This study comprehensively investigated the bioactive compounds of Rheum emodi and their potential therapeutic impact on rheumatoid arthritis (RA). Initial screening identified six unique compounds with favourable drug-likeness, which collectively targeted 320 proteins. Network analysis revealed 27 gene overlaps with RA, highlighting five hub genes (MET, NFKB1, ABCG2, PARP1, ABCB1), wherein MET, NFKB1, and PARP1 were significantly upregulated in RA. Pathway enrichment analysis implicated these genes in lipid transport, cell communication, and key signa;ling pathways (NF-kappa B, PI3K-Akt, ABC transporters). Molecular docking and dynamics simulations indicated emodin exhibited strong, stable binding to MET and ABCG2 hubs. In vitro, R. emodi extract inhibited SW-982 cell viability (IC50 = 21.1/ mu g/mL), induced apoptosis and ROS, and reduced cell migration. qRT-PCR confirmed downregulation of MET and NFKB1 post-treatment. Collectively, the findings support multi-target inhibitory actions of R. emodi extract in RA, underpinned by gene, pathway, and cellular effects.
Marfan syndrome (MFS) exhibits an irregular dominant connective tissue defect with clinical variability. It generally affects the skeletal, ocular, and cardiovascular systems. The variants in the FBN1 gene are the main causes of this disease. In this study, Exome sequencing and Sanger sequencing were utilised to explore the pathogenic variant of a Chinese MFS family. A nonsense variant c.612C>A (C204X) of FBN1 was identified in the both affected brothers with different clinical phenotypes and in their unaffected mother. Nevertheless, the variant was absent in 200 healthy controls. The further cell function experiment demonstrated that the FBN1 C204X mutant exhibited a lower level of mRNA and protein expression than the wild-type. The results supplemented the data of genotype-phenotype relationships in regard to FBN1 variants, and expanded the FBN1 variants spectrum in Asian populations. This study confirmed that MFS was a semidominant genetic disorder probably involving the special hereditary modifiers and environmental risk factors.
Brain Derived Neurotrophic Factor (BDNF) plays a significant role in the synaptic plasticity and memory processes. Its contribution to the pathogenesis of cognitive symptoms in pathological situations has a direct impact on memory function in both healthy and diseased animals. For this purpose, computational tools (Provean with mutant score cut-off -2.5 and PolyPhen 2 score ranging from 0 to 1) have been used in this study to evaluate the deleterious or damaging effect of non-synonymous SNPs (nsSNPs) that are harmful to the structure and function of the BDNF gene. Results of the present study found a total of 50 highly deleterious SNPs by both the tools which could be disease susceptible.
Disulfidoptosis, an emerging programmed cell death modality form, is linked to long non-coding RNAs (lncRNAs). This study aimed to develop a disulfidoptosis-related lncRNA (drlncRNA) predictive algorithm for endometrial carcinoma of uterine corpus (UCEC) and explore its association regarding overall survival (OS) and the tumour immune microenvironment (TME). Molecular profiling and patient-derived clinical information of UCEC individuals diagnosed in The Cancer Genome Atlas (TCGA) were analysed. Linear correlation coefficient identified drlncRNAs, and Cox and LASSO regression established a 4-drlncRNA prognostic model. Patients were grouped by risk score, with high-risk groups showing shorter OS. The model independently predicted OS, and high-risk patients had higher tumour mutation burden (TMB) and altered immune infiltration within tumour tissues. This drlncRNA model effectively predicts UCEC prognosis, aiding personalised treatment.
In the current study, the researchers cultured the hBMSCs in alpha-DMEM supplemented with foetal bovine serum. After an incubation period of 48 hours the exosome-containing cell culture supernatants were collected and subjected to PEG-based vesicle enrichment for purification. The enriched exosomes derived from hBMSCs, with or without miR-6087, were used to treat osteosarcoma (U2OS) cells. The cell viability was tested using Transwell invasion assay, CCK-8 test and scratch migration assay. The Western blotting and RT-PCR were employed to determine the levels of HSP70/ALIX and miR-6087 in the exosomes. The HBMSC derived exosomes exhibited significant impact on the growth of U2OS cells. The growth of tumour cells was notably inhibited when miR-6087 in exosomes was suppressed. This study marks the initial instance where the researchers successfully showcased the ability of exosome derivatives from hBMSCs to prevent the U2OS cells proliferation, through the modulation of miRNA-6087. The findings present a novel perspective on the involvement of hBMSCs in tumour advancement.
