspected of TBM.

L'articolo Cerebrospinal fluid IgG against TB-SA for diagnosis of tuberculous meningitis sembra essere il primo su European Review.

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Renal circulation and microcirculation during intra-abdominal hypertension in a porcine model

OBJECTIVE: The purpose of the study is to further investigate the effects of increased intra-abdominal pressure (IAP) on renal hemodynamics and renal perfusion, and to evaluate the renal cortical and sublingual microcirculation by sidestream dark field (SDF) imaging, both with a porcine model.

MATERIALS AND METHODS: IAP was increased stepwise to 10, 15, 20, 25 mmHg, during which hemodynamic parameters, urinary output, renal contrast-enhanced ultrasound (CEUS), sublingual and renal SDF videos were all recorded from 12 pigs.

RESULTS: Wash in time (WT) and time to peak (TTP) prolonged significantly (p<0.05), while peak intensity (PI) wash in slope (WS) and AUC (area under curve) in CEUS declined significantly (p<0.05) compared with baseline when IAP elevated to 25 mm Hg. With an increase of abdominal pressure, sublingual microvascular flow index (MFI) drop significantly, especially upon IAP was over 20 mmHg. But other parameters such as the total vascular density (TVD), De Backer Score, proportion of perfused vessels (PPV), perfused vessel density (PVD), and heterogeneity index (HI) of tongue were not significantly changed. With increasing IAP, renal vascular resistance increased and MFI decreased about 30%. RFG, instead of RFG showed a moderate correlation with AUC (R=0.47, p<0.05) and MFI (R=0.49, p<0.05).

CONCLUSIONS: CEUS is a safe, real-time dynamic, noninvasive and simple technique to evaluate renal microvascular perfusion in intra-abdominal hypertension. Descending slope, PI and AUC can be used for the diagnosis of the renal microvascular damage in a porcine model of IAP-induced renal impairment. Also, SDF on the surface of the kidney is a useful tool to evaluate the microcirculation of kidney but sublingual SDF imaging was barely useful.

L'articolo Renal circulation and microcirculation during intra-abdominal hypertension in a porcine model sembra essere il primo su European Review.

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Occult urinary incontinence in elderly women and its association with geriatric condition

OBJECTIVE: Many older women are hesitated to initiate discussions about urinary symptoms and their incontinence. The aim of this study is to determine the prevalence of occult urinary incontinence in outpatient older women and to evaluate its association with other geriatric conditions.

PATIENTS AND METHODS: 100 female patients 65 years and older were assessed at the geriatric outpatient clinic. The validated form of the Turkish version of the International Consultation on Incontinence Questionnaire-Short Form was used to evaluate urinary incontinence and quality of life. Comprehensive geriatric assessment including activities of daily living, instrumental activities of daily living, mini mental state examination and geriatrics depression scale was performed. The number of falls, comorbid conditions and number of medications were noted. The association between urinary incontinence and geriatric domains were evaluated with logistic regression analysis.

RESULTS: A total of 100 patients were evaluated, 64 of them included in the study. The median age of patients was 72.5. The rate of urinary incontinence was found 40.6%. The association between urinary incontinence and quality of life, performance status and comorbidity was found statistically significant with logistic regression (p = 0.033, p = 0.005, p = 0.031 respectively). Half of the patients with UI believe that it is part of normal aging and no definite treatment is available.

CONCLUSIONS: Occult urinary incontinence is a significant problem in older women that inversely affecting the quality of life. The study suggests that awareness and education regarding incontinence should be increased among elderly patients and screening of urinary incontinence is an important part of the geriatric assessment. The evaluation and management of functional status and comorbid conditions should be the initial step during incontinence management in elderly patients.

L'articolo Occult urinary incontinence in elderly women and its association with geriatric condition sembra essere il primo su European Review.

