Overexpression of REC8 induces aberrant gamete meiotic division and contributes to AML pathogenesis - a multiplexed microarray analysis and mendelian randomization study.

Acute myeloid leukemia (AML) is a notably lethal disease, characterized by malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study seeks to unveil potential therapeutic targets for AML, using a combined approach of microarray analysis and Mendelian randomization (MR). We collected data samples from the Gene Expression Omnibus (GEO) database and extracted pQTL data from genome-wide association studies (GWAS) to identify overlapping genes between the DEGs and GWAS data. Gene enrichment and pathway annotation analyses were performed on these genes. Furthermore, we validated gene expression levels and assessed their clinical relevance. By taking the intersection of these gene sets, we obtained a list of co-expressed genes, including four upregulated genes (REC8, TPM2, ZMIZ1, CD82) and two downregulated genes (IFNAR1, TMCO3). MR analysis demonstrated that genetically predicted protein levels of CD82, REC8, ZMIZ1, and TPM2 were significantly associated with increased odds of AML, while IFNAR1 and TMCO3 showed a protective effect. Gene ontology and KEGG pathway analyses revealed significant enrichment in functions related to female gamete generation, meiosis, p53 signaling pathway, and cardiac muscle contraction. Differences in immune cell profiles were observed between AML survivors and those with poor prognosis, including lower levels of neutrophils and higher levels of follicular helper T cells in the latter group. This study identifies a causal relationship between gene expression and AML and highlights the potential role of REC8 in leukemogenesis, possibly through its impact on gametocyte meiotic abnormalities. The findings provide new insights into the prevention and treatment of leukemia.

SIRPG promotes lung squamous cell carcinoma pathogenesis via M1 macrophages: a multi-omics study integrating data and Mendelian randomization.

Background: Squamous cell carcinoma of the lung (LUSC) is a severe and highly lethal malignant tumor of the respiratory system, and its molecular mechanisms at the molecular level remain unc\lear. Methods: We acquired RNA-seq data from 8 surgical samples obtained from early-stage LUSC and adjacent non-cancerous tissues from 3 different centers. Utilizing Deseq2, we identified 1088 differentially expressed genes with |LogFC| > 1 and a p-value < 0.05 threshold. Furthermore, through MR analysis of Exposure Data for 26,153 Genes and 63,053 LUSC Patients, incorporating 7,838,805 SNPs as endpoints, we identified 213 genes as potential exposure factors. Results: After intersecting the results, we identified 5 differentially expressed genes, including GYPE, PODXL2, RNF182, SIRPG, and WNT7A. PODXL2 (OR 95% CI, 1.169 (1.040 to 1.313)) was identified as an exposed risk factor, with p-values less than 0.01 under the inverse variance weighted model. GO and KEGG analyses revealed enhanced ubiquitin-protein transferase activity and activation of pathways such as the mTOR signaling pathway and Wnt signaling pathway. Immune infiltration analysis showed downregulation of Plasma cells, T cells regulatory (Tregs), and Dendritic cells activated by the identified gene set, while an enhancement was observed in Macrophages M1. Furthermore, we externally validated the expression levels of these five genes using RNA-seq data from TCGA database and 11 GEO datasets of LUSC, and the results showed SIRPG could induce LUSC. Conclusion: SIRPG emerged as a noteworthy exposure risk factor for LUSC. Immune infiltration analysis highlighted Macrophages M1 and mTOR signaling pathway play an important role in LUSC.

Case report: Creutzfeldt-Jakob disease: a case that initiated with the onset of obsessive-compulsive state.

Background: Obsessive-compulsive disorder (OCD) is a common reason for patients to seek symptomatic treatment in psychiatric departments, which makes it challenging to consider underlying organic nervous system diseases. However, Creutzfeldt-Jakob disease (CJD) can present with atypical symptoms, sometimes even as initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture and brain DWI are important diagnostic methods for CJD, and the detection of 1,433 protein can be performed to confirm the diagnosis. Case presentation: We present the case of a 63-year-old woman who was initially diagnosed with obsessive-compulsive disorder in 2022. Despite seven months of symptomatic treatment, her symptoms did not improve. She also developed symptoms of altered consciousness, such as upper limb tremors and mutism. Based on brain DWI and positive results from the detection of 1,433 protein, she was ultimately diagnosed with CJD. Conclusion: Creutzfeldt-Jakob disease (CJD) can manifest initially as obsessive-compulsive disorder (OCD) with atypical symptoms, making it prone to misdiagnosis. Therefore, it is crucial to conduct further investigations, including lumbar puncture and imaging, to exclude organic nervous system diseases before initiating symptomatic treatment for psychiatric disorders. This approach can facilitate early diagnosis of CJD and other potential organic neurological diseases.

Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, epileptic seizures, faciobrachial dystonic seizures (FBDS), and refractory hyponatremia. Recently, we found an atypical manifestation of anti-LGI1 encephalitis, in which paroxysmal limb weakness was the initial symptom. In this report, we describe five cases of anti-LGI1 encephalitis with paroxysmal limb weakness. Patients had similar presentations, where a sudden weakness involving a unilateral limb was observed, which lasted several seconds and occurred dozens of times each day, with the anti-LGI1 antibody being positive in both serum and cerebrospinal fluid (CSF). FBDS occurred after a mean of 12 days following paroxysmal limb weakness in three of five patients (Cases 1, 4, and 5). All patients were given high-dose steroid therapy, which had a good effect on their condition. Based on this report, we suggest that paroxysmal unilateral weakness may be a kind of epilepsy and be connected to FBDS. As an unusual neurological presentation, paroxysmal weakness can be included in the clinical manifestations of anti-LGI1 encephalitis, helping to raise awareness of the recognition of anti-LGI1 encephalitis in patients with this symptom and leading to early diagnosis and early treatment, which would contribute to improved clinical outcomes.

Comparison of multiple treatments in the management of transplant-related thrombotic microangiopathy: a network meta-analysis.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA.

Treatment with spexin mitigates diet-induced hepatic steatosis in vivo and in vitro through activation of galanin receptor 2.

It was reported that spexin as an adipocyte-secreted protein could regulate obesity and insulin resistance. However, the specific metabolic contribution of spexin to fatty liver remains incompletely understood. Herein, we investigated the effects of spexin on hepatosteatosis and explored the underlying molecular mechanisms. HFD-fed mice were injected with spexin and/or GALR2 antagonist M871, while PA-induced HepG2 cells were treated with spexin in the absence or presence of M871 for 12 h, respectively. Gene expression in liver tissues and hepatocytes was assessed by qRT-PCR and western blotting, respectively. The results showed that body weight, visceral fat content, liver lipid droplet formation, hepatic intracellular triglyceride, and serum triglyceride were reduced in spexin-treated mice. Furthermore, spexin increased the expression of hepatic CPT1A, PPARα, SIRT1, KLF9, PGC-1α and PEPCK in vivo and in vitro. Additionally, spexin treatment improved glucose tolerance and insulin sensitivity in mice fed the HFD. Interestingly, these spexin-mediated beneficial effects were abolished by the GALR2 antagonist M871 in mice fed HFD and PA-induced HepG2 cells, suggesting that spexin mitigated HFD-induced hepatic steatosis by activating the GALR2, thereby increasing CPT1A, PPARα, SIRT1, KLF9, PGC-1α and PEPCK expression. Taken together, these data suggest that spexin ameliorates NAFLD by improving lipolysis and fatty acid oxidation via activation of GALR2 signaling.

Efficacy of azacitidine in preventing relapse after hematopoietic stem cell transplantation for advanced myeloid malignancies: a systematic review and meta-analysis.

BACKGROUND: Relapse is the leading cause of death from myeloid malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Azacitidine has gained attention in recent years in the prophylaxis of relapsed refractory hematologic malignancies. This study evaluated the efficacy of AZA in preventing relapse after HSCT in patients with myeloid malignancies. METHODS: A systematic review and meta-analysis of all available cohort studies were performed regarding the application of AZA for prophylaxis of relapse after HSCT for advanced MDS and AML. Databases were searched for relevant studies. Endpoints included 2-year relapse rate, survival, relapse-related mortality, as well as the incidence of graft-versus-host disease (GVHD). RESULTS: A total of 444 patients from 13 studies were included in this analysis. The pooled estimate of the cumulative incidence of relapse after two years in enrolled patients was 25% (95% confidence interval [CI], 18%-33%). The pooled estimates of 2-year survival probabilities were 65% (95% CI, 50%-79%). The pooled cumulative incidence of relapse-related mortality was 28% (95% CI, 22%-34%). The pooled estimated incidence of acute and chronic GVHD, respectively, were 28% (95% CI, 22%-34%) and 38% (95% CI, 27%-49%). CONCLUSION: AZA administration is efficacious for relapse prevention after HSCT in myeloid malignancies.

