Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

The neuroprotective effect of sodium pyruvate on mouse hippocampal neural HT22 cells / 中国药理学通报

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

MYOZ2 Promoted Adipogenic Differentiation of C3H10T1 / 2 Cells by Negatively Regulating the Expression of TCAP / 中国生物化学与分子生物学报

The objective of this study was to investigate the expression profile of the myozenin2 (MYOZ2) gene and elucidate its effect on adipogenic differentiation of C3H10T1 / 2 cells and its possible mechanism∙ The longissimus dorsi‚ subcutaneous fat and liver tissue was collected from 180-day-old Mashen pigs‚ 60-day-old ICR mice‚ 35-day-old Ross broiler and 12-month-old Small tail han sheep‚ and the expression profile of the MYOZ2 gene mRNA was detected∙ The results showed that the MYOZ2 gene has similar patterns of tissue expression in examined species‚ with the highest expression level in longissimus dorsi‚ and a small amount of expression in the subcutaneous fat and liver tissue∙ After the MYOZ2 gene was silenced in C3H10T1 / 2 cells‚ qRT-PCR results showed that the expression levels of key adipogenic genes PPARγ and FABP4 were significantly down-regulated compared with the control group (P < 0∙ 01) ; Western Blotting results showed that the PPARγ protein content was significantly decreased (P < 0∙ 05) ; Oil red O staining showed that the number of lipid droplets and the content of triglyceride were significantly decreased after silencing MYOZ2 (P < 0∙ 05) ∙ The expression of fatty acid metabolism related genes SCD‚ FASN‚ SREBP1‚ NR1H3‚ DGAT1‚ PNPLA2‚ HSL‚ CES1‚ CPT1 after MYOZ2 silencing were detected by qRT-PCR∙ The results showed that SCD‚ FASN‚ SREBP1‚ PNPLA2 and HSL were significantly down-regulated (P < 0∙ 01) ‚ NR1H3 was significantly reduced (P < 0∙ 05) ‚ DGAT1 expression was down-regulated but the difference was not significant‚ CES1 and CPT1 were significantly up-regulated (P < 0∙ 05) ∙ The STRING database was used to construct a MYOZ2-related protein interaction network map‚ and it was found that MYOZ2 may affect the adipogenic differentiation through the interaction of titin-cap (TCAP) and PPARγ∙ After silencing TCAP‚ qRT-PCR results showed that compared with the control group‚ the expression of key adipogenic genes PPARγ and FABP4 were significantly up-regulated (P < 0∙ 01) ; Western Blotting results showed that PPARγ protein was significantly increased (P< 0∙ 05) ; Oil red O staining showed that the number of lipid droplets and the content of triglyceride were significantly increased after TCAP silencing (P < 0∙ 05) ∙ qRT-PCR was used to detect the expression of TCAP after silencing MYOZ2‚ and the results showed that the expression of TCAP was significantly increased (P<0∙ 01) ∙ In summary‚ MYOZ2 was highly expressed in longissimus dorsi and lower expressed in subcutaneous fat and liver tissues∙ In addition‚ MYOZ2 may regulate the expression of key adipogenic genes PPARγ and FABP4 through the interaction of MYOZ2-TCAP -PPARγ‚ and to further regulate the expression of fatty acid metabolism related genes SCD‚ FASN‚ SREBP1‚ NR1H3‚ DGAT1‚ PNPLA2‚ HSL‚ CES1 and CPT1‚ thus playing an important role in the process of adipogenic differentiation∙

Clinical characteristics and plasma antibody titer of patients with COVID-19 in Zhejiang, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first affected humans in China on December 31, 2019 (Shi et al., 2020). Coronaviruses generally cause mild, self-limiting upper respiratory tract infections in humans, such as the common cold, pneumonia, and gastroenteritis (To et al., 2013; Berry et al., 2015; Chan et al., 2015). According to the Report of the World Health Organization (WHO)-China Joint Mission on COVID-19 (WHO, 2020), the case fatality rate of COVID-19 increases with age, while the rate among males is higher than that among females (4.7% and 2.8%, respectively). Since an effective vaccine and specific anti-viral drugs are still under development, passive immunization using the convalescent plasma (CP) of recovered COVID-19 donors may offer a suitable therapeutic strategy for severely ill patients in the meantime. So far, several studies have shown therapeutic efficacy of CP transfusion in treating COVID-19 cases. A pilot study first reported that transfusion of CP with neutralizing antibody titers above 1:640 was well tolerated and could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases (Chen et al., 2020). Immunoglobulin G (IgG) and IgM are the most abundant and important antibodies in protecting the human body from viral attack (Arabi et al., 2015; Marano et al., 2016). Our study aimed to understand the aspects of plasma antibody titer levels in convalescent patients, as well as assessing the clinical characteristics of normal, severely ill, and critically ill patients, and thus provide a basis for guiding CP therapy. We also hoped to find indicators which could serve as a reference in predicting the progression of the disease.

