Showing papers by "Fifth Affiliated Hospital of Xinjiang Medical University published in 2021"

Mir-142-3p Regulates Inflammatory Response by Contributing to Increased TNF-α in Chronic Rhinosinusitis With Nasal Polyposis:

Abstract: Objective:Previous studies suggested that microRNAs played an important role in the progression of inflammation and remodeling of chronic rhinosinusitis with nasal polyposis. However, the abnormal ...

Exosomal LINC00161 promotes angiogenesis and metastasis via regulating miR-590-3p/ROCK axis in hepatocellular carcinoma

Abstract: Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. While exosomal LINC00161 has been identified as a potential biomarker for HCC, its regulatory function and clinical values remain largely unknown. LINC00161 expressions in serum-derived exosomes from HCC patients and HCC cells were determined by qRT-PCR. The ability of proliferation, migration, and angiogenesis in HUVECs was assessed by MTT, Transwell, and tube formation. Luciferase reporter assay and AGO2-RIP assay were conducted to explore the interactions among LINC00161, miR-590-3p, and ROCK2. The level of ROCK signal-related proteins was examined by Western blotting and immunohistochemistry (IHC) assay. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of HCC cells. High levels of LINC00161 were detected in both serum-derived exosomes from HCC patients and the supernatants of HCC cell lines and were significantly associated with poor survival. Functional study demonstrated that exosomal LINC00161 derived from HCC-cells were significantly associated with enhanced proliferation, migration, and angiogenesis in HUVECs in vitro, all of which were effectively inhibited when LINC00161 was sliced with shRNA in HCC-cells. In vivo experiment showed that LINC00161 loss inhibited tumorigenesis and metastasis of HCC. Mechanistic study revealed that exosome-carried LINC00161 directly targeted miR-590-3p and induced its downstream target ROCK2, finally activating growth/metastasis-related signals in HCC. Exosome-carried LINC00161 promotes HCC tumorigenesis through inhibiting miR-590-3p to activate the ROCK2 signaling pathway, suggesting that LINC00161 may be used as potential targets to improve HCC treatment efficiency.

Activation of Toll-like receptor 7 provides cardioprotection in septic cardiomyopathy-induced systolic dysfunction

Abstract: Background As a pattern recognition receptor, Toll-like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy. Methods We generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7-knockout (TLR7-/- ), wild-type (WT) mice, cardiac-specific TLR7-transgenic (cTG-TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad-TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca2+ imaging, western blotting, immunostaining, and quantitative real-time polymerase chain reaction (qPCR). Results We found that TLR7 knockout markedly exacerbated sepsis-induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7-/- mice displayed weaker Ca2+ handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS-induced systolic dysfunction, and loxoribine (TLR7-specific agonist) improved LPS-induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)-protein kinase A (PKA) pathway, which upregulated phosphorylate-phospholamban (p-PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca2+ ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca2+ handling in response to sepsis. While improved Ca2+ handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG-TLR7 mice. Consistently, TLR7 overexpression improved LPS-induced Ca2+ -handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype. Conclusions Our data demonstrated that activation of TLR7 protected against sepsis-induced cardiac dysfunction through promoting cAMP-PKA-PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis.

High Red Meat Intake Exacerbates Dextran Sulfate-Induced Colitis by Altering Gut Microbiota in Mice.

Abstract: Inflammatory bowel disease (IBD) is a serious hazard to public health, but the precise etiology of the disease is unclear. High intake of red meat diet is closely related to the occurrence of IBD. In this study, we investigated whether the high intake of red meat can increase the sensitivity of colitis and the underlying mechanism. Mice were fed with different levels of red meat for 8 weeks and then the colonic contents were analyzed by 16S rRNA sequencing. Then 3% dextran sulfate sodium was used to induce colitis in mice. We observed the severity of colitis and inflammatory cytokines. We found that high-dose red meat caused intestinal microbiota disorder, reduced the relative abundance of Lachnospiraceae_NK4A136_group, Faecalibaculum, Blautia and Dubosiella, and increased the relative abundance of Bacteroides and Alistipes. This in turn leads to an increase in colitis and inflammatory cytokine secretion. Moreover, we found that high red meat intake impaired the colon barrier integrity and decreased the expression of ZO-1, claudin, and occludin. We also found high red meat intake induced the production of more inflammatory cytokines such as IL-1β, TNF-α, IL-17, and IL-6 and inflammatory inducible enzymes such as COX-2 and iNOS in dextran sulfate sodium-induced colitis. These results suggest that we should optimize the diet and reduce the intake of red meat to prevent the occurrence of IBD.