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Suppression of collagen-induced arthritis by lipopolysaccharide in DBA/1 mice

OBJECTIVE: Injection of lipopolysaccharide (LPS) has both promotion and inhibition effects on the autoimmune disease. Given the variable roles of LPS in autoimmune diseases, the role of LPS played in collagen-induced arthritis (CIA, autoimmune disease) model remains to be further determined.

MATERIALS AND METHODS: CIA was induced by intradermal injection of collagen type II (CII) in DBA/1 mice (day 0) followed by a booster injection on day 21. Mice of CIA with LPS injection group (CIA+ LPS group) were intraperitoneally injected with 50 µg LPS on day 42. Tissues such as carpal joints and fingers were stained with hematoxylin and eosin (H&E) for histopathology analysis. Inflammation, pannus formation and bone resorption were monitored by a macroscopic scoring system. Serum level of IgG2a antibody was determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS: The incidence of arthritis in CIA group was much higher than that in CIA+ LPS group (100%: 46.5%, p < 0.05), as same as the arthritis score (5.38:1.37, p = 8.16 × 10-6). Besides, the histopathologic score was also higher in CIA group than that in CIA+ LPS group (15.0:5.36). Compared with CIA group, mild synovial hyperplasia and no articular cartilage damage were observed in CIA+ LPS group. Besides, mice of CIA group produced a significantly higher level of IgG2a than CIA+ LPS group (3922 ng/ml: 2084 ng/ml, p = 0.0333) when arthritis developed.

CONCLUSIONS: Our findings showed that LPS might suppress CIA progression under special conditions, opening up a new understanding of the roles of LPS in arthritis and new possibilities for a clinical therapy of CIA.

L'articolo Suppression of collagen-induced arthritis by lipopolysaccharide in DBA/1 mice sembra essere il primo su European Review.

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Expression profile analysis of new candidate genes for the therapy of primary osteoporosis

OBJECTIVE: Primary osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and density which can lead to an increased risk of fracture. Most of present treatments are effective for osteoporosis, but have limitations and side-effects. With the aging of the world population is increasing, the incidence of osteoporosis is rising. Therefore, the purpose of this study was to identify new candidate genes used as the therapeutic targets of primary osteoporosis.

MATERIALS AND METHODS: In this study, microarray data GSE35958 were downloaded from Gene Expression Omnibus, then the differentially expressed genes (DEGs) were identified by limma package. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for both up- and down-regulated DEGs using DAVID. In addition, the transcription factor analysis was conducted for DEGs. The protein-protein interaction (PPI) network was constructed by STRING and Cytoscape. Finally, CFinder was used to analyze the PPI sub-network.

RESULTS: Totally, 327 up-regulated DEGs and 396 down-regulated DEGs were identified. The DEGs such as EGFR and AKT1 were mainly enriched in the pathway of focal adhesion. EGFR was also involved in cell adhesion based on GO enrichment analysis. Functional analysis of DEGs indicated that 26 transcription factors were screened. Moreover, EGFR, AKT1 and transcription factor CTNNB1 were the key nodes with high degrees according to PPI network and sub-network.

CONCLUSIONS: The literature suggested that AKT1, EGFR and CTNNB1 were closely related to osteoblastic differentiation and osteoclastogenesis. Some crucial DEGs such as EGFR, AKT1 and CTNNB1 might be connected with primary osteoporosis and could be used as therapeutic targets of osteoporosis.

L'articolo Expression profile analysis of new candidate genes for the therapy of primary osteoporosis sembra essere il primo su European Review.

