Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

STIP1 correlates with tumor immune infiltration and prognosis as a potential immunotherapy target: a pan-cancer bioinformatics analysis / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of stress-inducible phosphoprotein 1 (STIP1) expression level with prognosis of different cancers and its potential role in immunotherapy.@*METHODS@#TCGA, TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers. We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues. We further analyzed the correlation of STIP1 expression level with tumor mutational burden, microsatellite instability, immune cell infiltration, immune regulators and outcomes of different cancers. STIP1- related proteins were identified using protein- protein interaction (PPI) network analysis, and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1.@*RESULTS@#Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues (P < 0.05), which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues. STIP1 expression level was correlated with clinical stages of multiple cancers (P < 0.05), and in some cancer types, an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival, disease-specific survival, disease-free survival and progression-free survival (P < 0.05). STIP1 expression was significantly correlated with tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors in most tumors (P < 0.05). PPI network analysis indicated that STIP1-related proteins included HSPA4, HSPA8, and HSP90AA1. KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism, tryptophan metabolism, and butyrate metabolism pathways; HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism.@*CONCLUSION@#STIP1 is up-regulated in multiple cancer types and its expression level is correlated with clinical tumor stage, tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors.

Bioinformatics analysis of survival-related genes in pancreatic cancer based on GEO and TCGA database / 西安交通大学学报(医学版)

【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.

Autophagy and Inflammation in Fish / 中国生物化学与分子生物学报

Autophagy and inflammation are the important physiological reactions, especially in innate immunity. Autophagy, as a conservative metabolic process, can degrade its own disorder components through lysosomes to maintain cell homeostasis. Autophagy plays a pivotal role in degrading damaged organelles, resisting pathogenic infection and regulating inflammatory response. In the past decades, the study of autophagy in yeast and mammals has greatly increased our understanding for autophagy and its relationship with the diseases. In human, the regulation on autophagy levels can be used to prevent or treat neurodegenerative diseases, inflammatory diseases, tumors and various pathogenic microbial infections. However, in fish, the researches on autophagy and application are limited. Inflammation is a highly complex biological process, which is a natural defense response under the stimulation of ultraviolet, pathogen infection, oxidative stress and mechanical damage. Fish, as a lower vertebrate, has an incomplete acquired immune system. Innate immunity plays an important role in defensing against pathogen infection. Compared with higher vertebrate animals, although the researches on autophagy in fish cells were carried out lately, the great progress has been made in recent years on autophagy phenomenon, expression regulation of autophagy-related genes, and mechanism caused by pathogenic infection. As an important part of innate immunity, autophagy is involved in a variety of fish pathogenic infections, and fish diseases are usually accompanied by inflammatory reaction. In this review, we summarized the update findings in recent references on the autophagy and inflammatory response caused by pathogenic infection in fish, and the correlation between them, in order to deeply understand the correlation relationship between autophagy and inflammatory response in fish. This review could provide the guidance for understanding the immune mechanism of fish, and supply the foundation for developing new strategy to prevent and control fish disease.

The role of autophagy-related gene 9B in lichen planus

Background: Lichen planus (LP) is an idiopathic, chronic, relapsing, inflammatory, autoimmune dermatological disease. The etiopathogenesis of LP is still unclear. Autophagy is a strictly regulated lysosomal degradation pathway that is crucial for maintaining intracellular homeostasis and normal development. The dysregulation of autophagy-associated genes was recognized to increase the susceptibility to multiple diseases, including inflammation, autoimmune disorders and cancer. Aims: Our study aimed to detect the expression of autophagy-related gene 9 b (ATG9B) in LP patients compared to normal control persons to investigate the possible role of autophagy in pathogenesis of this disease. Methods: This case–control study included 30 LP patients and 30 age-, gender-matched healthy controls. Four millimeters punch skin biopsies were obtained from LP lesions and from the controls and they were kept in lysis solution for the stability of the studied parameters and were kept frozen at –80°C till analysis of ATG9B using real-time polymerase chain reaction. Results: The level of ATG9B in lesional skin of LP was significantly decreased compared to normal control persons (P < 0.01); also, there was a non-significant relation between ATG9B level and age, sex, duration and family history among LP patients. Limitations: Limited number of patients included in our study (30 patients). Conclusion: Autophagy may play a role in the pathogenesis of cutaneous LP.