Masquelet technique: Effects of vancomycin concentration on quality of the induced membrane.

Abstract: Purpose The purpose of this study was to determine the effects of polymethylmetnacrylate (PMMA) spacer loaded with different concentrations of vancomycin on the proliferative, osteogenic, and angiogenic capacity of the induced membrane. Methods Varying concentrations of vancomycin (0, 1, 2, 4, 6, 8, and 10 g) were fully mixed with bone cement powder (40 g), resulting in seven experimental groups. Hollow cylindrical PMMA spacers (10-mm height, 3-mm external diameter, and 0.8-mm internal diameter) were formed by a mold and submerged in phosphate-buffered saline for antibiotic release by spectrophotometry. Eighty-four New Zealand white rabbits were evenly randomized into seven groups, and segmental radius shaft defects (10-mm) were created. Defects were filled with cylindrical PMMA spacers containing different vancomycin concentrations, and subsequently underwent intramedullary fixation with a retrograde Kirschner's wire. Tissue toxicity was assessed and the proliferative, osteogenic, and angiogenic capacity of induced membranes were qualitatively analyzed by immunohistochemistry and real-time PCR. Results No obvious toxicity was observed in the animal model. Alizarin red s staining and qualitative detection of type I collagen, CD31, Ki67, and STRO-1 by immunohistochemistry revealed an obvious decrease in the percentage of positively stained cells and in osteogenic capacity when the concentration of vancomycin was more than 6 g per cement dose. Quantitation of gene expression related to osteogenesis (Col1a, Alp, and Runx2), vascularization (Vegf, Tgfb1, and vWF), and proliferation (Oct4 and Stro-1) by real-time PCR revealed slight increases in the expression of selected genes at low vancomycin concentrations (1–4 g per cement dose), and relatively lower gene expression when the concentration of vancomycin was more than 6 g per cement dose. Conclusion PMMA spacers loaded with relatively low concentrations of vancomycin (1–4 g per cement dose) did not interfere with the proliferative, osteogenic, and angiogenic capacity of induced membranes, and even promoted their capacity. In contrast, spacers loaded with relatively high concentrations of vancomycin (6–10 g per cement dose) had negative effects on osteoblast viability, angiogenesis, and proliferation.

Enhanced atrial internal-external neural remodeling facilitates atrial fibrillation in the chronic obstructive sleep apnea model.

Abstract: Objective Autonomic imbalance plays a crucial role in obstructive sleep apnea (OSA) associated atrial fibrillation (AF). Here, we investigated the potential neural mechanism of AF induced by OSA. Methods Ten dogs were divided into control group (n = 5) and OSA group (n = 5). The chronic OSA model was established by repeat apnea-ventilation cycles for 4 hours a day for 12 weeks. During the process of model establishment, arterial blood gases, atrial effective refractory period (AERP), AF inducibility, normalized low-frequency power (LFnu), normalized high-frequency power (HFnu), and LFnu/ HFnu were evaluated at baseline, 4th week, 8th week, and 12th week. Nerve activities of left stellate ganglion (LSG) and left vagal nerve(LVN) were recorded. Tyrosine hydroxylase(TH), choline acetyltransferase(CHAT), PGP9.5, nerve growth factor(NGF), and c-Fos were detected in the left atrium, LSG, and LVN by immunohistochemistry and western blot. Moreover, high-frequency stimulations of LSG and LVN were conducted to observe the AF inducibility. Results Compared with the control group, the OSA group showed significantly enhanced neural activity of the LSG, increased AF inducibility, and shortened AERP. LFnu and LFnu/HFnu were markedly increased in the OSA group, while no significant difference in HFnu was observed. TH-positive and PGP9.5-positive nerve densities were significantly increased in the LSG and left atrium. Additionally, the protein levels of NGF, c-Fos, and PGP9.5 were upregulated both in the LSG and left atrium. AF inducibility was markedly increased under LSG stimulation without a stimulus threshold change in the OSA group. Conclusions OSA significantly enhanced LSG and left atrial neural remodeling, and hyperactivity of LSG may accelerate left atrial neural remodeling to increase AF inducibility.

Low-Level Vagus Nerve Stimulation Reverses Obstructive Sleep Apnea-Related Atrial Fibrillation by Ameliorating Sympathetic Hyperactivity and Atrial Myocyte Injury.

