Phytochemicals and Medicinal Properties of Indigenous Tropical Fruits with Potential for Commercial Development

Hundreds of fruit-bearing trees are native to Southeast Asia, but many of them are considered as indigenous or underutilized. These species can be categorized as indigenous tropical fruits with potential for commercial development and those possible for commercial development. Many of these fruits are considered as underutilized unless the commercialization is being realized despite the fact that they have the developmental potential. This review discusses seven indigenous tropical fruits from 15 species that have been identified, in which their fruits are having potential for commercial development. As they are not as popular as the commercially available fruits, limited information is found. This paper is the first initiative to provide information on the phytochemicals and potential medicinal uses of these fruits. Phytochemicals detected in these fruits are mainly the phenolic compounds, carotenoids, and other terpenoids. Most of these phytochemicals are potent antioxidants and have corresponded to the free radical scavenging activities and other biological activities of the fruits. The scientific research that covered a broad range of in vitro to in vivo studies on the medicinal potentials of these fruits is also discussed in detail. The current review is an update for researchers to have a better understanding of the species, which simultaneously can provide awareness to enhance their commercial value and promote their utilization for better biodiversity conservation.

from #Medicine via ola Kala on Inoreader http://ift.tt/1Y17LEA
via IFTTT

Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation

Publication date: August 2016
Source:Free Radical Biology and Medicine, Volume 97
Author(s): Wen-Jing Yan, Qi Wang, Cui-Hong Yuan, Fu Wang, Yuan Ji, Fang Dai, Xiao-Ling Jin, Bo Zhou
Piperlongumine (PL), a natural electrophilic alkaloid bearing two α, β-unsaturated imides, is a promising anticancer molecule by targeting the stress response to reactive oxygen species (ROS). Considering that ROS generation depends on electrophilicity of PL, PL-CL was designed as its analog by introducing the α-substituent chlorine on the lactam ring to increase moderately its electrophilicity. In comparison with the parent molecule, this molecule was identified as a stronger ROS (O2^∙− and H2O2) inducer and cytotoxic agent, and manifested more than 15-fold selectivity toward A549 cells over normal WI-38 cells. Mechanistic study uncovers for the first time that the selenoprotein thioredoxin reductase (TrxR) is one of the targets by which PL-CL promotes the ROS generation. Stronger intracellular TrxR inhibition and higher accumulation of ROS (O2^∙− and H2O2) are responsible for more effective S-phase arrest and mitochondria-mediated apoptotic induction of A549 cells by PL-CL than PLvia p53-p21-cyclinA/CDK2 and ASK1-JNK/p38 signaling cascade pathways, respectively. This work provides an example of successfully designing PL-directed anticancer agent by an electrophilicity-based prooxidant (ROS-generating agent) strategy and gives added confidence for extending this strategy to other natural products.

Graphical abstract

from #Medicine via ola Kala on Inoreader http://ift.tt/1Ub3Gba
via IFTTT

Detailed protocol to assess in vivo and ex vivo myeloperoxidase activity in mouse models of vascular inflammation and disease using hydroethidine

Publication date: August 2016
Source:Free Radical Biology and Medicine, Volume 97
Author(s): Jihan Talib, Ghassan J. Maghzal, David Cheng, Roland Stocker
Myeloperoxidase (MPO) activity contributes to arterial inflammation, vascular dysfunction and disease, including atherosclerosis. Current assessment of MPO activity in biological systems in vivo utilizes 3-chlorotyrosine (3-Cl-Tyr) as a biomarker of hypochlorous acid (HOCl) and other chlorinating species. However, 3-Cl-Tyr is formed in low yield and is subject to further metabolism. Recently, we reported a method to selectively assess MPO-activity in vivo by measuring the conversion of hydroethidine to 2-chloroethidium (2-Cl-E⁺) by liquid chromatography with tandem mass spectrometry (LC–MS/MS) (J. Biol. Chem., 289, 2014, pp. 5580–5595). The hydroethidine-based method has greater sensitivity for MPO activity than measurement of 3-Cl-Tyr. The current methods paper provides a detailed protocol to determine in vivo and ex vivo MPO activity in arteries from mouse models of vascular inflammation and disease by utilizing the conversion of hydroethidine to 2-Cl-E⁺. Procedures for the synthesis of standards, preparation of tissue homogenates and the generation of 2-Cl-E⁺ are also provided in detail, as are the conditions for LC–MS/MS detection of 2-Cl-E⁺.



from #Medicine via ola Kala on Inoreader http://ift.tt/1Ub3B7r
via IFTTT

Natural resource-based industries and prostate cancer risk in Northeastern Ontario: a case-control study

Objective

Prostate cancer continues to be the most commonly diagnosed cancer in men, and there is limited knowledge on its preventable risk factors. A number of occupational exposures in natural resource-based industries are suspected to be related to prostate cancer risk. This study investigates associations between employment in these industries and prostate cancer.

