Correlations of IL-1 and IL-6 Gene polymorphisms with hypertrophic cardiomyopathy.

The purpose of this study was to explore the correlations of interleukin-1 (IL-1) and IL-6 gene polymorphisms with hypertrophic cardiomyopathy (HCM). A total of 200 patients with HCM were enrolled as disease group, and 200 healthy individuals were included as control group. Peripheral blood was collected from all subjects in both disease and control groups. Gene polymorphisms and serum expression levels of IL-1 and IL-6 were detected, and conjoint analysis was performed based on results of cardiac color Doppler ultrasound examination. The allele distribution of IL-1 rs1878320 showed a difference between disease and control groups (P=0.000). The frequency of the allele T was lower in disease group. The genotype distribution of IL-1 rs1878320 (P=0.001) and IL-6 rs1474347 (P=0.000) in disease group was different from that in control. The frequency of TC genotype of IL-1 rs1878320 was lower in disease group, and that of CA genotype of IL-6 rs1474347 was higher in disease group. There was a difference in the distribution of the dominant model of IL-6 rs1474347 between disease and control groups (P=0.021), and the frequency of CC + CA in the dominant model was 171 (0.855). The frequency of AC haplotype of IL-1 gene was overtly higher in disease group (P=0.000), while the frequency of AT haplotype was lower in disease group (P=0.000). The IL-1 rs1516792 polymorphism had an association with serum IL-1 level (P<0.05), the IL-1 level was notably increased in the patients with the genotype AA, and it was higher in disease group. The polymorphism of rs1878320 locus in IL-1 gene was correlated with interventricular septal (IVS) (P=0.047), and IVS was reduced in the patients with TC genotype. The polymorphism of rs1516792 locus in IL-1 gene was distinctly related to left ventricular outflow tract (LVOT) (P=0.041), and LVOT was lowered in the patients with GG genotype. The IL-6 rs2069831 polymorphism was associated with left ventricular ejection fraction (LVEF) (P=0.035), and LVEF declined in the patients with TT genotype. The IL-1 and IL-6 gene polymorphisms are correlated with the susceptibility and progression of HCM.

Intra-sample reversed pairs based on differentially ranked genes reveal biosignature for ovarian cancer.

Ovarian cancer, a major gynecological malignancy, often remains undetected until advanced stages, necessitating more effective early screening methods. Existing biomarker based on differential genes often suffers from variations in clinical practice. To overcome the limitations of absolute gene expression values including batch effects and biological heterogeneity, we introduced a pairwise biosignature leveraging intra-sample differentially ranked genes (DRGs) and machine learning for ovarian cancer detection across diverse cohorts. We analyzed ten cohorts comprising 872 samples with 796 ovarian cancer and 76 normal. Our method, DRGpair, involves three stages: intra-sample ranking differential analysis, reversed gene pair analysis, and iterative LASSO regression. We identified four DRG pairs, demonstrating superior diagnostic performance compared to current state-of-the-art biomarkers and differentially expressed genes in seven independent cohorts. This rank-based approach not only reduced computational complexity but also enhanced the specificity and effectiveness of biomarkers, revealing DRGs as promising candidates for ovarian cancer detection and offering a scalable model adaptable to varying cohort characteristics.

Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature.

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

The dual role of the DREAM/G2M pathway in non-tumorigenic immortalization of senescent cells.

Anti-aging and tumorigenesis share common genes and pathways, and thus targeting these genes as part of anti-aging interventions carries the risk of tumorigenesis. It is essential to understand the gene signatures that balance tumorigenesis and aging. To achieve this goal, we analyzed RNA-sequencing data from three non-tumorigenic immortalized cell lines that spontaneously escaped from senescence. By single sample gene set enrichment assay (ssGSEA) and GSEA analysis, we found that both cell growth signaling (E2F targets, MYC targets) and tumor surveillance mechanisms (DNA repair, G2M checkpoint, mitotic spindle) were up-regulated in all three cell lines, suggesting that these genes are potential signatures for non-tumorigenic immortalization. Further analysis revealed that the 182 commonly up-regulated genes in these three cell lines overlapped with the DREAM/G2M pathway, which is known to be the upstream regulator of E2F, Myc targets, DNA repair, G2M checkpoint and mitotic spindle pathways in its cell cycle activation or inhibitory form. By western blotting, quantitative PCR and co-immunoprecipitation, we verified that both forms of the DREAM pathway are up-regulated in all three cell lines; this pathway facilitates control of cell cycle progression, supporting a new mechanism for non-tumorigenic immortalization. Thus, we propose that the DREAM/G2M pathway plays important dual roles with respect to preventing tumorigenesis in the process of immortalization. Our data might serve as the basis for the identification of new signature pathways or gene biomarkers for non-tumorigenic immortalization, and may aid in the discovery of new targets for tumor-free anti-aging drug screening.

