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1.
Horm Metab Res ; 54(2): 94-103, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35130570

RESUMO

Glycated hemoglobin (HbA1c) variability is emerging as an indicator of long-term glycemic control, which may play a significant role during vascular complications. We conducted a systematic review and meta-analysis to assess the association between the scope of HbA1c variability and vascular complications in patients with type 2 diabetes mellitus. PubMed and Embase were searched for studies that evaluated the association of HbA1c variability with vascular complications in patients with type 2 diabetes. Two reviewers independently completed data extraction. Random-effects meta-analysis was conducted with stratification according to the type of vascular complications. Nine studies were eligible for inclusion in our systematic review and meta-analysis. Six studies evaluated the impact of the standard deviation of HbA1c (HbA1c-SD) on cardiovascular events and showed an association of HbA1c-SD with cardiovascular events (HR: 1.25, 95% CI 1.18-1.32, 5 studies). Six studies evaluated renal disease associated with HbA1c-SD and showed that HbA1c-SD was correlated with an increased risk of renal disease (HR: 1.19, 95% CI 1.13-1.24). Two studies evaluated HbA1c-SD and the risk of retinopathy and showed that no significant association was found between retinopathy and HbA1c-SD (HR 1.08, 95% CI 0.92-125). For HbA1c-SD ranging from 0.6 to 0.8%, HbA1c-SD was associated with an increased risk of cardiovascular events (HR: 1.25, 95% CI 1.15-1.35) and renal disease (HR: 1.16, 95% CI 1.11-1.22). For individuals with index HbA1c variability greater than or equal to 0.6%, HbA1c variability was significantly associated with vascular complications in patients with type 2 diabetes mellitus.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Glicemia/análise , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Hemoglobina A Glicada/análise , Humanos , Estudos Prospectivos
2.
Front Vet Sci ; 9: 960250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090173

RESUMO

In this study, we detected the expression of mRNAs, lncRNAs, and miRNAs in primary cultured leydig cells (LCs) and sertoli cells (SCs) of yak by RNA sequencing technology. A total of 84 differently expression mRNAs (DEmRNAs) (LCs vs. SCs: 15 up and 69 down), 172 differently expression lncRNAs (DElncRNAs) (LCs vs. SCs: 36 up and 136 down), and 90 differently expression miRNAs (DEmiRNAs) (LCs vs. SCs: 72 up and 18 down) were obtained between the two types of cells. GO enrichment and KEGG analysis indicated that the differential expression genes (DEGs) were more enriched in the regulation of actin cytoskeleton, Rap1/MAPK signaling pathway, steroid biosynthesis, focal adhesion, and pathways associated with metabolism. Targeted regulation relationship pairs of 3ß-HSD and MSTRG.54630.1, CNTLN and MSTRG.19058.1, BRCA2 and MSTRG.28299.4, CA2 and novel-miR-148, and ceRNA network of LAMC3-MSTRG.68870.1- bta-miR-7862/novel-miR-151/novel-miR-148 were constructed by Cytoscape software. In conclusion, the differences between LCs and SCs were mainly reflected in steroid hormone synthesis, cell proliferation and metabolism, and blood-testicular barrier (BTB) dynamic regulation, and 3ß-HSD, CNTLN, BRCA2, CA2, and LAMC3 may be the key factors causing these differences, which may be regulated by ncRNAs. This study provides a basic direction for exploring the differential regulation of LCs and SCs by ncRNAs.

3.
Mol Ther Oncolytics ; 26: 314-329, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36090477

RESUMO

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

4.
ACS Omega ; 7(35): 31338-31347, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092597

RESUMO

Protein solubility is very important for protein crystallization, bioprocess development, and protein application. In this study, a method based on the stability of a protein dispersion system is proposed for fast assessment of protein solubility, which mainly involves ultrasonic dispersion, differential centrifugation, and spectral measurement (UDDCS) and curvature estimation. The appropriate ultrasonic time and centrifugal time were experimentally determined at first. The results show that the relationship between the standard deviation and the protein concentrations originally added accords with the modified exponential equation, and the corresponding concentration of the maximum curvature point is defined as the solubility of the protein. Lysozyme solubility data in NaCl aqueous solutions and zein solubility data in ethanol aqueous solutions are selected to verify the UDDCS method by comparing the data obtained by the UDDCS method and the results from references, and the results indicate that the UDDCS method is reliable, universal, and time-saving. Finally, measurements of zein solubility in NaOH solution and casein solubility in urea aqueous solution were conducted as test cases by the UDDCS method.