This study investigated physiological effects of miRNA-146a in Kawasaki disease with THP-1 cells. An inflammatory Kawasaki disease-like environment was established in THP-1 cells with lipopolysaccharide induction, which were then transfected with miRNA-146a mimics or a control. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that miRNA-146a significantly downregulated the expression of key pro-inflammatory cytokines, including interleukin (IL)-1 beta, IL-6, and tumour necrosis factor (TNF)-alpha. After Annexin V/PI application, flow cytometric technique was used to quantify apoptosis, revealing a marked reduction in both early and late apoptotic cells following miRNA-146a overexpression. Western blot analysis further indicated increased anti-apoptotic B-cell lymphoma 2 (Bcl-2) expression, as well as decreased caspase-3 activation and BCL2-Associated X (Bax) expression. By demonstrating miRNA-146a's critical function in attenuating inflammatory responses and suppressing apoptosis, this study positions it as a promising novel therapeutic target for Kawasaki disease.
Patients undergoing elective laparoscopic abdominal surgery were enrolled from January to December 2022 and randomly assigned 1:1 to daytime surgery (8:00 to 12:00 hours) and nighttime surgery (18:00 to 22:00 hours). Sleep quality was assessed using the Pittsburgh Sleep Scale (PSQI), and melatonin concentrations were measured in urine. The dose of remifentanil and propofol in the daytime group was higher than that in the night group, and the difference was statistically significant (P<0.05). Compared with the daytime group, PSQI in the night group was higher at 3 days after surgery, and urine melatonin concentration was lower at 1 and 3 days after surgery (P<0.05). Compared to the daytime group, the nighttime group also showed a significant increase in SpO2, MAP, and HR levels. Compared to the daytime group, the nighttime group showed a statistically significant decrease in the occurrence rate of difficulty falling asleep, early awakening, feeling unwell after waking up, interrupted sleep, and urinary retention.
Esophageal adenocarcinoma (EAC) is among the most aggressive and lethal malignancies in gastrointestinal tumours. Recently, immunotherapy has gained prominence, highlighting the need for systematic exploration of immunerelated genes (IRGs) in EAC to advance treatment and prognostication. Differential gene expression profiles from EAC and adjacent tissues were retrieved through applying the TCGA database. Cross-referencing with immune gene lists from TCGA and GEO (GSE19417) was to identify differentially expressed IRGs (DEIRGs). The researchers established a prognostic mode via employing lasso-penalised Cox regression and this model was validated using GSE19417, which also assessed six tumour-infiltrating immune cell subtypes. A total of 259 DEIRGs were identified, with 10 significantly correlating with overall survival (OS) in EAC. Functional enrichment analysis revealed involvement in extracellular region and cytokine-cytokine receptor interaction. High-risk scores and the AJCC stage were found to be independently linked with worse OS. The study underscores the prognostic relevance of IRGs, informing future EAC prognosis and immunotherapy strategies.
The researchers have assessed the effect of Bushen Zhichan Formula (BSZCF) on the neurofunction and Fas/Fas ligand (FasL) signal in rats with Parkinson's disease (PD) by regulating microglial polarisation. Sham group, PD group, BSZCF group and DBSJ (levodopa and benserazide hydrochloride tablets) group were established for random allocation. The pole-climbing time, neurological function score, tumor necrosis factor-& aacute; and interleukin-6 levels in the substantia nigra, ionised calcium-binding adaptor molecule 1 (IBA1) cluster of differentiation 86 (CD86) cell count, CD86/CD206 ratio and Fas and FasL protein expressions significantly declined, whereas the Tamm-Horsfall protein expression, hanging score, and number of IBA1+CD206+ cells in the substantia nigra significantly increased in BSZCF and DBSJ groups compared to those in the PD group (P<0.05). BSZCF can alleviate neurological injuries and repress dopaminergic neuron loss mediated by the Fas/FasL signalling pathway.
The researchers aimed to find the mechanism of IL-17-producing T helper (Th17) or Treg imbalance in recurrent spontaneous abortion (RSA). Peripheral blood was collected from 8 RSA patients and 6 healthy pregnant women, and peripheral blood mononuclear cells were isolated. Flow cytometry was used to analyse the expression of Th17 cells, Treg cells and CD154 molecules in lymphocytes. Compared with healthy pregnant women, Th17 cells and CD154 in peripheral blood mononuclear cells of RSA patients were significantly increased, while Treg cells were significantly decreased. The up-regulation of CD154 can lead to Th17/Treg imbalance and RSA, and can provide a new direction for the treatment of RSA.
