Cancers, Vol. 10, Pages 178: p53 and the Viral Connection: Back into the Future ‡

Cancers, Vol. 10, Pages 178: p53 and the Viral Connection: Back into the Future ‡

Cancers doi: 10.3390/cancers10060178

Authors: Ronit Aloni-Grinstein Meital Charni-Natan Hilla Solomon Varda Rotter

The discovery of the tumor suppressor p53, through its interactions with proteins of tumor-promoting viruses, paved the way to the understanding of p53 roles in tumor virology. Over the years, accumulating data suggest that WTp53 is involved in the viral life cycle of non-tumor-promoting viruses as well. These include the influenza virus, smallpox and vaccinia viruses, the Zika virus, West Nile virus, Japanese encephalitis virus, Human Immunodeficiency Virus Type 1, Human herpes simplex virus-1, and more. Viruses have learned to manipulate WTp53 through different strategies to improve their replication and spreading in a stage-specific, bidirectional way. While some viruses require active WTp53 for efficient viral replication, others require reduction/inhibition of WTp53 activity. A better understanding of WTp53 functionality in viral life may offer new future clinical approaches, based on WTp53 manipulation, for viral infections.

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Cancers, Vol. 10, Pages 179: Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia

Cancers, Vol. 10, Pages 179: Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia

Cancers doi: 10.3390/cancers10060179

Authors: Jodi J. Lipof Kah Poh Loh Kristen O'Dwyer Jane L. Liesveld

Acute myeloid leukemia (AML) is a disease that affects adults aged 65 years and above, and survival in this population is poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for these patients but is underutilized due to frequent comorbidities and perceived higher risk of treatment-related mortality and non-relapse mortality. Increasing data supports the utility of allo-HCT in fit older patients after intensive chemotherapy resulting in improvement of outcomes. With the development of reduced intensity and non-myeloablative conditioning regimens that are associated with lower rates of treatment-related toxicity and mortality, this has allowed more older patients with AML to receive allo-HCT. In this review, we provide some guidance on appropriate selection of older patients as transplant candidates, benefits and risks associated with allo-HCT, conditioning regimen choice, and stem cell transplant sources as they relate to the conduct of stem cell transplantation in older patients.

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Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study

Abstract

Despite recent advances, chemoimmunotherapy remains a standard for fit previously untreated chronic lymphocytic leukaemia patients. Lenalidomide had activity in early monotherapy trials, but tumour lysis and flare proved major obstacles in its development. We combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab (FR), followed by lenalidomide/rituximab maintenance. In 45 chemo-naive patients, included in this trial, individual tolerability of the combination was highly divergent and no systematic toxicity determining a maximum tolerated dose was found. Grade 3/4 neutropenia (71%) was high, but only 7% experienced grade 3 infections. No tumour lysis or flare > grade 2 was observed, but skin toxicity proved dose-limiting in nine patients (20%). Overall and complete response rates after induction were 89 and 44% by intention-to-treat, respectively. At a median follow-up of 78.7 months, median progression-free survival (PFS) was 60.3 months. Minimal residual disease and immunoglobulin variable region heavy chain mutation state predicted PFS and TP53 mutation most strongly predicted OS. Baseline clinical factors did not predict tolerance to the immunomodulatory drug lenalidomide, but pretreatment immunophenotypes of T cells showed exhausted memory CD4 cells to predict early dose-limiting non-haematologic events. Overall, combining lenalidomide with FR was feasible and effective, but individual changes in the immune system seemed associated with limiting side effects. clinicaltrials.gov (NCT00738829) and EU Clinical Trials Register (www.clinicaltrialsregister.eu, 2008-001430-27)

https://ift.tt/2JrTJMh

Oxidation of 1-N2-etheno-2′-deoxyguanosine by singlet molecular oxygen results in 2′-deoxyguanosine: a pathway to remove exocyclic DNA damage?