5.
Front Cardiovasc Med ; 9: 905737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093132

RESUMO

Background: Although the roles of m6A modification in the immune responses to human diseases have been increasingly revealed, their roles in immune microenvironment regulation in coronary heart disease (CHD) are poorly understood. Methods: The GSE20680 and GSE20681 datasets related to CHD were acquired from the Gene Expression Omnibus (GEO) database. A total of 30 m6A regulators were used to perform LASSO regression to identify the significant genes involved in CHD. Unsupervised clustering analysis was conducted using the m6A regulators to distinguish the m6A RNA methylation patterns in patients with CHD. The differentially expressed genes (DEGs) and biological characteristics, including GO and KEGG enrichment results, were assessed for the different m6A patterns to analyse the impacts of m6A regulators on CHD. Hub genes were identified, and subsequent microRNAs-mRNAs (miRNAs-mRNAs) and mRNAs-transcriptional factors (mRNA-TFs) interaction networks were constructed by the protein and protein interaction (PPI) network method using Cytoscape software. The infiltrating proportion of immune cells was assessed by ssGSEA and the CIBERSORT algorithm. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of the significant m6A regulators and hub genes. Results: Four of 30 m6A regulators (HNRNPC, YTHDC2, YTHDF3, and ZC3H13) were identified to be significant in the development of CHD. Two m6A RNA methylation clusters were distinguished by unsupervised clustering analysis based on the expression of the 30 m6A regulators. A total of 491 genes were identified as DEGs between the two clusters. A PPI network including 308 mRNAs corresponding to proteins was constructed, and 30 genes were identified as hub genes that were enriched in the bioprocesses of peptide cross-linking, keratinocyte differentiation. Twenty-seven hub genes were found to be related to miRNAs, and seven hub genes were found to be related to TFs. Moreover, among the 30 hub genes, eight genes were found to be upregulated in CHD, and three were found to be downregulated in CHD compared to the normal people. The high m6A modification pattern was associated with a higher infiltrated abundance of immune cells. Conclusion: Our findings demonstrated that m6A modification plays crucial roles in the diversity and complexity of the immune microenvironment in CHD.

6.
RSC Adv ; 12(37): 23786-23795, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36093248

RESUMO

Design and fabrication of novel multifunctional nanomaterials as novel "theranostic nanoagents"with high efficiency and low side effects is important for cancer treatment. Herein, we synthesized manganese-oxide and palladium nanoparticle-co-decorated polypyrrole/graphene oxide (MnO2@Pd@PPy/GO) nanocomposites, which could be used as a novel "theranostic nanoagent" for cancer treatment. Various spectroscopic and microscopic characterizations of the synthesized MnO2@Pd@PPy/GO nanocomposites suggest that the nanocomposites are assembled sequentially by graphene oxide, polypyrrole, palladium nanoparticles and manganese-oxide nanoplates. Further research revealed that the nanocomposites had excellent photothermal conversion performance (reached near 50 °C after 10 min of irradiation), pH responsive enzymatic-like catalytic activity and enhanced magnetic resonance imaging (MRI) performance (r 1 = 7.74 mM-1 s-1 at pH 5.0 and glutathione (GSH)). Cell experiments also testified that combined cancer treatment (the viability of cancer cells is 30%) with photothermal therapy (PTT, the viability of cancer cells is 91% only with irradiation) and chemodynamic therapy (CDT, the viability of cancer cells is 74.7% only with nanocomposites) guided by MRI was achieved when the as-prepared nanocomposites were employed as theranostic nanoagents. This work could provide some new ideas for the controllable synthesis and application of multicomponent nanomaterials.