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Novel approach of treating Gorham-Stout disease in the humerus – Case report and review of literature

Gorham-Stout disease or the so-called vanishing bone syndrome is a rare disorder characterized by intra-osseous proliferation of vascular channels resulting in destruction and resorption of the osseous matrix. The exact pathology of this disease showed no evidence of malignant, neuropathic, or infectious components involved in the causation of this disorder except for the culprit of lympho-vascular malformations in the bone. The mechanism of bone resorption is yet to be clarified. The clinical presentation of Gorham's disease varies according to the organ of involvement. Patients diagnosed with Gorham's disease in the bone may initially present with insidious onset of dull aching pain, progressive weakness, or pathologic fractures as the initial presentation. Gorham's disease is progressive in most patients; yet it can be self-limiting in a few reported cases. The axes of treating this disease as reported in the literature include the use of medical treatment, surgical intervention, radiotherapy and/or the combination of any them. However, there is no consensus about the most effective approach for treating this rare disease. The challenge in this disease lies in both: how to diagnose and how to treat. Our novel approach combined surgical intervention, medication and radiotherapy as a treatment of Graham-Stout disease in the humerus, and showed no progression of the disease our case.

L'articolo Novel approach of treating Gorham-Stout disease in the humerus – Case report and review of literature sembra essere il primo su European Review.

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Pears and renal stones: possible weapon for prevention? A comprehensive narrative review

Urinary stones have been recognized as a human disease since dawn of history and treatment of this condition is reported by Egyptian medical writings. Also, pears have a very long history, being one of the earliest cultivated fruit trees and also known for medicinal use. Urinary tract stone formation represents a common condition and also a significant burden for health care service, due also to possible frequent relapses. Furthermore, urinary stones have been reported to have relationship with different metabolic derangements, and appropriate diet could contribute to avoid or reduce urinary stone formation. Citrate is an inhibitor of crystal growth in the urinary system, and hypocitraturia represents a main therapeutical target in stone formers. Pears contain a significant amount of malic acid, a precursor of citrate, and have antioxidant activity as well. A diet supplemented with pears, and associated with low consumption of meat and salt could impact positively cardiometabolic risk and urinary tract stone formation. However, very few studies evaluated the impact of pears utilization on health, and none on urinary tract stone formation in particular. High content in malate could warrant protection against stone formation, avoiding patients at high risk to be compelled to assume a considerable and expensive amount of pills.

L'articolo Pears and renal stones: possible weapon for prevention? A comprehensive narrative review sembra essere il primo su European Review.

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Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto’s thyroiditis: a single-blind, controlled clinical study

OBJECTIVE: This study was performed to investigate the levels of platelet activation marker SCUBE-1 and sCD40L which plays some role in the progression of atherosclerosis, in patients with hypothyroidism due to Hashimoto's thyroiditis.

PATIENTS AND METHODS: The cohort of this study includes 90 patients and 35 healthy volunteers, who admitted to the internal medicine out-patient. Simultaneously in the same samples; SCUBE-1 and sCD40L measurements were accomplished by enzyme-linked immunosorbent assay (ELISA). The data obtained were analyzed statistically.

RESULTS: Hypothyroidism due to Hashimoto's thyroiditis in comparison to the control group that includes healthy volunteers; SCUBE-1 and sCD40L, were increased. And these results were statistically significant (p < 0.05).

CONCLUSIONS: SCUBE-1 and sCD40L levels were increased in Hashimoto's hypothyroidism patients. This may indicate an increased endothelial dysfunction, platelet activation and cardiovascular risk in hypothyroidism. SCUBE-1 and sCD40L may be helpful in cardiovascular risk assessment of hypothyroid patients.

L'articolo Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto's thyroiditis: a single-blind, controlled clinical study sembra essere il primo su European Review.

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Hypoxia responsive miR-210 promotes cell survival and autophagy of endometriotic cells in hypoxia

OBJECTIVE: Hypoxia may play a role in the survival of ectopic endometrial cells. This study aimed to explore how hypoxia responsive miR-210 is involved in cell survival and autophagic response of endometriotic cells.

MATERIALS AND METHODS: The expression of hypoxia-inducible factor 1-alpha (HIF-1α) and miR-210 in eutopic and ectopic endometrial tissues were measured. The expression changes of HIF-1α and miR-210 in ovarian endometriotic cell line CRL-7566 after hypoxic culture were further explored. The influence of miR-210 on cell viability and apoptosis was quantified using CCK-8 assay and flow cytometry analysis. The effect of miR-210 on Bcl-2 expression and the effect of miR-210/Bcl-2 axis on autophagy in the cells were measured by Western blot analysis.