Clinical characteristics of idiopathic inflammatory myopathy patients with positive anti-melanoma differentiation-associated gene 5 antibody / 中华风湿病学杂志

Objective:To investigate the clinical characteristics and prognosis of idiopathic inflammatory myopathy (IIM) patients with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:A total of 194 hospitalized IIM patients who were tested for myositis-specific autoantibodies (MSAs) in the Departments of Rheumatology and Immunology of Tianjin Medical University General Hospital from January 2015 to September 2020 were collected, including 29 cases with positive anti-MDA5 antibody and 165 cases with negative anti-MDA5 antibody. Their clinical data were analyzed retrospectively. T test was used for measurement data with normal distribution. Measurement data with non-normal distribution were tested by Mann-Whitney U rank sum test. χ2 test was used for counting data. Risk factors were analyzed by binary Logistic regression, survival analysis by Kaplan-Meier method and Cox regression analysis. Results:IIM patients with positive anti-MDA5 antibody had a high incidence of dermatomyositis specific skin rash, and the skin rash was the most common presenting symptom. In the positive anti-MDA5 antibody group, muscle symptoms were mild; and the patients were prone to have fever, arthritis, oral ulcer and weight loss. All patients were complicated with interstitial lung disease (ILD). In patients with negative anti-MDA5 antibody, white blood cell (WBC) count [7.59(5.61, 9.89)×10 9/L vs 4.07(3.17, 5.50×10 9/L, Z=-5.05, P<0.001], platelet (PLT) [249.00 (200.00, 302.00)×10 9/L vs 205.00 (178.00, 244.00)×10 9/L, Z=-2.59, P=0.010], lymphocyte (LY) [1.34(0.85, 1.94)×10 9/L vs 0.64(0.40, 0.83)×10 9/L, Z=-5.78, P<0.001), serum creatine kinase (CK) [558.00 (72.00, 2 959.00) U/L vs 64.00 (35.00, 149.50) U/L, Z=-3.97, P<0.001], creatine kinase isoenzymes (CK-MB) [38.00 (17.00, 127.00) U/L vs 16.00 (14.00, 25.00) U/L, Z=-3.84, P<0.001], myoglobin (MYO) [243.65 (60.50, 829.83) ng/ml vs 34.55(21.00, 104.23) ng/ml, Z=-3.98, P<0.001], troponin T (TnT) [0.09(0.03, 0.44) ng/ml vs 0.02(0.01, 0.04) ng/ml, Z=-4.17, P<0.001], albumin (ALB) [34.00(30.00, 38.00) g/L vs 31.00 (26.50, 36.00) g/L, Z=-2.68, P=0.007], cluster of differentiation 4 (CD4) + T cells [498.00(276.00, 752.00) cells/μl vs 259.50 (179.00, 498.25) cells/μl, Z=-2.79, P=0.005], partial pressure of carbon dioxide (PaCO 2) [39.00(36.13, 42.00) mmHg vs 35.35 (31.30, 38.88) mmHg, Z=-3.75, P<0.001], partial pressure of oxygen (PaO 2) [82.00(71.90, 90.20) mmHg vs 73.25(64.30, 84.05) mmHg, Z=-2.08, P=0.037], arterial oxygen saturation (SaO 2) [96.50% (95.05%, 97.30)% vs 95.80%(93.70%, 96.55%), Z=-2.11, P=0.035], diffusion capacity for carbon monoxide of the Lung (DLco) [(63±21) % vs (52±14)%, t=0.96, P=0.006] were significantly reduced, while UTP [260.50 (172.25, 401.25) g vs 331.00 (252.75, 666.25) g, Z=-2.18, P=0.029], alanine aminotransferase (ALT) [40.00 (21.00, 83.00) U/L vs 56.00(40.00, 107.50), Z=-2.27, P=0.023], glutamyltranspeptidas (GGT) [22.50(15.00, 42.00) U/L vs 57.00 (38.00, 101.50) U/L, Z=-4.98, P<0.001], D-Dimer [850.00 (485.00, 1 799.50) ng/ml vs 1 346.00 (896.50, 2 527.00) ng/ml, Z=-2.55, P=0.011], immunoglobulin (Ig)E [60.00 (25.60, 147.50) U/ml vs 173.00(68.25, 471.50) U/ml, Z=-3.06, P=0.002], C4[20.25(16.68, 25.03) mg/L vs 23.60(20.20, 28.35) mg/L, Z=-2.38, P=0.017], Fer [228.01 (115.40, 513.36) ng/ml vs 1 636.39 (851.80, 3 888.82) ng/ml, Z=-6.01, P<0.001], krebsvondenlungen-6 (KL-6) [365.00 (180.25, 1 018.75) U/ml vs 788.00 (406.00, 1 364.00) U/ml, Z=-2.10, P=0.035] were higher when compared to patients with positive anti-MDA5 antibody. In the anti-MDA5 antibody positive group, patients had high mortality rate [8.5%(14/165) vs 34.5%(10/29), χ2=13.07, P<0.001], and the use of intravenous immunoglobulin [32.7%(54/165) vs 65.5%(19/29), χ2=11.30, P=0.001] and steroid pulse therapy [4.8%(86/165) vs 27.6%(8/29), χ2=13.98, P<0.001] were more frequent. Patients in the positive anti-MDA5 antibody group were classified into two sub groups based on lung features: the rapidly progressive interstitial lung disease (RP-ILD) group (48.28%, 14/29) and the chronic interstitial lung disease (C-ILD) group (51.72%, 15/29). RP-ILD patients had significantly elder disease onset age, higher C-reaction protein (CRP), Fer, IgE levels and the positive rate of anti-Ro52 antibody, while ALT was lower. The difference was statistically significant. Regression analysis suggested that older onset age [ HR (95% CI)=1.154 (1.069, 1.246), P<0.001], male [ HR(95% CI)=6.383(1.038, 39.242), P=0.045], positive anti-MDA5 antibody [ HR(95% CI)=17.180 (2.900, 101.766), P=0.002], LY decrease [ HR (95% CI)=0.083 (0.008, 0.817), P=0.033], high serum Fer level [ HR (95% CI)=1.001(1.000, 1.001), P=0.016], increased D-Dimer [ HR(95% CI)=1.000(1.000, 1.001), P=0.004] and compicated with carcinoma [ HR (95% CI)=11.849 (1.978, 70.970), P=0.007] were independent risk factors for death in IIM patients. Binary logistic regression analysis suggested that late onset age [ OR(95% CI)=1.090 (1.005, 1.183), P=0.038], high Fer level [ OR (95% CI)=1.001 (1.000, 1.001), P=0.022] and decreased ALB [ OR (95% CI)=0.818 (0.696, 0.963), P=0.016] might be risk factors for RP-ILD in patients with positive anti-MDA5 antibody. Conclusion:In patients with positive anti-MDA5 antibody group, typical skin damage, mild muscle symptoms, high proportion of ILD and poor prognosis are chardcteristic when compared to patients without this autoantibody. It is necessary to monitor the disease activity closely and explore the treatment strategy.

