Roles of Platelets in Tumor Metastasis / 中国生物化学与分子生物学报

Platelets are small anucleated fragments derived from megakaryocytes participating in coagulation and hemostasis. In recent years, more and more experimental and clinical evidences show that platelets also promote tumor metastasis. When tumor cells detach from the primary tumor and access the blood, platelets are the first host cells they encounter. As an important member of tumor metastasis microenvironment, platelets and tumor cells interact and affect each other. On the one hand, tumor cells can regulate the function of platelets by inducing platelets activation and aggregation; on the other hand, platelets can promote tumor metastasis by directly contacting and releasing bioactive mediators. Numerous studies have shown that platelets can promote tumor metastasis through the following approaches: 1. Reducing the shear force-induced damage; 2. Helping tumor cells escape immune surveillance; 3. Promoting tumor cells migration and stationary adhesion in blood vessels; 4. Promoting epithelial-mesenchymal transition of tumor cells; 5. Promoting tumor cell extravasation; 6. Forming a metastatic niche suitable for the survival of tumor cells. Therefore, targeting the interaction between platelets and tumor cells has become a potential tumor treatment strategy. Based on the latest research progress at home and abroad, this paper reviews the roles of platelets in different stages of tumor metastasis and the application of antiplatelet drugs in tumor therapy.

The Role of B and T Lymphocyte Attenuator in Immune Regulation and Immune Related Diseases / 中国生物化学与分子生物学报

B / T lymphuocyte attenuator (BTLA) is one of the important checkpoint molecules in immune regulation. BTLA belongs to the CD28 superfamily, and its protein structure is similar to programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4). BTLA is mainly expressed in B and T cells, and has also been found in some innate immune cells such as dendritic cells and monocytes. To date, the herpesvirus entry mediator (HVEM) is the only ligand for BTLA found in human cells. HVEM belongs to the Tumor necrosis factor receptor (TNFR) superfamily, and its interaction with BTLA directly connects CD28 and TNFR families. The binding of BTLA with HVEM often mediates immunosuppressive effects and plays an important role in maintaining immune tolerance. However, recent studies have found that the BTLA / HVEM pathway not only provides negative regulatory signals, but also promotes the survival of T cells. This bidirectional signaling system renders BTLA-mediated immune regulation more sophisticated and complex. Growing evidence has shown that BTLA is involved in T cells, B cells and dendritic cell-mediated immune regulation, and therefore plays an important role in a variety of immune related diseases, such as inflammation, tumor, infectious diseases and autoimmune diseases. Based on the latest research progress at home and abroad, this paper reviews the role of BTLA in immune regulation and immune related diseases.

Meta-analysis of Danhong Injection in treatment of diabetes mellitus complicated with coronary heart disease / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of Danhong Injection combined with conventional therapy in improving diabetes mellitus complicated with coronary heart disease. Based on the online literature database(CNKI, Wanfang, VIP, PubMed, Web of Science, Cochran Library), the Chinese and English papers about the randomized controlled trial(RCT) of Danhong Injection in the treatment of diabetes mellitus complicated with coronary heart disease were searched comprehensively from the establishment of the databases to January 1, 2020. The papers were screened strictly according to the inclusion and exclusion criteria. Based on Jadad scale, the risk assessment of literature was carried out, and Meta-analysis was performed by STATA 12.0 software. Seventeen RCTs were included, involving 1 453 patients. The results of Meta-analysis showed that the combination of Danhong Injection and conventio-nal treatment could improve the clinical comprehensive effective rate(RR=1.47, 95%CI[1.38, 1.58], P<0.000 1), electrocardiogram(ECG) efficiency(RR=1.30, 95%CI[1.16, 1.46], P<0.000 1), efficiency of the angina pectoris(RR=1.41, 95%CI[1.25, 1.58], P<0.000 1), cholesterol level(SMD=-1.05, 95%CI[-1.95,-0.16], P=0.02), low-density lipoprotein(LDL) level(SMD=-0.50, 95%CI[-0.79,-0.21], P<0.000 1), coronary angina attack frequency(SMD=-3.71, 95%CI[-4.05,-3.36], P<0.000 1) and duration of angina pectoris(SMD=-2.96, 95%CI[-3.25,-2.66], P<0.000 1), with statistically significant differences. But the differences in fasting plasma glucose(FPG)(SMD=-0.19, 95%CI[-0.45, 0.08], P=0.16), plasma glucose of two hours after meal(2 hPG)(SMD=0.19, 95%CI[-0.11, 0.49], P=0.22), and high-density lipoprotein(HDL) level(SMD=0.10, 95%CI[-0.30, 0.49], P=0.62) after treatment were not statistically significant. Compared with the control group, there was no significant difference in adverse reactions(SMD=-2.96, 95%CI[-3.25,-2.66], P=0.75). The existing evidence shows that the combination of Western medicine and Danhong Injection can improve the clinical effect for diabetes mellitus complicated with coronary heart disease and has no obvious adverse reactions. However, due to the low level of overall literature evidence, high risk and some kind of publication bias, it still needs more high-quality randomized controlled trials and low-bias studies for further verification.