Abstract: Background: Previous studies have proved that low-level vagus nerve stimulation (LLVS) could suppress acute obstructive sleep apnea (OSA), which is associated with atrial fibrillation (AF). Objective: This study investigates the underlying electrophysiological, neural, and cardiomyocyte injury mechanisms on acute OSA-induced AF, examining whether LLVS can attenuate or reverse this remodeling. Methods and Results: Eighteen mongrel dogs received endotracheal intubation under general anesthesia and were randomly divided into three groups: the OSA group (simulated OSA with clamping of the trachea cannula at the end of expiration for 2min followed ventilation 8min, lasting 6h, n=6), the OSA+LLVS group (simulated OSA plus LLVS, n=6), and a control group (sham clamping the trachea cannula without stimulation, n=6). In the OSA+LLVS group, the atrial effective refractory period was significantly lengthened while the sinus node recovery time and AF duration decreased after the 4th hour, and the expression level of Cx40 and Cx43 was significantly increased compared to the OSA group. Norepinephrine, TH, and ChAT were significantly decreased in the OSA+LLVS group compared with the OSA group. Mitochondrial swelling, cardiomyocyte apoptosis, and glycogen deposition, along with a higher concentration of TNF-α, IL-6 were observed in the OSA group, and the LLVS inhibited the structural remodeling and expression of inflammatory cytokines. Conclusion: LLVS decreased the inducibility of AF partly by ameliorating sympathetic hyperactivity and atrial myocyte injury after acute OSA-induced AF.

Ganglionated Plexi Ablation Suppresses Chronic Obstructive Sleep Apnea-Related Atrial Fibrillation by Inhibiting Cardiac Autonomic Hyperactivation.

Abstract: Background: Previous studies have reported that right pulmonary artery ganglionated plexi (GP) ablation could suppress the onset of atrial fibrillation (AF) associated with obstructive sleep apnea (OSA) within 1 h. Objective: This study aimed to investigate the effect of superior left GP (SLGP) ablation on AF in a chronic OSA canine model. Methods and Results: Fifteen beagles were randomly divided into three groups: control group (CTRL), OSA group (OSA), and OSA + GP ablation group (OSA + GP). All animals were intubated under general anesthesia, and ventilation-apnea events were subsequently repeated 4 h/day and 6 days/week for 12 weeks to establish a chronic OSA model. SLGP were ablated at the end of 8 weeks. SLGP ablation could attenuate the atrial effective refractory period (ERP) reduction and decrease ERP dispersion, the window of vulnerability, and AF inducibility. In addition, chronic OSA leads to left atrial (LA) enlargement, decreased left ventricular (LV) ejection fraction, glycogen deposition, increased necrosis, and myocardial fibrosis. SLGP ablation reduced the LA size and ameliorated LV dysfunction, while myocardial fibrosis could not be reversed. Additionally, SLGP ablation mainly reduced sympathovagal hyperactivity and post-apnea blood pressure and heart rate increases and decreased the expression of neural growth factor (NGF), tyrosine hydroxylase (TH), and choline acetyltransferase (CHAT) in the LA and SLGP. After SLGP ablation, the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, cholesterol metabolism pathway, and ferroptosis pathway were notably downregulated compared with OSA. Conclusions: SLGP ablation suppressed AF in a chronic OSA model by sympathovagal hyperactivity inhibition. However, there were no significant changes in myocardial fibrosis.

Echinococcus multilocularis induces surface high expression of inhibitory killer immunoglobulin-like receptor on natural killer cells.

Abstract: Alveolar echinococcosis (AE) is a malignant and fatal parasitic disease caused by the larvae of Echinococcus multilocularis (E. multilocularis), which inhibits the activity and proliferation of natural killer (NK) cells. In this study, the functional alteration of hepatic NK cells and their related molecules were studied. The AE-infected patient's tissue was fixed with formalin, embedded in paraffin, and stained with Masson's trichrome or hematoxylin and eosin (H&E). Single cells from AE-infected patient or E. multilocularis-infected mice were blocked with Fc-receptor (FcR), and stained with monoclonal antibodies, including CD16, CD56, CD3, KIR2DL1, granzyme B, perforin, Interferon gamma (IFN-γ), and tumor necrosis factor-α (TNFα) or isotype control, to measure molecules and cytokines of NK cells and analyzed by flow cytometry. The Sirius red staining was used to quantitate hepatic fibrosis by calculating quantitative collagen deposition. AE can adjust both the number of hepatic CD56+ NK cells and its KIR2DL1 expression processes. Moreover, the overexpression of KIR2DL1 in NK cells could downregulate the functioning of immune cells in the liver area close to parasitic lesions. The number and dysfunction of NK cells in E. multilocularis infection could be related to the molecule dynamics of cell surface inhibitory receptor Ly49A, leading to hepatic damage and progression of fibrosis. This study illustrated significant increase in hepatic fibrogenesis and apparent upregulation of hepatic CD56+ NK cell population and its KIR2DL1 expression in AE-infected patients. This opposite variation might be related to the impaired NK cells functioning, such as granzyme B, IFN-γ, and TNF-α secretion. In addition, the cell surface inhibitory receptor Ly49A was related to the intracellular cytokine secretion functions of NK cells.