RESULTS: Ectopic lesion had stronger HIF-1α positive signals, as well as more HIF-1α positive cells per visual field than the eutopic endometrium. MiR-210 expression was also elevated in the ectopic lesions. In in-vitro models, CRL-7566 cells had significantly higher expression of HIF-1α and miR-210 after hypoxic treatment. MiR-210 overexpression partly preserved cell viability in hypoxia, while miR-210 knockdown facilitated the loss of cell viability. In addition, miR-210 significantly attenuated hypoxia-induced apoptosis in CRL-7566 cells. Enforced miR-210 overexpression significantly promoted autophagy in hypoxia. Knockdown of endogenous Bcl-2 significantly enhanced autophagy, the effect of which was similar to that of miR-210.

CONCLUSIONS: The hypoxia-induced higher miR-210 expression may contribute to pathological development of endometriosis at least through enhancing cell survival and promoting autophagy via Bcl2/Beclin-1 axis.

L'articolo Hypoxia responsive miR-210 promotes cell survival and autophagy of endometriotic cells in hypoxia sembra essere il primo su European Review.

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Challenges, Vol. 7, Pages 4: Use of Bacteriocinogenic Cultures without Inhibiting Cheese Associated Nonstarter Lactic Acid Bacteria; A Trial with Lactobacillus plantarum

Bacteriocinogenic cultures can represent a natural way to increase the safety of cheeses made from raw milk, in which a relevant role in ripening and flavor formation is exerted by the nonstarter lactic acid bacteria (NSLAB). Since the latter can be inhibited by bacteriocin producers, this study evaluated to which extent a nisinogenic culture inoculated at low initial levels can affect the growth rate and peptide degradation activity of the nisin-sensitive cheese isolate Lactobacillus plantarum LZ by comparison with its isogenic variant, L. plantarum LZNI, with increased immunity to nisin. A growth delay of the nisin sensitive strain was observed only when its initial number was 100-fold lower than the nisin producer and nisin was added as an inducer of its own production. In this case, the amount of free α-amino groups was significantly different between cultures of L. plantarum LZ and LZNI only at Day 1. Reverse Phase High Performance Liquid Chromatography (RP-HPLC) highlighted a few differences between the peptide profiles of co-cultures L. plantarum LZ and LZNI. However, results showed that the bacteriocin producer did not dramatically influence the behavior of the sensitive NSLAB and that the evaluation of the effects on microbial contaminants in cheese is worthwhile.

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Agronomy, Vol. 6, Pages 12: Impact of the Disruption of ASN3-Encoding Asparagine Synthetase on Arabidopsis Development

The aim of this study was to investigate the role of ASN3-encoded asparagine synthetase (AS, EC 6.3.5.4) during vegetative growth, seed development and germination of Arabidopsis thaliana. Phenotypic analysis of knockout (asn3-1) and knockdown (asn3-2) T-DNA insertion mutants for the ASN3 gene (At5g10240) demonstrated wild-type contents of asparagine synthetase protein, chlorophyll and ammonium in green leaves at 35 days after sowing. In situ hybridization localized ASN3 mRNA to phloem companion cells of vasculature. Young siliques of the asn3-1 knockout line showed a decrease in asparagine but an increase in glutamate. The seeds of asn3-1 and asn3-2 displayed a wild-type nitrogen status expressed as total nitrogen content, indicating that the repression of ASN3 expression had only a limited effect on mature seeds. An analysis of amino acid labeling of seeds imbibed with (15N) ammonium for 24 h revealed that asn3-1 seeds contained 20% less total asparagine while 15N-labeled asparagine ((2-15N)asparagine, (4-15N)asparagine and (2,4-15N)asparagine) increased by 12% compared to wild-type seeds. The data indicate a fine regulation of asparagine synthesis and hydrolysis in Arabidopsis seeds.