Methods

Data were from a population-based, case–control study previously conducted in Northeastern Ontario. Incident cases (N=760) aged 45–85 years and diagnosed with prostate cancer between 1995 and 1998 were identified from the Ontario Cancer Registry. Controls (N=1632) were recruited using telephone listings, and were frequency matched to cases by age. Lifetime occupational history was collected for all participants. Logistic regression was used to estimate ORs and their associated 95% CIs.

Results

Elevated risks were observed for employment in forestry and logging industries (OR=1.87, 95% CI 1.32 to 2.73) and occupations (OR=1.71, 95% CI 1.24 to 2.35), and these risks increased with duration of employment for ≥10 years. Elevated risks were also found for employment in wood products industries (OR=1.45, 95% CI 1.07 to 1.97), and paper and allied products industries (OR=1.43, 95% CI 1.03 to 2.00), and when duration of employment was ≥10 years. There were also elevated risks in agriculture and mining-related work; however, these findings were not consistent across industry and occupation categories.

Conclusions

Prostate cancer risk may be associated with work in several natural resource industries, primarily in the forest industries. To further evaluate observed associations, studies should focus on natural resource-based exposures in larger populations with improved exposure assessment.

from #Medicine via ola Kala on Inoreader http://ift.tt/1O2eNH0
via IFTTT

Simple benchmark for mesothelioma projection for Great Britain

Background

It is of considerable interest to forecast the future burden of mesothelioma mortality. Data on deaths are available, whereas no measure of asbestos exposure is available.

Methods

We compare two Poisson models: a response-only model with an age-cohort specification and a multinomial model with epidemiologically motivated frequencies.

Results

The response-only model has 5% higher peak mortality than the dose–response model. The former performs slightly better in out-of-sample comparison.

Conclusions

Mortality is predicted to peak at about 2100 deaths around 2017 among males in cohorts until 1966 and below 90 years of age. The response-only model is a simple benchmark that forecasts just as well as more complicated models.

from #Medicine via ola Kala on Inoreader http://ift.tt/1Ub3CrS
via IFTTT

Subchronic oral administration of crude khat extract (Catha edulis forsk) induces schizophernic-like symptoms in mice

Chewing fresh leaves of the khat plant (Catha edulis forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat on healt...

from #Medicine via ola Kala on Inoreader http://ift.tt/1UaYzYw
via IFTTT

Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells

Apoptosis of endothelial cells caused by reactive oxygen species plays an important role in ischemia/reperfusion injury after cerebral infarction. Buyang Huanwu Decoction (BYHWD) has been used to treat stroke ...

from #Medicine via ola Kala on Inoreader http://ift.tt/1VsU4xw
via IFTTT

Amomum cardamomum L. ethyl acetate fraction protects against carbon tetrachloride-induced liver injury via an antioxidant mechanism in rats

Medicinal herb-derived drug development has become important in the relief of liver pathology. Amomun cardamomum is traditionally used therapeutically in Korea to treat various human ailments including dyspepsia,...

from #Medicine via ola Kala on Inoreader http://ift.tt/1UaYB2u
via IFTTT

Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21 waf-1

Abstract

Stress-induced premature senescence (SIPS) is quite similar to replicative senescence that is committed by cells exposed to various stress conditions viz. ultraviolet radiation (DNA damage), hydrogen peroxide (oxidative stress), chemotherapeutic agents (cytotoxic threat), etc. Here, we report that cristacarpin, a natural product obtained from the stem bark of Erythrina suberosa, promotes endoplasmic reticulum (ER) stress, leading to sub-lethal reactive oxygen species (ROS) generation and which eventually terminates by triggering senescence in pancreatic and breast cancer cells through blocking the cell cycle in the G1 phase. The majority of cristacarpin-treated cells responded to conventional SA-β-gal stains; showed characteristic p21^waf1 upregulation along with enlarged and flattened morphology; and increased volume, granularity, and formation of heterochromatin foci—all of these features are the hallmarks of senescence. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly reduced the expression of p21^waf1, confirming that the modulation in p21^waf1 by anti-proliferative cristacarpin was ROS dependent. Further, the elevation in p21^waf1 expression in PANC-1 and MCF-7 cells was consistent with the decrease in the expression of Cdk-2 and cyclinD1. Here, we provide evidence that cristacarpin promotes senescence in a p53-independent manner. Moreover, cristacarpin treatment induced p38MAPK, indicating the ROS-dependent activation of the MAP kinase pathway, and thus abrogates the tumor growth in mouse allograft tumor model.