Survivin Regulates Bad Gene Expression by Binding to Its Promoter and Modulates Cell Cycle and Apoptosis in Esophageal Carcinoma Cell.

Abstract: Esophageal cancer (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. As an antiapoptotic and a proapoptotic protein, respectively, survivin and Bad play an important role in carcinogenesis of the most human cancers including EC. However, the regulatory relationships between them remain unclear. We sought to investigate the effects of survivin knockdown and overexpression on the expression of Bad gene, cell cycle progression, and apoptosis of esophageal carcinoma cell. The mRNA expression levels of survivin and Bad were determined in EC tissue samples. The knockdown and overexpression experiments were performed in ECA109 and KYSE450 cells via transfection with survivin overexpression and shRNA plasmids. A Bad overexpression experiment was conducted to confirm the biological effect on knockdown of survivin via modulating Bad expression. RT-qPCR and Western blot analysis were used to detect mRNA and protein expression, respectively. Cell cycle and apoptosis were analyzed by flow cytometry. The chromatin immunoprecipitation (ChIP) was conducted to determine the binding sites of survivin on the promoter of Bad gene. By analyzing the mRNA expression of survivin and Bad in 40 ESCC patient specimens, we found that the positive expression rate of survivin in tumor tissues (88%, 35/40) was remarkably high, compared with the distal nontumor tissues (48%, 19/40, p < 0.01). On the other hand, the positive expression rate of Bad in tumor tissues (70%, 28/40) was remarkably low, compared with the distal nontumor tissues (95%, 38/40, p < 0.01). Overexpression of survivin decreases Bad mRNA and protein expression and promotes transformation of cell cycle to S phase. Conversely, knockdown of survivin increases Bad mRNA and protein expression and induces cell cycle arrest and apoptosis. Bad overexpression inducing apoptosis of esophageal carcinoma cell shows the similar apoptotic effect with survivin knockdown. ChIP assays indicate that survivin directly binds to the Bad promoter region, diminishing the transcriptional activity of Bad. In conclusion, the result suggested that survivin regulates Bad gene expression by binding to its promoter and modulates cell cycle and apoptosis in esophageal carcinoma cell.

Desmoglein 3 contributes to tumorigenicity of pancreatic ductal adenocarcinoma through activating Src–FAK signaling

Abstract: Desmogleins (DSGs), with the ability to link adjacent cells, have been shown to participate in the development of malignancy. DSG3 was up-regulated in various cancers, including lung, head and neck...

Chemopreventive effect of galangin against benzo(a)pyrene-induced stomach tumorigenesis through modulating aryl hydrocarbon receptor in Swiss albino mice:

Abstract: The present study was aimed to evaluate the chemopreventive potential of galangin against benzo(a)pyrene (BaP)-induced stomach carcinogenesis in Swiss albino mice. Stomach cancer was induced in experimental mice using BaP oral administration. The mice were treated with galangin (10 mg/kg b.wt.) before and during BaP administration. Oral administration of galangin at a dose of 10 mg/kg b.wt. significantly (p < 0.05) prevented the tumor incidence, tumor volume in the experimental animals. Further, galangin pretreatment prevents BaP-induced lipid peroxidation and restores BaP-mediated loss of cellular antioxidants status. It has also been found that galangin prevents BaP-induced activation of phase I detoxification enzymes. Furthermore, galangin pretreatment prevented the BaP-induced overexpression of cytochrome P450s isoform genes (CYP1A1, CYP1B1), aryl hydrocarbon receptor system (AhR, ARNT), transcriptional activators (CBP/p300, NF-kB), tumor growth factors, proto-oncogenes, invasion markers (TGFB, SRC-1, MYC, iNOS, MMP2, MMP9) and Phase II metabolic isoenzyme genes (GST) in the stomach tissue homogenate when compared to the control groups. The western blot results confirm that galangin (10 mg/kg. b.wt.) treatment significantly prevented the BaP-mediated expression of ArR, ARNT, and CYP1A1 proteins in the mouse stomach tissue. Therefore, the present results confirm that galangin prevents BaP-induced stomach carcinogenesis probably through modulating ArR and ARNT expression in the experimental mice.