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Micromachines, Vol. 7, Pages 27: Oocytes Polar Body Detection for Automatic Enucleation

Enucleation is a crucial step in cloning. In order to achieve automatic blind enucleation, we should detect the polar body of the oocyte automatically. The conventional polar body detection approaches have low success rate or low efficiency. We propose a polar body detection method based on machine learning in this paper. On one hand, the improved Histogram of Oriented Gradient (HOG) algorithm is employed to extract features of polar body images, which will increase success rate. On the other hand, a position prediction method is put forward to narrow the search range of polar body, which will improve efficiency. Experiment results show that the success rate is 96% for various types of polar bodies. Furthermore, the method is applied to an enucleation experiment and improves the degree of automatic enucleation.

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Pathogens, Vol. 5, Pages 20: Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli

Histone deacetylase 6 (HDAC6) is a non-canonical, mostly cytosolic histone deacetylase that has a variety of interacting partners and substrates. Previous work using cell-culture based assays coupled with pharmacological inhibitors and gene-silencing approaches indicated that HDAC6 promotes the actin- and microtubule-dependent invasion of host cells by uropathogenic Escherichia coli (UPEC). These facultative intracellular pathogens are the major cause of urinary tract infections. Here, we examined the involvement of HDAC6 in bladder colonization by UPEC using HDAC6 knockout mice. Though UPEC was unable to invade HDAC6−/− cells in culture, the bacteria had an enhanced ability to colonize the bladders of mice that lacked HDAC6. This effect was transient, and by six hours post-inoculation bacterial titers in the HDAC6−/− mice were reduced to levels seen in wild type control animals. Subsequent analyses revealed that the mutant mice had greater bladder volume capacity and fluid retention, along with much higher levels of acetylated -tubulin. In addition, infiltrating neutrophils recovered from the HDAC6−/− bladder harbored significantly more viable bacteria than their wild type counterparts. Cumulatively, these changes may negate any inhibitory effects that the lack of HDAC6 has on UPEC entry into individual host cells, and suggest roles for HDAC6 in other urological disorders such as urinary retention.

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Sustainability, Vol. 8, Pages 169: Biochar Based Microbial Fuel Cell for Enhanced Wastewater Treatment and Nutrient Recovery

Waste-wood derived biochar was evaluated for the first time as both an anode and cathode material, simultaneously, in an overflow style microbial fuel cell (MFC) using actual industrial wastewater. Results show that the average chemical oxygen demand (COD) removal was 95% with a reduction rate of 0.53 kg·COD·m−1·d−1 in closed operation mode. The ammonia and phosphorous reductions from wastewater was 73% and 88%, respectively. Stable power production was observed with a peak power density measured at 6 W/m3. Preliminary contributions of physical, biological, and electrochemical COD removals were evaluated, and the results show such combined mechanisms give BC an advantage for MFC applications. Nutrient recovery data showed high levels of macronutrients adsorbed onto the spent biochar electrodes, and phosphorus concentration increased from 0.16 g·kg−1 in raw BC to up to 1.9 g·kg−1 in the cathode. These findings highlight the use of biochar as electrodes in MFCs to facilitate simultaneous wastewater treatment and power production with additional agronomic benefits.

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IJMS, Vol. 17, Pages 36: Drosophotoxicology: An Emerging Research Area for Assessing Nanoparticles Interaction with Living Organisms