7.
ACS Synth Biol ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36099191

RESUMO

Expanding the base conversion type is expected to largely broaden the application of base editing, whereas it requires decipherment of the machinery controlling the editing outcome. Here, we discovered that the DNA polymerase V-mediated translesion DNA synthesis (TLS) pathway controlled the C-to-A editing by a glycosylase base editor (GBE) in Escherichia coli. However, C-to-G conversion was surprisingly found to be the main product of the GBE in Corynebacterium glutamicum and subsequent gene inactivation identified the decisive TLS enzymes. Introduction of the E. coli TLS pathway into a TLS-deficient C. glutamicum mutant completely changed the GBE outcome from C-to-G to C-to-A. Combining the canonical C-to-T editor, a pioneering C-to-N base editing toolbox was established in C. glutamicum. The expanded base conversion capability produces greater genetic diversity and promotes the application of base editing in gene inactivation and protein evolution. This study demonstrates the possibility of engineering TLS systems to develop advanced genome editing tools.

8.
J Colloid Interface Sci ; 629(Pt A): 813-821, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36108552

RESUMO

Flexible fiber-shaped supercapacitors (FSSCs) are promising candidates as electrode materials for the development of deformable electronic devices. Although tremendous efforts have been focused on the preparation of flexible electrode materials, traditional FSSCs materials face problems of inferior stability and complicated processes. Boron-doped diamond (BDD) holds promise as a FSSC electrode, owing to its well-established preparation process, strong acid and alkali corrosion resistance, environmentally and skin-friendly characteristics. Here, we reported a novel strategy for the construction of BDD-based FSSCs by growing a BDD film on a flexible tantalum (Ta) fiber substrate through hot filament chemical vapor deposition technique. Results showed that the BDD fiber film featured 10 folds improvement in specific capacitance than a planar BDD electrode. A symmetric supercapacitor device was assembled using the BDD fiber electrode and achieved an energy density of 25.6 mJ cm-2 at a power density of 0.6 mW cm-2, and a desirable stability with higher capacitance retention of 93.5% after 20,000 cycles. Furthermore, the symmetric BDD fiber device exhibited satisfactory bendability with high specific capacitance retention under various bending deformations. The findings in this research work hold promise for the fabrication of high performance flexible FSSCs.

9.
Phytochem Anal ; 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36117130

RESUMO

INTRODUCTION: The characteristics of chemical components or groups of chemical components in traditional Chinese medicines (TCMs) determine their clinical efficacy. Quality markers (Q-markers) is of great significance for standardizing the quality control system of TCM. OBJECTIVES: We aimed to develop a new strategy to discover potential Q-markers of TCM by integrating chemometrics, network pharmacology, and molecular docking, using Centipeda minima (also known as ebushicao [EBSC]) as an example. MATERIALS AND METHODS: First, fingerprints of different batches of EBSC and its counterfeit Arenaria oreophila (also known as zaozhui [ZZ]) were established. Second, chemometric analysis was conducted to determine the influence of varying authenticity/batches of herbs on quality and the chemical markers were screened out. Third, network pharmacology and molecular docking simulations were used to verify the relationship between active ingredients and targets. Lastly, potential Q-markers were selected based on TCM theory. RESULTS: The chemical profiles of EBSC and ZZ were investigated. It was found that different batches of EBSC have differences in chemical composition. Based on our chemometric analysis, chlorogenic acid, rutin, isochlorogenic acid A, quercetin, arnicolide D, and brevilin A were selected as candidate active ingredients. ATIL6, EGFR, CASP3, MYC, HIF1A, and VEGFA were the main targets. Molecular docking was used to verify the binding ability. Based on the concept of Q-marker, arnicolide D and brevilin A were identified as potential Q-markers for EBSC. CONCLUSIONS: Our strategy could be used as a practical approach to discover Q-markers of TCM to evaluate overall chemical consistency.

