Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie
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Biomed. Pharmacother. · Nov 2020
ReviewThe role of IL-1β and TNF-α in intervertebral disc degeneration.
Low back pain (LBP), a prevalent and costly disease around the world, is predominantly caused by intervertebral disc (IVD) degeneration (IDD). LBP also presents a substantial burden to public health and the economy. IDD is mainly caused by aging, trauma, genetic susceptibility, and other factors. ⋯ Therefore, anti-IL-1β and anti-TNF-α therapies may have the potential to alleviate disc degeneration and LBP. In this paper, we reviewed the expression pattern and signal transduction pathways of IL-1β and TNF-α, and we primarily focused on their similar and different roles in IDD. Because IL-1β and TNF-α inhibition have the potential to alleviate IDD, an in-depth understanding of the role of IL-1β and TNF-α in IDD will benefit the development of new treatment methods for disc degeneration with IL-1β and TNF-α at the core.
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Biomed. Pharmacother. · Nov 2020
ReviewInsights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2.
Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. ⋯ Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.
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Biomed. Pharmacother. · Nov 2020
Comparative StudyIn vitro and in vivo antimicrobial activities of a novel piperazine-containing benzothiazinones candidate TZY-5-84 against Mycobacterium tuberculosis.
A piperazine-containing benzothiazinones lead compound PBTZ169, served as DprE1 inhibitor, displays nanomolar bactericidal activity against Mycobacteria tuberculosis. Here, we systematically evaluate anti-tuberculosis activity of one of PBTZ169 analogues, TZY-5-84, in vitro and in vivo. The MIC value of TZY-5-84 against M. tuberculosis H37Rv ranged from 0.014 to 0.015 mg/L, lower than those of INH, RFP and BDQ. ⋯ No antagonism was observed in any combination between TZY-5-84 and seven commonly used anti-tuberculosis drugs in an in vitro checkerboard assay. In murine infection model, TZY-5-84 at lower dosage (12.5 mg/kg) was found to be comparatively efficacious as PBTZ169 at 25 mg/kg. Our research suggests TZY-5-84 can be a promising preclinical candidate for further study on TB treatment.
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Biomed. Pharmacother. · Nov 2020
ReviewACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19.
At the end of 2019, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Currently, it is breaking out globally and posing a serious threat to public health. The typically clinical characteristics of COVID-19 patients were fever and respiratory symptoms, and a proportion of patients were accompanied by extrapulmonary symptoms including cardiac injury, kidney injury, liver injury, digestive tract injury, and neurological symptoms. ⋯ SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.
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Biomed. Pharmacother. · Nov 2020
ReviewMacrophages in pancreatitis: Mechanisms and therapeutic potential.
Macrophages play a crucial role in the pathogenesis of pancreatitis that is a common gastrointestinal disease. Particularly, macrophages differentiate into different phenotypes and exert diverse functions in acute pancreatitis (AP) and chronic pancreatitis (CP), respectively. In AP, macrophages in the pancreas and other related organs are mainly activated and differentiated into a pro-inflammatory M1 phenotype, and furthermore secrete inflammatory cytokines and mediators, causing local inflammation of the pancreas, and even intractable systemic inflammatory response or multiple organ failure. ⋯ The discovery of macrophages in the pathogenesis of pancreatitis has promoted the research of targeted drugs, which provides great potential for the effective treatment of pancreatitis. This paper provides an overview of the roles of various macrophages in the pathogenesis of pancreatitis and the current research status of pancreatitis immunotherapy targeting macrophages. The findings addressed in this review are of considerable significance for understanding the pivotal role of macrophages in pancreatitis.