Simulation study on the effect of resistance exercise on the hydrodynamic microenvironment of osteocytes in microgravity.

Osteoporosis occurs in astronauts after long-term space flight owing to the lack of gravity. The mechanical microenvironment of osteocytes in load-bearing bone are changed during resistance exercise, which prevents massive bone loss in the human body. A cylindrical fluid-structure coupling finite element model for osteons with a two-stage pore structure (i.e., Haversian canal, lacunar-canalicular system) was established with the software COMSOL. In the Earth's gravity field and in microgravity, considering the effects of pulsating pressure of arterioles, a comparative study was performed on the changes in hydrodynamic microenvironment of osteocytes during human body high-intensity exercise at different frequencies (defined as causing bone to produce 3000 µÎµ) and the body is at rest. Positive and negative liquid pressure (with respect to one atmosphere pressure) alternately acted on osteocytes during human exercising, but only positive pressure acted on osteocytes during human resting. The variation range of liquid pressure acted on osteocytes during human exercising was significantly higher than that during resting. The liquid flow velocity around osteocytes during body exercise was about four orders of magnitude higher than that during resting. In microgravity, moderate physical exercise can obviously improve the hydrodynamic microenvironment of osteocytes in load-bearing bone, which could compensate for the lack of mechanical stimulation to osteocytes caused by the lack of gravity, thereby promoting the normal physiological function of osteocytes. To a certain extent, these results revealed the biomechanical mechanism by which exercise has an effect in fighting osteoporosis in astronauts.

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

Comparison of clinical characteristics between fecal/perianal swab nucleic acid-positive and -negative patients with COVID-19.

INTRODUCTION: We analyzed the clinical characteristics of COVID-19 fecal/perianal swab nucleic acid-positive patients in our hospital and evaluated the effect of SARS-CoV-2 on the gastrointestinal tract. METHODOLOGY: Ninety-seven patients in the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 2, 2020 with fecal/perianal swab samples were selected as subjects and the results of real-time fluorescence reverse transcriptase-PCR SARS-CoV-2 nucleic acid detection of fecal/perianal swabs were used to divide subjects into positive and negative groups. RESULTS: Fecal/perianal swabs of 53.61% (52/97) patients were positive including 31 males (59.62%) and 21 females (40.38%). The negative group had more females than males (P = 0.001). The distribution of case classification based on the most severe condition observed after admission was different between groups: five (5.15%) critical type patients were all from the positive group (P = 0.029). There was no statistical difference in clinical manifestations between the groups. In the positive group, the mean nucleic acid-negative conversion time was 14.13 ± 8.61 days, which was significantly later than the negative group (6.98 ± 5.16 days; P < 0.001). In the positive group, 92% (48/52) had nucleic acid-negative conversion with a mean nucleic acid-negative conversion time of 22.58 ± 10.30 days. Among them, 41 (78.85%) cases were delayed compared with pharynx/nasal swab nucleic acid-negative conversion time. CONCLUSIONS: The positive rate of fecal/perianal swab nucleic acid in male patients was higher than that in female patients. Fecal/perianal swab nucleic acid positive may be an indicator of critical conditions in those with COVID-19.

Angiopoietin-1 and Angiopoietin-2 Expression Imbalance Influence in Early Period After Subarachnoid Hemorrhage.

PURPOSE: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional-an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other's expression. METHODS: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6-72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. RESULTS: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. CONCLUSIONS: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

[Effect of ginsenoside Rg1 on expression of p21, cyclin E and CDK2 in the process of cell senescence].

AIM: To explore the possible role of p21, cyclin E and cyclin-dependent kinase 2 (CDK2) in the protection of ginsenoside Rg1 against tert-butylhydroperoxide (t-BHP)-induced senescence in WI-38 cells. METHODS: The cellular ultrastructure, cytometric assay and beta-galactosidase (beta-gal) cytochemistry staining were used to evaluate cell senescence. The levels of of p21, cyclin E and CDK2 protein were detected by Western blot. RESULTS: Pretreatment with Rg1 significantly attenuated t-BHP-induced senescence in WI-38 cells. Simultaneously, compared with cells treated with t-BHP alone, Rg1 pretreatment markedly decreased the level of p21 protein and increased the levels of CDK2 and cyclin E. CONCLUSION: p21, cyclin E and CDK2 may be involved in the process of ginsenoside Rg1 protection against t-BHP-induced senescence in WI-38 cells.

Involvement of CDK4, pRB, and E2F1 in ginsenoside Rg1 protecting rat cortical neurons from beta-amyloid-induced apoptosis.

AIM: To explore the possible mechanism of beta-amyloid (Abeta)-induced apoptosis in rat cortical neurons and the protective effect of ginsenoside Rg1. METHODS: AO-EB staining was used to quantify the apoptotic cells. DNA fragmentation was observed by gel electrophoresis. The levels of cyclin-dependent kinases-4 (CDK4) and phosphorylated pRB were detected by Western blot. RT-PCR was used to examine the expression of E2F1 mRNA. RESULTS: Treatment with Abeta1-40 at the concentration of 20, 40, 80 mg/L for 48 h induced rat cortical neuron apoptosis from 12.5 %+/-1.5 % (control) to 22.3 %+/-1.4 %, 38.8 %+/-1.3 %, 36.7 %+/-1.4 %, respectively. Pretreatment with Rg1 at the dose of 0.5, 1, 2, 4, 8, 16 micromol/L for 24 h, then treatment with Abeta1-40 40 mg/L for 24 h, the percentage of apoptotic neurons decreased from 38.8 %+/-1.3 % to 14.5 %+/-1.3 %, 13.3 %+/-1.0 %, 11.6 %+/-0.29 %, 11.8 %+/-1.0 %, 6.2 %+/-0.8 %, 5.8 %+/-0.8 %, respectively. After treatment with Abeta1-40 40 mg/L for 24 h, there were transient increases in CDK4 and phosphorylated pRB protein level, as well as the expression of E2F1 mRNA. However, the above levels decreased markedly after pretreatment with Rg1 8 micromol/L for 24 h. CONCLUSION: Ginsenoside Rg1 attenuated Abeta1-40-induced apoptosis in rat cortical neurons via inhibiting the activity of CDK4, decreasing the phosphorylation of pRB and downregulating the expression of E2F1 mRNA.

Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress.

In Parkinson's disease, neuroprotective therapy to rescue dopamine neurons has been proposed. Ginsenoside Rg1, one of the biologically active ingredients of ginseng, may be a candidate neuroprotective drug. In the present study, the mechanism underlying the neuroprotection provided by ginsenosde Rg1 was studied against apoptosis induced by exogenous dopamine in PC12 cells. Pretreatment with ginsenoside Rg1 markedly reduced the generation of dopamine-induced reactive oxygen species and the release of mitochondrial cytochrome c into the cytosol, and subsequently inhibited the activation of caspase-3. In addition, Rg1 pretreatment also reduced inducible nitric oxide (NO) synthase protein level and NO production. These results suggested that ginsenoside Rg1 may attenuate dopamine-induced apoptotic cell death through suppression of intracellular oxidative stress, and that it may rescue or protect dopamine neurons in Parkinson's disease.