Characterization of bZIP transcription factors from Dimocarpus longanDimocarpus longan Lour. and analysis of their tissue-specific expression patterns and response to heat stress

Members of the bZIP transcription factor family play crucial roles in the regulation of plant development, biosynthesis of secondary metabolites, and response to abiotic and biotic stresses. To date, multiple bZIPs have been identified and investigated in numerous plant species. However, few studies have characterized bZIPs from Dimocarpus longan Lour. In this study, nine bZIPs from D. longan were identified from RNA-Seq data and further verified using the NCBI conserved domain search tool and Pfam database. Bioinformatics tools were used to systematically analyse the physicochemical properties, protein structures, multiple sequence alignment, motif compositions, evolutionary relationships, secondary structures, subcellular localization, phosphorylation sites, signal peptides, GO annotations and protein–protein interactions of the DlbZIPs. The expression patterns of the nine DlbZIPs were evaluated by qRT-PCR in roots and leaves and in response to varying durations of a 38C heat treatment. DlbZIP3, DlbZIP5, DlbZIP6 and DlbZIP7 were differentially expressed between root and leaf tissues. All nine DlbZIPs responded to heat treatment in both roots and leaves, but their specific expression levels differed. DlbZIP4 and DlbZIP8 were highly expressed in roots after heat treatment, whereas DlbZIP1 and DlbZIP5 were highly expressed in leaves after heat treatment. These findings lay a foundation for increasing active secondary metabolite content and improving abiotic stress tolerance in D. longan using transgenic technology

Preliminary exploration of the mechanism of Qingfei Paidu decoction against novel coronavirus pneumonia based on network pharmacology and molecular docking technology / 药学学报

Traditional Chinese medicine (TCM) network pharmacology and molecular docking technology were applied to explore the mechanism of anti-coronavirus pneumonia (coronavirus disease 2019, COVID-19) of Qingfei Paidu decoction. The Chinese Pharmacopoeia (2015 edition) and Traditional Chinese Medicine Systems Pharmacology (TCMSP), OMIM (Online Mendelian Inheritance in Man), GeneCard, STRING, and others online databases are used for building a series of network, and selecting the core target and analyzing the signal pathway. Finally, we make molecular docking predictions for the important compounds. The results showed that the Qingfei Paidu decoction compound-pneumonia target network contained 292 compounds and 214 corresponding targets, and the core targets involved AKT1 (AKT serine/threonine kinase 1), IL6 (interleukin 6), MAPK8 (mitogen-activated protein kinase 8), MAPK1 (mitogen-activated protein kinase 1), and JUN (jun proto-oncogene). GO (Gene Ontology) function enrichment analysis yielded 858 GO entries, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment screening yielded 122 related pathways, including hypoxia inducible factor-1 (HIF-1) and Toll-like receptor (TLRs) signaling pathways related to pneumonia, as well as T-cell receptor (TCR) signaling pathway related to lung injury protection. The molecular docking results showed that some core compounds of the Chinese herbal medicine of Qingfei Paidu decoction have a certain degree of affinity for 2019-novel coronavirus (2019-nCoV) main protease (3C-like protease, 3CLpro) and angiotensin-converting enzyme 2 (ACE2). In this paper, we preliminarily explored the potential therapeutic mechanism for Qingfei Paidu decoction to against COVID-19 and predicted the active ingredients. We hope that the results will help to the further study on the active ingredients and mechanism of Qingfei Paidu decoction to COVID-19.

Betaine supplementation improved L-threonine fermentation of Escherichia coli THRD by upregulating zwf (glucose-6-phosphate dehydrogenase) expression

BACKGROUND: The supplementation of betaine, an osmoprotective compatible solute, in the cultivation media has been widely used to protect bacterial cells. To explore the effects of betaine addition on industrial fermentation, Escherichia coli THRD, an L-threonine producer, was used to examine the production of L-threonine with betaine supplementation and the underlying mechanism through which betaine functions was investigated. RESULTS: Betaine supplementation in the medium of E. coli THRD significantly improved L-threonine fermentation parameters. The transcription of zwf and corresponding enzyme activity of glucose-6-phosphate dehydrogenase were significantly promoted by betaine addition, which contributed to an enhanced expression of zwf that provided more nicotinamide adenine dinucleotide phosphate (NADPH) for L-threonine synthesis. In addition, as a result of the betaine addition, the betaine-stimulated expression of enhanced green fluorescent protein (eGFP) under the zwf promoter within a plasmid-based cassette proved to be a transcription-level response of zwf. Finally, the promoter of the phosphoenolpyruvate carboxylase gene ppc in THRD was replaced with that of zwf, while L-threonine fermentation of the new strain was promoted by betaine addition. Conclusions: We reveal a novel mode of betaine that facilitates the microbial production of useful compounds. Betaine supplementation upregulates the expression of zwf and increases the NADPH synthesis, which may be beneficial for the cell growth and thereby promote the production of L-threonine. This finding might be useful for the production of NADPH-dependent amino acids and derivatives in E. coli THRD or other E. coli strains.

