Rapid bactericidal and anti-virulence effects of Quercus infectoria gall extract against the pharyngitis causing pathogen Streptococcus pyogenes.

This study aimed to investigate the function of KLF11 in regulating radiosensitivity (RT) in esophageal squamous cell carcinoma (ESCC) and to elucidate the underlying mechanisms. A nude mouse ESCC xenograft model was established by injecting KYSE150 cells into the left dorsal flank. Cell proliferation was assessed using cell counting kit-8 (CCK-8) and colony formation assays, while DNA damage was evaluated via a neutral comet assay. Key gene and protein expression levels were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry. Additionally, coimmunoprecipitation and immunofluorescence were employed to validate proteinprotein interactions. KLF11 expression was upregulated in both ESCC and RT-resistant tissues. At the cellular level, KLF11 expression was higher in ESCC cell lines than in the normal esophageal epithelial cell line HET-1A, with the most pronounced upregulation in KYSE150 cells and the least in TE1 cells. Notably, KLF11 knockdown under ionizing radiation exposure suppressed proliferation and colony formation, promoted apoptosis, and increased the expression of the DNA damage marker γ-H2AX as well as overall DNA damage levels in KYSE150 cells. Conversely, KLF11 overexpression in TE1 cells led to the opposite phenotype, suggesting that KLF11 confers RT resistance in ESCC by mitigating DNA damage. Further investigations revealed that KLF11 primarily repairs RT-induced DNA damage through the homologous recombination (HR) pathway rather than through nonhomologous end joining (NHEJ). Additionally, the expression of MDM2, E2F1, and RAD51 was significantly elevated in ESCC and RT-resistant ESCC tissues. Mechanistically, KLF11 promotes MDM2 expression, which inhibits E2F1 ubiquitination, thereby stabilizing E2F1 protein levels and enhancing RAD51-mediated HR repair, ultimately leading to RT resistance in ESCC. This study elucidates the critical role and molecular mechanism through which KLF11 drives radiotherapy resistance in ESCC by regulating the MDM2/E2F1 axis and enhancing HR repair, thereby providing a solid theoretical foundation and potential target for the development of KLF11-targeted radiosensitization therapies for ESCC.

Parameria laevigata (Juss.) Moldenke healing wound via PI3K/AKT/MAPK pathway.

Exploring estrogen synthesis and metabolism related markers and immune dynamics in osteoporosis-insights from single-cell RNA sequencing and Mendelian randomization.

Dachengqi decoction alleviates constipation by inhibiting the 5-HT pathway-mediated PANoptosis and improving metabolic abnormalities.

Bidirectional transfer of influenza virus between hands and environmental surfaces under multifactorial conditions.

Effects of the Dental Implant Surface Topography and Macrophage Polarisation on Osteogenesis and Angiogenesis.

Hemorrhage is a frequent manifestation in patients with moyamoya disease (MMD). Compared with MMD patients with other subtypes, patients with hemorrhagic MMD (hMMD) are at higher risk of poor prognostic outcomes, Circular RNAs (circRNAs) frequently display dysregulated expression in several human diseases. In the present study, the role of circRNAs in the pathogenesis of hemorrhage in MMD was investigated. Microarray profiling on 12 moyamoya disease samples, consisting of six hMMD and six matching ischemic MMD (iMMD) samples, was performed. Reverse transcription-quantitative PCR was then used to confirm the microarray analysis findings. Bioinformatics tools, including Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were used for further assessment. A network map of circRNA-microRNA-gene interactions was also constructed. In total, 3,607 differentially expressed circRNAs, in which 1,940 circRNAs were upregulated and 1,967 circRNAs were downregulated, were identified in hMMD (fold change ≥2.0 and P<0.05) samples. Gene Ontology revealed that the differentially expressed circRNAs were mainly involved in 'cell cycle phase transition' and 'mitotic cell cycle phase transition'. In addition, the ubiquitin mediated proteolysis pathway was found to be the most significantly enriched pathway in hMMD samples. The results of the present study suggested that clusters of circRNAs were differently expressed in hMMD compared with those in iMMD samples, which provides novel insights into hemorrhage in moyamoya disease pathophysiology and potential targets for future therapy.

