ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); host cell entry by this virus relies on the interaction between the receptor-binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on cell membranes. In addition to serving as a receptor for SARS-CoV-2, ACE2 was originally discovered as a protective factor in the renin-angiotensin system (RAS) that catalyses the degradation of angiotensin II (Ang II) to Ang 1-7, which is involved in multiple organ pathology. Recent genetic and clinical studies reported that ApoE4 expression is associated with increased susceptibility to SARS-CoV-2 infection and the development of severe COVID-19, but the underlying mechanism is currently unclear. In the present study, by using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) and coimmunoprecipitation (Co-IP) combined with a biolayer interferometry (BLI) assay, we found that ApoE interacts with both the spike protein and ACE2 but does not show obvious isoform-dependent binding effects. These data suggest that ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Importantly, further immunoblotting and immunofluorescence staining results showed that ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7, which could worsen tissue lesions; these findings provide a possible explain by which ApoE4 exacerbates COVID-19 disease.

Effects of pueraria total flavone on inflammatory cytokine and stat3 expression in brain tissue of exhaustive exercise rats / 中国组织工程研究

BACKGROUND: The physiological and pathological mechanisms underlying the inflammatory response of rat brain tissue caused by exhaustive exercise are very complicated. Studies have shown that Pueraria total flavonoids have anti-oxidative, neuroprotective, and cardio-cerebrovascular protective effects against brain injury. OBJECTIVE: To investigate the effect of Pueraria total flavone on inflammatory cytokines and signal transducer and activator of transcription-3 (STAT3) expression in rat brain tissue after exhaustive exercise. METHODS: Fifty healthy male Sprague-Dawley rats were randomly divided into a quiet control group, an exercise control group, low, middle, high dose Pueraria total flavone groups. Each training group conducted a 6-week sports training. At the end of 6-week exercise, the rats were confirmed to be exhausted. The rats were intragastrically administered 50, 100 and 200 mg/kg Pueraria total flavone in low, middle and high dose groups, respectively. Administration in each Pueraria total flavone group began at 30 minutes before exercise, once a day, and ended until the completion of the experiment. The activities of tumor necrosis factor-α, interleukin-8, interleukin-1β and interleukin-10 in serum and brain tissue of rats were determined by ELISA. The expression of STAT3 in rat brain tissue was detected by RT-PCR and western blot. The study protocol was approved by the Animal Ethics Committee of Guangxi Normal University (approval No. GXMU201703049). RESULTS AND CONCLUSION: The levels of tumor necrosis factor-α, interleukin-8, interleukin-1β and interleukin-10 in serum and brain tissue of exercise control rats were higher than those in the quiet control group (P < 0.01). The levels of tumor necrosis factor-α and interleukin-10 in serum and brain tissue of rats with middle and high dose of Pueraria total flavone were significantly lower than those in the exercise control group (P < 0.01). The levels of interleukin-8 and interleukin-1β in serum and brain tissue of rats with low, middle and high dose of Pueraria total flavone were significantly lower than those in the exercise control group (P < 0.01 or P < 0.05). The expression levels of STAT3 mRNA and protein in brain tissue of exercise control rats were significantly higher than those in the quiet control group (P < 0.01). The expression levels of STAT3 mRNA and protein in the brain tissue of rats with low, middle and high doses of Pueraria total flavone were significantly higher than those in the quiet control group (P < 0.01). To conclude, exhaustive exercise can cause inflammatory reaction and up-regulate STAT3 expression in rat brain tissue. The total flavonoids of Puerariae can regulate the expression of STAT3 in brain tissues and inhibit the inflammatory response of brain tissue, thus protecting damaged brain tissue.