Authors: Martinez, Glaucia Regina / Brum, Hulyana / Sassaki, Guilherme Lanzi / de Souza, Lauro Mera / Loureiro, Ana Paula de Melo / de Medeiros, Marisa Helena Gennari / Di Mascio, Paolo


https://ift.tt/2J7iLNz

Frontmatter

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HER2 positive rates are enriched amongst colorectal cancer brain metastases: a study amongst 1920 consecutive patients

https://ift.tt/2LVpjAo

Temozolomide and irinotecan (TEMIRI regimen) as salvage treatment of irinotecan-sensitive advanced colorectal cancer patients bearing MGMT methylation

Abstract

Background

Non-randomized studies showed that temozolomide (TMZ) achieves an average 10% response rate in heavily pretreated metastatic colorectal cancer (mCRC) patients with promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). In this phase II trial, irinotecan and temozolomide (TEMIRI) combination regimen was assessed in irinotecan-sensitive, MGMT methylated/microsatellite stable (MSS) pretreated mCRC patients.

Patients and methods

Key inclusion criteria were: centrally confirmed MGMT methylation by methylation-specific PCR, MSS mCRC, progression after at least two prior chemotherapy regimens for advanced disease and irinotecan-free interval (IFI) >3 months. TEMIRI (TMZ 150mg/sqm on days 1-5 plus irinotecan 100mg/sqm on days1,15 q28 days) was administered for six cycles, followed by maintenance with TMZ. The primary endpoint was overall response rate (ORR). Exploratory translational analyses included MGMT immunoistochemistry (IHC) and methylBEAMing (MB).

Results

Between December 2014 and June 2017, 25 patients were enrolled. The primary endpoint was met, since 6 patients achieved a partial response (ORR 24%, 95% CI, 11%-43%). At a median follow-up of 15.6 months, median progression-free survival (mPFS) and overall survival (mOS) were 4.4 and 13.8 months, respectively. Only 4 (16%) patients had ≥ grade 3 adverse events. All patients whose cancer was MGMT-positive IHC were non-responders. Consistently, patients with MGMT-negative/low tumors had a significantly longer mPFS than others (6.9 versus 2.0 months; HR = 0.29, 95%CI, 0.02-0.41; p = 0.003) and a non-significant trend for longer mOS. MB testing showed similar accuracy.

Conclusions

TEMIRI regimen is a safe and active option in pre-treated, irinotecan-sensitive mCRC patients with MGMT methylation.

https://ift.tt/2Je30V1

Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft tissue sarcomas

Abstract

Background

Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management.

Methods

A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated.

Results

CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared to FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI 1.25-15.72).

Conclusion

CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind^®) in routine clinical practice on FFPE blocks to predict metastatic outcome.

https://ift.tt/2LSkQyp

International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I

Authors: Andrade, Luis E.C. / Klotz, Werner / Herold, Manfred / Conrad, Karsten / Rönnelid, Johan / Fritzler, Marvin J. / von Mühlen, Carlos A. / Satoh, Minoru / Damoiseaux, Jan / Cruvinel, Wilson de Melo / Chan, Edward K.L. /


https://ift.tt/2JgoWC1

Retraction of: External Quality Assessment Programs in the US with an emphasis on urinary sediment testing: the College of American Pathologists experience

Authors: Glassy, Eric F. / Blomberg, David J.


https://ift.tt/2x6MCnL

The Theranos saga and the consequences

Authors: Lackner, Karl J. / Plebani, Mario


https://ift.tt/2wKa2ip

The meteoric rise and dramatic fall of Theranos: lessons learned for the diagnostic industry

Authors: Fiala, Clare / Diamandis, Eleftherios P.


https://ift.tt/2Kgz4aN

Trueness, precision and stability of the LIAISON 1-84 parathyroid hormone (PTH) third-generation assay: comparison to existing intact PTH assays

Authors: Valcour, Andre / Zierold, Claudia / Blocki, Frank A. / Hawkins, Douglas M. / Martin, Kevin J. / Rao, Sudhaker D. / Bonelli, Fabrizio


https://ift.tt/2wzvN4j

Analysis of protein glycation in human fingernail clippings with near-infrared (NIR) spectroscopy as an alternative technique for the diagnosis of diabetes mellitus

