Potential biomarkers as a predictive factor of response to primary chemotherapy in breast cancer patients

In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.

Advances in the effect of inflammatory factors on immune mechanism of aplastic anemia / 新乡医学院学报

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

The pathogenesis of diabetes retinopathy:progress in miRNAs / 眼科新进展

Diabetic retinopathy,a main microvascular complication of diabetes,remains the leading cause of blindness in the working-age population,but its specific pathogenesis has not been fully elucidated.microRNAs(miRNAs)are small non-coding RNAs,acting as post-transcriptional regulators of gene expression.Its aberrant expression plays a key role in modulating pathological processes associated to many diseases.Studies confirmed the role of miRNAs in the regulation of oxidative stress,inflammation,cell death and angiogenesis which influences the development of DR.This review focuses on the role of miRNAs in DR,which may provide a reference basis for diagnosis,prognosis and therapeutics.

The expression changes and clinical significance of serum microRNA-155 and 135b-5p in patients with peptic ulcer complicated with Helicobacter pylori infection / 中国医师进修杂志

Objective:To investigate the expression levels and clinical significance of serum microRNA (miR) -155 and miR-135b-5p in patients with peptic ulcer complicated with Helicobacter pylori ( Hp) infection. Methods:A prospective study was conducted, and 263 patients with peptic ulcer were selected consecutively from July 2021 to February 2023 at the Affiliated Hospital of Jining Medical College. Among them, 146 cases were confirmed as Hp infection ( Hp infection group) and 117 cases were not complicated with Hp infection (non Hp infection group) by 14C breath test; type Ⅰ Hp infection was in 110 cases, and type Ⅱ Hp infection was in 36 cases by immunoblotting method. The serum expression levels of miR-155 and miR-135b-5p were detected by real-time fluorescence quantitative polymerase chain reaction, serum gastrin level was detected by radioimmunoassay method, and the serum pepsinogen (PG) Ⅰ and PG Ⅱ were detected by enzyme linked immunosorbent assay. The clinical data were recorded. Multivariate Logistic regression analysis was used to analyze the independent risk factors of Hp infection in patients with peptic ulcer; receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum miR-155 and miR-135b-5p in diagnosis the Hp infection in patients with peptic ulcer. Results:The gastrin, PG Ⅰ, PG Ⅱ, ulcer bleeding rate and recurrence rate in Hp infection group were significantly higher than those in non Hp infection group: (108.47 ± 15.35) ng/L vs. (79.63 ± 10.58) ng/L, (295.41 ± 37.26) pg/L vs. (236.75 ± 29.17) pg/L, (44.08 ± 8.52) pg/L vs. (39.29 ± 6.74) pg/L, 25.34% (37/146) vs. 15.38% (18/117) and 21.92% (32/146) vs. 11.97% (14/117), and there were statistical differences ( P<0.01 or <0.05). The serum miR-155 and miR-135b-5p in Hp infection group were significantly higher than those in non Hp infection group (1.94 ± 0.63 vs. 0.95 ± 0.29 and 1.86 ± 0.57 vs. 1.03 ± 0.31), and there were statistical differences ( P<0.01). The serum miR-155 and miR-135b-5p in patients with typeⅠ Hp infection were significantly higher than those in patients with type Ⅱ Hp infection (2.05 ± 0.66 vs. 1.60 ± 0.54 and 1.97 ± 0.61 vs. 1.52 ± 0.45), and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that serum miR-155, miR-135b-5p, gastrin and PG Ⅰwere independent risk factors of Hp infection in patients with peptic ulcer ( OR = 1.443, 1.436, 1.452 and 1.438; 95% CI 1.165 to 1.787, 1.146 to 1.799, 1.187 to 1.777 and 1.150 to 1.798; P<0.01). ROC curve analysis result showed that the area under the curve of serum miR-155 combined with miR-135b-5p in the diagnosis of Hp infection in patients with peptic ulcer was significantly greater than that of serum miR-155 and miR-135b-5p alone (0.907 vs. 0.839 and 0.836, Z = 2.57 and 2.81, P = 0.010 and 0.005). Conclusions:The serum levels of miR-155 and miR-135b-5p are high in patients with peptic ulcer complicated with Hp infection, and the combination of the two has high diagnostic value for Hp infection in patients with peptic ulcer.