Melatonin alleviates hypoxia-induced injury of PC12 cells by inhibiting SOX2 expression / 国际生物医学工程杂志

Objective:To investigate the effect of melatonin (MT) on hypoxia-induced injury of PC12 cells and its mechanism.Methods:PC12 cells cultured in vitro were divided into the control, the hypoxic, and three groups of hypoxic cells combined with different doses (low, medium, and high) of MT at 12.5, 25, and 50 μmol/L, respectively. Cell viability was measured by MTT. The expression of cysteine-containing aspartate 3 (cleaved caspase-3) and SOX2 proteins was detected by Western blot. The expression of SOX2 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (PCR). The activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected by the kit. The combined treatment group with the most significant effect was selected as the hypoxia+MT group, and then the effects of hypoxia+MT, hypoxia+siRNA-NC, hypoxia+siRNA-SOX2, hypoxia+MT+pcDNA, and hypoxia+MT+pcDNA-SOX2 on cell viability, apoptosis, protein expression level of cleaved-caspase-3, protein and mRNA levels of SOX2, SOD activity, and MDA levels, respectively, were investigated.Results:Compared with the control group, cell survival rate and SOD activity in the hypoxia group were significantly decreased, while cell apoptosis rate, cleaved caspase-3 protein expression level, MDA content, SOX2 mRNA, and protein expression level were significantly increased (all P<0.05). The effects of low, medium, and high levels of MT and the low expression of SOX2 could ameliorate the above changes induced by hypoxia (all P<0.05), while the overexpression of SOX2 could alleviate the effects of MT on the viability, apoptosis, and oxidative stress of hypoxia-induced PC12 cells (all P<0.05). Conclusions:MT can reduce hypoxia-induced injury to PC12 cells by inhibiting the expression of SOX2.