Application of Enhanced MR Multi-Phase Dynamic Scanning with 3D-VIBE Sequence in Hepatocellular Carcinoma / 中山大学学报(医学科学版)

[Objective]To investigate the value of multi-phase dynamic enhanced MR scanning with 3D-VIBE sequence in HCC by comparing with enhanced multiple slice computer tomography(MSCT)scanning.[Method]23 patients who were pathologi?cally proven of HCC,and underwent both abdominal enhanced 3.0T MR multi-phase dynamic scanning with 3D-VIBE sequence and enhanced MSCT scanning were enrolled. The enhancement features of HCC on enhanced MR multi-phase dynamic scanning and en?hanced CT scanning were compared.[Results]There were 23 lesions confirmed by pathology. All the 23 lesions were detected by en?hanced MR multi-phase dynamic scanning with 3D-VIBE sequence,and 21 lesions were detected by enhanced MSCT scanning. The enhanced features of"fast enhanced and fast washout"in HCC can be observed more frequently on enhanced MR multi-phase dynam?ic scanning with 3D-VIBE sequence than enhanced MSCT scanning (78.3% vs 54.5%). Obvious enhancement feature can be ob?served more frequently on the enhanced MR multi-phase dynamic scanning when the tumor diameter ≤ 3 cm(P=0.037).[Conclu?sion]The enhanced MR multi-phase dynamic scanning with 3D-VIBE sequence can greatly improve the sensitivity and accuracy of HCC diagnosis,especially for the small HCC(tumor diameter≤3 cm).

Estrogen aggravates inflammatory bowel disease in rats through estrogen receptor alpha / 第二军医大学学报

Objective To explore the specific mechanism by which estrogen affects the inflammatory bowel disease (IBD) in rats. Methods The model of IBD in rats was established with 30% of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) ethanol solution through the rectocolon. The body weight, disease activity index(DAI) score, colorectal length, myeloperoxidase (MPO) concentration, and H-E staining were used to verify the successful IBD model. The IBD rats were separately treated with saline(500 μL), estrogen(1 mg/kg,in 500 μL normal saline), and PPT, a specific agonist of estrogen receptor alpha (ERα; 3 mg/kg, in 500 μL normal saline), or estrogen(1 mg/kg,in 500 μL normal saline) + ERα specific antagonist MPP(3 mg/kg, in 500 μL normal saline). And the inflammation status was observed. Results The model of IBD in rats was successfully induced by TNBS. Compared with the normal saline group, rats in TNBS group had significantly reduced body weight and increased DAI scores, with MPO value increased and with notable inflammatory response of the rectocolon. Compared with normal saline group, estrogen or PPT significantly aggravated the inflammation response. Estrogen treatment significantly reduced the body weight of IBD rats, increased DAI scores, and aggravated the inflammatory response, with the colorectal length reduced; PPT reduced the colorectal length. MPP treatment reversed the effect of estrogen. Compared with the estrogen group, MPP+estrogen treatment significantly increased the body weight and reduced the DAI scores, with colorectal length increased. Conclusion Estrogen can promote the development and progression of TNBS-induced IBD, which might be mediated through ERα.

Pteridic acid hydrate and pteridic acid C produced by StreStreptomyces pseudoverticillus YN17707 induce cell cycle arrest / 中国天然药物

The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on tsFT210 cells. Compounds were isolated through various chromatographic methods and elucidated by spectroscopic analyses. Flow cytometry was used to evaluate the cell cycle inhibitory activities of the fractions and compounds. Two compounds were obtained and identified as pteridic acid hydrate (1) and pteridic acid C (2), which arrested the tsFT210 cells at the G0/G1 phase with the MIC values being 32.8 and 68.9 μmol·L(-1), respectively. These results provide a basis for future development of Compounds 1 and 2 as novel cell cycle inhibitors for cancer therapy.