10.
Front Plant Sci ; 13: 987240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119567

RESUMO

Superficial scald is a serious physiological disorder in "Yali" pear (Pyrus bretschneideri Rehd. cv. Yali) after long-term cold storage. Changes in superficial scald, ethylene production, α-farnesene and phenylpropane metabolism with associated gene expression in "Yali" pear treated with and without (control) 1-methylcyclopropene (1-MCP) were investigated. Compared with the control group (without 1-MCP), 1-MCP (1.0 µl L-1) significantly lowered the superficial scald index after 180 days of cold storage. During cold storage and shelf life, the contents of α-farnesene, conjugated trienols, chlorogenic acid, and epicatechin in the peel were reduced, while quercetin was enhanced in 1-MCP-treated fruit, and the expression of genes associated with ethylene synthesis (ACS1, ACO1), receptors (ETR2, ERS1) and signal transduction (ERF1), α-farnesene metabolism (AFS1, HMGR2, GST7), phenolic biosynthesis (PAL1, C4H1, C4H2, HCT3, 4CL2, C3H), and oxidases (PPO1, PPO5, and LAC7) were significantly downregulated by 1-MCP. These results suggested that the onset and development of superficial scald was closely related to the ethylene receptor, conjugated trienols, chlorogenic acid and epicatechin and related genes expression in "Yali" pear.

11.
World J Emerg Med ; 13(5): 373-378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119774

RESUMO

BACKGROUND: Paraquat (PQ)-induced acute lung injury (ALI) and pulmonary fibrosis are common diseases with high mortality but without effective antidotes in emergency medicine. Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ. We wondered whether arctigenin could also have a protective effect on PQ-induced ALI. METHODS: A PQ-induced A549 cell injury model was used, and the effect of arctigenin was determined by a cell counting kit-8 (CCK-8) cell viability assay. In addition, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis. The generation of reactive oxygen species (ROS) was reflected by dihydroethidium (DHE) staining and a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Moreover, immunoblotting studies were used to assess the expression of mitogen-activated protein kinases (MAPKs) and p38 MAPK. RESULTS: Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner. Arctigenin also significantly reduced PQ-induced A549 cell apoptosis, as reflected by the TUNEL assay and mitochondrial membrane potential assay, which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation. CONCLUSION: Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis, and arctigenin might be considered a potential candidate drug for PQ-induced ALI.

12.
Chin Herb Med ; 14(2): 273-282, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36117665

RESUMO

Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein-protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

13.
World J Mens Health ; 40(4): 570-579, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36047069

RESUMO

PURPOSE: This study aimed to evaluate the influences of SARS-CoV-2 vaccination (CoronaVac) on male fertility and investigate the impact of a history of the CoronaVac vaccination in males on gamete and embryo development and in vitro fertilization (IVF) outcomes. MATERIALS AND METHODS: A prospective cohort study enrolled couples undergoing IVF cycles between June and August 2021 at Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in China. According to the history of SARS-CoV-2 vaccination in males, the participants were divided into the vaccination group and the non-vaccination group. A self-controlled study of semen analyses for males before and after CoronaVac vaccination was conducted. Baseline characteristics were matched using propensity score matching. Participants were categorized into the unexposed group (non-vaccination) and exposed group (vaccination), and the population was 271 for each. Semen parameters and IVF outcomes were the main outcomes. RESULTS: Generally, no statistically significant differences were exhibited between the matched cohorts regarding embryo developmental parameters, including fertilization rate, cleavage rate, high-quality embryo rate, blastocyst formation rate, and available blastocyst rate, as well as clinical outcomes, such as implantation rate, biochemical pregnancy rate, and clinical pregnancy rate. Moreover, males after vaccination seemed to have fluctuating semen parameters including increased semen volume, lower motility, and decreased normal forms of sperm, while the motile sperm counts were similar. In addition, all semen parameters were above the lower reference limits. CONCLUSIONS: Our findings suggested that CoronaVac vaccinations in males may not have adverse effects on patient performance or the gamete and embryonic development potential during assisted reproductive technology (ART) treatments.