Increased Serum VEGF-B Level Is Associated With Renal Function Impairment in Patients With Type 2 Diabetes.

Aims/Introduction: Renal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients. Materials and Methods: Serum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR<90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR. Results: Serum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR<90 mL/min/1.73m2. Conclusions: Serum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease.

Signature of m5C-Related lncRNA for Prognostic Prediction and Immune Responses in Pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) has a high mortality and dismal prognosis, predicting to be the second most lethal malignancy. 5-Methylcytosine (m5C) and long noncoding RNAs (lncRNAs) are both crucial in the prognostic outcome and immunotherapeutic effect for PC patients. Therefore, we aimed to create an m5C-related lncRNA signature (m5C-LS) for PC patients' prognosis and treatment. METHODS: Clinicopathological information and RNAseq data were acquired from The Cancer Genome Atlas (TCGA) database. Pearson's correlation analysis was used to extract m5C-related lncRNAs in PC. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were adopted to build an m5C-LS. Kaplan-Meier (K-M), principal component analysis (PCA), and nomogram were utilized to assess model accuracy. In addition, we explored the model's possible immunotherapeutic responses and drug sensitivity targets. RESULTS: Three m5C-related lncRNAs were finally established to construct the risk signature, which has a good and independent predictive ability for PC patients. Based on the m5C-LS, patients were classified into the low- and high-m5C-LS group, with the latter having a worse prognosis. Furthermore, the m5C-LS allowed us to better discriminate the immunotherapeutic responses of PC patients in different subgroups. CONCLUSIONS: Our study constructed an m5C-LS and established a nomogram model that accurately predicted the prognosis of PC patients, as well as provides promising immunotherapeutic strategies in the future.

Characterization of m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration in acute myeloid leukemia.

BACKGROUND: Previous studies have confirmed the existence of epigenetic regulation of immune responses in acute myeloid leukemia. However, the potential role of RNA N6-methyladenosine (m6A) remodeling in tumor microenvironment (TME) infiltration remains unclear. METHODS AND MATERIALS: m6A patterns of 469 AML patients (420 of which provided survival data) based on 18 m6A regulators were systematically evaluated. Based on the expression of 18 m6A regulators, unsupervised agglomerative cluster analysis was applied to recognize the various m6A modification types and to classify patients. We linked these patterns to TME infiltration characteristics and identified three distinct populations of m6A modifications. RESULTS: These three TME cell infiltration patterns are characterized by a high degree of concordance with the three tumor immunophenotypes, which include immunoinflammatory, immunorejection, and immune inert patterns. We showed that assessment of m6A modification patterns within individually neoplasms can forecast the stage of neoplasmic inflammation, TME basal activity, subtype, hereditary mutation, and clinical patient prognosis. Limited low m6Ascore, featuring increased mutational load and immune activation, indicates an inflammatory phenotype of TME with a 5-year survival rate at 14.4% compared to the high-m6Ascore group (40.9%). CONCLUSIONS: Data from two different cohorts demonstrated that a higher m6Ascore showed a marked therapeutic superiority as well as clinical advantage. Assessing m6A modification patterns in AML patients could improve our knowledge of the TME infiltrative profile as well as directing effective immunotherapeutic approaches.

Spexin ameliorates skeletal muscle insulin resistance through activation of GAL2 receptor.