Authors: Monteyne, Tinne / Coopman, Renaat / Kishabongo, Antoine S. / Himpe, Jonas / Lapauw, Bruno / Shadid, Samyah / Van Aken, Elisabeth H. / Berenson, Darja / Speeckaert, Marijn M. / De Beer, Thomas / Delanghe, Joris R.


https://ift.tt/2rzsmps

Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations

Authors: Ozarda, Yesim / Higgins, Victoria / Adeli, Khosrow


https://ift.tt/2KHc05U

Quantification of human complement C2 protein using an automated turbidimetric immunoassay

Authors: Tange, Clare Elizabeth / Johnson-Brett, Bridget / Cook, Alex / Stordeur, Patrick / Brohet, Fabian / Jolles, Stephen / Steven, Rachel / Ponsford, Mark / Roberts, Andrew / El-Shanawany, Tariq / Harding, Stephen / Wallis, Gregg / Parker, Antony Richard


https://ift.tt/2FLMGbz

Improved Registration of 3D CT Angiography with X-ray Fluoroscopy for Image Fusion During Transcatheter Aortic Valve Implantation

The aim of this study was to improve the co-registration for image fusion (IF) of pre-interventional CT data with real-time x-ray (XR) fluoroscopy during transfemoral transcatheter aortic valve implantation (TAVI).

https://ift.tt/2LWiqz5

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Here we present a robust method to reprogram primary embryonic fibroblasts into functional cardiomyocytes through overexpression of GATA4, Hand2, Mef2c, Tbx5, miR-1, and miR-133 (GHMT2m) alongside inhibition of TGF-β signaling. Our protocol generates beating cardiomyocytes as early as 7 days post-transduction with up to 60% efficiency.

https://ift.tt/2Je7UBa

Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis

Here, we describe a protocol for a reproducible laser capture microdissection (LCM) for isolating trabecular meshwork (TM) for downstream RNA analysis. The ability to analyze changes in gene expression in the TM will help in understanding the underlying molecular mechanisms of TM-related ocular diseases.

https://ift.tt/2sGInKa

Development of an Electrochemical DNA Biosensor to Detect a Foodborne Pathogen

A protocol for the development of an electrochemical DNA biosensor comprising a polylactic acid-stabilized, gold nanoparticles-modified, screen-printed carbon electrode to detect Vibrio parahaemolyticus is presented.

https://ift.tt/2JdUchG

The Bioactive Substance Secreted by MSC Retards Mouse Aortic Vascular Smooth Muscle Cells Calcification

Background. Vascular calcification, which is associated with low-level chronic inflammation, is a complication that occurs during aging, atherosclerosis, chronic kidney disease, diabetes mellitus, and hyperlipaemia. In this study, we used conditioned media from mesenchymal stem cells (MSC-CM), a source of autologous cytokines, to test the hypothesis that MSC-CM inhibits vascular smooth muscle cell (VSMC) calcification by suppressing inflammation and apoptosis. Methods. VSMCs were treated with β-glycerophosphate (β-GP) to induce calcification and MSC-CM was used as a treatment. Calcium deposition was evaluated using alizarin red and von Kossa staining after a 7-day induction period. Intracellular calcium contents were measured via the o-cresolphthalein complexone method, and alkaline phosphatase (ALP) activity was determined using the para-nitrophenyl phosphate method. The expressions of specific-osteogenic markers, inflammatory cytokines, and apoptosis-associated genes/proteins were examined by real-time polymerase chain reaction or western blotting. Results. MSC-CM inhibited β-GP-induced calcium deposition in VSMCs and decreased intracellular calcium content and ALP activity. Additionally, MSC-CM suppressed the β-GP-induced increases in BMP2, Msx2, Runx2, and osteocalcin expression. Additionally, MSC-CM decreased the expression of TNF-α, IL-1β, and IL-6 in VSMC. MSC-CM also partly blocked β-GP-induced VSMC apoptosis, which was associated with an increase in the Bcl-2/Bax expression ratio and a decrease in caspase-3 expression. Conclusion. Our study results suggest that MSC-CM can inhibit VSMC calcification. This suggests a potential novel clinical application for MSCs in the treatment of vascular calcification and associated diseases.

