As of April 9, 2020, a novel coronavirus (SARS‐CoV‐2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, ...little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS‐CoV‐2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS‐CoV‐2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS‐CoV‐2.
Corona Virus Disease 2019 (COVID-19) broke out in 2019 and spread rapidly around the world. There is still no specific antiviral therapy to the current pandemic. In China, historical records show ...that Traditional Chinese Medicine (TCM) is effective in prevention and enhancing the resistance to pandemic with unique insights. To fight with COVID-19, National Health and Commission of PRC has recommended some TCM in the guideline, such as HuoxiangZhengqi, LianhuaQingwen ShufengJiedu and XueBijing, and actually displayed a remarkable effect in clinical treatment strategic for COVID-19. We review studies to provide an in-depth understanding into the effect of TCM, and also introduce the possible mechanism involved in COVID-19 treatment. Keywords: Traditional Chinese medicine, SARS-CoV-2, COVID-19, Treatment, Mechanism
The conventional grid displacements-based implementation of the extended peridynamic model with bond rotation may give rise to some difficulty in predicting non-uniform deformation field, essentially ...due to the existence of local rigid rotation in solid. This paper presents a novel alternative local strain-based implementation technique for handling the numerical issue. The key is to formulate the relative displacement between particles in terms of the strain tensor approximated locally rather than the direct use of displacements at peridynamic particles. It is critically proved that bond stretch is independent of the rigid rotation tensor. Local strain is thus required only for approximating local shear deformation. The model is currently implemented for static problems in a hybrid manner and in a finite element/peridynamics coupling framework, the latter allowing direct and correct imposition of boundary conditions. To illustrate the performance of the proposed method in numerical accuracy and computational efficiency, various examples are performed with varying Poisson’s ratio and comparisons with the results from finite element analysis are presented.
•A novel hybrid implementation method for the peridynamic model with bond rotation.•Shear displacement measured via local strain to eliminate the influence of rigid rotation.•FEM/PD coupling for direct and correct imposition of boundary conditions.•Validation and simulation with a large range of the values of Poisson’s ratio.
A porous MOF platform (SNNU-65s) formed by creatively combining paddle-wheel-like Cu2(COO)4 and trigonal prismatic M3(μ3-O)(COO)6 building blocks was designed herein. The mixed and high-density open ...metal sites and the OH-functionalized pore surface promote SNNU-65s to exhibit ultra-high C2H2 uptake and separation performance. Impressively, SNNU-65-Cu-Ga stands out for the highest C2H2/CO2 (18.7) and C2H2/CH4 (120.6) selectivity among all the reported MOFs at room temperature.
Objectives
miR‐92b has been reported to play critical roles in several carcinomas; however, our understanding of the mechanisms by which miR‐92b stimulates gastric cancer (GC) is incomplete. The aim ...of this study was to investigate the clinical significance and functional relevance of miR‐92b in GC.
Materials and methods
Expression of miR‐92b in GC and peritumoural tissues was determined using qRT‐PCR, in situ hybridization and bioinformatics. CCK‐8, colony formation and fluorescence‐activated cell sorting assays were utilized to explore the effect of miR‐92b on GC cells. A luciferase reporter assay and Western blotting were employed to verify miR‐92b targeting of DAB2IP. Furthermore, Western blotting was used to evaluate the levels of DAB2IP and PI3K/Akt signalling pathway‐related proteins.
Results
In this study, we found that miR‐92b was upregulated in GC tissues compared with peritumoural tissues. Overexpression of miR‐92b promoted cell proliferation, colony formation, and G0/G1 transition and decreased apoptosis. Our results indicated that miR‐92b repressed the expression of DAB2IP and that loss of DAB2IP activated the PI3K/AKT signalling pathway. Overexpression of DAB2IP rescued the effects of miR‐92b in GC cells. Finally, our results demonstrated a significant correlation between miR‐92b expression and DAB2IP expression in GC tissues.
Conclusions
Our results suggest that miR‐92b promotes GC cell proliferation by activating the DAB2IP‐mediated PI3K/AKT signalling pathway. The miR‐92b/DAB2IP/PI3K/AKT signalling axis may be a potential therapeutic target to prevent GC progression.
Infectious disease epidemics have become more frequent and more complex during the 21
century, posing a health threat to the general public and leading to psychological symptoms. The current study ...was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14
, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: 13.9-32.2) in survivors to 43.3% (95% CI: 27.1-59.6) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: 12.0-38.0) in older adults to 43.3% (95% CI: 23.3-63.3) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: 24.4-34.9) in the general public to 58.4% (95% CI: 28.1-88.6) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.
