Excess pancreatic elastase alters acinar- β cell communication by impairing the mechano-signaling and the PAR2 pathways
Cell Metab. 2023 Jun 16:S1550-4131(23)00184-5. doi: 10.1016/j.cmet.2023.05.007. Online ahead of print.ABSTRACTType 1 (T1D) or type 2 diabetes (T2D) are caused by a deficit of functional insulin-producing β cells. Thus, the identification of β cell trophic agents could allow the development of therapeutic strategies to counteract diabetes. The discovery of SerpinB1, an elastase inhibitor that promotes human β cell growth, prompted us to hypothesize that pancreatic elastase (PE) regulates β cell viability. Here, we report that PE is up-regulated in acinar cells and in islets from T2D patients, and negatively impacts β c...
Source: Cell Metabolism - June 20, 2023 Category: Cytology Authors: Giorgio Basile Amedeo Vetere Jiang Hu Oluwaseun Ijaduola Yi Zhang Ka-Cheuk Liu Amira M Eltony Dario F De Jesus Kazuki Fukuda Grace Doherty Colin A Leech Oleg G Chepurny George G Holz Seok-Hyun Yun Olov Andersson Amit Choudhary Bridget K Wagner Rohit N Kul Source Type: research
Interventions for dialysis patients with hepatitis C virus (HCV) infection
CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.PMID:37096802 | PMC:PMC10130818 | DOI:10.1002/14651858.CD007003.pub3 (Source: Cochrane Database o...
Source: Cochrane Database of Systematic Reviews - April 25, 2023 Category: General Medicine Authors: Attur Ravindra Prabhu Indu Ramachandra Rao Shankar Prasad Nagaraju Eti Rajwar Bhumika T Venkatesh Sreekumaran Nair N Ganesh Pai Nageswara P Reddy Deepak Suvarna Source Type: research
Interventions for dialysis patients with hepatitis C virus (HCV) infection
CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.PMID:37096802 | PMC:PMC10130818 | DOI:10.1002/14651858.CD007003.pub3 (Source: Cochrane Database o...
Source: Cochrane Database of Systematic Reviews - April 25, 2023 Category: General Medicine Authors: Attur Ravindra Prabhu Indu Ramachandra Rao Shankar Prasad Nagaraju Eti Rajwar Bhumika T Venkatesh Sreekumaran Nair N Ganesh Pai Nageswara P Reddy Deepak Suvarna Source Type: research
Interventions for dialysis patients with hepatitis C virus (HCV) infection
CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.PMID:37096802 | DOI:10.1002/14651858.CD007003.pub3 (Source: Cochrane Database of Systematic Reviews)
Source: Cochrane Database of Systematic Reviews - April 25, 2023 Category: General Medicine Authors: Attur Ravindra Prabhu Indu Ramachandra Rao Shankar Prasad Nagaraju Eti Rajwar Bhumika T Venkatesh Sreekumaran Nair N Ganesh Pai Nageswara P Reddy Deepak Suvarna Source Type: research
Molecules, Vol. 28, Pages 3020: Development of FRET and Stress Granule Dual-Based System to Screen for Viral 3C Protease Inhibitors
Zhigang Jin
3C proteases (3Cpros) of picornaviruses and 3C-like proteases (3CLpros) of coronaviruses and caliciviruses represent a group of structurally and functionally related viral proteases that play pleiotropic roles in supporting the viral life cycle and subverting host antiviral responses. The design and screening for 3C/3CLpro inhibitors may contribute to the development broad-spectrum antiviral therapeutics against viral diseases related to these three families. However, current screening strategies cannot simultaneously assess a compound’s cytotoxicity and its impact on enzymatic activity and ...