Peptide composition analysis, structural characterization, and prediction of iron binding modes of small molecular weight peptides from mung bean.

Iron supplementation is a proactive approach to limit instances of iron deficiency anemia. This study is based on the enzymatic hydrolysis and fractionation of mung bean proteins (MBPs) followed by the determination of the Fe2+ chelating activities of these peptide-containing fractions. MBP-Fe complex was generated using a chemical chelation method and subsequently characterized. Following Sephadex G15 separation of MBPs, one of the fractions containing 10 different peptides, demonstrated maximum Fe2+ chelating activity of 39.97 ± 0.07 µg/mg. The sequences of these peptides were determined using liquid chromatography-tandem mass spectrometry. The Fe2+ ion content of the MBP-Fe complex was determined using X-ray photoelectron spectroscopy and 80% of the iron was found to be in Fe2+ oxidation state. After iron chelation, there was an increase in the peptide's particle size, with an average value of 550.67 ± 0.70 nm. This increase in size was attributed to the contributions of the amino proline and glycine, which extended the peptides to form the MBP-Fe complex. Finally, molecular docking studies revealed that Fe2+ mainly bound to carboxy-oxygen of glutamate and aspartate residues of mung bean peptides to form MBP-Fe complex. This research could serve as a scientific foundation for the development of dietary iron supplements using plant-derived peptides.

Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance.

The G-rich DNA, such as telomere, tends to form G-quadruplex (G4) structure, which slows down the replication fork progression, induces replication stress, and becomes the chromosome fragile sites. Here we described a molecular strategy that cells developed to overcome the DNA replication stress via DNA helicase regulation. The p53N236S (p53S) mutation has been found in the Werner syndrome mouse embryo fibroblast (MEFs) escaped from senescence, could be the driving force for cell escaping senescence. We revealed that the p53S could transcriptionally up-regulate DNA helicases expression, including Wrn, Blm, Timeless, Ddx, Mcm, Gins, Fanc, as well as telomere specific proteins Terf1, Pot1, through which p53S promoted the unwinding of G4 structures, and protected the cells from DNA replication stress induced by G4 stabilizer. By modified iPOND (isolation of proteins on nascent DNA) assay and telomere assay, we demonstrated that the p53S could promote the recruitment of those helicases to the DNA replication forks, facilitated the maintenance of telomere, and prevent the telomere dysfunction induced by G4 stabilizer. Interestingly, we did not observe the function of promoting G4 resolving and facilitating telomere lengthening in the cells with Li-Fraumeni Syndrome mutation-p53R172H (p53H), which suggests that this is the specific gain of function for p53S. Together our data suggest that the p53S could gain the new function of releasing the replication stress via regulating the helicase function and G4 structure, which benefits telomere lengthening. This strategy could be applied to the treatment of diseases caused by telomere replication stress.

Effects of Mind-Body Exercises for Osteoporosis in Older Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Introduction: Osteoporosis is a major cause of fractures and even life-threatening fractures in the elderly. Mind-body exercise is a beneficial intervention to improve flexibility, control body balance and reduce pain. We aimed to evaluate the effects of physical and mental exercise on osteoporosis in the elderly. Methods: Randomized controlled trials (RCTs) focusing on mind-body exercises for osteoporosis were included. Web of Science, PubMed, Science Direct, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang were searched from inception to January 2023. Outcomes included bone mineral density (BMD), bone mineral content (BMC), body balance (BB), pain, indicators of bone metabolism (BMI), lower extremity function, fearing level, and quality of life (QOL). The quality of study reporting was rated by 2 reviewers independently, and Review Manager software (version 5.3) was used for meta-analysis. Results: Thirty-nine trials with 2325 participants were included. The pooled results showed that mind-body exercises have encouraging effect on elderly people with osteoporosis, especially in aspects of BMD, BMC, QOL, improving the function of lower extremity, reducing pain and fearing level. While, dance and eight-section brocade could not improve the quality of life,or dance and eight-section brocade have no effect on BMD. Conclusions: Mind-body exercises may have potential efficacy for osteoporosis in the elderly. However, due to the poor methodological quality of the included trials, more clinical trials with precise methodological design and rigorous reporting are needed.