High glucose (HG) is one of the basic factors of diabetic nephropathy (DN), which leads to high morbidity and disability. During DN, the expression of glomerular glucose transporter 1 (GLUT1) ...increases, but the relationship between HG and GLUT1 is unclear. Glomerular mesangial cells (GMCs) have multiple roles in HG‐induced DN. Here, we report prominent glomerular dysfunction, especially GMC abnormalities, in DN mice, which is closely related to GLUT1 alteration. In vivo studies have shown that BBR can alleviate pathological changes and abnormal renal function indicators of DN mice. In vitro, BBR (30, 60 and 90 μmol/L) not only increased the proportion of G1 phase cells but also reduced the proportion of S phase cells under HG conditions at different times. BBR (60 μmol/L) significantly reduced the expression of PI3K‐p85, p‐Akt, p‐AS160, membrane‐bound GLUT1 and cyclin D1, but had almost no effect on total protein. Furthermore, BBR significantly declined the glucose uptake and retarded cyclin D1‐mediated GMC cell cycle arrest in the G1 phase. This study demonstrated that BBR can inhibit the development of DN, which may be due to BBR inhibiting the PI3K/Akt/AS160/GLUT1 signalling pathway to regulate HG‐induced abnormal GMC proliferation and the cell cycle, supporting BBR as a potential therapeutic drug for DN.
Single-dose intravenous (IV) injection of ketamine has shown rapid but transient antidepressant effects. The strategy of repeated-dose ketamine infusions to maintain antidepressant effects has ...received little systematic study. This study was conducted to examine the efficacy and tolerability of six ketamine infusions in Chinese patients with unipolar and bipolar depression.
Ninety seven patients with unipolar (n = 77) and bipolar (n = 20) depression received repeated ketamine infusions (0.5 mg/kg over 40 min) with continuous vital sign monitoring. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Suicidal ideation was assessed using the Scale for Suicidal Ideations (SSI)-part 1. Anxiety symptoms were evaluated with the 14-item Hamilton Anxiety Scale (HAMA). Adverse psychopathological and dissociative effects were assessed using the Brief Psychiatric Rating Scale (BPRS)-positive symptoms and Clinician Administered Dissociative States Scale (CADSS), respectively. Patients were assessed at baseline, 4 and 24 h, and 3, 4, 5, 6, 8, 9, 10, 11, 12, 13 and 26 days.
After six ketamine infusions, the response and remission rates were 68.0% and 50.5%, respectively. There were significant decreases in MADRS, SSI-part 1, and HAMA scores within four hours following the first ketamine infusion, and the decreases were sustained over the subsequent infusion period. The nonresponder subgroup manifested rapid significant improvement in suicidal ideations throughout the course of treatment. After the six ketamine infusions, the response was positively associated with the response at 24 h after the first infusion (OR = 8.94), personal income ≥4000 yuan/month (OR = 3.04), and no history of psychiatric hospitalization (OR = 3.41). Only CADSS scores had a mild but marginally significant increase after the first infusion but with a significant BPRS score decrease.
Six ketamine infusions were safe and effective in patients with unipolar and bipolar depression. The rapid and robust antidepressant and antisuicidal effects of ketamine infusion within four hours were sustained following the subsequent infusions.
•The strategy of repeated-dose ketamine infusions to maintain antidepressant effects has received little systematic study.•The rapid antidepressant effects of ketamine infusion within four hours were sustained following the subsequent infusions.•The response of ketamine treatment was positively associated with the response at 24h after the first infusion.
Diabetic nephropathy is a progressive kidney disorder and is pathologically characterized by thickened glomerular and tubular basement membranes, accumulation of the extracellular matrix and ...increased mesangial hypertrophy. Growing evidence has suggested that diabetic nephropathy is induced by multiple factors, such as dyslipidemia, hyperglycemia, hemodynamic abnormalities and oxidative stress, based on genetic susceptibility. Berberine (BBR; C20H18NO4+), an isoquinoline alkaloid, is the major active constituent of Rhizoma coptidis and Cortex phellodendri. Recent studies have demonstrated that berberine has various pharmacological activities, including lowering blood glucose, regulating blood lipids and reducing inflammation in addition to its antioxidant activity. These findings suggest that berberine has potential applications as a therapeutic drug for diabetic nephropathy, and has significant research value. However, the possible mechanisms have not been fully established. The purpose of this paper is to investigate the renoprotective mechanisms of berberine in diabetic nephropathy and highlight the importance of berberine as a potential therapeutic reagent for diabetic nephropathy treatment.
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