The rapid development of nanotechnology allowed the fabrication of a wide range of different nanomaterials, raising many questions about their safety and potential risks for the human health and environment. Most of the current nanotoxicology research is not standardized, hampering any comparison or reproducibility of the obtained results. Drosophotoxicology encompasses the plethora of methodological approaches addressing the use of Drosophila melanogaster as a choice organism in toxicology studies. Drosophila melanogaster model offers several important advantages, such as a relatively simple genome structure, short lifespan, low maintenance cost, readiness of experimental manipulation comparative to vertebrate models from both ethical and technical points of view, relevant gene homology with higher organisms, and ease of obtaining mutant phenotypes. The molecular pathways, as well as multiple behavioral and developmental parameters, can be evaluated using this model in lower, medium or high throughput type assays, allowing a systematic classification of the toxicity levels of different nanomaterials. The purpose of this paper is to review the current research on the applications of Drosophila melanogaster model for the in vivo assessment of nanoparticles toxicity and to reveal the huge potential of this model system to provide results that could enable a proper selection of different nanostructures for a certain biomedical application.

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IJMS, Vol. 17, Pages 36: Drosophotoxicology: An Emerging Research Area for Assessing Nanoparticles Interaction with Living Organisms

The rapid development of nanotechnology allowed the fabrication of a wide range of different nanomaterials, raising many questions about their safety and potential risks for the human health and environment. Most of the current nanotoxicology research is not standardized, hampering any comparison or reproducibility of the obtained results. Drosophotoxicology encompasses the plethora of methodological approaches addressing the use of Drosophila melanogaster as a choice organism in toxicology studies. Drosophila melanogaster model offers several important advantages, such as a relatively simple genome structure, short lifespan, low maintenance cost, readiness of experimental manipulation comparative to vertebrate models from both ethical and technical points of view, relevant gene homology with higher organisms, and ease of obtaining mutant phenotypes. The molecular pathways, as well as multiple behavioral and developmental parameters, can be evaluated using this model in lower, medium or high throughput type assays, allowing a systematic classification of the toxicity levels of different nanomaterials. The purpose of this paper is to review the current research on the applications of Drosophila melanogaster model for the in vivo assessment of nanoparticles toxicity and to reveal the huge potential of this model system to provide results that could enable a proper selection of different nanostructures for a certain biomedical application.

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Information, Vol. 7, Pages 5: The Treewidth of Induced Graphs of Conditional Preference Networks Is Small

Conditional preference networks (CP-nets) are recently an emerging topic as a graphical model for compactly representing ordinal conditional preference relations on multi-attribute domains. As we know, the treewidth, which can decrease the solving complexity for many intractability problems, is exactly a fundamental property of a graph. Therefore, we can utilize treewidth to solve some reasoning tasks on induced graphs, such as the dominance queries on the CP-nets in the future. In this paper, we present an efficient algorithm for computing the treewidth of induced graphs of CP-nets; what we need is to make an assumption that the induced graph of a CP-net has been given. Then, we can leverage the Bucket Elimination technique to solve treewidth within polynomial time. At last, it is revealed that by our experiment, the treewidth of induced graphs of CP-nets is much smaller with regard to the number of vertices. For example, for an induced graph of CP-net with 1024 vertices, its treewidth is only 10. As far as we know, this is the first time, using the Bucket Elimination, to compute the treewidth of an induced graph of a CP-net. This approach for solving the treewidth may lay a good foundation for efficiently solving dominance queries on CP-nets in the future.

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Sustainability, Vol. 8, Pages 153: Measuring the Level of Industrial Green Development and Exploring Its Influencing Factors: Empirical Evidence from China’s 30 Provinces

Nowadays, with the green economy becoming mainstream in the world, an industrial revolution as the core of green development has emerged. Based on the empirical evidence from China's 30 provinces, this study establishes an evaluation index system of China's industrial green development and applies the analytic hierarchy process to determine the indices' weights and properties to measure the level of industrial green development in China's 30 provinces. Then, an empirical study is conducted to explore the relevant factors influencing China's industrial green development by using the dynamic panel data model and a panel threshold test. The results show that China's level of industrial green development has the characteristic of typical regional differentiation with a ladder-like distribution from the east and middle to the west, and the eastern region has the highest level on industrial green output, industrial green efficiency and industrial green innovation. Technological progress and innovation can stimulate industrial green development. The impact of environmental regulation and foreign investment on industrial green development presents a nonlinear "N"-type trend, and the positive effects are mainly observed in eastern China. Capital deepening, heavy chemical industries and an unreasonable energy structure are not effective in industrial green development. There is no direct relation between the enterprise scale and industrial green development.