14.
Front Cell Infect Microbiol ; 12: 969526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051242

RESUMO

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Disbiose/prevenção & controle , Medicina Herbária , Humanos , Inflamação
15.
Front Cell Dev Biol ; 10: 997734, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105354

RESUMO

Background: Exosomes are extracellular vesicles between 40 and 150 nm in diameter and are cargoes for a wide range of small biological molecules. Recent studies have reported that lncRNAs, miRNAs, circRNAs in serum exosomes may serve as biomarkers to predict hepatocellular carcinoma (HCC) prognosis. However, the prognostic values of exosomes-related mRNAs in HCC are still unclear. Methods: Data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The serum exosome sequencing data of HCC patients and healthy individuals were obtained from the exobase database. Univariate cox regression analysis was used to identify prognostic exosomes-related genes. LASSO and multivariate cox regression analyses were applied to construct prognostic signature. Results: 22 exosomes-related mRNAs differentially expressed between HCC tissues and normal tissues were identified. Then, 8 prognostic exosomes-related mRNAs were screened. Subsequently, G6PD and ADAMTS5, selected by LASSO and multivariate cox regression analyses, were used to construct a prognostic signature. The patients with high-risk scores had a poor prognosis in TCGA cohort as well as ICGC cohort. Notably, this prognostic signature was also validated in a local cohort collected from the First Affiliated Hospital of Wenzhou Medical University. Receiver Operating Characteristic (ROC) analyses indicated that the signature had a good performance in all the cohorts. The gene set enrichment analysis revealed that this signature was associated with cell cycle and metabolism pathways. Immune infiltration analysis indicated that the patients with high-risk scores had a higher M0 macrophages infiltration. The univariate and multivariate cox regression analyses identified that the risk score is an independent risk factor for HCC. In addition, a nomogram containing age, gender, stage and risk score was constructed to precisely predict HCC prognosis. Conclusion: In conclusion, we develop a novel exosomes-related gene signature that helps to predict HCC prognosis.

16.
Front Pharmacol ; 13: 931453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110548

RESUMO

Background: Heart failure, especially chronic heart failure, is generally induced by the accumulation of reactive oxygen species (ROS), as well as the subsequent loss of mitochondrial permeability transition pore (mPTP) openings and pathological mitochondrial dysfunction. Herein, we explored the therapeutic effects of the Chinese medicine Yangxin Keli (YXXKL) on chronic heart failure and its underlying working mechanism. Methods: To mimic oxidative stress-induced chronic heart failure, a rat heart failure model was induced by the administration of DOX. Transthoracic echocardiography was performed to confirm the successful establishment of the heart failure model by observing significantly decreased cardiac function in the rats. Mitochondrial membrane potential, function, and ATP synthesis activity were measured after YXXKL was employed. Results The administration of YXXKL not only significantly improved cardiac function but also reversed the myocardium loss and fibrosis induced via DOX. Moreover, the administration of YXXKL also increased ATP synthesis and mitochondrial DNA mass in left ventricular tissues, which indicated that mitochondria may be a key target of YXXKL. Thus, we employed rat cardiomyocyte H9c2 and primary rat cardiac myocytes (RCMs) to induce oxidative stress-induced myocardial injury via DOX treatment. YXXKL-medicated serum promoted cell proliferation, which was inhibited by the addition of IC30 DOX, and the serum also inhibited cell apoptosis, which was promoted by the addition of IC50 DOX. YXKL-medicated serum was able to scavenge ROS and maintain the mitochondrial membrane potential as well as promote mitochondrial function, including the promotion of ATP synthesis, mitochondrial DNA mass, and transcriptional activity. Furthermore, we also observed that YXXKL-medicated serum inhibited DOX-induced autophagy/mitophagy by scavenging ROS. Conclusion: Taken together, we conclude that YXXKLI may exert therapeutic effects on oxidative stress-related heart failure via the regulation of mitochondria.