Removing the by-products acetic acid and NH4 + from the L-tryptophan broth by vacuum thin film evaporation during L-tryptophan production

Background: During L-tryptophan production by Escherichia coli, the by-products, acetic acid and NH4 +, accumulate in the fermentation broth, resulting in inhibited cell growth and activity and decreased L-tryptophan production. To improve the L-tryptophan yield and glucose conversion rate, acetic acid and NH4 + were removed under low-temperature vacuum conditions by vacuum scraper concentrator evaporation; the fermentation broth after evaporation was pressed into another fermenter to continue fermentation. To increase the volatilisation rate of acetic acid and NH4 + and reduce damage to bacteria during evaporation, different vacuum evaporation conditions were studied. Results: The optimum operating conditions were as follows: vacuum degree, 720 mm Hg; concentration ratio, 10%; temperature, 60°C; and feeding rate, 300 mL/min. The biomass yield of the control fermentation (CF) and fermentation by vacuum evaporation (VEF) broths was 55.1 g/L and 58.3 g/L at 38 h, respectively, (an increase of 5.8%); the living biomass yield increased from 8.9 (CF) to 10.2 pF (VEF; an increase of 14.6%). L-tryptophan production increased from 50.2 g/L (CF) to 60.2 g/L (VEF) (an increase of 19.9%), and glucose conversion increased from 18.2% (CF) to 19.5% (VEF; an increase of 7.1%). The acetic acid concentrations were 2.74 g/L and 6.70 g/L, and the NH4 + concentrations were 85.3 mmol/L and 130.9 mmol/L in VEF and CF broths, respectively. Conclusions: The acetic acid and NH4 + in the fermentation broth were quickly removed using the vacuum scraper concentrator, which reduced bacterial inhibition, enhanced bacterial activity, and improved the production of L-tryptophan and glucose conversion rate.

Role of hepatic transporters and metabolic enzymes in chemical substances-induced liver injury / 药物评价研究

Liver is an important metabolic and detoxification organ in the body.Hepatic transporters are a series of functional membrane proteins that are extensively expressed in the liver.They are responsible for the uptake of endogenous and exogenous substances such as medicines into hepatocytes and excretion of their metabolic products into bile.Recent studies have provided that transporters and metabolic enzymes play important roles in the chemical substances-induced liver injury,and its various regulatory mechanisms have become hot topics of research.In this paper,we summarize the classification of hepatic transporters and metabolic enzymes and the changes of transporters and metabolic enzymes in the chemical substances-induced liver injury and its regulatory mechanism.

Reducing lactate secretion by ldhA Deletion in L-glutamate- producing strain Corynebacterium glutamicum GDK-9

L-lactate is one of main byproducts excreted in to the fermentation medium. To improve L-glutamate production and reduce L-lactate accumulation, L-lactate dehydrogenase-encoding gene ldhA was knocked out from L-glutamate producing strain Corynebacterium glutamicum GDK-9, designated GDK-9ΔldhA. GDK-9ΔldhA produced approximately 10.1% more L-glutamate than the GDK-9, and yielded lower levels of such by-products as α-ketoglutarate, L-lactate and L-alanine. Since dissolved oxygen (DO) is one of main factors affecting L-lactate formation during L-glutamate fermentation, we investigated the effect of ldhA deletion from GDK-9 under different DO conditions. Under both oxygen-deficient and high oxygen conditions, L-glutamate production by GDK-9ΔldhA was not higher than that of the GDK-9. However, under micro-aerobic conditions, GDK-9ΔldhA exhibited 11.61% higher L-glutamate and 58.50% lower L-alanine production than GDK-9. Taken together, it is demonstrated that deletion of ldhA can enhance L-glutamate production and lower the unwanted by-products concentration, especially under micro-aerobic conditions.

Hyperlipidaemia in patients with sleep-related breathing disorders: Prevalence & risk factors.

