Study on the protective mechanism of Bawei chenxiang powder containing serum on H9c2 cells injured by oxygen-glucose deprivation / 中国药房

OBJECTIVE To study the protective mechanism of Bawei chenxiang powder containing serum on H9c2 cells injured by oxygen-glucose deprivation （OGD）. METHODS H9c2 cells were divided into blank group， model group and Bawei chenxiang powder low-dose， medium-dose and high-dose groups （the dose of drug containing serum 2.5， 8， 12 g/kg）. H9c2 cells were cultured in vitro to establish OGD model. After intervention with drug-containing serum， survival rate of cell was detected. The cell morphology was observed； the levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， superoxide dismutase （SOD）， catalase （CAT）， respiratory chain complexⅠ （ComplexⅠ）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected. The contents of reactive oxygen species （ROS）， mitochondrial membrane potential and apoptosis were also detected. The expressions of oxidative stress-related proteins [Kelch ECH association protein 1 （Keap1）， nuclear factor erythroid 2- related factor 2 （Nrf2）， heme oxygenase 1 （HO-1）， NADH oxidoreductase coenzyme 10 （Ndufa10）， thioredoxin （Trx）] and apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3 and cytochrome C （Cytc）] were detected. RESULTS Compared with blank group， the cell morphology of model group was damaged； the levels of LDH， CK and MDA were significantly increased （P＜0.01）， while the levels of CAT， ComplexⅠ， SOD and GSH-Px and mitochondrial membrane potential were significantly decreased （P＜0.01）. The content of intracellular ROS and apoptotic rate were significantly increased （P＜0.01）； the expressions of oxidative stress-related proteins （Keap1， Nrf2， HO-1， Ndufa10 and Trx） and pro- apoptosis proteins （Bax， Caspase-3 and Cytc） were significantly increased （P＜0.05）， while the expression of anti-apoptotic protein Bcl-2 was significantly decreased （P＜0.05）. After administration of Bawei chenxiang powder containing serum， the cell morphology improved， and most of the above indexes were significantly reversed （P＜0.05 or P＜0.01）.CONCLUSIONS Bawei chenxiang powder containing serum E-mail：345783110@qq.com has a good protective effect on H9c2 cells damaged by OGD，the mechanism of which is related to the reduction of oxidative damage and inhibition of cell apoptosis.

Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Pathways and mechanisms of RNA interference mediated by viral siRNA / 生物工程学报

RNA interference (RNAi) is one of the important mechanisms to regulate gene expression in eukaryotes. One of the original functions of RNAi is to facilitate the antiviral strategy of host. Early studies reveal that invertebrates can use RNAi to resist viruses. However, if this mechanism exists in mammals is still controversial. The latest studies confirm that mammals do have the RNAi-based immunity, and researchers believe that RNAi-based antiviral immunity is a brand-new immunological mechanism that was neglected in the past. It is worthy to note that virus can also use RNAi to enhance its infectivity and immune escape in host cells. This review introduces the research history of RNAi-based antiviral immunity in animals and summarizes the main findings in this field. Last but not least, we indicate a series of unresolved questions about RNAi-based antiviral immunity, and explore the relationship between RNAi-based antiviral immunity and other innate immunological pathways. The virus-mediated RNAi pathway in animal is not only an interesting basic biology question, but also has important guiding roles in the development of antiviral drugs.

Role of 1'-Ribose Cyano Substitution for Remdesivir to Effectively Inhibit both Nucleotide Addition and Proofreading in SARS-CoV-2 Viral RNA Replication

COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is a promising but challenging drug target due to its intrinsic proofreading exoribonuclease (ExoN). Remdesivir targeting SARS-CoV-2 RdRp exerts high drug efficacy in vitro and in vivo. However, its underlying inhibitory mechanisms remain elusive. Here, we performed all-atom molecular dynamics simulations with an accumulated simulation time of 24 microseconds to elucidate the molecular mechanisms underlying the inhibitory effects of Remdesivir. We found that Remdesivirs 1-cyano group of possesses the dual role of inhibiting nucleotide addition and proofreading. The presence of its polar 1-cyano group at an upstream site in RdRp causes instability and hampers RdRp translocation. This leads to a delayed chain termination of RNA extension, which may also subsequently reduce the likelihood for Remdesivir to be cleaved by ExoN acting on the 3-terminal nucleotide. In addition, our simulations suggest that Remdesivirs 1-cyano group can also disrupt the cleavage active site of ExoN via steric interactions, leading to a further reduced cleavage efficiency. Our work provides plausible molecular mechanisms on how Remdesivir inhibits viral RNA replication and may guide rational design for new treatments of COVID-19 targeting viral replication.

Value of imaging technology in predicting the clinical end events of liver cirrhosis / 临床肝胆病杂志

The clinical end events of liver cirrhosis have great adverse influence on patients, among which esophageal and gastric varices, portal vein thrombosis, and primary liver cancer might lead to low quality of life and even death. The rapid development of imaging technology provides an important reference for the diagnosis and prediction of the clinical end events of liver cirrhosis. The imaging methods based on ultrasound, contrast-enhanced ultrasound, endoscopic ultrasound, computed tomography (CT), magnetic resonance imaging, multi-slice spiral CT angiography, digital subtraction angiography, and nuclear medicine examination provide great help for clinicians in the diagnosis and evaluation of the clinical end events of liver cirrhosis. However, different imaging techniques may have different features, and therefore, clinicians should use these techniques based on clinical needs.