Skeletal muscle is a principal tissue involved in energy expenditure and glucose metabolism. Although the results of our and other studies show that spexin could decrease food intake and obesity, the specific metabolic effect of spexin on glucose metabolism of skeletal muscle is still unclear. The aim of this study is to investigate whether spexin might mitigate obesity-induced insulin resistance in skeletal muscles and to explore its underlying mechanisms. The high fat diet-fed mice were treated with 50 µg/kg/d spexin for 21 consecutive days, and the differentiated myotubes of L6 were treated with spexin (200, 400, 800 nM) in the absence or presence of M871 (800 nM) for 12 h respectively. Besides, the galanin type 2 (GAL2) receptor knockdown myotubes were treated with 800 nM spexin for 12 h in this study. The present findings showed that spexin reversed hyperglycemia and glucose intolerance as well as insulin intolerance and insulin resistance in the mice fed with high fat diet. Furthermore, spexin markedly augmented the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression and deacetylation, and further triggered glucose transporter 4 (GLUT4) expression and trafficking in myotubes through p38 mitogen-activated protein kinase (P38MAPK) and protein kinase B (AKT) activation. More importantly, the elevation of glucose consumption related genes by spexin were abolished by GAL2 receptor antagonist or silencing of GAL2 receptor in myotubes. In conclusion, our findings provide a novel insight that spexin can protect against insulin resistance and increase glucose consumption in skeletal muscles mainly through activation of GAL2/GLUT4 signal pathway. Spexin might therefore be a novel therapeutic target for hyperglycemia and insulin resistance in clinic.

Baicalin protects against insulin resistance and metabolic dysfunction through activation of GALR2/GLUT4 signaling.

BACKGROUND: Type 2 diabetes mellitus is a complex metabolic disorder associated with obesity, glucose intolerance and insulin resistance. Activation of GALR2 has been proposed as a therapeutic target for the treatment of insulin resistance. The previous studies showed that baicalin could mitigate insulin resistance, but the detailed mechanism of baicalin on insulin resistance has not been fully explored yet. PURPOSE: In the present study, we evaluated whether baicalin mitigated insulin resistance via activation of GALR2 signaling pathway. STUDY DESIGN/METHODS: Baicalin (25 mg/kg/d and 50 mg/kg/d) and/or GALR2 antagonist M871 (10 mg/kg/d) were injected individually or in combinations into obese mice once a day for three weeks, and normal and GALR2 knockdown myotubes were treated with baicalin (100 µM and 400 µM) or metformin (4 mM) in the absence or presence of M871 (800 nM) for 12 h, respectively. The molecular mechanism was explored in skeletal muscle and L6 myotubes. RESULTS: The present findings showed that baicalin mitigated hyperglycemia and insulin resistance and elevated the levels of PGC-1α, GLUT4, p-p38MAPK, p-AKT and p-AS160 in skeletal muscle of obese mice. Strikingly, the baicalin-induced beneficial effects were abolished by GALR2 antagonist M871 in obese mice. In vitro, baicalin dramatically augmented glucose consumption and the activity of PGC1α-GLUT4 axis in myotubes through activation of p38MAPK and AKT pathways. Moreover, baicalin-induced elevations in glucose consumption related genes were abolished by GALR2 antagonist M871 or silencing of GALR2 in myotubes. CONCLUSIONS: The present study for the first time demonstrated that baicalin protected against insulin resistance and metabolic dysfunction mainly through activation of GALR2-GLUT4 signal pathway. Our findings identified that activation of GALR2-GLUT4 signal pathway by baicalin could be a new therapeutic approach to treat insulin resistance and T2DM in clinic.

Preparation and Performance of Chemotherapy Drug-Loaded Graphene Oxide-Based Nanosheets That Target Ovarian Cancer Cells via Folate Receptor Mediation.

Graphene oxide (GO) is one of the most popular nanomaterials that widely used to achieve effective cancer treatment. In this study, a novel, folic acid-decorated graphene oxide (FA-GO)-mediated drug delivery system was synthesized by loading the chemotherapy drug cisplatin (CDDP) or paclitaxel (PTX) to the large surface area of GO for ovarian cancer target therapy. In vitro study showed that the therapeutic effects of FA-GO-CDDP or FA-GO-PTX were increased with folate-binding protein (FBP) expression levels. The GO-CDDP or GO-PTX modified with FA enhanced cancer cell death by promoting DNA damage, ROS production, and apoptotic pathway activation. In vivo anticancer study demonstrated that FA-GO-CDDP nanosheets showed excellent therapeutic performance and attenuated the body weight loss evoked by CDDP treatment. Our results indicate that the chemotherapy agent-loaded FA-GO nanosheets have high potential therapeutic effects against FBP high expressing ovarian cancer.

Development of metabolic dysfunction in mice lacking chemerin.