This work explored the potential regulatory role of the miR-146a-5p/Notch2 signaling axis in directing the cementoblast-like differentiation of mesenchymal stem cells originating from human dental pulp. Cells received transfection with miR-146a-5p mimics or inhibitors, their respective negative controls, or a Notch2-knockdown plasmid, in addition to a non-transfected baseline group. Suppressing miR-146a-5p activity enhanced ALP levels, facilitated matrix mineral deposition, and elevated the expression of cementogenesisassociated genes (Notch2, CAP, BSP, OCN, OPN). In contrast, miR-146a-5p overexpression or interference with Notch2 resulted in reduced ALP activity and diminished mineralization and marker expression. A dual-luciferase assay confirmed that miR-146a-5p directly binds to the 32 UTR of Notch2. Collectively, reducing miR-146a-5p levels releases Notch2 from repression and accelerates cementoblastic commitment, highlighting the miR-146a5p/Notch2 pathway as a promising target for periodontal cementum regeneration.
Acute coronary syndrome (ACS) is a leading cause of death and illness worldwide. Previous studies explored connection between NFKB1 gene polymorphism and its role in development of atherosclerosis. The aim of the present study was to know the correlation of NFKB1 gene polymorphism with acute coronary syndrome (ACS). Comprehensive clinical data, biochemical profiles, electrocardiograms, and blood samples were collected from 92 patients with ACS and NFKB1 gene polymorphism was analysed using polymerase chain reaction. In this study, male were more than female patients and in the age group of 61-70 years. Chest pain and dyspnea were common symptoms and diabetes and high blood pressure were risk factors. Non-ST-segment elevation myocardial infarction was the frequent ECG finding. No mutations were detected in NFKB1 gene exons 2 and 10, indicating this particular genetic variant was not linked to ACS in the studied population.
The present study was designed to investigate potential effects and mechanisms of Shen-su-yin (SSY) on lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats. Forty-eight rats were randomly divided into 4 groups of control (Ctrl), LPS-induced ALI (ALI), low- (SSY-LD) and high- (SSY-HD) dose SSY-treated ALI group. Twentyfour hours after SSY administration, bronchoalveolar lavage fluid determination, Western blot analysis, and histopathological analysis were performed. The results showed that SSY administration 24 hours post-treatment showed improved lung histopathology, reduced pro-inflammatory and oxidative markers, and increased antiinflammatory and antioxidative cytokines. SSY also inhibited NF-& ecirc;B signalling and activated the Keap1-Nrf2-ARE pathway. The high-dose SSY group exhibited significant improvements. The results indicate that the preventive use of SSY can alleviate ALI through the anti-inflammatory and antioxidant effects mediated by inhibition of NF-& ecirc;B signalling pathway and activation of Keap1-Nrf2-ARE signalling pathway, respectively
Mitochondrial dysfunction is a key contributor to nonsyndromic hearing loss (NSHL). This review aims to synthesise current knowledge on how mitochondrial mechanisms, including mtDNA mutations, oxidative stress, and ATP deficiency, influence auditory function. By analysing recent studies, the researchers highlight the role of genetic diagnostics (for example, next-generation sequencing) in uncovering mtDNA variants linked to NSHL and the interplay between oxidative stress and mitochondrial damage in cochlear cells. The review concludes by emphasising the need for innovative therapeutic strategies targeting mitochondrial dysfunction to mitigate NSHL.
Infections caused by drug-resistant pathogens in intensive care units (ICUs) pose a global health threat with 40 to 60 percent mortality rates. This study characterised seasonal patterns and genomic features of ICU-acquired multidrug-resistant organisms through systematic environmental and clinical sampling across four seasons (spring to winter). Whole-genome sequencing (performed on Illumina NovaSeq and Nanopore platforms) revealed significant seasonal variations in resistance gene distribution. Autumn isolates showed 100 percent blaCTX-M-3 carriage, strongly associated with increased bed turnover (59.4% rise, p<0.001) and extended disinfection intervals (OR=2.31, 95% CI: 1.47-3.62). Winter demonstrated 75 percent qacE Delta 1-positive clones with elevated resistance indices (0.82 +/- 0.08 versus 0.3 +/- 0.2, p<0.001). These findings support two seasonally-adjusted interventions, that is, antibiotic stewardship during autumn peaks, and enhanced disinfection protocols for qacE Delta 1-positive clones in winter.