MiR-145-5p targeting TLR4 participates in inflammation and oxidative stress of atherosclerosis foam cells / 中华老年心脑血管病杂志

Objective To explore the role of microRNA-145-5p(miR-145-5p)in the regulation of inflammatory response and oxidative stress process in cellular model of atherosclerosis.Methods Human monocytic leukemia THP-1 cells-derived foam cells were constructed in vitro.Then,the relative expression of miR-145-5p in the model and control groups of cells were detected by qRT-PCR.TargetScan database was used to predict the targeting relationship between miR-145-5p and Toll-like receptor 4(TLR4).The 293T cells were divided into wild-type+mimic group,wild-type+mimic negative control(NC)group,and mutant+mimic group,mutant+mimic NC group,and dual luciferase assay was employed to verify the targeting relationship of miR-145-5p and TLR4.Foam cells were cultured in vitro and divided into miR-145-5p mimic group,mimic NC group,miR-145-5p inhibitor group,and inhibitor NC group according to the corresponding treat-ments.The expression of TLR4 at mRNA and protein levels was detected by qRT-PCR and Wes-tern blotting.The contents of TNF-α,IL-1β and IL-6 were detected by ELISA.Biochemical reagent kits were applied for generation of reactive oxygen species(ROS),content of MDA and activity of SOD.Results The expression of miR-145-5p was significantly reduced in the model group than the control group(0.29±0.01 vs 1.00±0.08,t=11.180,P＜0.01).Dual luciferase assay showed that luciferase activity was significantly lower in the miR-145-5p mimic group than the mimic NC group(t=8.612,P＜0.01).Compared with the mimic NC group,the mimic group had obviously lower mRNA and protein levels of TLR4 and contents of TNF-α,IL-1β,lL-6,ROS and MDA,and higher miR-145-5p expression level and SOD activity(P＜0.05,P＜0.01).The treatment of inhibi-tor resulted in increased TLR4 mRNA and protein levels and TNF-α,IL-1β,IL-6,ROS and MDA contents,and decreased miR-145-5p expression and SOD activity when compared with the above levels in the inhibitor NC group(P＜0.05,P＜0.01).Conclusion MiR-145-5p inhibits inflamma-tion and oxidative stress in cellular model of atherosclerosis by targeting TLR4.

Progressive Changes of Colitis Into Colorectal Cancer Associated With Changes in Neutrophil Lymphocyte Ratio, Serum, Micrornas and Infiltrate Neutrophils

@#Introduction: Understand the progression of colorectal cancer from the beginning until the advance stages is difficult and challenging. However, this could be overcome with a good animal model. Methods: In this study, a modified approach had been used to develop colorectal cancer model. The model was developed and monitored from colitis formation until the late stage of colorectal cancer. The changes of neutrophil lymphocyte ratio (NLR), serum microRNAs and infiltrate neutrophil in different stages of colorectal cancer were assessed in this study. Results: Results showed that the progression of the disease is correlated with NLR as early as the formation of colitis (r=0.121, p<0.026). Meanwhile, the size of the tumor at each stage is also associated with the NLR value (r=0.185, p<0.0012). In the serum microRNAs study, it was found microRNAs expression in blood serum change in different stages of colorectal cancer. In the early stage of colitis formation, miR223 (> 3 fold expression, p < 0.0025) were abundantly found in the blood serum. Meanwhile in others stage mild (miRNA345 > 2.5 fold, p<0.0011), moderate (miRNA347 & miR512 > 3 fold, p<0.002) and severe (miR31 & miR145 > 2 fold, p<0.0001) microRNAs were also found expressed differently. The quantities of infiltrate neutrophil were varied in different stages of the disease. Conclusion: This study provides an insight into the immunity and molecular level of colorectal cancer and it allows a progressive monitoring on the changes in the molecular, cellular and histological level.