Source: Molecules - March 28, 2023 Category: Chemistry Authors: Jingjing Zhang Yingpei Jiang Chunxiu Wu Dan Zhou Jufang Gong Tiejun Zhao Zhigang Jin Tags: Article Source Type: research
An in-silico pharmacophore-based molecular docking study to evaluate the inhibitory potentials of novel fungal triterpenoid Astrakurkurone analogues against a hypothetical mutated main protease of SARS-CoV-2 virus
CONCLUSION: To conclude, Astrakurkurone analogues ZINC89341287 and ZINC12128321 can be potential therapeutic agents against the highly infectious SARS-CoV-2 virus.PMID:36565483 | DOI:10.1016/j.compbiomed.2022.106433 (Source: Molecular Medicine)
Source: Molecular Medicine - December 24, 2022 Category: Molecular Biology Authors: Anish Nag Adhiraj Dasgupta Sutirtha Sengupta Tapan Kumar Lai Krishnendu Acharya Source Type: research
An in-silico pharmacophore-based molecular docking study to evaluate the inhibitory potentials of novel fungal triterpenoid Astrakurkurone analogues against a hypothetical mutated main protease of SARS-CoV-2 virus
CONCLUSION: To conclude, Astrakurkurone analogues ZINC89341287 and ZINC12128321 can be potential therapeutic agents against the highly infectious SARS-CoV-2 virus.PMID:36565483 | DOI:10.1016/j.compbiomed.2022.106433 (Source: Molecular Medicine)
Source: Molecular Medicine - December 24, 2022 Category: Molecular Biology Authors: Anish Nag Adhiraj Dasgupta Sutirtha Sengupta Tapan Kumar Lai Krishnendu Acharya Source Type: research
Virus-CKB 2.0: Viral-Associated Disease-Specific Chemogenomics Knowledgebase
ACS Omega. 2022 Oct 10;7(42):37476-37484. doi: 10.1021/acsomega.2c04258. eCollection 2022 Oct 25.ABSTRACTTransmissible and infectious viruses can cause large-scale epidemics around the world. This is because the virus can constantly mutate and produce different variants and subvariants to counter existing treatments. Therefore, a variety of treatments are urgently needed to keep up with the mutation of the viruses. To facilitate the research of such treatment, we updated our Virus-CKB 1.0 to Virus-CKB 2.0, which contains 10 kinds of viruses, including enterovirus, dengue virus, hepatitis C virus, Zika virus, herpes simplex...
Source: Herpes - October 31, 2022 Category: Infectious Diseases Authors: Yixuan Hao Maozi Chen Yasmin Othman Xiang-Qun Xie Zhiwei Feng Source Type: research
Virus-CKB 2.0: Viral-Associated Disease-Specific Chemogenomics Knowledgebase
ACS Omega. 2022 Oct 10;7(42):37476-37484. doi: 10.1021/acsomega.2c04258. eCollection 2022 Oct 25.ABSTRACTTransmissible and infectious viruses can cause large-scale epidemics around the world. This is because the virus can constantly mutate and produce different variants and subvariants to counter existing treatments. Therefore, a variety of treatments are urgently needed to keep up with the mutation of the viruses. To facilitate the research of such treatment, we updated our Virus-CKB 1.0 to Virus-CKB 2.0, which contains 10 kinds of viruses, including enterovirus, dengue virus, hepatitis C virus, Zika virus, herpes simplex...
Source: Herpes - October 31, 2022 Category: Infectious Diseases Authors: Yixuan Hao Maozi Chen Yasmin Othman Xiang-Qun Xie Zhiwei Feng Source Type: research
Molecules, Vol. 27, Pages 4292: From Repurposing to Redesign: Optimization of Boceprevir to Highly Potent Inhibitors of the SARS-CoV-2 Main Protease
Hilgenfeld
The main protease (Mpro) of the betacoronavirus SARS-CoV-2 is an attractive target for the development of treatments for COVID-19. Structure-based design is a successful approach to discovering new inhibitors of the Mpro. Starting from crystal structures of the Mpro in complexes with the Hepatitis C virus NS3/4A protease inhibitors boceprevir and telaprevir, we optimized the potency of the alpha-ketoamide boceprevir against the Mpro by replacing its P1 cyclobutyl moiety by a γ-lactam as a glutamine surrogate. The resulting compound, MG-78, exhibited an IC50 of 13 nM versus the recombinant Mpro...
Source: Molecules - July 4, 2022 Category: Chemistry Authors: Matthias G öhl Linlin Zhang Haifa El Kilani Xinyuanyuan Sun Kaixuan Zhang Mark Br önstrup Rolf Hilgenfeld Tags: Article Source Type: research
Adoption of new therapies in the treatment of hepatitis: a verification of the accuracy of Budget Impact Analysis to guide investment decisions
CONCLUSION: This study demonstrates appreciable divergence (US$156.58 million) between the theoretical budget impact and RWE expenditures due to underestimated purchase prices and overestimated populations. The greater the degree of accuracy the more reliable and usable BIAs become for decision making.PMID:35320682 | DOI:10.1080/14737167.2022.2057950 (Source: Expert Review of Pharmacoeconomics and Outcomes Research)
Source: Expert Review of Pharmacoeconomics and Outcomes Research - March 23, 2022 Category: Health Management Authors: Daniel Resende Faleiros Everton Nunes da Silva Andreia C Santos Brian B Godman Ramon Goncalves Pereira Augusto A Guerra Junior Source Type: research