Background & objectives: several studies have shown a close relationship between obstructive sleep apnoea (OSA) and dyslipidaemia. This study was designed to clarify the relationship of metabolic dysfunctions in sleep related-breathing disorders (SRBD), including OSA and simple snoring. The end point was to determine the prevalence of hyperlipidaemia and hyperuricaemia in SRBD. Factors contributing to hyperlipidaemia and hyperuricaemia in SRBD were also evaluated. Methods: Outpatients >20 yr old with complaint of habitual snoring were prospectively enrolled. All patients underwent an overnight polysomnography (PSG) in a sleep laboratory and blood assay after overnight fasting. The factors of gender, age, body mass index (BMI), apnoea-hypopnoea index (AHI), and desaturation index (DI) were recorded in the PSG report. A logistic regression analysis was conducted to investigate the relationship between metabolic dysfunctions and these factors. Results: Of the 275 patients (88.4% male), 236 (85.8%) were diagnosed with OSA (AHI>5/h). The mean (± SD) of age, BMI, AHI, and DI were 44.2 ± 11.4 yr, 27.4 ± 4.0 kg/m2, 37.9 ± 30.6/h, and 21.2 ± 23.2/h, respectively. The overall prevalence of hypercholesterolaemia, hypertriglyceridaemia, and hyperuricaemia in this study was 61.1, 55.3, and 25.8 per cent, respectively. Logistic regression analysis revealed that DI was a significant independent factors contributing to hypercholesterolaemia [odds ratio (OR)=1.016, P=0.010, 95% confidence interval (CI)=1.004-1.028] and hypertriglyceridaemia (OR=1.021, P=0.002, 95% CI=1.008-1.034). Interpretation & conclusions: The data of the present study support a high prevalence of hyperlipidaemia in SRBD. DI may be a determining factor contributing to hyperlipidaemia in SRDB. Underdiagnosis of hyperlipidaemia in SRBD is a critical problem.

Impact of genetic polymorphism of SDF1 3A on efficacy of captopril in Chinese patients with essential hypertension / 中南大学学报(医学版)

Objective To explore the association of SDF1 3A genetic polymorphism with susceptibility of essential hypertension and captopril efficacy in patients with essential hypertension.Methods A total of 214 patients with essential hypertension and 228 healthy controls were genotyped for SDF1 3A polymorphism by polymerase chain reaction-restriction fragment length polymorphism assay. Among 39 subjects with different SDF1 3A of genotypes, 13 hypertensive patients simultaneously took oral captopril (25 mg/d) and nitrendipine (30 mg/d), and 12 patients orally received nitrendipine alone for 8 consecutive weeks, and 14 healthy controls did not take any agents. The blood pressure of all subjects was measured to evaluate the therapeutic efficacy. Results There was a significant difference in the plasma SDF-1 level in individuals with AA+AG genotypes or GG genotypes of SDF1 3A treated with nitrendipine plus captopril compared with healthy control (P<0.05). Carriers with AA genotypes of SDF1 3A had lower total protein and globulin than those with GG genotypes (P<0.05). After captopril treatment, hypertensive patients with AA+AG genotypes had bigger attenuated systolic blood pressure compared with those with GG genotypes (P<0.05). Conclusion Genetic polymorphism of SDF1 3A could influence the therapeutic efficacy of captopril in Chinese hypertensive patients.

Effect of integrin-linked kinase on renal tubular epithelial cell transdifferentiation in diabetic rats / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of integrin-linked kinase(ILK) in renal tubular epithelial cells and its relation to tubular epithelial-myofibroblast transdifferentiation.@*METHODS@#Wistar rats were randomly divided into 3 groups, Group normal control (n=10), Group diabetic without therapy(n=10) and Group diabetic with Losartan 20mg/(kg . d)(n=10). Five rats were killed in each group at the 8th and 16th week. The left kidneys were kept for HE and Masson staining to observe the pathological variations in the renal interstitium. ILK, alpha-SMA and Vimentin in renal tubular epithelial cells were detected by immunohistochemistry analysis.@*RESULTS@#Compared with the control group, ILK, alpha-SMA and Vimentin in renal tubular epithelial cells in Group diabetes gradually increased in immunohistochemistry (P<0.01); ILK was consistent with the pathological variation of renal interstitium and was positively correlated to alpha-SMA(rs=0.621, P<0.05). In comparison with the Group diabetes, the expression of ILK, alpha-SMA and Vimentin in renal tubular epithelial cells was apparently declined (P<0.01) in Group diabetes with Losartan.@*CONCLUSION@#Tubular epithelial myofibroblast transdifferentiation and the over-expression of ILK, between which there may be significant connections, are important events in the progression of diabetic nephropathy. Losartan, a blocker of angiotension II type I receptor, which may down-regulate the expression of ILK in diabetic renal tubular epithelial cells, can restrain the procession of epithelial-myofibroblast transdifferentiation.