Serum levels of inhibitory costimulatory molecules and correlations with levels of innate immune cytokines in patients with pulmonary tuberculosis.

Abstract: OBJECTIVE To analyze serum levels of inhibitory costimulatory molecules and their correlations with innate immune cytokine levels in patients with pulmonary tuberculosis (PTB). METHODS Data for 280 PTB patients and 280 healthy individuals were collected. Serum levels of immune molecules were measured using ELISA. Univariate, multivariate, subgroup, matrix correlation, and receiver operating characteristic curve analyses were performed. RESULTS Host, environment, lifestyle, clinical features, and medical history all influenced PTB. Serum levels of soluble programmed death ligand 1 (sPD-L1), soluble T-cell immunoglobulin- and mucin-domain-containing molecule 3 (sTim-3), soluble galectin-9 (sGal-9), interleukin (IL)-4, and IL-33 were significantly higher in patients with PTB, while levels of IL-12, IL-23, IL-18, and interferon (IFN)-γ were significantly lower. Serum levels of sTim-3 were higher in alcohol users. Levels of sTim-3 were negatively correlated with those of IL-12. Levels of IL-12, IL-23, and IL-18 were positively correlated with those of IFN-γ, while levels of IL-12 were negatively correlated with those of IL-4. The areas under the curve of sPD-L1, sTim-3, sGal-9, IL-12, IL-23, IL-18, IFN-γ, IL-4, and IL-33 for identifying PTB were all >0.77. CONCLUSIONS Inhibitory costimulatory molecules may be targets for controlling PTB. Immune molecules may be helpful for diagnosis of PTB.

Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis

Abstract: The Patched 1 (PTCH1) gene encodes a membrane receptor involved in the Hedgehog (Hh) signaling pathway, an abnormal state of which may result in congenital defects or human tumors. In this study, we conducted whole-exome sequencing on a three-generation Chinese family characterized with variable penetrance of orofacial clefts. A rare heterozygous variant in the PTCH1 gene (c.2833C > T p.R945X) was identified as a disease-associated mutation. Structural modeling revealed a truncation starting from the middle of the second extracellular domain of PTCH1 protein. This may damage its ligand recognition and sterol transportation abilities, thereby affecting the Hh signaling pathway. Biochemical assays indicated that the R945X protein had reduced stability compared to the wild-type in vitro. In addition, we reviewed the locations and mutation types of PTCH1 variants in individuals with clefting phenotypes, and analyzed the associations between clefts and locations or types of variants within PTCH1. Our findings provide further evidence that PTCH1 variants result in orofacial clefts, and contributed to genetic counseling and clinical surveillance in this family.

Circ_0000043 promotes the proliferation, migration, invasiveness, and epithelial-mesenchymal transition in breast cancer cells via the miR-136-Smad3 axis.

Abstract: Circular RNAs (circRNAs) are tissue-specific RNAs with a more stable structure than linear RNAs, and their association with breast cancer (BC) is poorly understood. This study examined the biological effects of circ_0000043 in the progression of BC. In this study, expression of circ_0000043 in BC tissue samples was measured using quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect the expression of Smad family member 3 (Smad3). CCK-8, wound healing, and Transwell assays were used to assess the effect of circ_0000043 on the proliferation, migration, and invasiveness of BC cells. Moreover, the binding relationships between circ_0000043 and miR-136, and miR-136 and Smad3 were detected by dual-luciferase reporter assay. Additionally, Western blot was used to detect the expressions of markers related to epithelial-mesenchymal transition, including E-cadherin, N-cadherin, and vimentin. Our results show that the expression of circ_0000043 is up-regulated in BC tissues and cell lines. The proliferation, migration, invasiveness, and epithelial-mesenchymal transition of BC cells were significantly inhibited by knockdown of circ_0000043, and overexpression of circ_0000043 had the opposite effects. Additionally, circ_0000043 up-regulate the expression of Smad3 by sponging miR-136. In conclusion, our study demonstrates that circ_0000043 promote the progression of BC via regulating the miR-136-Smad3 axis.