from #Medicine via ola Kala on Inoreader http://ift.tt/1TV31yq
via IFTTT

Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats

Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: 100, 400, and 800 mg·kg−1·day−1 (CJF 100, 400, and 800, resp.). Our results showed that CJF possessed strong cholesterol-lowering potency as indicated by the decrease in serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), accompanied by an increase in serum high-density lipoprotein (HDL). Furthermore, CJF reduced serum lipid peroxidation by suppressing the formation of thiobarbituric acid reactive substance. In addition, oil red O (ORO) staining of rat arteries showed decreased lipid-positive staining in the CJF-treated groups compared to the control HFD group. Taken together, these results suggest that CJF could be a potent herbal therapeutic option and source of a functional food for the prevention and treatment of atherosclerosis and other diseases associated with hypercholesterolemia.

from #Medicine via ola Kala on Inoreader http://ift.tt/1r0m6nl
via IFTTT

Inductive Effect of Palmatine on Apoptosis in RAW 264.7 Cells

Osteoporosis is a serious public health problem characterized by low bone density and deterioration of the bone microarchitecture. Current treatment options target either osteoclast resorption or osteoblast formation. It has been reported that berberine, a close structural analog of palmatine, inhibited bone loss in an osteoporosis model. In this study, osseous metabolism was observed in vitro with osteoclast bone resorbing cells. We proved that mouse preosteoclastic cell line (RAW 264.7) has a higher sensitivity to palmatine than mouse osteoblastic cell line (MC3T3-E1); the cell survival rates significantly decreased at 40 μM palmatine. The level, a metabolic product of nitric monoxide (NO), and iNOS mRNA expression, an osteoclast with NO induced enzyme, also increased with higher dosage of palmatine. Furthermore, it was recognized that the cell viability decrease from palmatine was caused by apoptosis rather than necrosis. Additionally, osteoclast apoptosis from palmatine did not occur when iNOS was inhibited with -nitro-L-arginine methyl ester hydrochloride (pan NOS inhibitor). These results indicate that palmatine plays an important role in osteoclast apoptosis via the NOS system. Hence, palmatine could be considered as a viable pharmaceutical candidate for osteoporosis bone resorption inhibitor.

from #Medicine via ola Kala on Inoreader http://ift.tt/1Urr2fd
via IFTTT

IJMS, Vol. 17, Pages 700: Pesticides Drive Stochastic Changes in the Chemoreception and Neurotransmission System of Marine Ectoparasites

Scientific efforts to elucidate the mechanisms of chemical communication between organisms in marine environments are increasing. This study applied novel molecular technology to outline the effects of two xenobiotic drugs, deltamethrin (DM) and azamethiphos (AZA), on the neurotransmission system of the copepod ectoparasite Caligus rogercresseyi. Transcriptome sequencing and bioinformatics analyses were conducted to evaluate treatment effects on the glutamatergic synaptic pathway of the parasite, which is closely related to chemoreception and neurotransmission. After drug treatment with DM or AZA, stochastic mRNA expression patterns of glutamatergic synapse pathway components were observed. Both DM and AZA promoted a down-regulation of the glutamate-ammonia ligase, and DM activated a metabotropic glutamate receptor that is a suggested inhibitor of neurotransmission. Furthermore, the delousing drugs drove complex rearrangements in the distribution of mapped reads for specific metabotropic glutamate receptor domains. This study introduces a novel methodological approach that produces high-quality results from transcriptomic data. Using this approach, DM and AZA were found to alter the expression of numerous mRNAs tightly linked to the glutamatergic signaling pathway. These data suggest possible new targets for xenobiotic drugs that play key roles in the delousing effects of antiparasitics in sea lice.

from #Medicine via ola Kala on Inoreader http://ift.tt/25ypLvH
via IFTTT

Impact of the increased adoption of prenatal cfDNA screening on non-profit patient advocacy organizations in the United States

Abstract

The "Stakeholder Perspectives on Noninvasive Prenatal Genetic Screening" Symposium was held in conjunction with the 2015 annual meeting of the International Society for Prenatal Diagnosis. During the day-long meeting, a panel of patient advocacy group (PAG) representatives discussed concerns and challenges raised by prenatal cfDNA screening, which has resulted in larger demands upon PAGs from concerned patients receiving prenatal cfDNA screening results. Prominent concerns included confusion about the accuracy of cfDNA screening and a lack of patient education resources about genetic conditions included in cfDNA screens. Some of the challenges faced by PAGs included funding limitations; lack of consistently implemented standards of care and oversight; diverse perspectives among PAGs and questions about neutrality; and lack of access to training and genetic counselors. PAG representatives also put forward suggestions for addressing these challenges, including improving educational and PAG funding and increasing collaboration between PAGs and the medical community.