17.
Mol Immunol ; 151: 84-94, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36113364

RESUMO

In this research, we screened out two genes upregulated in mice with acute pancreatitis (AP) by gene sequencing: microRNA (miR)-320-3p and matrix metalloprotease 8 (MMP8). This study was designed to determine whether miR-320-3p and MMP8 participate in AP development and explore the mechanisms, with a new idea for clinical diagnosis and treatment of AP. Expression of miR-320-3p, DNA methyltransferase 3a (DNMT3a), and MMP8 in mouse pancreatic tissues and AR42J cells was tested by RT-qPCR and western blot assays. Pancreatic pathological changes, serum amylase and lipase, and inflammatory factors in mouse serum and cell supernatant were measured by hematoxylin-eosin staining, automation analyzer, and enzyme-linked immunosorbent assay, respectively. Cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry. The interaction between miR-320-3p, DNMT3a, and MMP8 was verified by luciferase activity assay, ChIP-qPCR, and MSP assay. High expression of miR-320-3p and MMP8, and low expression of DNMT3a were observed in pancreatic tissues of AP mice and caerulein-induced AP cellular model. Downregulation of miR-320-3p alleviated injury of mouse pancreas, reduced the levels of serum amylase and lipase, and blocked inflammatory factor levels in AP mice. In caerulein-induced AP cellular models, inhibiting miR-320-3p facilitated proliferation and inhibited apoptosis. Upregulation of MMP8 resulted in the opposite results, which could be reversed by simultaneous inhibition of miR-320-3p. miR-320-3p targeted DNMT3a, and downregulating miR-320-3p promoted DNMT3a expression. Moreover, DNMT3a promoted DNA methylation in MMP8 promoter region, thereby inhibiting MMP8 expression in AP mouse and cellular models. This research suggests that miR-320-3p inhibits DNMT3a to reduce MMP8 methylation and increase MMP8 expression, thereby promoting AP progression.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36101984

RESUMO

The detection of molecules from highly diluted solutions with a limited amount is vital for precancer diagnosis, food safety, and forensic analysis. The sensitivity and convenience of detection techniques are the primary concerns. In this study, a hybrid superhydrophobic/-philic (SH/SHL) microporous platform is designed and fabricated by a femtosecond laser to improve surface-enhanced Raman scattering (SERS) performances. Relying on the micropores fabricated at the center of SHL patterns, sediments distributed at the central regions are avoided, leading to the further enrichment of the target molecules. The engineered micropores with high identification further improve the speed of Raman tests, and the fabricated SERS substrate shows an advantage in outdoor handheld detection and automated inspection applications. The optimized SERS sensor is sufficient for attomolar-level detection (10-17 M) of rhodamine 6G using analyte volumes of just 5 µL, corresponding to an enhancement factor of 5.19 × 1013. Meanwhile, a relative standard deviation of 7.48% at 10-10 M shows the excellent uniformity of this proposed SERS platform. This work further pushes forward the practical applications of SERS technology in ultratrace molecular detections.

19.
J Neuroinflammation ; 19(1): 218, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068612

RESUMO

BACKGROUND: Triggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear. METHOD: Genetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied. RESULTS: We inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio [OR] per one standard deviation [SD] increase = 1.064, 95% CI 1.012-1.119, P = 0.014, PFDR = 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016-1.072, P = 0.002, PFDR = 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes. CONCLUSIONS: Taken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.


Assuntos
Doença de Alzheimer , Esclerose Amiotrófica Lateral , Doença de Parkinson , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana/métodos , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor Gatilho 1 Expresso em Células Mieloides/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-36103625

RESUMO

The tin oxide (SnO2) electron transport layer (ETL) plays a crucial role in perovskite solar cells (PSCs). However, the heterogeneous dispersion of commercial SnO2 colloidal precursors is far from optimized, resulting in dissatisfied device performance with SnO2 ETL. Herein, a multifunctional modification material, ammonium citrate (TAC), is used to modify the SnO2 ETL, bringing four benefits: (1) due to the electrostatic interaction between TAC molecules and SnO2 colloidal particles, more uniformly dispersed colloidal particles are obtained; (2) the TAC molecules distributed on the surface of SnO2 provide nucleation sites for the perovskite film growth, promoting the vertical growth of the perovskite crystal; (3) TAC-doped SnO2 shows higher electron conductivity and better film quality than pristine SnO2 while offering better energy-level alignment with the perovskite layer; and (4) TAC has functional groups of C═O and N-H containing lone pair electrons, which can passivate the defects on the surface of SnO2 and perovskite films through chemical bonding and inhibit the device hysteresis. In the end, the device based on TAC-doped ETL achieved an increased power conversion efficiency (PCE) of 21.58 from 19.75% of the reference without such treatment. Meanwhile, the PSCs using the TAC-doped SnO2 as the ETL maintained 88% of their initial PCE after being stored for about 1000 h under dark conditions and controlled RH of 10-25%.

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