Evaluation of liver stiffness using ultrasonic shear wave elastography in patients with COVID-19 induced pneumonia.

In patients with COVID-19-induced pneumonia, shear wave elasticity (SWE) was used to assess liver stiffness. This study included 48 cases of COVID-19-induced pneumonia and 48 cases of normal physical examination. Basic and clinical data, including aspartate aminotransferase (AST), were evaluated. Color ultrasonography was used to test the liver's SWE. A biopsy of the liver was also performed. In patients with COVID-19-induced pneumonia, AST and alanine aminotransferase (ALT) levels were higher than those in the control group. Liver SWE showed that liver stiffness is hard (8.745 ± 0.2104) compared with the control group (7.386 ± 0.1521) (P < 0.0001). Pathological biopsy showed that liver inflammation accounted for 89.58%, steatosis accounted for 81.25%, necrosis accounted for 10.42%, and fibrosis accounted for 33.33% in patients with COVID-19-induced pneumonia. ROC curve analysis showed that the SWE is highly sensitive and specific for the diagnosis of liver inflammation and steatosis. The sensitivity was 88.76% and the specificity was 77.01% for the evaluation of liver inflammation. For steatosis, the sensitivity was 90.20%, and the specificity was 78.40%. The SWE of liver is useful to assess liver function and pathological status in COVID-19 patients.

Immunomodulatory effect of Ganoderma lucidum polysaccharide extract on peritoneal macrophage function of BALB/c mice.

Ganoderma lucidum has been suggested as a natural immunomodulator. It is not yet clear exactly which combination of this extract is responsible for its immunomodulatory effects. Still, it appears that the 3-complement (CR3) receptor on the surface of immune cells acts as a receptor for beta-glucans (glucan-8), which is the main component of this extract. Since glucose-6-phosphate dehydrogenase (G6PD) plays a vital role in regulating macrophage functions, including nitric oxide production, we considered the effect of this extract on viability, G6PD enzyme activity, and nitric oxide (NO) production in peritoneal BALB/c macrophages. First, peritoneal macrophages of BALB/c mice were isolated and treated with concentrations (0.001, 0.01, 0.1, 1, 10, and 100 g/ml) of Ganoderma lucidum polysaccharide extract (GL-PS). After 24 hours of incubation by MTT test, we evaluated the viability of macrophages, and the effective dose was determined to be 0.1g/ml. To determine the specific activity of glucose-6-phosphates, they were incubated with GI-PS for 24 hours at a 0.1 mg/ml dose. Determination of protein concentration was obtained by the Bradford method in cell supernatant extract. Also, after 18 hours of incubation, the amount of nitric oxide (NO) production was measured using Grace colorimetric method. According to the results, a dose of 0.1µg/ml of Ganoderma lucidum polysaccharide extract had the most significant effect on the viability (stimulation coefficient) of peritoneal macrophages compared to other amounts (p <0.05). It was also found that a dose of 0.1µg/ml GL-PS increases NO production and the specific activity of the G6PD enzyme (p <0.05). Ganoderma lucidum, a medicinal fungus, is widely used in East Asian countries, especially in China, to increase the quality of life and longevity. After this study, we concluded that GL-PS extract has an immunomodulatory effect on macrophage activity. Therefore, the polysaccharide extract of this fungus can be used as a strengthening agent of the phagocytic system against infectious agents and pathogens such as the Leishmania parasite because of the production of nitric oxide by macrophages plays an essential role in defense against them.

Visnagin ameliorates myocardial ischemia/reperfusion injury through the promotion of autophagy and the inhibition of apoptosis.

Visnagin is a furanochromone and one of the main compounds of Ammi visnaga L. that had been used to treat nephrolithiasis in Ancient Egypt. Nowadays, visnagin was widely used to treat angina pectoris, urolithiasis and hypertriglyceridemia. The potential mechanisms of visnagin involved in inflammation and cardiovascular disease were also identified. But the protective effect of visnagin on myocardial ischemia/reperfusion injury has not been confirmed. Our aim was, for the first time, to investigate the potential protective effect of visnagin on cardiac function after myocardial ischemia-reperfusion injury in a rat model, and to identify its underlying mechanism involving the inhibition of apoptosis and induction of autophagy. Thirty SD rats were randomly divided into sham group, ischemia/reperfusion group (IR), ischemia/reperfusion with visnagin (IR + visnagin) group. Myocardial ischemia/Reperfusion injury model was established. Hemodynamic measurements and echocardiography were used to analyze cardiac function, TUNEL staining and caspase activity, LC3 dots were detected with immunofluorescence staining, LC3 expression was evaluated by western blot analysis, transmission electron microscopy (TEM) was used to detect autophagosomes. Compared with the sham group and visnagin group, the cardiac dysfunction, LC3II, autophagy flow in the IR+ visnagin group increased significantly (P<0.01), but the activity of caspase-3 and caspase-9 and the apoptotic in the IR + visnagin group decreased significantly (P<0.01). In conclusion, visnagin may play a protective role in ischemia/reperfusion injury by inducing autophagy and reducing apoptosis.

GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway.

BACKGROUND: Gap junction beta-4 protein (GJB4), or connexin 30.3, a member of integral membrane proteins, has been shown to involve and may function as a tumor promoter in tumorigenesis. However, the role of GJB4 in gastric cancer (GC) is still unclear. MATERIALS AND METHODS: We used Progression-free survival Kaplan-Meier analysis and Western blot analysis to detect the expression of GJB4 in GC tissues and cells. In addition, both in vitro and in vivo assays were used to determine the effect of GJB4 on malignant behavior in GC cells. RESULTS: We found that GJB4 was overexpressed in gastric cancer tissues and cells compared with normal tissues and cells. The high GJB4 expression was significantly associated with poor overall survival of GC patients. Knocking down GJB4 in GC cells significantly suppressed cell proliferation and migration. We found that the effects of GJB4-knockdown on GC cells were associated with downregulation of CTNNB1 and its downstream MYC, MMP7 and CCND1 expression. In addition, we found that the promotive effect of GJB4 overexpression on cell proliferation and migration was negated by XAV-939, which is the inhibitor of Wnt/CTNNB1 pathway. Therefore, we revealed a novel mechanism by which GJB4 could activate the Wnt/CTNNB1 pathway to promote GC cell's proliferation and migration. CONCLUSION: This study offer insights into GJB4 function and indicate that GJB4 is a promising biomarker and therapeutic target for gastric cancer patients.

NIPAAm-MMA nanoparticle-encapsulated visnagin ameliorates myocardial ischemia/reperfusion injury through the promotion of autophagy and the inhibition of apoptosis.

The main method for the treatment of acute myocardial infarction (AMI) is percutaneous coronary intervention; however percutaneous coronary intervention will induce ischemia/reperfusion (IR) injury, resulting in the loss of cardiac function and cardiomyocyte death. An effective drug to target this condition is necessary. N-isopropylacrylamide and methacrylic acid were used to synthesize drug delivery nanoparticles (NP) containing the natural compound visnagin for IR injury treatment. It was demonstrated that NP containing fluorescein isothiocyanate localized to the site of myocardial IR, and that NP-visnagin treatment induced cardioprotection, reducing the size of the MI and ameliorating cardiac dysfunction through the induction of autophagy and the inhibition of apoptosis. In the future, visnagin may be suitable as a drug for IR injury treatment, and NP may be an effective drug delivery system.

A novel INDEL mutation in the PTCH1 gene in a Chinese family with Gorlin syndrome.

Gorlin syndrome is a rare autosomal dominant disorder, and 50% of the cases are due to the mutation of PTCH1, the major receptor of the hedgehog signaling pathway. Here we report a new Gorlin syndrome family found in Xinzhou, China. A further sequence analysis found a novel PTCH1 INDEL mutation, NM_001083602.2: c.1516_1524delinsTGAGCTGGAGCTCCG (p. Ala506*), leading an N Terminal truncated protein. This truncated PTCH1 was considered as non-functional version as it loses almost all functional domains, including the 4-12 transmembrane domains and the intracellular and extracellular domains accordingly. Although the effect of the N-terminal truncated PTCH1 is not clear, Gorlin syndrome in these cases is due to haploinsufficiency. Our report enriches the Gorlin syndrome database and will help to unveil the molecular basis of this condition.

Effects of recombinant adeno-associated virus-mediated CD151 gene transfer on the expression of rat vascular endothelial growth factor in ischemic myocardium.

The aim of this study was to observe the effects of cluster of differentiation (CD) 151 on the expression of vascular endothelial growth factor (VEGF) in ischemic myocardium by the injection of a recombinant adeno-associated virus (rAAV) vector carrying the human CD151 gene. A rat acute myocardial infarction model was established, and rAAV-CD151 was injected into the ischemic myocardium. Four weeks later, the ischemic myocardium was removed in order to detect the expression of exogenous CD151 mRNA by reverse transcriptase polymerase chain reaction. In addition, the expression of CD151 and VEGF was detected by western blot analysis to evaluate the effect of CD151 overexpression on VEGF expression. Four weeks after injection of the vector, exogenous CD151 mRNA was expressed in the myocardial tissues of the CD151 group, whereas it was not detected in sham surgery, model control or rAAV-green fluorescent protein (GFP) gene-treated groups. The expression levels of CD151 protein were significantly higher in the CD151 group compared with those in the other three groups (P<0.05). The VEGF expression level in the CD151 group was higher compared with those in the control and GFP groups (P>0.05). These results indicate that rAAV-CD151 effectively transfects rat myocardial tissues, and may promote angiogenesis of the ischemic myocardium, improve left ventricular function and increase VEGF expression to improve ventricular function.