https://ift.tt/2JfRsAn

The Effect of Breed, Gender, and Acid Stimulation in Dog Saliva Proteome

Saliva gained interest as a potential noninvasive source of biomarkers in humans and that interest starts to be extended also to other animal species. For this purpose, the knowledge of the salivary proteome in healthy conditions and the factors that affect it and how they affect it are necessary. The aim of the present study was to assess the effect that gender and breed have in saliva proteome and the changes in it induced by stimulation with acid. Saliva from 4 different purebred dogs (Portuguese Podengo, Greyhound, Rafeiro Alentejano, and Beagle) of both genders was collected without and after stimulation with lemon juice. SDS-PAGE and two-dimensional gel electrophoresis (2-DE) profiles were compared and the proteins of interest in-gel digested and identified by mass spectrometry. Acid stimulation decreased total protein concentration and the relative amounts of some protein bands/spots. Gender appeared to have minimal effect in saliva proteome, whereas the influence of breed varies. Beagles and Portuguese Podengos were the two breeds with higher differences. In conclusion, stimulation procedures and dog breed should be considered in data analysis when using salivary proteins for diagnostic purposes.

https://ift.tt/2Jen89k

In Vitro and Ex Vivo Chemopreventive Action of Mauritia flexuosa Products

Mauritia flexuosa (Arecaceae), known as "Buriti," is a Brazilian palm tree with high economic potential for local communities. Herein, we investigated the phytochemistry profile and antioxidant potential of M. flexuosa fruits and determined the bioaccessibility of phenolic compounds. Peels revealed upper values for phenols, flavonoids, carotenoids, tannins, and ascorbic acid when compared to the pulps and endocarps. All samples showed capacity to scavenger free radicals (0.5, 1.0, 2.0, 4.0, and 8.0 mg/mL) but peels presented higher scavenger action in all methods explored. Phenolic compounds identified by HPLC displayed reduced bioaccessibility after in vitro simulated gastrointestinal digestion for pulp (38.7%), peel (18.7%), and endocarp (22.3%) extracts (). Buriti fruits also protected rat blood cells against lysis induced by peroxyl radicals. We demonstrated the promising chemopreventive potentialities of M. flexuosa fruits and their by-products and peels with higher quantities of bioactive compounds and phenolic substances before and after in vitro bioaccessibility investigation. In Brazil, these parts are discarded or underused, mainly as feed for ruminant animals. Consequently, it is extremely important to explore nutritional characteristics of these by-products for human/livestock foods and to install biofriendly techniques and sustainable biotechnology handling of natural resources.

https://ift.tt/2JtlrZi

Impact of self-inflicted injury on nontherapeutic laparotomy in patients with abdominal stab wounds

Publication date: Available online 2 June 2018
Source:Injury
Author(s): Shokei Matsumoto, Kei Hayashida, Shintaro Furugori, Masayuki Shimizu, Kazuhiko Sekine, Mitsuhide Kitano
IntroductionBecause Japan has high suicide rates and low violent crime rates, it is likely that most abdominal stab wounds (ASWs) in Japan are self-inflicted. Although physical examination is one of the most important factors in surgical decision making, such evaluations can be difficult in patients with self-inflicted ASWs due to patient agitation and uncooperative behavior. Therefore, the self-inflicted nature of an injury may strongly affect clinical practice, particularly in Japan, but its influence remains uncertain. We hypothesized that the rates of exploratory laparotomy and nontherapeutic laparotomy (NTL) would be higher in self-inflicted patients.MethodsWe reviewed ASW patients from 2004–2014 in the Japan Trauma Data Bank. The rates of exploratory laparotomy and NTL were compared between self-inflicted and non-self-inflicted ASWs.ResultsOf the 1,705 eligible patients, 1,302 patients (76.4%) had self-inflicted ASWs, and 403 patients (23.6%) had non-self-inflicted ASWs. Self-inflicted patients had a significantly higher rate of psychiatric history, but lower injury severity. The in-hospital mortality rate was similar between the two groups (4.5% vs. 5.2%, p = 0.576). Self-inflicted patients had significantly higher rates of exploratory laparotomy and NTL (69.1% vs. 56.7%, p < 0.001, 22.5% vs. 13.6%, p = 0.03, respectively). Self-inflicted patients were also associated with significantly longer hospital stays (10.0 [5.0-21.0] vs. 9.0 [4.0-18.0] days, P = 0.045). In a multivariable analysis, self-inflicted patients were independently associated with exploratory laparotomy (odds ratio [OR], 2.05; 95% confidence interval [CI]: 1.55-2.72) and NTL (OR, 1.61; 95% CI: 1.01-2.56).ConclusionASWs in Japan were predominantly self-inflicted. The clinical patterns of self-inflicted ASWs had some unique features. Patients with self-inflicted ASWs had higher rates of laparotomy and NTL. Further studies are needed to develop a useful protocol specific to self-inflicted ASWs.