Selective adsorption of multi-walled carbon nanotubes with liquiritin and isoliquiritin / 药学学报

Selective adsorption of active ingredients liquiritin and isoliquiritin from Glycyrrhiza uralensis Fisch with multi-walled carbon nanotubes (MWNTs) has been studied. Distribution coefficients of liquiritin between ethanol solvent and r-MWNTs or o-MWNTs in 293K is 37.5 and 43.3, while the distribution coefficients of isoliquiritin between ethanol solvent and r-MWNTs or o-MWNTs is 717 and 1080, respectively. It was indicated that the distribution coefficient of isoliquiritin adsorbed by MWNTs was much larger than that of liquiritin, and oxidation treatment of MWNTs could obviously enhance their adsorption ability. The possible reasons that MWNTs can selectively adsorb isoliquiritin other than liquiritin were discussed on the bases of molecular structure of the active ingredients and their interaction with nanotubes.

Studies on Establishment of Co-expression System and Function of Human Complement Regulatory Proteins MCP and CD59 / 中国生物工程杂志

Recombinant expression vector pcDNA3-MCPCD59DP containing human membrane complement regulatory proteins(hCRPs) MCP and CD59 cDNA was constructed successfully by using two independent promoters.After transfected into NIH3T3 cells with calcium phosphate-DNA precipitate method,NIH3T3 pcDNA3-MCPCD59-DP transfectants were obtained by G418 selection.Extraneous genes integration was identified by PCR.The co-expression of human CD59 and MCP at both mRNA and protein levels was confirmed by using RT-PCR and Western blot analysis.Human MCP and CD59 cDNA were integrated in NIH3T3 pcDNA3-MCPCD59-DP genomic DNA after continuous 30 times passages,indicating that NIH3T3 pcDNA3-MCPCD59-DP were stable cell lines.Human complement-mediated cytolysis assays showed that NIH3T3 cells transfected stably with pcDNA3-CD59,pcDNA3-MCP,and pcDNA3-MCPCD59-DP were protected from C-mediated damage and co-expressed human MCP and CD59 provided more excellent protection against C-mediated attack as compared with either CD59 or MCP expressed alone.The dicistronic vector represents an effective and efficacy strategy to overcome C-mediated damage and has potential therapeutic value for effectively controlling complement activation and finally for preventing hyperacute rejection in clinical gene therapy.

Integrated Model of Rehabilitation and Education of Cerebral Palsy in Hospital / 中国康复理论与实践

@#ObjectiveTo explore the new rehabilitation model of medication combined with education of cerebral palsy.MethodsThe cross-professionals were organized to assess and observe 126 children with cerebral palsy. Then, individual education plan (IEP) combined with medication, family, feeding was made and performed.ResultsAfter educational rehabilitation, the children with cerebral palsy got improvement in intellection, social adaptation, communion aspiration, thinking and etc. They became more cooperated in medical rehabilitation.ConclusionInterdisciplinary cooperation, IEP, participation of parents are the conditions for success of medical rehabilitation combined with education.

Genomic DNA sequences and functional expression, purification of BmalphaTX14 neurotoxin from scorpion Buthus martensii Karsch / 生物工程学报

Based on the full-length cDNA of BmalphaTX14 from Chinese scorpion Buthus martensii Karsch (BmK), gene of the mature peptide of BmalphaTX14 was cloned into the yeast expression vector pPIC9K. After transforming, screening and inducing, tricine-SDS-PAGE and Western blot proved that rBmalphaTX14 protein was expressed in the medium for up to 84 hours, getting nearly 120 mg/L. Recombinant BmalphaTX14 was purified rapidly and efficiently through Ni-NTA-agarose, polyethylene glycol precipitation and gel filtration chromatography. The purified rBmalphaTX14 proved to have the anti-insect activity by toxicity assay. Meanwhile, genomic gene of BmalphaTX14 was cloned and sequenced by PCR method, sequence analysis of this gene showed that BmalphaTX14 had an intron of 408 base pairs located at the signal peptide encoding region, which was similar with the characteristic of other alpha-type sodium ion-channel toxin. Considering both the genomic organization and the peptide function, BmaTX14 proved to be a membership belonging to alpha-type sodium ion-channel toxin.

IL-15 and autoimmune disease / 中国医学科学院学报

This review attempts to define the relationship between IL-15 and autoimmune disease (AID) from IL-15's tissue distribution, expression regulation and biologic function. Meanwhile, five IL-15 dysregulation-related AIDs and four IL-15/IL-15R-targeted AID therapies are described.