Analysis of Risk Factors for Postherpetic Neuralgia in Patients With Postmalignancy Herpes Zoster.

BACKGROUND: The high risk of developing postherpetic neuralgia (PHN) is associated with severe immunosuppressive diseases. A malignancy itself, as well as surgery, radiotherapy, and other treatments, can lead to changes in the immune status of the body and predispose patients with a malignancy to PHN. OBJECTIVE: To investigate the risk factors of postherpetic neuralgia in herpes zoster (HZ) after a malignant tumor and to provide better preventive strategies for clinical practice. STUDY DESIGN: A retrospective cohort study. SETTING: The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China. METHODS: Patients who developed HZ after being diagnosed with a malignant tumor in the Affiliated Hospital of Southwest Medical University from September 2018 through March 2022 were included in the research. A total of 70 patients were included, including 31 men and 39 women, aged 18- 82 years old (mean, SD: 59.77 ± 13.95). According to the occurrence of PHN, they were divided into a non-PHN (n = 46) and a PHN group (n = 24). General information about the patients was collected, including clinical data, treatment status, and prognosis. Univariate and multivariate analyses were conducted of influencing factors. RESULTS: A total of 19 factors, including gender, age, and white blood cell count, were included. A univariate analysis showed that there were differences in age, tumor stage, Numeric Rating Scale (NRS-11) score, and the use of antiviral drugs between the 2 groups; these differences were statistically significant, P <0.05. A multifactorial analysis revealed that the acute phase NRS-11 score (odds ratio [OR] = 4.21; 95% CI, 1.59-2.24, P = 0.004), antiviral drug use (OR = 0.28; 95% CI, 0.10-0.82, P = 0.020), and tumor stage (OR = 0.28, 95% CI, 0.08-0.98, P = 0.047) were statistically significant for the effect of PHN occurring in postmalignancy HZ. There was a statistically significant difference between the group with severe pain in the acute phase NRS-11 score and the group with mild and moderate pain, P < 0.05. There was a statistically significant difference between the group treated with 2 antivirals and the group not treated with antivirals, P < 0.05. LIMITATIONS: There are some limitations in our research. It was conducted at a single center, with a single race, and had a small sample size. A larger-scale study should be conducted to analyze the influencing factors of PHN in patients with herpes zoster after a malignant tumor. CONCLUSIONS: The NRS-11 score in the acute phase, whether the use of antiviral drugs in sufficient quantities, and tumor staging are the influencing factors of PHN after malignant tumors.

New Insights into the Roles of p53 in Central Nervous System Diseases.

The transcription factor p53, a widely accepted tumor suppressor, regulates the expression of many oncogenes and their downstream signaling pathways, resulting in a series of biological outcomes. Mutations and deletions of the p53 gene often occur in tumor tissues and are involved in their development. In addition to its role in tumors, p53 has a widespread expression in the brain and participates in most cell processes, such as dendrite formation, oxidative stress, apoptosis, autophagy, DNA repair, and cell cycle arrest. Therefore, abnormalities in p53 and its related signaling pathways play an important role in the diagnosis and treatment of central nervous system diseases. This review mainly discusses the latest findings regarding the role of p53 in some central nervous system diseases, such as brain tumors, Alzheimer disease, Parkinson disease, autism, epilepsy, spinocerebellar ataxia, and so on, to provide a comprehensive interpretation of the treatment of neurological diseases from a new perspective.

Bisphenol A interferes with lncRNA Fhadlos2 and RUNX3 association in adolescent mouse ovary.

Bisphenol A (BPA) has a number of adverse effects on the reproductive development of females. In particular, the mechanism of disruption of ovarian development in adolescent mice is still unclear. Based on transcriptome sequencing results, a differentially expressed lncRNA, Fhad1os2, was detected in the ovaries of BPA-exposed pubertal mice. In our study, the lncRNA Fhad1os2, localized in the ovarian granulosa cell cytoplasm, could regulate the proliferation of mouse ovarian granulosa cells. Mechanistically, the results of RNA pull-down experiments as well as mass spectrometry analysis showed that ERα, an interfering signaling molecule of BPA, could directly bind lncRNA Fhad1os2 and decrease the transcription of lncRNA Fhad1os2 in response to the estrogen-like effect of BPA. BPA exposure also caused abnormal lncRNA Fhad1os2 pulldown protein-related signaling pathways in the ovaries of adolescent mice. Furthermore, lncRNA Fhad1os2 interacted with RUNX3, a transcription factor related to follicle development and hormone synthesis. As a negative regulator, lncRNA Fhad1os2 transactivated the expression of Runx3, which in turn induced RUNX3 to positively regulate aromatase (Cyp19a1) expression in mouse ovarian granulosa cells and promote estrogen synthesis. In conclusion, our study indicates that BPA exposure interferes with ERα-regulated lncRNA Fhad1os2 interactions with RUNX3 in pubertal mice, affecting estrogen synthesis in mouse granulosa cells and contributing to premature ovarian maturation in pubertal mice.