Expression and significance of HERG protein in Cajal interstitial cells of gallbladder tissue in patients with gallbladder stones / 中华肝胆外科杂志

Objective:To investigate the expression and significance of human ether-a-go-go related gene (HERG) protein in interstitial cells of Cajal (ICC) in patients with gallbladder stones.Methods:The gallbladder tissues of 60 patients with gallbladder diseases who underwent cholecystectomy from January 2018 to December 2020 in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were collected, including 36 males and 24 females, aged (46.0±14.0) years. They were divided into two groups according to whether there were gallstones: gallstone group and control group (patients with gallbladder polyps and gallbladder adenomyosis), with 30 cases in each group. Color ultrasound was used to detect and calculate the gallbladder contraction rate. The neck, body and bottom tissues of the gallbladder were excised and sectioned. The expression of HERG protein and CD117 ( marker of ICC) was detected by immunofluorescence staining, immunohistochemistry and Western blot.Results:The gallbladder contraction rate in the gallstone group was (65.8±4.1)%, lower than that in the control group (73.8±5.3)%, with a statistically significant difference ( t=4.14, P<0.001). Immunohistochemistry showed that HERG protein was mainly distributed in the mucosal layer of gallbladder tissue, which was pale brown. The relative expression of HERG protein at the bottom of gallbladder in the gallstone group was (0.293±0.102), lower than that in the control group (0.694±0.059), with a statistically significant difference ( t=3.38, P=0.027). Immunofluorescence staining showed that HERG protein was mainly distributed in ICC of gallbladder epithelium. HERG protein expression in ICC at the bottom of gallbladder in gallstone group was lower than that in control group, while HERG protein expression at the neck and body of gallbladder had no significant difference. Conclusion:There are ICC and HERG protein in gallbladder tissue of patients with gallstone. The decrease of gallbladder contraction rate may be related to the decrease of HERG protein expression in ICC in gallbladder bottom tissue.

Research progress on the role of autophagy pathway in acute renal injury and targeted treatment strategies / 中国综合临床

Autophagy is a highly conserved intracellular catabolic process used to degrade cytoplasmic components. In recent years, it has attracted much attention because of its importance in the pathogenesis and targeted therapy of acute and chronic kidney disease. Autophagy plays an important role in maintaining renal homeostasis under physiological and pathological conditions. The study of conditional autophagy related gene knockout specific to various renal cells has gradually revealed the role of autophagy in renal diseases. Recent studies have found that autophagy deficiency may play a key role in different pathological states of the kidney. Activated autophagy shows cytoprotective function in both glomerulus and renal tubulointerstitium, suggesting that the up regulation of autophagy may become a potential therapeutic strategy. However, there is also contrary evidence that autophagy may be harmful, which poses a great challenge to the development of therapeutic strategies for up-regulated autophagy.

Ferroptosis-related gene and its relationship with prognosis of differentiated thyroid carcinoma patients / 中华内分泌外科杂志