Research progress on non-coding small RNA in oral submucosal fibrosis / 口腔疾病防治

@#Oral submucous fibrosis (OSF) is one of the most common precancerous lesions of the oral mucosa, and its pathogenesis has not been fully elucidated. Small noncoding RNAs (SncRNAs), a class of RNA molecules that do not code for proteins, have been widely reported to be involved in the regulation of a variety of human diseases. An increasing number of studies have shown that a variety of SncRNAs play important roles in the pathogenesis of OSF. Current studies have shown that microRNAs (miRNAs) are involved in OSF disease progression by regulating the expression of related transcription factors and genes or epithelial mesenchymal transformation to regulate the activation of fibroblasts (FBs). Long noncoding RNAs (lncRNAs) that transform growth factor-β/suppressor of mothers against decapentaplegic (TGF-β/Smad) signaling pathways or interact with miRNAs are involved in the development of OSF. Circular RNAs (circRNAs) play a role in OSF by interacting with miRNAs. tRNA-derived small RNAs (tsRNAs) are involved in the progression of various fibrotic diseases, but their specific mechanism of action in OSF still needs to be further explored. In the future, it is still necessary to focus on the targets of SncRNAs mediating OSF progression and explore their function and molecular mechanism in OSF to provide new ideas for the diagnosis and treatment of OSF.

Expert consensus on the molecular diagnosis of early-stage pancreatic cancer （2023 edition） / 临床肝胆病杂志

Pancreatic cancer is a relatively common tumor of the digestive system， with difficulties in early-stage diagnosis and an extremely high degree of malignancy. Molecular diagnostic technology based on tumor biomarkers， combined with the existing gold standard in clinical practice， is of great clinical significance to achieve early accurate identification， timely treatment and intervention， and reduction in mortality. Previous studies have shown that miRNAs show high specificity in terms of types and expression levels in different pathological stages of pancreatic cancer and can thus be used in monitoring the development and progression of pancreatic cancer. Since a single miRNA has a limited diagnostic potential， the combination of different miRNAs may effectively improve the diagnostic efficiency of early-stage pancreas carcinogenesis. Based on related research advances in recent years， this consensus document aims to fill the gap in molecular diagnostic technology in the guidelines for the clinical diagnosis and treatment of pancreatic cancer and provide expert guidance and recommendations.

Effect of oxaliplatin on the activation of hepatic stellate cells and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the effect of oxaliplatin on the activation of hepatic stellate cells （HSCs）， as well as the association of oxaliplatin with microRNA-30a-5p and autophagy. MethodsHSC-LX2 cells were cultured and divided into groups according to the following three protocols： control group， PDGF treatment group， oxaliplatin treatment group， oxaliplatin+PDGF treatment group； control group， microRNA-30a-5p transfection group， PDGF treatment group， microRNA-30a-5p transfection+PDGF treatment group； control group， 3-MA group， microRNA-30a-5p inhibitor group， microRNA-30a-5p inhibitor+3-MA group. Western Blot was used to measure the expression of HSC activation-related proteins （Collagen-I and alpha-smooth muscle actin ［α- SMA］） and HSC autophagy-related proteins （Beclin-1， P62， and LC3B）； LysoTracker staining and immunofluorescence assay were used to measure the expression of LC3B autophagosomes； RT-PCR was used to measure the expression level of microRNA-30a-5p； bioinformatics techniques were used to predict the potential targets of microRNA-30a-5p in HSCs. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAfter the cells were treated with oxaliplatin， RT-PCR results showed that the oxaliplatin treatment group had a significantly higher expression level of microRNA-30a-5p than the control group （P<0.01）； Western Blot showed that the oxaliplatin treatment group had significant reductions in the expression levels of the HSC activation-related proteins α-SMA and Collagen-‍Ⅰ and the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ （all P<0.001）； immunofluorescence assay showed that the oxaliplatin treatment group had a significantly lower number of autophagosomes than the control group （P<0.05）. After HSC-LX2 cells were transfected with microRNA-30a-5p mimic， compared with the control group， the microRNA-30a-5p mimic group had significant reductions in the expression levels of the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ （P<0.05） and the HSC activation-related protein Collagen-‍‍Ⅰ （P<0.001）； after HSC-LX2 cells were transfected with microRNA-30a-5p inhibitor， Western Blot showed that compared with the control group， the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC activation-related proteins Collagen-‍Ⅰ and α-SMA and the autophagy-related protein Beclin 1 （t=2.41， 2.32， and 4.57， all P<0.05）. Western Blot showed that compared with the control group， the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC autophagy-related protein Beclin 1 and the HSC activation-related protein α-SMA （both P<0.05）， and after the treatment with the autophagy inhibitor 3-MA， there were no significant differences in the expression of these proteins between the two groups （P>0.05）. The bioinformatics analysis using TargetScan， PicTar， and miRanda databases showed that the autophagy-related protein Beclin-1 might be a potential target of miRNA-30a-5p. ConclusionOxaliplatin can inhibit the activation of HSCs by upregulating the expression of microRNA-30a-5p， which provides new ideas and a new target for the treatment of liver fibrosis.