BPA exposure enhances the metastatic aggression of ovarian cancer through the ERα/AKT/mTOR/HIF-1α signaling axis.

Long-term exposure to bisphenol A (BPA) in humans may promote ovarian cancer development. In present study, the mechanisms by which BPA mediates the aggression metastatic behavior of ovarian cancer were investigated in vitro/in vivo. The results showed that BPA (10 µM) significantly promoted the proliferation, migration and invasion of human ovarian cancer cells (ES-2 and OVCAR-3 cells); moreover, it promoted ES-2 and OVCAR-3 cell glucose uptake, lactic acid release and intracellular ATP synthesis. After administration of 5 µg/kg/day BPA, tumor volume was increased compared with that in control group. KEGG and GO enrichment analyses showed that the genes from ES-2 cell in 10 µM BPA-treated group were enriched mainly in central carbon metabolism and PI3K-AKT signaling pathway. Then, qRT‒PCR and western blotting results showed that BPA (10 µM) increased the mRNA and protein expression levels of glycolysis-related genes and mTOR, p-AKT HIF-1α and ERα in vitro/vivo; whereas this effect was reduced after treatment with the ERα inhibitor methyl-piperidino-pyrazole. Furthermore, coimmunoprecipitation and mass spectrometry showed that BPA promoted the direct interaction of ERα with lactate dehydrogenase A. These results show that BPA directly promoted the proliferation, migration and invasion of ovarian cancer cells through the ERα/AKT/mTOR/HIF-1α signaling axis to enhance glycolysis.

Three new tetrahydrobenzofuran derivatives from Ferula sinkiangensis K.M.Shen and their cytotoxic activities.

Phytochemical investigation the resins of Ferula sinkiangensis K.M.Shen yielded three new tetrahydrobenzofuran derivatives named as Sinkiangensis A-C (1-3). The structures of the new compounds were elucidated by analysis of their NMR, HRMS, and ECD spectra, and the absolute configurations were established through the comparison of experimental and calculated ECD spectra. Compound 3 exhibited moderate antitumor activities against AGS cancer cell with IC50 values of 15.6 µM. Moreover, assays demonstrated that compound 3 could induce AGS cancer cell apoptosis.

Clinical value of conventional magnetic resonance imaging combined with diffusion-weighted imaging in predicting pelvic lymph node metastasis of cervical cancer.