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Effect of the Use of Different Acoustic Stimuli on Cortical Auditory Evoked Potentials and Autonomic Cardiac Modulation

Purpose. The aim of this study was to analyze the relationship between Cortical Auditory Evoked Potentials (CAEPs) measurements and autonomic cardiac modulation in relation to different acoustic stimuli and to verify which of these stimuli have more influence on the autonomic nervous system. Methods. Sixty healthy women, aged between 18 and 25 years, participated in this study. Prior to the CAEP examination, blood pressure and resting heart rate were measured using a stethoscope, sphygmomanometer, and the Polar RS800CX cardiofrequency measures. After the collection of these measures, the CAEP test was started simultaneously with the HRV collection. Results. All the HRV indices presented correlations with the components of the CAEPs. During the acoustic stimulation, a predominance of the modulation of the autonomic parasympathetic nervous system was observed. The harmonic and disharmonic stimuli were the ones that presented the most correlations between the measures analyzed in this study. Conclusions. There was an association between CAEP and cardiac autonomic modulation in relation to different acoustic stimuli. Among the acoustic stimuli used in this study, the ones that most influenced the autonomic cardiac modulation were harmonic and disharmonic stimuli, which are acoustically more complex stimuli.

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Can a Traditional Korean Manual Therapy Be a Complementary and Alternative Strategy for Cervicogenic Dizziness? A Study Protocol for a Randomized Controlled Trial

Cervicogenic dizziness is dizziness triggered by movement or positioning of the cervical spine and is often accompanied by neck pain or stiffness. This is a prospective, pragmatic, assessor-blind, randomized controlled trial aimed at testing the efficacy and safety of adjuvant Chuna Manual Therapy (CMT) in patients with cervicogenic dizziness under usual care treatments. Fifty patients with cervicogenic dizziness will be randomly allocated to CMT or usual care (UC) groups in a 1 : 1 ratio. Extensive screening procedures, including examinations for central nervous system problems and nystagmus, will be applied to exclude other dizziness-inducing disorders. The eligible participants will receive 12 sessions of CMT plus UC or only UC over 6 weeks. CMT includes mandatory and discretionary techniques, whereas UC includes electrotherapy, thermotherapy, and patient education. The efficacy will be evaluated primarily as Dizziness Handicap Inventory score. The severity and frequency of dizziness, the level of neck pain or stiffness, and the cervical range of motion will also be evaluated. Safety will be assessed by adverse events. The data will be statistically analyzed at . Trial Registration. This trial was registered with Clinical Research Information Service (CRIS) in Korea, KCT0002565, on 29 November 2017, https://ift.tt/2LR1WYJ.