Effects of drinking water-borne arsenic exposure on mammary gland development of female mice in early life / 中华地方病学杂志

Objective:To investigate the effects of drinking water-borne arsenic exposure on mammary gland development of female mice in early life.Methods:Healthy and sexually mature C57BL/6J mice were paired according to the female to male ratio of 2∶1. After confirmation of pregnancy, female mice were randomly divided into control (drinking double distilled water), low- (0.5 mg/L) and high- (5.0 mg/L) dose arsenic exposure groups, 10 mice in each group. The exposure time of arsenic in drinking water ranged from day 0 of pregnancy to day 28 after birth. At the end of arsenic exposure, female offspring (10 mice in each group) were sacrificed and mammary glands were dissected for whole tissue staining to evaluate the development of mammary glands and quantitative analysis of mammary gland development indexes. The expression of proliferating cell associated antigen Ki67 was detected by immunohistochemistry.Results:There were no significant differences in body weight and organ coefficients of liver, kidney and mammary glands between female offspring in low- and high-dose arsenic exposure groups and control group ( F=1.018, 1.033, 1.764, 0.199, P > 0.05). Compared with control group, low- and high- dose arsenic exposure groups showed more terminal end buds (TEB) and ductal branches as well as stronger longitudinal growth ability in mammary gland morphological analysis. Quantitative analysis results showed that the numbers of TEB in the low- and high-dose arsenic exposure groups (11.83 ± 4.40, 11.00 ± 3.74) were significantly higher than that in the control group (4.00 ± 1.83, P < 0.05). The ductal lengths in the low- and high-dose arsenic exposure groups [(6.43 ± 1.08), (6.08 ± 1.74) mm] were also significantly longer than that in the control group [(3.71 ± 0.61) mm, P < 0.05]. The distance of leading edge of ducts to the midpoint of lymph nodes in the low- and high-dose arsenic exposure groups [(0.58 ± 1.12), (- 0.02 ± 1.57) mm] was significantly shorter than that in the control group [(- 2.67 ± 0.87) mm, P < 0.05]. The mean maximum area of TEB in the low-dose arsenic exposure group [(0.04 ± 0.01) mm 2] was significantly larger than that in the control group [(0.02 ± 0.01) mm 2, P < 0.05]. Immunohistochemistry staining indicated strong staining of Ki67 within TEB in the low- and high-dose arsenic exposure groups. Conclusion:Early life inorganic arsenic exposure promotes the development of TEB, ductal extension and cell proliferation within TEB in female mice, indicating that early life arsenic exposure alters mammary gland development.

Direct sampling introduction and atomic fluorescence spectrometry for determination of selenium content in mice liver and urine / 中华地方病学杂志

Objective Through determination of selenium content in liver and urine of selenium-induced mice, direct sampling atomic fluorescence spectrometry was established to provide a more accurate and convenient determination method for detection of selenium-related biological samples. Methods Selenium in the sample was released by the electrically heated quartz tube,the selenium in the atomic state was captured by the quartz tube,and the selenium released by the heating quartz tube was carried by the argon-hydrogen mixed gas into the argon-argon flame atomic fluorescence detector for determination; standard curve was established based on selenium content and fluorescence area, and then the content of selenium in the sample was calculated. Results The detection limit of selenium in samples by direct sampling atomic fluorescence spectrometry was 0.28 μg/kg, the correlation coefficient of standard curve was 0.999 3, and the relative standard deviation range was 1.82% - 4.19%. The adding standard recovery of the liver in mice was 87.30%- 100.20%; meanwhile the adding standard recovery of the urine in mice was 93.10% - 96.60%. Conclusions Direct sampling atomic fluorescence method is simple and easy to operate, accuracy and precision are better, the linear range is wide. The samples need not be processed by complex pretreatment,such as acid,etc.,elements loss is avoided and efficiency of detection is improved.The method can be used in a variety of samples for rapid detection of trace selenium.

Effect of Tibetan medicine zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2 / 药学学报

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.

Adiabatic and diabatic process of sum frequency conversion.

Based on the dressed state formalism, we obtain the adiabatic criterion of the sum frequency conversion. We show that this constraint restricts the energy conversion between the two dressed fields, which are superpositions of the signal field and the sum frequency field. We also show that the evolution of the populations of the dressed fields, which in turn describes the conversion of light photons from the seed frequency to the sum frequency during propagation through the nonlinear crystal. Take the quasiphased matched (QPM) scheme as an example, we calculate the expected bandwidth of the frequency conversion process, and its dependence on the length of the crystal. We demonstrate that the evolutionary patterns of the sum frequency field's energy are similar to the Fresnel diffraction of a light field. We finally show that the expected bandwidth can be also deduced from the evolution of the adiabaticity of the dressed fileds.

Observations on 52 Patients with Diabetic Peripheral Neuropathy Treated by Needling Combined with Drug / 针灸推拿医学（英文版）

To observe the clinical therapeutic effect of diabetic peripheral neuropathy (DPN) treated by needling combined with drug, 104 patients with DPN were randomly divided into acupuncture plus drug group and control group, and each group had 52 patients. After treatment of two months, the clinical effective rate in acupuncture plus drug group was 51.9%, and the total effective rate was 88.5%, both of them were better than those in control group (P＜0.05). The needling method of nourishing the kidney and dredging the meridian combined with drug had good clinic effect in the treatment of DPN.