Effect of miRNA-933 on the apoptosis and proliferation of LX-2 cells and its molecular mechanism / 临床肝胆病杂志

ObjectiveTo investigate the regulatory effect of miRNA-933 on the apoptosis and proliferation of human hepatic stellate cell line LX-2 and its mechanism. MethodsFirstly， with human liver tissue for research， gene microarray technology was used to detect the differentially expressed genes in liver tissue between liver cirrhosis/chronic hepatitis B tissue and normal liver tissue， among which the significantly differentially expressed miRNAs were identified， and thus miRNA-933 was determined as the research object. Then， with the human hepatic stellate cell line LX-2 for research， miRNA-933 mimic and inhibitor （miRNA-933 siRNA） were used to construct the LX-2 models of overexpression and knockdown， and the cells transfected with mimic-NC （overexpression） or siRNA-NC （knockdown） were established as the negative control group. Quantitative real-time PCR and Western blot were used to measure the expression levels of miRNA-933 and activation biomarkers； techniques such as cell proliferation assay and flow cytometry were used to investigate the effect and mechanism of miRNA-933 on cell apoptosis， proliferation， and activation. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and Bonferroni correction was also performed. ResultsA total of 18 significantly differentially expressed miRNAs were obtained based on the results of gene microarray， among which miRNA-933 was significantly downregulated （P<0.05）. After LX-2 cells were transfected with miRNA-933 mimic or siRNA， compared with the negative control group， miRNA-933 siRNA significantly downregulated the expression of miRNA-933 （P=0.000 7）， while miRNA-933 mimic significantly upregulated the expression of miRNA-933 （P=0.000 3）. Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly upregulated the expression of collagen I and α-SMA （P<0.001）， while miRNA-933 mimic significantly inhibited the expression of collagen I and α-SMA （P<0.05）. Flow cytometry showed that compared with the negative control group， miRNA-933 siRNA significantly downregulated the apoptosis rate of LX-2 cells （P=0.031 9）， and miRNA-933 mimic significantly upregulated the apoptosis rate of LX-2 cells （P=0.005 5）. Western blot showed that compared with the negative control group， miRNA-933 siRNA could inhibit the expression of Caspase-3 （P=0.006 7） and poly（ADP-ribose） polymerase-1 （PARP-1） （P=0.003 0） and upregulate the expression of B-cell lymphoma-2 （Bcl-2） in LX-2 cells （P=0.002 0）， while miRNA-933 mimic could significantly upregulate the expression of Caspase-3 （P=0.011 8） and PARP-1 （P=0.049 5） and downregulated the expression of Bcl-2 （P=0.002 1）. Cell proliferation assay showed that compared with the negative control group， miRNA-933 siRNA could promote the proliferation of LX-2 cells （P=0.011 5）， while on the contrary， miRNA-933 mimic could inhibit the proliferation of LX-2 cells （P=0.001 2）. Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly inhibited the expression of Kruppel-like factor 6 （KLF6） and downregulated the expression of activating transcription factor 4 （ATF4）， activating transcription factor 3 （ATF3）， and C/EBP homologous protein （CHOP）， while miRNA-933 mimic promoted the expression of the above proteins （all P<0.05）. ConclusionThis study shows that miRNA-933 may promote cell apoptosis and inhibit cell activation and proliferation by promoting the activation of the KLF6/ATF4/ATF3/CHOP/Bcl-2 signal axis in LX-2 cells.