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Functional Improvements in Parkinson’s Disease Following a Randomized Trial of Yoga

Individuals with Parkinson's Disease (PD) experience significant limitations in motor function, functional gait, postural stability, and balance. These limitations often lead to higher incidences of falls, which have significant complications for individuals with PD. Yoga may improve these functional deficits in individuals with PD. The objective of this study was to determine changes in motor function, functional gait, postural stability, and balance control for community dwelling individuals with PD. This randomized, wait-list controlled pilot study examined the influence of an 8-week yoga intervention for people with PD who met the following inclusion criteria: endorsing a fear of falling, being able to speak English, scoring 4/6 on the minimental state exam, and being willing to attend the intervention twice weekly for 8-weeks. Participants in the yoga group (n=15) experienced improvements in motor function, postural stability, functional gait, and freezing gait, as well as reductions in fall risk. Participants in the wait-list control (n=12) also significantly improved in postural stability, although their fall risk was not reduced. Individuals in the yoga group significantly reduced their fall risk. An 8-week yoga intervention may reduce fall risk and improve postural stability, and functional and freezing gait in individuals with PD. This clinical trial is registered as protocol record Pro00041068 in clinicaltrials.gov.

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Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML

New England Journal of Medicine, Ahead of Print.


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Fecal Microbiota Transplantation for Primary Clostridium difficile Infection

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2LTcS8l

Development of a SCAR Marker-Based Diagnostic Method for the Detection of the Citrus Target Spot Pathogen Pseudofabraea citricarpa

Target spot, a recently observed citrus disease that is caused by Pseudofabraea citricarpa, can cause substantial economic losses in citrus production. In this study, a 797 bp marker specific to Ps. citricarpa was identified via random amplified polymorphic DNA (RAPD) technique. The primer pair Pc-SFP/Pc-SRP, which was designed from RAPD amplicons, was utilized as a sequence-characterized amplified region (SCAR) marker. This marker identified Ps. citricarpa with a single and distinct band of 389 bp but did not amplify DNA from other tested fungal species. The PCR assay was highly sensitive to the target DNA at picogram levels and could reliably amplify Ps. citricarpa sequences with the Pc-SFP/Pc-SRP primer pair. The SCAR marker that was identified in the present study can facilitate rapid decision-making and precise disease forecasting and management.

https://ift.tt/2LiC7zM

Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2Jbr0I9

Fecal Microbiota Transplantation for Primary Clostridium difficile Infection

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2LTcS8l

Anti-Inflammatory Effect of ETAS®50 by Inhibiting Nuclear Factor-κB p65 Nuclear Import in Ultraviolet-B-Irradiated Normal Human Dermal Fibroblasts

Ultraviolet (UV) irradiation induces proinflammatory responses in skin cells, including dermal fibroblasts, accelerating premature skin aging (photoaging). ETAS 50, a standardized extract from the Asparagus officinalis stem, is a novel and unique functional food that suppresses proinflammatory responses of hydrogen peroxide-stimulated skin fibroblasts and interleukin- (IL-) 1β-stimulated hepatocytes. To elucidate its antiphotoaging potencies, we examined whether ETAS 50 treatment after UV-B irradiation attenuates proinflammatory responses of normal human dermal fibroblasts (NHDFs). UV-B-irradiated NHDFs showed reduced levels of the cytosolic inhibitor of nuclear factor-κB α (IκBα) protein and increased levels of nuclear p65 protein. The nuclear factor-κB nuclear translocation inhibitor JSH-23 abolished UV-B irradiation-induced IL-1β mRNA expression, indicating that p65 regulates transcriptional induction. ETAS 50 also markedly suppressed UV-B irradiation-induced increases in IL-1β mRNA levels. Immunofluorescence analysis revealed that ETAS 50 retained p65 in the cytosol after UV-B irradiation. Western blotting also showed that ETAS 50 suppressed the UV-B irradiation-induced increases in nuclear p65 protein. Moreover, ETAS 50 clearly suppressed UV-B irradiation-induced distribution of importin-α protein levels in the nucleus without recovering cytosolic IκBα protein levels. These results suggest that ETAS 50 exerts anti-inflammatory effects on UV-B-irradiated NHDFs by suppressing the nuclear import machinery of p65. Therefore, ETAS 50 may prevent photoaging by suppressing UV irradiation-induced proinflammatory responses of dermal fibroblasts.

https://ift.tt/2szjvDW