Objective:To analyze the marker of ferroptosis-related genes in differentiated thyroid carcinoma (DTC) based on TCGA database.Methods:The mRNA expression profiles and survival information of thyroid cancer patients and normal thyroid samples were downloaded from the TCGA database. The genetic difference analysis added 653 normal thyroid samples from the GETx database. Twenty-two ferroptosis-related genes were selected for univariate Cox regression analysis. Genes associated with prognostic in the TCGA cohort were further screened and prognostic models using LASSO regression was constructed. Adjusted P<0.05 and | log2FC>1" as the threshold, 22 differentially expressed genes were selected. The genes were screened by multivariate Cox regression analysis for prognosis-related genes and displayed in a line diagram. Results:22 of the 24 ferroptosis-related genes were differentially expressed between the tumor and normal tissues, with13 high expression, 9 low expression, 1 gene expression without difference and 1 gene not expressed in half of the samples. Univariate Cox regression analysis found that DPP4 and TFRC were associated with the degree of disease risk (HR was<1 and>1, respectively) . When integrating GPX4, TFRC and DPP4 into the LASSO model screening, it was found to be related to prognosis after dividing the patients into risk groups according to lambda. min=0.0027, Riskscore= (0.7316) * TFRC+ (-0.2539) *DPP4 (Log rank P=0.00635. Multivariate Cox regression analysis found that DPP4 and TFRC were related to the degree of disease risk (HR were<1 and>1, respectively) . Conclusion:The model of TFRC and DPP4 constructed by ferroptosis-related differential expression genes may be potential predictive markers of DTC patients, which still needs further verification and will provide theoretical basis for further clinical treatment.

MicroRNA-34c-5p provokes isoprenaline-induced cardiac hypertrophy by modulating autophagy via targeting ATG4B

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

Two strongly linked blocks within the KIF16B gene significantly influence wool length and greasy yield in fine wool sheep (Ovis aries)

BACKGROUND A previous genome-wide association study (GWAS) identified the kinesin family member 16B (KIF16B) as a candidate gene related to sheep wool production. In this work, DNA pool sequencing and SNPscanTM high-throughput genotyping methods were used to detect single-nucleotide polymor phisms (SNPs) in the sheep KIF16B gene. The correlations between the SNPs and wool length and greasy wool yield were systematically assessed. RESULTS Forty-five SNPs were identified and 37 of them were genotyped, including 10 exon mutations, 26 intron mutations, and 1 promoter region mutation. Most of the SNPs were of medium genetic diversity and at Hardy-Weinberg equilibrium (HWE). Among them, 10 SNPs were associated with greasy wool yield and 28 SNPs impact the wool length. Five specific SNPs were found to exert significant effects on the wool length in all body parts analyzed in this study. Furthermore, linkage disequilibrium (LD) analysis was conducted among SNP loci and they were found to be significantly associated with economically important traits. Two strongly linked SNP blocks were identified within these SNPs and they might exert significant impacts on the greasy wool yield and wool length. CONCLUSIONS The identified SNPs exert significant effects on wool production and could be considered as potential DNA markers for selecting the individuals with superior phenotypes

Effects of Autophagy-related Genes and Signal Pathways on Occurrence and Development of Oral Tumors / 肿瘤防治研究

Autophagy is a highly conservative cellular self-protective behavior dependent on lysosomes, and can be used as an important factor in promoting or preventing cancer, and its effect is related to the type and development of tumors. A full understanding of autophagy pathway is helpful to improve the diagnosis and treatment of tumors. Studies have shown that autophagy is closely related to the occurrence and development of oral tumors. Autophagy-related genes and signal pathways play a dual regulatory role on oral tumors. This article reviews the latest progress in the regulatory mechanism and therapeutic effect of autophagy on oral tumors.

Analysis of the relationship between Helicobacter pylori cytotoxin-associated gene A, Helicobacter pylori isolate vacuole-forming toxin gene A and gastric cancer occurrence and clinicopathological factors / 中国医师进修杂志