The Roles of Small Extracellular Vesicles and Small Extracellular Vesicles-derived Non-coding RNA in Non-alcoholic Fatty Liver Disease / 生物化学与生物物理进展

Extracellular vesicles (EVs) are a kind of exsomes secreted by cells, which all cells release them as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories by their sizes, small EVs (sEVs) and medium/large EVs (m/l EVs). As a kind of extracellular vesicle, sEVs are mostly discoid vesicles with diameters ranging from 40 nm to 200 nm. The medium/large EVs are elliptical with a diameter more than 200 nm. sEVs play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of liver diseases. In this review, we discussed the current understanding of the role of sEVs, particularly sEV derived non-coding RNA in non-alcoholic fatty liver disease (NAFLD) and their potential as diagnostic and therapeutic targets. sEVs are small membrane-bound particles secreted by cells, which fuse with plasma membrane and release to extracellular matrix. Depending on the cell of origin, sEVs could contain many cell constituents, including various DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins, biomolecules. In addition, many RNA and DNA molecules contained by sEVs, such as mRNA, microRNA (miRNA), long noncoding RNA (lncRNA) and mitochondrial DNA (mtDNA), can be transferred to recipient cells to effectively promote their biological response, physiological and pathological functions. Such sEVs-mediated responses can be disease promoting or restraining. The intrinsic properties of sEVs in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in sEVs, suggesting that they have a role in regulating intercellular communication. Many studies have also shown the involvement of sEVs’ noncoding RNAs (ncRNAs) in controlling cell activities and their crucial functions in regulating lipid metabolism. sEVs ncRNAs, including miRNAs, lncRNAs, and circular RNAs (circRNAs) regulate physiological functions and maintain lipid metabolism homeostasis. miRNA are small non-coding RNA molecules that regulate posttranscriptional gene expression by repressing messenger RNA-targets. These circulating miRNAs are easily accessible, disease-specific and sensitive to small changes, which makes them ideal biomarkers for diagnostic, prognostic, predictive or monitoring purposes. Specific miRNA signatures can be reflective of disease status and development or indicators of poor treatment response in liver diseases. And lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. Then circRNAs contributed to NAFLD progression by acting as miRNA sponges, functional protein sponges, or novel templates for protein translation. Finally, sEVs could be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides and so on, with an ability to direct their delivery to a desired target. The potential of targeting sEVs with lncRNAs and miRNAs not only could be potential diagnostic biomarkers for NAFLD, but also have potential therapeutic effects on NAFLD, which might provide new ideas for the NAFLD treatment. In conclusion, this review provides an overview of the current understanding of the roles of sEVs ncRNAs in NAFLD, so we suggest that further research into sEVs could lead to new diagnostic tools and therapeutic strategies for NAFLD.

Relationship between serum miR-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma / 实用医学杂志

Objective To explore the relationship between serum miRNA-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma.Methods A total of 118 patients with renal clear cell carcinoma admitted to the Qinghai University Hospital from February 2019 to April 2021 were selected as the study subjects,and another 118 healthy patients in the same period as the control group.Real time fluorescence quantitative polymerase chain reaction(PCR)was used to detect the expression of miR-21 and miR-27b in the serum of all subjects.The relative expression levels of serum miR-21 and miR-27b between the patients with renal clear cell carcinoma and healthy control patients were compared.The expression and correlation of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma of different pathological stages and Fuhrman grading were analyzed.The relationship between the expression of serum miR-21 and miR-27b and the survival and prognosis of the patients was explored as well.Results The expression levels of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma were higher than those in the healthy control group(P＜0.05).The serum miR-21 expression level in stage Ⅲ patients was higher than in stageⅠ(P＜0.05),while the serum miR-21 expression level in the stage Ⅳ patients was higher than that in stagesⅠ,Ⅱ,and Ⅲ(P＜0.05).The expression level of miR-27b in the serum of patients gradually increased across the four stages,with a significant difference(P＜0.05).The pathological staging was positively correlated with the expression of miR-21 and miR-27b(P＜0.001).The expression levels of miR-21 and miR-27b in serum of patients gradually increased across grades Ⅰ,Ⅱ and Ⅲ by Fuhrman grading,with significant difference(P＜0.05).Fuhrman grading was positively correlated with the serum miR-21 and miR-27b expression(P＜0.001).There was a statistically significant difference in the survival curve between the miR-21 high expression group and the low expression group(P＜0.05).There was a statistically significant difference in the survival curve between the high expression group and the low expression group of miR-27b(P＜0.05).Conclusion The expression levels of serum miR-21 and miR-27b in patients with renal clear cell carcinoma is indicative of the progression and prognosis of the patient's condition.