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Applied Sciences, Vol. 6, Pages 50: Dynamics of Carrier Transport in Nanoscale Materials: Origin of Non-Drude Behavior in the Terahertz Frequency Range

It is known that deviation from the Drude law for free carriers is dramatic in most electronically conductive nanomaterials. We review recent studies of the conductivity of nanoscale materials at terahertz (THz) frequencies. We suggest that among a variety of theoretical formalisms, a model of series sequence of transport involving grains and grain boundaries provides a reasonable explanation of Lorentz-type resonance (non-Drude behavior) in nanomaterials. Of particular interest is why do free carriers exhibit a Lorentz-type resonance.

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Pathogens, Vol. 5, Pages 19: Why Serological Responses during Cystitis are Limited

The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host's memory immune response. It has been known for many decades that, whereas kidney infections evoked an antibody response to the infecting bacteria, infections limited to the bladder failed to do so. We have identified the existence of a broadly immunosuppressive transcriptional program associated with the bladder, but not the kidneys, during infection of the urinary tract that is dependent on bladder mast cells. This involves the localized secretion of IL-10 and results in the suppression of humoral immune responses in the bladder. Mast cell-mediated immune suppression could suggest a role for these cells in critically balancing the needs to clear infections with the imperative to prevent harmful immune reactions in the host.

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Sensors, Vol. 16, Pages 227: Removing the Interdependency between Horizontal and Vertical Eye-Movement Components in Electrooculograms

This paper introduces a method to remove the unwanted interdependency between vertical and horizontal eye-movement components in electrooculograms (EOGs). EOGs have been widely used to estimate eye movements without a camera in a variety of human-computer interaction (HCI) applications using pairs of electrodes generally attached either above and below the eye (vertical EOG) or to the left and right of the eyes (horizontal EOG). It has been well documented that the vertical EOG component has less stability than the horizontal EOG one, making accurate estimation of the vertical location of the eyes difficult. To address this issue, an experiment was designed in which ten subjects participated. Visual inspection of the recorded EOG signals showed that the vertical EOG component is highly influenced by horizontal eye movements, whereas the horizontal EOG is rarely affected by vertical eye movements. Moreover, the results showed that this interdependency could be effectively removed by introducing an individual constant value. It is therefore expected that the proposed method can enhance the overall performance of practical EOG-based eye-tracking systems.

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IJMS, Vol. 17, Pages 143: Hyaluronidase Inhibitory Activity of Pentacylic Triterpenoids from Prismatomeris tetrandra (Roxb.) K. Schum: Isolation, Synthesis and QSAR Study

The mammalian hyaluronidase degrades hyaluronic acid by the cleavage of the β-1,4-glycosidic bond furnishing a tetrasaccharide molecule as the main product which is a highly angiogenic and potent inducer of inflammatory cytokines. Ursolic acid 1, isolated from Prismatomeris tetrandra, was identified as having the potential to develop inhibitors of hyaluronidase. A series of ursolic acid analogues were either synthesized via structure modification of ursolic acid 1 or commercially obtained. The evaluation of the inhibitory activity of these compounds on the hyaluronidase enzyme was conducted. Several structural, topological and quantum chemical descriptors for these compounds were calculated using semi empirical quantum chemical methods. A quantitative structure activity relationship study (QSAR) was performed to correlate these descriptors with the hyaluronidase inhibitory activity. The statistical characteristics provided by the best multi linear model (BML) (R2 = 0.9717, R2cv = 0.9506) indicated satisfactory stability and predictive ability of the developed model. The in silico molecular docking study which was used to determine the binding interactions revealed that the ursolic acid analog 22 had a strong affinity towards human hyaluronidase.

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