Study on the nutritional risks in elderly patients with prostate cancer and its influencing factors / 中华老年医学杂志

Objective To study the nutritional risks in elderly patients with prostate cancer and explore its related factors.Methods 346 elderly patients with prostate cancer in Wuhan area from May 2013 to May 2014 were chosen as the objects in this study.Nutritional risk screening 2002 was used to evaluate nutritional risk.The sleep quality,anxiety,lower urinary tract symptoms,differentiation and other data of patients were collected.The influencing factors for nutritional risk in the patients were analyzed.Results The ratio of nutritional risk in elderly advanced prostate cancer patients was 35.3％ (122/346).The nutritional risk was increased with age (P＜0.05).The prostate cancer patients with nutritional risk had a higher international prostate symptom score (IPSS) (P＜ 0.05).Monovariate factor analysis showed that sleep quality,operation,pathology staging,radiotherapy,chemotherapy,lower urinary tract symptoms (LUTS) were the impact factors for nutritional status in elderly patients with prostate cancer (P＜0.05).Logistic regression analysis showed that age (OR=0.29),sleep quality (OR=0.25) were the protective factors for the nutritional status,while surgery (OR=12.67),pathological staging (OR=1.65),radiotherapy (OR=2.65),SPSS (OR=1.55),chemotherapy (OR=1.85) were the risk factors for nutritional status (P＜ 0.05).Conclusions The incidence of nutritional risk is high in elderly prostate cancer patients.Age,sleep quality are the protective factors,and operation,pathology staging,SPSS,chemotherapy,and radiotherapy are the risk factors for nutritional status.

The study of the relationship between influenza virus infection and the dysfunction of vascular smooth muscle cells / 中华微生物学和免疫学杂志

Objective To research the influenza virus infection on rat vascular smooth cells number,proliferation,apoptosis,the amount of IL-6,sFas,platelet-derived growth factor(PDGF) and the mechanism of atherosclerosis.Methods Flow cytometry,enzyme-linked immunosorbent assay and cell count experiments were used to detect these indicators at 0 h,6 h,12 h,24 h,48 h.Results After influenza virus infected at 0 h,proliferation,apoptosis condition were 10.39％,0.44％,respectively; at 6 h,proliferation,apoptosis respectively increased to 12.68％,0.73％ ; proliferation reached the peak at 12 h (18.01％),instead apoptosis decreased to 0.14％ ; at 24 h,proliferation decreased to 12.89％ and apoptosis markedly increased to 1.09％ ; at 48 h,proliferation further reduced to 7.07％ and apoptosis reached the peak(4.61％).The number of cells and the cytokine secretion were statistically significant to control group (P＜0.05).Conclusion Influenza virus infection might lead to change of cell proliferation and apoptosis and involve the atherosclerosis form and development,and cytokines played an important role in them.

Leptin induced apoptosis in rat adipose-derived stem cells cultured in vitro / 生物工程学报

To determine the direct effect of leptin on adipose tissue apoptosis in vitro using rat adipose-derived stem cells (ADSCs), we isolated the ADSCs of rat epididymis adipose tissue by collagenase digestion, filtration, and subsequent centrifugation. Cell cultures with or without leptin (10(-9) mol/L, 10(-8) mol/L, 10(-7) mol/L and 10(-6) mol/L) were incubated for different time. We examined the cell surface phenotype by immunofluorescence and detected the apoptosis morphological changes of ADSCs by laser scanning confocal microscope (LCSM). The number of apoptotic cells was determined by flow cytometry assay after annexin V binding and PI staining. Caspase-3 activity was measured by spectrofluorometry. The present study demonstrates that leptin treatment causes a marked increase in adipose-derived stem cell apoptosis. With the LCSM, after being treated with leptin, ADSCs showed the typical characteristic of apoptosis. Leptin in used concentrations (0 mol/L, 10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L) caused a marked increase in cell apoptosis after 48 h incubation time (for 2.50% +/- 0.72%, 6.78% +/- 1.99%, 11.99% +/- 1.58% and 17.93% +/- 4.82%, respectively, P < 0.05). Caspase-3 activity increased and reached a maximal level after 48 h in a linear fashion. The effect of leptin was dose-dependent and time-dependent. Leptin has been demonstrated to induce preadipocyte and adipocyte apoptosis, and today we demonstrate that leptin can induce ADSCs apoptosis, which can contribute to the decrease of adiposity. To our knowledge, this is the first study demonstrating the direct peripheral effect of leptin on ADSCs.

Apoptosis of preadipocytes and its influencing factors / 医学研究生学报

The quantity of adipocytes has a direct impact on the levels of obesity,and the apoptotic factors of preadipocytes are also related to adipositas.The apoptosis of preadipocytes is influenced by many genes and other factors.Findings in the studies on the apoptosis of preadipocytes and its influencing factors have contributed a lot to the researches on obesity and many other diseases.