Long Noncoding RNA RP11-115N4.1 Promotes Inflammatory Responses by Interacting With HNRNPH3 and Enhancing the Transcription of HSP70 in Unexplained Recurrent Spontaneous Abortion.

Abstract: Background Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis. Objective To investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA. Methods We profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated in vitro. Results RP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients (P = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and in vitro overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes (HSPA1A and HSPA1B) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis (HSPA1A (P = 4.39E-08, Fold change = 4.17), HSPA1B (P = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and HNRNPH3 knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1β, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA. Conclusion Our results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 via binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA.

Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang.

Abstract: Essential hypertension is a common cardiovascular disease with complex etiology, closely related to genetic and environmental factors. The pathogenesis of hypertension involves alteration in vascular resistance caused by sympathetic nervous system (SNS) and renin angiotensin system (RAS). Susceptibility factors of hypertension vary with regions and ethnicities. In this study, we conducted target capture sequencing on 54 genes related to SNS and RAS derived from a collection of Han nationality, consisting of 151 hypertension patients and 65 normal subjects in Xinjiang, China. Six non-synonymous mutations related to hypertension were identified, including GRK4 rs1644731 and RDH8 rs1801058, Mutations are predicted to affect 3D conformation, force field, transmembrane domain and RNA secondary structure of corresponding genes. Based on protein interaction network and pathway enrichment, GRK4 is predicted to participate in hypertension by acting on dopaminergic synapse, together with interacting components. RDH8 is involved in vitamin A (retinol) metabolism and consequent biological processes related to hypertension. Thus, GRK4 and RDH8 may serve as susceptibility genes for hypertension. This finding provides new genetic evidence for elucidating risk factors of hypertension in Han nationality in Xinjiang, which in turn, enriches genetic resource bank of hypertension susceptibility genes.

miRNA‐138‐5p suppresses cigarette smoke‐induced apoptosis in testicular cells by targeting Caspase‐3 through the Bcl‐2 signaling pathway

Abstract: Long-term cigarette smoking (CS) can cause testicular toxicity, which interferes with normal spermatogenesis and leads to male infertility. One possible mechanism for this is the activation of the apoptosis signaling pathway, which leads to the irreversible apoptosis of testicular cells. However, the exact mechanism for this is not completely understood. Cell viability, cell apoptosis, and lactate dehydrogenase release assays were performed to elucidate the function of micro RNA (miRNA) in the pathogenesis of male testicular cell injury induced by CS. The results suggested that testicular cell injury was associated with CS both in vitro and in vivo. CS extract (CSE)-treated Leydig and Sertoli cells showed noticeable apoptosis. Based on the results of Agilent miRNA microarray and bioinformatics analyses, miRNA-138-5p was used in subsequent experiments. Quantitative polymerase chain reaction and Western blot assays showed a negative correlation between miR-138-5p and Caspase-3 expression. Transfection of miR-138-5p mimic significantly inhibited apoptosis and downregulated the expression of Caspase-3 in TM3 and TM4 cells. Furthermore, a dual-luciferase reporter assay demonstrated that miR-138-5p directly targeted Caspase-3 to regulate the apoptosis of testicular cells mediated by CSE. In addition, overexpression of miR-138-5p markedly downregulated the expression of p53 and Bak, which played critical roles in the Bcl-2 pathway. These results demonstrate that miRNA-138-5p inhibits CS-induced apoptosis in testicular cells by targeting Caspase-3 through the Bcl-2 signaling pathway.

Equisetum arvense L aqueous extract: a novel chemotherapeutic supplement for treatment of human colon carcinoma

Abstract: Introduction One of the plants that has long been considered by humans is Equisetum arvense L Equisetum arvense L is now recommended for external use to heal wounds and for internal use to relieve urinary tract and prostate disorders. Material and methods In the current study, the antioxidant, cytotoxicity, and anti-human ling cancer properties of Equisetum arvense were investigated in the in vitro condition. Total phenolic content, total flavonoid content, radical scavenging activity, and ferrous ion chelating were run to evaluate the antioxidant activity. MTT assay was chosen to investigate anticancer activity of the plant extract. Results The plant extract scavenged DPPH as a free radical with an IC50 of 12.3±0.7 µg/mL better than positive controls. The plant also was rich in phenolic compounds with an amount of 396.2±3.2 mg GAE/g for total phenolic content. In the MTT assay, human colorectal carcinoma (HCT-8 [HRT-18], Ramos.2G6.4C10, HT-29, and HCT 116) and normal cell lines (HUVEC) were used to study the cytotoxicity and anticancer potential of human colorectal over the Equisetum arvense L. The cell viability of Equisetum arvense L was very low against human colorectal carcinoma cell lines without any cytotoxicity on the normal (HUVEC) cell line. Conclusions The best anti-human colorectal carcinoma properties of Equisetum arvense L against the above cell lines was in the case of HT 29 cell line.