This study explores the expression of YWHAE and CDC6 in colorectal cancer (CRC) and their association with clinicopathological features and prognosis. mRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA), and correlations with clinical data were analysed. Tissue microarrays from CRC patients were assessed using RNAscope and immunohistochemistry (IHC). Survival outcomes were evaluated by Kaplan-Meier and COX regression analyses. Both YWHAE and CDC6 mRNA were significantly upregulated in CRC tissues (P < 0.05) and showed a positive correlation (P < 0.01). IHC revealed high protein expression of YWHAE and CDC6 in CRC tissues, which was significantly associated with lymph node metastasis, pathological stage, and reduced survival (P < 0.05). Multivariate analysis confirmed both as independent prognostic factors. These findings suggest that YWHAE and CDC6 play a role in CRC progression and may serve as valuable biomarkers and potential therapeutic targets.
This study aimed to explore pathogenic genes associated with pediatric dyslipidemia using second-generation sequencing and analyse their correlation with clinical phenotypes. The researchers retrospectively analysed clinical and genetic data from 20 pediatric patients. Skin xanthoma (60%) and hypercholesterolemia (55%) were common presentations. Second-generation sequencing targeting lipid metabolism genes was performed. Causative mutations were identified in 14 of 18 tested patients, involving genes such as LDLR, LPL, ABCG5, ABCA1, and HFE2. Distinct genotype-phenotype correlations were observed, for example, ABCG5, HFE2, LDLR, and ABCA1 mutations were associated with xanthomas, while LPL and LDLR mutations were linked to hypertriglyceridemia and hypercholesterolemia patterns, respectively. These findings suggest that pediatric dyslipidemia presents with diverse clinical phenotypes that are strongly associated with mutations in specific genes. Molecular genetic diagnosis based on sequencing significantly improves clinical assessment and deepens the understanding of these disorders, offering valuable guidance for early detection and precision medicine.
The current study investigated Tomentin-A as an inhibitory agent against lung cancer cells. Tomentininducing antiproliferative effects on the A549 cisplatin-resistant NSCLC line were examined using an MTT test, revealing cell colonies through microscopy. Apoptosis-inducing activity was assessed via DAPI labelling and Western blotting, while intracellular-ROS and mitochondrial-membrane-potential were measured using DCFH-DA and Rh-123 assays. Migration and invasion were evaluated using transwell assays, and Western blotting explored Tomentin-A's regulation of the Ras/Raf/MEK/ERK pathway. Results showed that Tomentin substantially (p<0.05) suppressed A549 drug-resistant NSCLC cell growth and targeted colonies dose-dependently. DNA condensation and fragmentation were observed in nuclear morphology after DAPI labelling, while ROS and MMP assays indicated oxidative stress-induced cell death. Migration and invasion investigations demonstrated Tomentin's strong inhibitory effects, and Western blotting showed considerable downregulation of phosphorylated Ras, Raf, MEK, and ERK. These findings highlight Tomentin's potential as a multifunctional treatment for drug-resistant NSCLC, warranting further clinical investigation.
The purpose of this study was to build advanced genetic diagnosis by identifying biomarkers associated with Myocardial Infarction (MI) related disorders and to investigate the genetic predisposition to MI and genes causative. For this investigation and identification, the researchers have chosen genes most predominant in the Indian population towards cardiovascular disorders and designed a customised panel comprising a set of selected genes implicated in cardiovascular health, atherosclerosis, and thrombosis, which is used for further sequencing and screening of the subjects involved in the study. The researchers observed mutations in genes CELSR2, MRPS6 and APOB show clear involvement in MI and cardiovascular related disorders and identified as the most repetitive across all the subjects. This comprehensive analysis from cases to controls can contribute to valuable insights into developing precision medicine strategies focused on examining the individual genes and variants included with MI to elucidate their specific contributions to MI-related conditions and developing Polygenic risk scores.
Pai syndrome (PS) is a multiple phenotypic rare syndrome of cleft lip and palate with an unclear diagnostic criteria and etiology. This research reported the clinical phenotypes for two cases of PS and collected the two trios families. Genomic DNA was extracted from blood and sequenced by whole-genome sequencing (WGS) on two probands and their parents. Variant Effect Predictor (VEP) was utilized to determine causative variants of the patients. Identified causal mutations were further confirmed by Sanger Sequencing. WGS analysis identified 153 single-nucleotide polymorphisms (SNPs) and 69 indels in patient 1, while 165 SNPs and 57 indels were identified in patient 2. After multiple filtrations, the researchers identified four de novo missense mutations (FLG, DHX57, ANXA7, and GOLGA3) in patient 1 and two de novo missense mutations (PRSS23 and USP7) in patient 2. These findings still need to be validated but already provide more information on the genetic basis.