Chemerin, an adipocyte-secreted adipokine, is hypothesized to participate in energy homeostasis and glucoregulation. However, the physiologic effect of endogenous chemerin on glucose metabolism is unclear. The present studies tested the hypotheses that chemerin deficiency alters whole-body glucose homeostasis following switches to high-fat diet. Adult, male chemerin knockout and C57BL/6J control wild type mice were studied. During the following 4 weeks, chow- or high-fat diet maintained chemerin knockout mice showed elevated fasting glucose levels and glucose intolerance as well as insulin intolerance. Chemerin deficiency impaired adaptation to glucose and insulin challenge, leading to increased glucose levels. Moreover, the mRNA and protein levels of GLUT4 and PGC-1α expression in both skeletal muscle and adipose tissue were significantly decreased in chemerin knockout mice relative to the wild type, respectively. Taken together, the results support the hypotheses that chemerin helps adapt glucose metabolism to changes in dietary fat and modulates glucose consumption in mice by activation of PGC-1α/GLUT4 axis. Chemerin may play a significant role in elevation of glucose uptake and insulin sensitivity to promote glucose clearance.

Clinical significance of FLT3-ITD/CEBPA mutations and minimal residual disease in cytogenetically normal acute myeloid leukemia after hematopoietic stem cell transplantation.

PURPOSE: Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. METHODS: We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years. RESULTS: A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPAwt were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPAmut/FLT3-ITDwt had the best prognosis, and patients with CEBPAwt/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. CONCLUSIONS: We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.

Self-efficacy, Hope as Mediators Between Positive Coping and Resilience Among Patients With Gastric Cancer Before the First Chemotherapy.

BACKGROUND: Patients with gastric cancer experience severe psychological distress as a result of their cancer diagnosis and chemotherapy. Resilience is a defense mechanism that enables one to thrive amid distress. However, little research has been done to explore the formation and development mechanism of resilience among patients with gastric cancer before their first chemotherapy treatment. OBJECTIVE: The mediating roles of self-efficacy and hope on the relationship between positive coping and resilience among patients with gastric cancer before their first chemotherapy treatment were examined to inform the future resilience intervention. METHODS: A total of 253 patients with gastric cancer before their first chemotherapy treatment were investigated using the Simplified Coping Style Questionnaire, the General Self-efficacy Scale, the Herth Hope Index, and the 14-Item Resilience Scale. Structural equation modeling was conducted using Mplus version 7.03 to test the hypothesized mediational model. RESULTS: Structural equation modeling analysis showed self-efficacy and hope completely mediated the relationship between positive coping and resilience; the indirect effects were 0.242 (P < .01) and 0.258 (P < .01), respectively; indirect effects accounted for 81% of the total effect. CONCLUSIONS: Positive coping is not the independent predictor that may contribute to resilience among patients with gastric cancer before their first chemotherapy treatment, but it can indirectly affect resilience through self-efficacy and hope. IMPLICATIONS: Self-efficacy and hope may increase the positive influence of positive coping on resilience among patients with gastric cancer before their first chemotherapy treatment. Resilience intervention might be enhanced by addressing the impact of positive coping on self-efficacy and hope.

Prediction of Potential Associations Between miRNAs and Diseases Based on Matrix Decomposition.

It is known that miRNA plays an increasingly important role in many physiological processes. Disease-related miRNAs could be potential biomarkers for clinical diagnosis, prognosis, and treatment. Therefore, accurately inferring potential miRNAs related to diseases has become a hot topic in the bioinformatics community recently. In this study, we proposed a mathematical model based on matrix decomposition, named MFMDA, to identify potential miRNA-disease associations by integrating known miRNA and disease-related data, similarities between miRNAs and between diseases. We also compared MFMDA with some of the latest algorithms in several established miRNA disease databases. MFMDA reached an AUC of 0.9061 in the fivefold cross-validation. The experimental results show that MFMDA effectively infers novel miRNA-disease associations. In addition, we conducted case studies by applying MFMDA to three types of high-risk human cancers. While most predicted miRNAs are confirmed by external databases of experimental literature, we also identified a few novel disease-related miRNAs for further experimental validation.

RNA-Seq Revealed a Circular RNA-microRNA-mRNA Regulatory Network in Hantaan Virus Infection.