Background: In cervical cancer (CC), the involvement of pelvis lymph nodes is a crucial factor for patients' outcome. We aimed to investigate the value of conventional magnetic resonance imaging (MRI) combined with diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) in predicting CC pelvic lymph node metastasis (PLNM). Methods: This retrospective study included CC patients who received surgical treatments. Surgical pathology results served as the gold standard for investigating the diagnostic performance of conventional MRI combined with DWI. We analyzed the association between tumor ADC and PLNM, as well as other pathological factors. The areas under the receiver operating characteristic curves (AUCs) for ADC in assessing PLNM and pathological factors were evaluated, and optimal cut-off points were obtained. Results: A total of 261 CC patients were analyzed. PLNM patients had significantly lower tumor ADC (0.829 ± 0.144×10-3mm2/s vs. 1.064 ± 0.345×10-3mm2/s, p<0.0001), than non-PLNM CC. The agreement between conventional MRI combined with DWI and pathological results on PLNM diagnosis was substantial (Kappa=0.7031, p<0.0001), with 76% sensitivity, 94.31% specificity, and 90.8% accuracy. The AUC of tumor ADC was 0.703, and the optimal cut-off was 0.95×10-3 mm2/s. In multivariate analysis model 1, tumor ADC<0.95×10-3mm2/s was significantly associated with PLNM (OR, 2.83; 95%CI, 1.08-7.43; p= 0.0346) after adjusting for age and pathological risk factors. In multivariate analysis model 2, tumor ADC<0.95×10-3mm2/s (OR, 4.00; 95%CI, 1.61-9.89; p=0.0027), age<35 years old (OR, 2.93; 95%CI, 1.04-8.30; p=0.0428), increased tumor diameter on MRI (OR, 2.17; 95%CI, 1.18-3.99; p=0.0128), vaginal vault involvement on MRI (OR, 2; 95%CI, 1.002-3.99; p=0.0494) were independent predictors for PLNM. Tumor ADC<0.95×10-3mm2/s was significantly associated with higher risk of tumor diameter ≥4cm (OR, 2.60; 95%CI, 1.43-4.73; p=0.0017), muscular layer infiltration >1/2 (OR, 5.46; 95%CI, 3.19-9.34; p<0.0001), vaginal vault involvement (OR, 2.25; 95%CI, 1.28-3.96; p=0.0051), and lymphovascular space involvement (OR, 3.81; 95%CI, 2.19-6.63; p<0.0001). Conclusion: Conventional MRI combined with DWI had a good diagnostic performance in detecting PLNM. The tumor ADC value in PLNM patients was significantly lower than that in non-PLNM patients. Tumor ADC <0.95×10-3mm2/s, age <35 years old, increased tumor diameter on MRI, vaginal vault involvement on MRI were independent predictors for PLNM.

Gastrointestinal Langerhans cell histiocytosis with unifocal, single-system involvement in adults: Cases report and literature review.

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by unifocal, multifocal single-system, or multi-system disease that occurs in all age groups, while it primarily attacks pediatric patients. Solitary gastrointestinal (GI) LCH in adults is exceedingly rare, so we aimed to investigate GI LCH in adults with unifocal single-system involvement and clarified the clinicopathologic characteristics of this disease. METHODS: Two cases of solitary GI LCH in adults were presented, and the clinicopathologic features of this diagnosis in the literature were reviewed. RESULTS: The main diagnostic feature of LCH is the morphologic identification of the characteristic Langerhans cells with prominent nuclear grooves and abundant eosinophilic cytoplasm, accompanied by a variable number of lymphocytes, eosinophils, and plasma cells. The distinctive cells expressed S100, CD1a, and langerin (CD207) on immunohistochemistry. BRAF V600E mutations were detected in the two patients. CONCLUSIONS: Gastrointestinal Langerhans cell histiocytosis in adults with unifocal, single-system involvement is extremely rare. Most patients were asymptomatic and usually a small solitary polyp in GI tract can be observed under routine endoscopy. Although the overall prognosis of unifocal single-system LCH is favorable, long-term follow-up is still necessary to rule out systemic disease.

Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer.

BACKGROUND: Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer. CASE PRESENTATION: AC1 A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported. DISCUSSION: For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.

CircRNF144B/miR-342-3p/FBXL11 axis reduced autophagy and promoted the progression of ovarian cancer by increasing the ubiquitination of Beclin-1.

Circular RNAs (circRNAs) can regulate autophagy and ovarian cancer (OC) progression. However, autophagy-associated circRNAs involved in OC progression are largely unknown. Bioinformatics, RNA sequencing, and qRT-PCR were conducted to detect circRNF144B expression in OC as well as its relationship with patient prognosis. Functional experiments were used to determine the effects of circRNF144B on the proliferation, mobility and autophagy of OC. Double luciferase reporter assays, immunoprecipitation, and ubiquitination detection were performed to determine the molecular mechanisms of circRNF144B in autophagy and OC progression. CircRNF144B was elevated in OC tissues with low autophagy levels, and associated with poor prognosis. CircRNF144B promoted the malignant biological properties of OC cells, and inhibited the autophagy. Mechanistically, circRNF144B acts as a sponge for miR-342-3p and inhibits miR-342-3p-induced degradation of lysine demethylase 2 A (FBXL11) mRNA, leading to elevated FBXL11 protein levels. Elevated FBXL11 promoted the ubiquitination and degradation of Beclin-1, thus inhibiting autophagy. In conclusion, CircRNF144B increased FBXL11 level by sponging miR-342-3p, whereas elevated FBXL11 promoted the ubiquitination and protein degradation of Beclin-1, thus suppressing autophagy flux and promoting OC progression. Thus, circRNF144B may be an effective target for OC therapy.

Whole transcriptome analysis reveals non-coding RNA's competing endogenous gene pairs as novel form of motifs in serous ovarian cancer.