Objective:To investigate the relationship between Helicobacter pylori(HP) cytotoxin-associated gene A (HP-CagA), HP isolate vacuole-forming toxin gene A (HP-VacA) and gastric cancer occurrence and clinical pathological factors.Methods:Eighty-eight patients with gastric cancer from January 2018 to January 2020 in Suzhou Hospital Affiliated of Anhui Medical University was selected as the observation group, 80 patients with benign gastric lesions during the same period was selected as the benign control group, and 80 healthy patients was selected as the healthy control group. The clinical data, HP-CagA, HP-VacA positive expression rates of the three groups were compared, the risk factors of gastric cancer were analyzed, and the relationship between HP-CagA, HP-VacA and gastric cancer clinicopathological factors were evaluated.Results:Family history of gastric cancer, high-salt diet, preference for hot food, decreased pepsinogen (PG)Ⅰ/PGⅡ, combined with fatty liver, increased triglyceride, total cholesterol and low density lipoprotein cholesterin, smoking and depression were risk factors of gastric cancer ( P<0.05). The positive rate of HP-CagA, HP-VacA in the observation group were higher than those in the benign control group and the healthy control group: 82.93%(73/88) vs. 62.50%(50/80) and 26.25%(21/80), 30.68%(27/88) vs. 7.50%(6/80) and 0, the differences were statistically significant ( P<0.05). The positive of HP-CagA and HP-VacA had correlation with age, pathological type, and degree of differentiation of gastric cancer ( P<0.05). The 1-year survival rate of HP-CagA and HP-VacA positive patients was lower than that of negative patients by Kaplan-Meier analysis ( P<0.05). Conclusions:The positive of HP-CagA and HP-VacA in HP infections are closely related togastric cancer. Strengthening the treatment of HP infection patients with positive HP-CagA and HP-VacA has important clinical value and social significance for cutting off the early stage of gastric cancer and improving prognosis.

Molecular Cloning and Functional Analysis of Autophagy-related Gene Atg5 in Planarian Dugesia japonica / 中国生物化学与分子生物学报

Autophagy-related gene 5 (Atg5) plays an essential role in autophagy, the loss of its function impairs neurogenesis and axon regeneration. However, the biological function of Atg5 has not been characterized in planarian. Planarian is an ideal model for the study of brain regeneration. It can regenerate a new brain de novo in 1 week following amputation. To explore the role of Atg5 in planarian brain regeneration, we dissected the molecular characteristics of Atg5 in planarian Dugesia japonica (DjAtg5) and examined its function by RNAi. The full-length cDNA of DjAtg5 is 1 014 bp encoding 284 amino acids. The deduced amino sequence of DjAtg5 contains the functional Pfam domain of ATG5 and highly conserved residues for ATG5-ATG12 interaction. After amputation, the transcrips of DjAtg5 are increased and mainly distributed in the newly regenerated brain on day 3-5 of regeneration. However, knockdown of DjAtg5 by RNAi does not impair the regeneration ability and brain structure reformation, nor affects the neoblasts proliferation. Our results suggest that DjAtg5 participates in re-formation of planarian brain structure following amputation, but it is not an important regulator for planarian regeneration. However, autophagy inhibitor 3-MA can block planarian regeneration, which suggests that autophagy is necessary for planarian regeneration.

Screening of mutations of common deafness-related genes in neonates in Changning District, Shanghai / 上海预防医学

Objective To determine the mutations of common deafness-related genes and explore the clinical significance of universal screening in neonates in Changning District of Shanghai. Methods Microarray gene screening was used to detect the following common mutation sites, including GJB2(c.35delG, c.176 del16, c.235delC, c.299 delAT); SLC26A4(c.IVS7-2A > G, c.2168A > G, c.1174A > T, c.1226G > A, c.1229C > T, c.IVS15+5G > A, c.1975G > C, c.2027T > A); mitochondrial DNA 12S rRNA(m.1555A > G; m.1494C > T)and GJB3(c.538C > T). In addition, hearing screening was conducted. Results In a total of 2 006 neonates, 90 cases(4.49%)had the mutations, including 40(1.99%)carrying a GJB2 single heterozygous mutation, 38(1.89%)carrying a SLC26A4 single heterozygous mutation, 4(0.20%)carrying a mitochondrial 12S rRNA homogeneous mutation, and 6(0.30%)carrying a GJB3 single heterozygous mutation. There were two double heterozygous mutations. In addition, 11 cases failed in the hearing screening. Conclusion There are mutations of deafness-related genes in neonates in Changning District of Shanghai, in which GJB2 and SLC26A4 are common. It remains crucial to combine screening of common deafness-related genes and hearing test in neonates for improving the health quality. Moreover, it is significant in preventing and controlling the hearing disability in three levels.