Efficacy analysis of a preeclampsia risk prediction model based on exosomal multiple miRNA expression levels / 天津医药

Objective To investigate the feasibility of constructing a preeclampsia(PE)risk model based on multiple exosomal micrornas(miRNA)expression levels and to verify its efficacy in predicting PE.Methods A total of 1037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects.The expression of exosomal miRNA(including miR-155-5p,miR-215-5p,miR-203a-3p,miR-199a-5p and miR-125a-3p)in all samples was detected by qRT-PCR.Then,all patients were followed up to the end of pregnancy.The occurrence of PE during the follow-up period was counted,and all samples were divided into the PE group and the control group according to results.Cox regression was used to analyze the influencing factors of PE.The multi-miRNA risk model was constructed with ggrisk package,and the predictive effect of the model on PE was evaluated by receiver operating characteristic(ROC)curve.Results By the end of follow-up on October 31,2022,974 cases were finally followed up,and the follow-up completion rate was 93.92%.Among all the 974 patients who completed the follow-up,65 patients developed PE,so they were finally divided into the PE group,and 909 cases were used as the control group.The age,pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group(P＜0.05).The proportions of smoking history and drinking history were higher in the PE group than those of the control group(P＜0.05).The contents of triglyceride(TG),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),alanyl aminotransferase(ALT),aspartate aminotransferase(AST),platelet distribution width(PDW),mean platelet volume(MPV),miR-155-5p,miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group,while contents of thyroid stimulating hormone(TSH),miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group(P＜0.05).The expression levels of miR-125a-3p,miR-155-5p,miR-199a-5p and miR-215-5p were independent predictors of PE(P＜0.05).The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE(AUC=0.998),with a sensitivity of 98.46%(63/65)and a specificity of 93.94%(854/909).Conclusion miR-125a-3p,miR-155-5p,miR-199a-5p,miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE,and the PE prediction model constructed with the above five miRNAs has better effect.

Research progress on the mechanism of microRNA regulation of cisplatin resistance in ovarian cancer / 国际肿瘤学杂志

Cisplatin resistance is an important factor in the poor treatment effect of ovarian cancer patients. MicroRNA (miRNA) can regulate cellular structural molecules, DNA repair, cell cycle, apoptosis and Wnt/β-catenin signaling pathway, autophagy, methylation and cancer stem cell, which are involved in the regulation of cisplatin resistance in ovarian cancer. Further understanding the mechanism of miRNA regulation of cisplatin resistance in ovarian cancer will help find new treatment options to optimize existing treatment plans and improve efficacy.

Characterization of the MicroRNA profile in rheumatoid arthritis plasma exosomes and their roles in B-cell responses

ABSTRACT Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles. Methods: Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments. Results: Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production. Conclusion: The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.

Biomarcadores Potenciais na Fibrose Miocárdica: Uma Análise Bioinformática / Potential Biomarkers in Myocardial Fibrosis: A Bioinformatic Analysis

Resumo Fundamento A fibrose miocárdica (FM) ocorre durante o início e a progressão da doença cardiovascular, e o diagnóstico precoce da FM é benéfico para melhorar a função cardíaca, mas há uma falta de pesquisa sobre biomarcadores precoces da FM. Objetivos Utilizando técnicas de bioinformática, identificamos potenciais biomarcadores para FM. Métodos Os conjuntos de dados relacionados à FM foram obtidos do banco de dados Gene Expression Omnibus (GEO). Após o processamento dos dados, genes diferencialmente expressos foram rastreados. Genes diferencialmente expressos foram enriquecidos e, subsequentemente, interação proteína-proteína (PPI) foi realizado para analisar os genes diferenciais. Os miRNAs associados e fatores de transcrição foram previstos para esses genes centrais. Finalmente, a validação ROC foi realizada nos genes centrais para determinar sua especificidade e sensibilidade como potenciais biomarcadores. O nível de significância adotado foi de 5% (p < 0,05). Resultados Um total de 91 genes diferencialmente expressos foram identificados, e a análise PPI produziu 31 genes centrais. A análise de enriquecimento mostrou que apoptose, colágeno, matriz extracelular, adesão celular e inflamação estavam envolvidos na FM. Cento e quarenta e dois miRNAs potenciais foram identificados. Os fatores de transcrição JUN, NF-κB1, SP1, RELA, SRF e STAT3 foram enriquecidos na maioria dos alvos principais. Por fim, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2 e ITGB8 tiveram maior precisão diagnóstica e sensibilidade na predição de FM com base na análise da curva ROC. Conclusão Oito genes, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2 e ITGB8, podem servir como biomarcadores candidatos para FM. Processos como apoptose celular, síntese de proteína de colágeno, formação de matriz extracelular, adesão celular e inflamação estão implicados no desenvolvimento da FM.