from #Medicine via ola Kala on Inoreader http://ift.tt/22vIHWF
via IFTTT

Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention

Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular-guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents.

from #Medicine via ola Kala on Inoreader http://ift.tt/1XbGNuQ
via IFTTT

Automated multistructure atlas-assisted detection of lymph nodes using pelvic MR lymphography in prostate cancer patients

Purpose:

To investigate whether atlas-based anatomical information can improve a fully automated lymph node detection system for pelvic MR lymphography (MRL) images of patients with prostate cancer.

Methods:

Their data set contained MRL images of 240 prostate cancer patients who had an MRL as part of their clinical work-up between January 2008 and April 2010, with ferumoxtran-10 as contrast agent. Each MRL consisted of at least a 3D T1-weighted sequence, a 3D T2*-weighted sequence, and a FLASH-3D sequence. The reference standard was created by two expert readers, reading in consensus, who annotated and interactively segmented the lymph nodes in all MRL studies. A total of 5089 lymph nodes were annotated. A fully automated computer-aided detection (CAD) system was developed to find lymph nodes in the MRL studies. The system incorporates voxel features based on image intensities, the Hessian matrix, and spatial position. After feature calculation, a GentleBoost-classifier in combination with local maxima detection was used to identify lymph node candidates. Multiatlas based anatomical information was added to the CAD system to assess whether this could improve performance. Using histogram analysis and free-receiver operating characteristic analysis, this was compared to a strategy where relative position features were used to encode anatomical information.

Results:

Adding atlas-based anatomical information to the CAD system reduced false positive detections both visually and quantitatively. Median likelihood values of false positives decreased significantly in all annotated anatomical structures. The sensitivity increased from 53% to 70% at 10 false positives per lymph node.

Conclusions:

Adding anatomical information through atlas registration significantly improves an automated lymph node detection system for MRL images.

from #Medicine via ola Kala on Inoreader http://ift.tt/1RIXCF4
via IFTTT

Oxidative Stress Relevance in the Pathogenesis of the Rheumatoid Arthritis: A Systematic Review

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease whose pathogenic mechanisms remain to be elucidated. The oxidative stress and antioxidants play an important role in the disease process of RA. The study of oxidants and antioxidants biomarkers in RA patients could improve our understanding of disease pathogenesis; likely determining the oxidative stress levels in these patients could prove helpful in assessing disease activity and might also have prognostic implications. To date, the usefulness of oxidative stress biomarkers in RA patients is unclear and the evidence supporting them is heterogeneous. In order to resume and update the information in the status of oxidants and antioxidants and their connection as biomarkers in RA, we performed a systematic literature search in the PubMed database, including clinical trials published in the last five years using the word combination "rheumatoid arthritis oxidative stress". In conclusion, this review supports the fact that the oxidative stress is an active process in RA pathogenesis interrelated to other better known pathogenic elements. However, some controversial results preclude a definite conclusion.

from #Medicine via ola Kala on Inoreader http://ift.tt/1WWrLbM
via IFTTT

IJMS, Vol. 17, Pages 700: Pesticides Drive Stochastic Changes in the Chemoreception and Neurotransmission System of Marine Ectoparasites

Scientific efforts to elucidate the mechanisms of chemical communication between organisms in marine environments are increasing. This study applied novel molecular technology to outline the effects of two xenobiotic drugs, deltamethrin (DM) and azamethiphos (AZA), on the neurotransmission system of the copepod ectoparasite Caligus rogercresseyi. Transcriptome sequencing and bioinformatics analyses were conducted to evaluate treatment effects on the glutamatergic synaptic pathway of the parasite, which is closely related to chemoreception and neurotransmission. After drug treatment with DM or AZA, stochastic mRNA expression patterns of glutamatergic synapse pathway components were observed. Both DM and AZA promoted a down-regulation of the glutamate-ammonia ligase, and DM activated a metabotropic glutamate receptor that is a suggested inhibitor of neurotransmission. Furthermore, the delousing drugs drove complex rearrangements in the distribution of mapped reads for specific metabotropic glutamate receptor domains. This study introduces a novel methodological approach that produces high-quality results from transcriptomic data. Using this approach, DM and AZA were found to alter the expression of numerous mRNAs tightly linked to the glutamatergic signaling pathway. These data suggest possible new targets for xenobiotic drugs that play key roles in the delousing effects of antiparasitics in sea lice.

from #Medicine via ola Kala on Inoreader http://ift.tt/25ypLvH
via IFTTT