Calcification sign for prediction of benignity in pulmonary nodules: A meta-analysis.

Abstract: Background The calcification sign assessed by computed tomography appears to be a potential marker for benignities among patients diagnosed with pulmonary nodules (PNs). The following meta-analysis has been purposefully designed to figure-out the diagnostic value of the calcification signature as a way of identifying benignities from PNs. Methods Cochrane Library, Embase and PubMed were considered as a reference to obtain the required data from January 2000 until October 2020. Stata v12.0 was used as a standard tool for statistical assessment. Results Eleven retrospective studies were assessed via this meta-analysis, which included 6136 PNs (1827 benign and 4309 malignant). The pooled diagnostic odd ratios, positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were 6.79, 6.06, 0.89, 13% and 98%, respectively. The value obtained for the area under the curve was 0.65, showing moderate overall diagnostic accuracy. A significant heterogeneity was found while calculating the pooled sensitivity (I2 = 85.5%), specificity (I2 = 75.0%), PLR (I2 = 59.0%), NLR (I2 = 79.5%) and DOR (I2 = 100.0%) in the current analysis. Sub-group analyses presented better PLR and specificity values for the study with a sample size ≥ 400. Deeks' funnel plot asymmetry test detected no potential evidence of significant publication bias (p = 0.091). Conclusions Calcification signs have been identified as moderate regulators corresponding to overall diagnostic performance (via marking a distinct differentiation between malignant and benign) for PNs. However, the manifestation of the calcification sign had a good directive property for benign PNs.

Human papillomavirus distribution and cervical cancer epidemiological characteristics in rural population of Xinjiang, China.

Abstract: Background Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang. This study aims to investigate the distribution of human papillomavirus (HPV) infection and cervical cancer in rural areas of Xinjiang, China. Methods Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang, China in 2017 through gynecological examination, vaginal discharge smear microscopy, cytology, and HPV testing. If necessary, colposcopy and biopsy were performed on women with suspicious or abnormal screening results. Results Of the 216,754 women screened, 15,518 received HPV testing. The HPV-positive rate was 6.75% (1047/15,518). Compared with the age 35-44 years group, the odds ratios (ORs) of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18 (95% confidence interval [CI]: 1.02-1.37) and 1.84 (95% CI: 1.53-2.21), respectively. Compared with women with primary or lower education level, the ORs for HPV infection rates of women with high school and college education or above were 1.37 (95% CI: 1.09-1.72) and 1.62 (95% CI: 1.23-2.12), respectively. Uyghur women were less likely to have HPV infection than Han women, with an OR (95% CI) of 0.78 (0.61-0.99). The most prevalent HPV types among Xinjiang women were HPV 16 (24.00%), HPV 33 (12.70%), and HPV 52 (11.80%). The detection rate of cervical intraepithelial neoplasia (CIN)2+ was 0.14% and the early diagnosis rate of cervical cancer was 85.91%. The detection rates of vaginitis and cervicitis were 19.28% and 21.32%, respectively. Conclusions The HPV infection rate in Xinjiang is low, but the detection rate of cervical cancer and precancerous lesions is higher than the national average level. Cervical cancer is a prominent public health problem in Xinjiang, especially in southern Xinjiang.

Treatment of humeral shaft fractures: a new minimally-invasive plate osteosynthesis versus open reduction and internal fixation: a case control study