Abstract Background Myocardial fibrosis (MF) occurs throughout the onset and progression of cardiovascular disease, and early diagnosis of MF is beneficial for improving cardiac function, but there is a lack of research on early biomarkers of MF. Objectives Utilizing bioinformatics techniques, we identified potential biomarkers for MF. Methods Datasets related to MF were sourced from the GEO database. After processing the data, differentially expressed genes were screened. Differentially expressed genes were enriched, and subsequently, protein-protein interaction (PPI) was performed to analyze the differential genes. The associated miRNAs and transcription factors were predicted for these core genes. Finally, ROC validation was performed on the core genes to determine their specificity and sensitivity as potential biomarkers. The level of significance adopted was 5% (p < 0.05). Results A total of 91 differentially expressed genes were identified, and PPI analysis yielded 31 central genes. Enrichment analysis showed that apoptosis, collagen, extracellular matrix, cell adhesion, and inflammation were involved in MF. One hundred and forty-two potential miRNAs were identified. the transcription factors JUN, NF-κB1, SP1, RELA, serum response factor (SRF), and STAT3 were enriched in most of the core targets. Ultimately, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2, and ITGB8 had higher diagnostic accuracy and sensitivity in predicting MF based on ROC curve analysis. Conclusion Eight genes, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2, and ITGB8, can serve as candidate biomarkers for MF. Processes such as cellular apoptosis, collagen protein synthesis, extracellular matrix formation, cellular adhesion, and inflammation are implicated in the development of MF.

A molecular approach to triple-negative breast cancer: targeting the Notch signaling pathway

ABSTRACT Introduction Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This phenotype renders triple-negative breast cancer cells refractory to conventional therapies, resulting in poor clinical outcomes and an urgent need for novel therapeutic approaches. Recent studies have implicated dysregulation of the Notch receptor signaling pathway in the development and progression of triple-negative breast cancer. Objective This study aimed to conduct a comprehensive literature review to identify potential therapeutic targets of the Notch pathway. Our analysis focused on the upstream and downstream components of this pathway to identify potential therapeutic targets. Results Modulating the Notch signaling pathway may represent a promising therapeutic strategy to treat triple-negative breast cancer. Several potential therapeutic targets within this pathway are in the early stages of development, including upstream (such as Notch ligands) and downstream (including specific molecules involved in triple-negative breast cancer growth). These targets represent potential avenues for therapeutic intervention in triple-negative breast cancer. Comments Additional research specifically addressing issues related to toxicity and improving drug delivery methods is critical for the successful translation of these potential therapeutic targets into effective treatments for patients with triple-negative breast cancer.

Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study

SUMMARY OBJECTIVE: The aim of this study was to determine the allelic and genotypic frequencies of the polymorphisms, rs2910164 miR-146a and rs11614913 miR-196a2, by investigating their association with endometriosis. METHODS: This is a case-control study performed with approximately 120 women. The polymorphisms were determined by real-time polymerase chain reaction. For the statistical analysis, the chi-square and logistic regression tests were used. RESULTS: There were no significant differences in the genotype and allele frequencies of rs2910164 and rs11614913 between cases and controls. The frequencies in both polymorphisms are in accordance with Hardy-Weinberg equilibrium regarding miR-146a (patients: χ2=1.64, p=0.20; controls: χ2=0.25, p=0.62) and miR-196a2 (patients: χ2=0.58, p=0.44; controls: χ2=2.78, p=0.10). No relationship was observed between rs2910164 and rs11614913 and endometriosis in the inheritance models analyzed. CONCLUSION: In this study, our results show that the studied polymorphisms are not implicated in the development of endometriosis.