Hantaan virus (HTNV), a Hantavirus serotype that is prevalent in Asia, causes hemorrhagic fever with renal syndrome (HFRS) with high mortality in human race. However, the pathogenesis of HTNV infection remains elusive. Circular RNAs (circRNAs), a new type of non-coding RNAs, play a crucial role in various pathogenic processes. Nevertheless, circRNA expression profiles and their effects on pathogenesis of HTNV infection are still completely unknown. In the present study, RNA sequencing was performed to analyze the circRNA, microRNA (miRNA), and mRNA expression profiles in HTNV-infected and mock-infected human umbilical vein endothelial cells (HUVECs). A total of 70 circRNAs, 66 miRNAs, and 788 mRNAs were differently expressed. Several differentially expressed RNAs were validated by RT-qPCR. Moreover, we verified that some differentially expressed RNAs, such as circ_0000479, miR-149-5p, miR-330-5p, miR-411-3p, RIG-I, CMPK2, PARP10, and GBP1, promoted or inhibited HTNV replication. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that the host genes of differentially expressed circRNAs were principally involved in the innate immune response, the type I interferon (IFN) signaling pathway, and the cytokine-mediated signaling pathway. Additionally, the circRNA-miRNA-mRNA regulatory network was integrally analyzed. The data showed that there were many circRNA-miRNA-mRNA interactions in HTNV infection. By dual-luciferase reporter assay, we confirmed that circ_0000479 indirectly regulated RIG-I expression by sponging miR-149-5p, hampering viral replication. This study for the first time presents a comprehensive overview of circRNAs induced by HTNV and reveals that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of HTNV infection, thus offering new insight into the mechanisms underlying HTNV-host interaction.

Epidemiology and persistence of cervical human papillomavirus infection among outpatient women in Heilongjiang province: A retrospective cohort study.

As persistent carcinogenic human papillomavirus (HPV) infection is a prominent driver of cervical cancer, it is essential to explore HPV persistence and its associated factors for cancer screening and prevention. A retrospective cohort study was performed in outpatient women between March 2010 and 2019 in Heilongjiang, northeast China. HPV genotyping was performed by polymerase chain reaction-membrane hybridization. An unconditional logistic regression model was used to analyze the association of factors with persistence. The overall prevalence of HPV at baseline was 27.1%, with a downward trend from 2010 to 2019 (P < .0001). The most commonly observed high- and low-risk HPVs were HPV16 (N = 1094, 5.9%) and HPV11 (N = 596, 3.2%), respectively. The probabilities of 6-month persistence were high for women infected with HPV16 (P = .0001), HPV58 (P = .018), and HPV53 (P = .014), as well as for women with multiple infections (P = .009), and those who were 51 to 60 years old (P = .004) or more than 60 years old (P = .007). The probabilities of 12-month persistence were high for women infected with HPV53 (P = .017) and 51- to 60-year-old women (P = .044). HPV16 is the dominant HPV type in Heilongjiang. An age in the range of 51 to 60 years and infection with HPV53 is associated with HPV infection persistence in the Heilongjiang population.

San-Huang-Tang protects obesity/diabetes induced NAFLD by upregulating PGC-1α/PEPCK signaling in obese and galr1 knockout mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: San-Huang-Tang (ST), a classic prescription, has been clinically used to cure diabetes and diabetes-associated metabolic disorders. Established studies have reported that ST can alleviate inflammation, obesity, hyperglycemia and insulin resistance. AIM OF THE STUDY: To the best of our knowledge, here, we reported for the first time the underlying mechanistic therapeutic efficacy of the ST against nonalcoholic fatty liver disease (NAFLD) in high-fat induced obese and galr1-deficient diabetic mice. MATERIALS AND METHODS: The obese and galr1-deficient mice were treated with ST at a dose of 10 g/kg every day for three weeks. Then food intake, body weight and insulin resistance indexes were measured. Western blotting, qRT-PCR, and plasma biochemical analyses were applied. RESULTS: ST reduced food intake, body weight, blood glucose level and insulin resistance, improved glucose tolerance in obese and galr1-deficient mice. Mechanistically, we confirmed that ST protected against NAFLD through activation of PGC-1α and its downstream signaling pathways as shown by the attenuated hepatic adipogenesis and lipid accumulation, increased hepatic fatty acid oxidation, regulated plasma lipid parameters, and increased energy expenditure and metabolic function in fat and muscle. CONCLUSIONS: Reduction in food intake produced by ST may contribute to the observed metabolic effects. Our findings strongly suggest that ST might be a potential novel therapeutic drug against obesity/diabetes-induced NAFLD and other metabolic disorders.