Abstract: BACKGROUND To evaluate the feasibility and safety of a new minimally-invasive surgical approach-anteromedial minimally-invasive plate osteosynthesis (MIPO)-in the treatment of middle and distal humeral shaft fractures. METHODS Fourteen patients with humeral shaft fracture treated with anteromedial MIPO from November 2016 to March 2020 (MIPO Group) were selected as the study subjects. Open reduction and internal fixation (ORIF) were used to treat 14 patients with humeral shaft fractures as the control group (ORIF group). The two groups were fixed with a locking compression plate (LCP) or LCP + multi-directional locking screw system (MDLS). The incision length, intraoperative blood loss, intraoperative fluoroscopy time, operation time, length of hospital stay, fracture healing time, QuickDASH score and Constant score were observed and compared between the two groups. RESULTS Fourteen patients were enrolled in each group. The incision length (7.79 ± 2.39 cm), intraoperative blood loss (96.07 ± 14.96 mL), operative time (110.57 ± 21.90 min), hospital stay (6.29 ± 1.49 days) and fracture healing time (14.94 ± 0.99 weeks) in the MIPO group were all lower than those in the ORIF group, and the difference was statistically significant for each parameter (P < 0.05). The intraoperative fluoroscopy time (20.07 ± 3.22) in the MIPO group was significantly higher than that in the ORIF group (P < 0.05). There were no significant differences in age (P = 0.078), QuickDASH score (P = 0.074) or Constant score (P = 0.293) between the two groups and no postoperative complications occurred in any of the patients. CONCLUSION The anteromedial approach MIPO technique has the advantages of less trauma, less bleeding, low risk of nerve injury and high rate of fracture healing. It is one of the most effective methods for the treatment of middle and middle-distal humeral shaft fractures.

Level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low regulatory T cells in vulvar lichen sclerosus

Abstract: This study is to investigate the pathogenesis of vulvar lichen sclerosus (VLS) by analyzing the level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low Regulatory T cells (Tregs). This study enrolled 15 VLS patients and 25 controls. Lesional and extralesional vulvar skin tissues, normal vulvar skin tissues and peripheral blood were collected. Compared with the control group, Foxp3 protein in the lesional and extralesional skin of VLS group was significantly reduced. The levels of DNMT1 and DNMT3b proteins in lesional skin of VLS group were significantly increased. There was no difference in the total methylation rates of the promoter region of the Foxp3 gene. The methylation rates of CpG1, CpG4, CpG9, and CpG10 were significantly higher in lesional skin of VLS group than in control group. There was no correlation between the total methylation rates of 10 CpG sites and the level of Foxp3 and DNMT1 proteins; there was a positive correlation between Foxp3 and DNMT1 protein in lesional skin of VLS group (r = 0.675, p < 0.05), and a negative correlation (r = -0.665, p < 0.05) in extralesional skin of VLS group. However, there was no correlation of Foxp3 with DNMT3b. The number of CD4 + CD25 + CD127low Tregs VLS decreased significantly. The expression of Foxp3 protein and the quantity of CD4 + CD25 + CD127low Tregs in patients with VLS decreased, which may cause local or systemic abnormal immunosuppression of Tregs, leading to the occurrence of VLS. This may be related with methylation or DNMT1, which needs further verification.

NLRC5 enhances autophagy via inactivation of AKT/mTOR pathway and ameliorates cardiac hypertrophy.

Abstract: The aim of this study was to investigate the effect of nucleotide-binding oligomerization domain (NOD)-like receptor family CARD domain containing 5 (NLRC5) in cardiac hypertrophy, and to explore the mechanism implicated in this effect Cardiac hypertrophy was induced in neonatal rat cardiac myocytes using 1 μM of angiotensin II (Ang II) for 12, 24 and 48 h. Overexpression of NLRC5 was induced in H9C2 cells, and the NLRC5 + Ang II-treated cells were exposed to SC9 and 3-methyladenine (3MA). An immunofluorescence assay was used for α-actinin staining, and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for NLRC5, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) determination. Western blot analysis was applied to measure the levels of NLRC5, microtubule-associated protein 1A/1B-light chain 3 type I (LC3I), LC3II, sequestosome 1 (p62), protein kinase B (AKT), phosphorylated Akt (pAKT), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (pmTOR). The level of NLRC5 was significantly decreased after Ang II treatment in cardiomyocytes, but the levels of ANP and BNP were increased. Overexpression of NLRC5 reduced the cell size, downregulated the levels of ANP and BNP, increased LC3II / LC3I, but decreased p62 in Ang II-induced cardiomyocyte hypertrophy. In addition, the results from Western blot showed that overexpression of NLRC5 distinctly decreased the ratios of pAKT/AKT and pmTOR/mTOR in cardiomyocyte hypertrophy. SC79 and 3MA significantly downregulated the ratio of LC3I/LC3II but increased the level of p62 in NLRC5 + Ang II-treated cells. These results provide a possible novel therapeutic strategy for cardiac hypertrophy that might be useful in a clinical setting.