3D-Structural Characterization of MicroRNA Expressed in Leprosy / Caracterização Estrutural em 3D de MicroRNAs Expressos na Hanseníase

Introduction: Hansen's disease, or leprosy is caused by Mycobacterium leprae (M. leprae), is a major public health problem in developing countries, and affecting the skin and peripheral nerves. However, M. leprae can also affect bone tissue, mucous membranes, liver, eyes, and testicles, producing a variety of clinical phenotypes. MicroRNAs (miRNAs) have been expressed in the various clinical forms of leprosy and could potentially be used for its diagnosis. Objective: in silico design of the molecular structure of miRNAs expressed in leprosy. Methodology: we performed a nucleotide sequence search of 17 miRNAs expressed in leprosy, designing in silico the molecular structure of the following miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA-29c, miRNA-34c, miRNA-92a-1, miRNA- 99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, and miRNA-660. We extracted the nucleotides were from the GenBank of National Center for Biotechnology Information genetic sequence database. We aligned the extracted sequences with the RNA Folding Form, and the three-dimensional molecular structure design was performed with the RNAComposer. Results: we demonstrate the nucleotide sequences, and molecular structure projection of miRNAs expressed in leprosy, and produces a tutorial on the molecular model of the 17 miRNAs expressed in leprosy through in silico projection processing of their molecular structures. Conclusion: we demonstrate in silico design of selected molecular structures of 17 miRNAs expressed in leprosy through computational biology.

Introdução: a doença de Hansen, ou hanseníase é causada pelo Mycobacterium leprae (M. leprae), é um grande problema de saúde pública nos países em desenvolvimento e afeta, a pele e os nervos periféricos. Entretanto, o M. leprae também pode comprometer o tecido ósseo, membranas mucosas, fígado, olhos e testículos, produzindo uma variedade de fenótipos clínicos. MicroRNAs (miRNAs) têm sido expressos nas várias formas clínicas da hanseníase e podem ser potencialmente utilizados para seu diagnóstico. Objetivo: objetivou-se com esse experimento modelar computacionalmente a estrutura molecular dos miRNAs expressos na hanseníase. Metodologia: realizou-se como metodologia uma pesquisa das sequências nucleotídicas de 17 miRNAs expressos na hanseníase, desenhando em modelo computacional a estrutura molecular dos seguintes miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA- 29c, miRNA-34c, miRNA-92a-1, miRNA-99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, e miRNA-660. Extraiu-se os nucleotídeos do banco de dados do GenBank of National Center for Biotechnology Information . Alinhou-se as sequências extraídas com o RNA Folding Form, e o projeto da estrutura molecular tridimensional foi realizado com o RNAComposer. Resultados: demonstrou-se como resultados as sequências dos nucleotídeos e a projeção da estrutura molecular dos miRNAs expressos na hanseníase, e produzimos um tutorial sobre o modelo molecular dos 17 miRNAs expressos em hanseníase através do processamento de suas estruturas moleculares em projeção computacional. Conclusão: foi demonstrado computacionalmente o projeto de estruturas moleculares selecionadas de 17 miRNAs expressos em hanseníase através da biologia computacional.

Association between microRNA expression and risk of male idiopathic infertility in Iraq

SUMMARY OBJECTIVE: The World Health Organization defines infertility as the inability to get pregnant after 12 months of unprotected sexual activity. This study was conducted to estimate the levels of gene expression for two mature miRNAs (i.e., miR-122 and miR-34c-5p) to evaluate susceptibility to male infertility. METHODS: This study included 50 male patients with idiopathic infertility who were admitted to hospital from the period November 2021 to May 2022 and another group consisting of 50 apparently healthy individuals used as controls. RESULTS: miR-122 level was significantly highest in azoospermia and followed by oligospermia, 39.22 (31.88) versus 37.34 (20.45), respectively. In addition, there was a very significant difference in miR-34c-5p levels between the study groups (p<0.05). CONCLUSION: Two miRNAs, namely, miR-34c-5p and miR-122, can be used as predictive and diagnostic biomarkers for infertility.