Multi-omics approaches identify

Autophagy is a critical cellular homeostatic mechanism, and its dysfunction is linked to invasive breast carcinoma (BRCA). Recently, several omics methods have been applied to explore autophagic regulators in BRCA; however, more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered. Thus, we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA, including gene expression (EXP), DNA methylation (MET) and copy number alterations (CNAs) from The Cancer Genome Atlas (TCGA). Newly identified candidate genes, such as

The role of autophagy-related gene mTOR signaling pathway in the pathogenesis of systemic lupus erythematosus / 医学研究生学报

Objective　The mechanism of autophagy-related gene mTOR signaling pathway is less studied in its pathogenesis of systemic lupus erythematosus. The aim of this study was to investigate the role of autophagy-related gene mTOR signaling pathway in the pathogenesis of SLE.　Methods　72 patients with systemic lupus erythematosus in the Department of Rheumatism and Immunity in the Second Affiliated Hospital of Hainan Medical College from February 2018 to March 2019 were selected as observation group. 67 healthy subjects in the same period were used as control group. The ENA antibody profiles were determined by immunoblotting, including anti-SSA, anti-SSB, anti-Sm, anti-nRNP antibodies, and ds-DNA antibodies. IgG, IgA, IgM, and complement C3, C4 were determined using an IMMAGE protein analyzer. Fluorescence PCR was used to detect the autophagy-related gene mTOR signaling pathway. SPSS Pearson correlation analysis software was used to analyze the correlation between autophagy-related gene mTOR signaling pathway(pI3K mRNA, Akt mRNA, mTOR mRNA) and humoral immunity level in the two groups.　Results　The level of IgG, IgA, and IgM in the observation group was significantly higher than that of the control group (P<0.05). The levels of complement C3 and C4 in the observation group were lower than those in the control group (P<0.05). The expression levels of PI3K mRNA, Akt mRNA and mTOR mRNA in SLE group (0.52±0.06, 0.61±0.08, 0.48±0.05) were significantly lower than those in control group (1.00±0.09, 0.89± 0.07, 0.95±0.08), with statistically significant differences (P<0.05). The results of SPSS Pearson correlation analysis showed that Akt and mTOR signals expression were negatively correlated with IgG, IgA, IgM level,and ds-DNA, anti-SSA, anti-SSB, anti-Sm, anti-nRNP expression leve(P<0.05). On the contrary, they were positively correlated with complement C3, C 4 levels(P<0.05).　Conclusion　The expression of PI3K mRNA, Akt mRNA and mTOR mRNA in mTOR signaling pathway of autophagy related genes in SLE patients is inhibited, which is closely related to immunoglobulin and complement level. Therefore, detection of the autophagy related gene mTOR signaling pathway will be helpful in assessing the status of SLE patients.

Advances in signal regulation and detection strategies for autophagy in fungal cells / 药学学报

Autophagy is a widespread and unique degradation process in eukaryotic cells. When cells are under various stress conditions such as nutritional deficiencies, growth factor deficiencies or hypoxia, autophagy will be initiated to maintain the stability of the internal environment and ensure normal proliferation and differentiation. At present, research on autophagy-related targets is mostly focused on tumor cells. In contrast, research on fungal autophagy targets is still limited. Autophagy plays an important role in growth, development and morphological changes of fungal cells, suggesting that research on fungal autophagy as a drug target should be useful. This article reviews the signal regulation and detection strategies for autophagy in fungal cells, and provides a research basis for the screening of antifungal drugs targeting autophagy-related proteins.

Concordant point mutation of ETS-related gene (ERG) in tumor tissues from a synchronous multiple primary lung cancer: A case report / 北京大学学报(医学版)

The rearrangement of the gene encoding the transcription factor ETS-related gene (ERG) is thought to play a key role in the development of prostate cancer. However, the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma (NSCLC). Here, we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs. The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography (CT) scan. After conducting lobectomies at the both lungs, the tumor nodules were all removed, and the histological analysis suggested adenocarcinoma at the both tumor lesions. The patient was diagnosed with synchronous multiple primary lung cancer (SMPLC) based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines. An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC. Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score. The read depth was ≥ 1 000× and the depth of coverage was 95%. The data revealed a discordant epidermal growth factor receptor (EGFR) from the separate lungs; additionally, a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions. This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC. This study suggests that the same environment may contribute certain gene(s) mutations in the same sites in the early stages of polyclonal tumor origins; meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.