The non-coding RNA (ncRNA) regulation appears to be associated to the diagnosis and targeted therapy of complex diseases. Motifs of non-coding RNAs and genes in the competing endogenous RNA (ceRNA) network would probably contribute to the accurate prediction of serous ovarian carcinoma (SOC). We conducted a microarray study profiling the whole transcriptomes of eight human SOCs and eight controls and constructed a ceRNA network including mRNAs, long ncRNAs, and circular RNAs (circRNAs). Novel form of motifs (mRNA-ncRNA-mRNA) were identified from the ceRNA network and defined as non-coding RNA's competing endogenous gene pairs (ceGPs), using a proposed method denoised individualized pair analysis of gene expression (deiPAGE). 18 cricRNA's ceGPs (cceGPs) were identified from multiple cohorts and were fused as an indicator (SOC index) for SOC discrimination, which carried a high predictive capacity in independent cohorts. SOC index was negatively correlated with the CD8+/CD4+ ratio in tumour-infiltration, reflecting the migration and growth of tumour cells in ovarian cancer progression. Moreover, most of the RNAs in SOC index were experimentally validated involved in ovarian cancer development. Our results elucidate the discriminative capability of SOC index and suggest that the novel competing endogenous motifs play important roles in expression regulation and could be potential target for investigating ovarian cancer mechanism or its therapy.

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. CONCLUSION: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

Simultaneous determination of three antituberculosis drugs in the serum of patients with spinal tuberculosis by capillary electrophoresis.

The pharmacokinetic variations of a single drug in an antituberculosis regimen are associated with acquired drug resistance and therapy failure. This study aimed to develop a simple and effective method for monitoring the serum levels of isoniazid (INH), rifampicin (RFP), and pyrazinamide (PZA), three antibiotics used in patients with spinal tuberculosis using capillary electrophoresis (CE). A standard solution of INH, RFP, and PZA was prepared and mixed with serum to prepare the standard curve. The detection limit, quantification limit, precision, stability, repeatability, and sample recovery were determined. Then, INH, RFP, and PZA were measured from the leftover serum samples of all patients with spinal tuberculosis who were treated with 2SHRZ/2.5H2R2Z2 combined with surgery in a tertiary hospital in Qinghai from October 2015 to September 2017. A total of 107 patients with spinal tuberculosis treated using the 2SHRZ/2.5H2R2Z2 regimen combined with surgery were included in this study. All three antibiotics had linear standard curves with high correlation coefficients (R2 = 0.9997, 0.9994, and 0.9986). The recovery rates were 98.1% for INH, 96.5% for PZA, and 97.2% for RFP. The results from the serum samples showed that the plasma concentrations of INH (4.989 ± 1.692 µg mL-1) and RFP (9.400 ± 1.711 µg mL-1) reached effective therapeutic concentrations in all patients, but not PZA (33.860 ± 1.830 µg mL-1). The CE method for measuring INH, RFP, and PZA simultaneously in serum samples of patients with spinal tuberculosis is simple, rapid, and sensitive. This method is suitable for the routine monitoring of INH, RFP, and PZA concentrations in the serum of patients with spinal tuberculosis.

Cytosolic dsDNA is a novel senescence marker associated with pyroptosis activation.

Cellular senescence has become a research focus because of its dual roles in ageing and tumorigenesis. The biomarkers of senescence are essential for detecting senescent cells and understanding the ageing process and its regulation. Here, we identify cytosolic double-stranded DNA (dsDNA) as a novel sensitive biomarker for cellular senescence of mouse embryonic fibroblasts (MEFs) in response to common types of stimuli, including replicative stress, genetic modification and oxidative stress. We found that the accumulation of cytosolic dsDNA was positively correlated with the senescence process in MEFs and was detectable earlier than senescence-associated ß-galactosidase (SA-ß-Gal) staining, which is the current gold standard for senescence detection. Due to the immunogenicity of dsDNA, we further investigated the stimulation of two dsDNA sensors, cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and absent in melanoma-2 (AIM2). The results showed that the cGAS protein level did not significantly change upon senescence stimulation, while AIM2 expression was significantly upregulated in senescent cells. Surprisingly, we found that ageing-related cytosolic dsDNA induced significant pyroptosis activation in the senescent MEFs. These data reveal novel easy-to-detect biomarker for cellular senescence. The activation of downstream immunological response pathways might add new experimental evidence for inflammatory ageing.