Although elevated soluble uric acid (SUA) levels enhance the production of IL-1β in macrophages stimulated with monosodium urate (MSU) crystals, the underlying mechanism remains unelucidated. The aim of this study was to examine the effects of SUA on inflammatory response-related gene expression in lipopolysaccharide-primed and MSU crystal-stimulated macrophages using mouse macrophage-like J774.1 cells. Differential gene expression in SUA-pretreated and untreated group cells was analyzed by RNA sequencing and quantitative reverse transcription-polymerase chain reaction. SUA upregulated the genes related to pro-inflammatory reactions and downregulated those related to anti-inflammatory reactions. SUA also upregulated M1 pro-inflammatory macrophage-related genes and enhanced mRNA expression of CD44 responsible for phagocytosis of MSU crystals. These results suggest that SUA enhances gouty inflammation via promoting the expression of genes related to pro-inflammatory reactions, polarization toward the M1 phenotype, and MSU crystal phagocytosis in macrophages. Enhanced expression of the transcription factor genes Nfkb1 and Stat1 may underlie the SUA-induced M1 polarization and resulting enhancement of inflammasome activation and IL-1β transcription.

The presence of Aedes aegypti in healthcare facilities represents a significant epidemiological threat, as it is the primary vector of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses. In the absence of effective alternatives to chemical insecticides for eliminating adult mosquitoes, healthcare facilities may become focal points for arbovirus transmission, compromising the safety of patients and healthcare employees. Vector control remains the main approach for mitigating arbovirus transmission. This study investigated the impact of an effective integrated control program (ICP) implemented in a hospital in Recife, Pernambuco, Brazil, where arbovirus circulation in mosquitoes was detected. Entomological monitoring was conducted through mechanical aspiration inside the Hospital das Clínicas (HC). Specimens were counted, identified, grouped by species, classified according to blood-feeding status, and recorded by capture station. Viral infection was assessed using nonstructural protein 1 (NS1) by enzyme-linked immunosorbent assay (ELISA) and a triplex reverse transcription quantitative polymerase chain reaction (RT-qPCR) for the detection of DENV, ZIKV, and CHIKV. Infection rates were calculated using the minimum infection rate (MIR). ICP actions included environmental management, larvicide application at breeding sites, ovitraps to collect and destroy eggs, toxic sugar baits, and intensified mechanical aspiration to eliminate adult mosquitoes. Three phases were defined: pre-ICP (initial survey), ICP (all actions), and post-ICP (larvicidal treatment). During the ICP, a sustained reduction in female mosquito density was observed, reaching 99% for Ae. aegypti and 88% for Culex quinquefasciatus. Six months after ICP, ELISA detected infected females in 9 of 14 stations (64%). The MIR for Ae. aegypti decreased from 50 to 44, while Cx. quinquefasciatus showed a slight increase. RT-qPCR revealed 11 ZIKV-positive pools (eight Ae. aegypti and three Cx. quinquefasciatus). After 12months of ICP, only one Ae. aegypti DENV-positive pool was detected by both techniques in a single station (pediatrics). Both techniques detected infection even in pools containing a single female, underscoring their high sensitivity. At 18months of ICP, all pools tested negative for arboviruses. Molecular and antigen-based approaches confirmed the mitigation of arbovirus circulation in hospital-associated mosquitoes, demonstrating that the continuous elimination of Ae. aegypti females (> 99%) is critical in these settings to prevent nosocomial transmission.

CC8, a heterodimeric disintegrin from Cerastes cerastes snake venom, triggers apoptosis and restrains the dissemination of human glioblastoma cells.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent itching, predominantly affecting children but also impacting adults. Geraniol, a monoterpene alcohol found in various aromatic plant-based essential oils, possesses a pleasant rose-like scent. This study aimed to investigate the therapeutic potential of geraniol in a mouse model of atopic dermatitis by elucidating its anti-inflammatory and immunomodulatory properties.Mice were subjected to 2% 2,4-Dinitrochlorobenzene (DNCB) to induce AD, and treated with both oral and topical administrations of prednisolone and geraniol from day 7 to day 19. Macroscopic assessments of ear and dorsal skin, as well as ear thickness, were conducted on days 0, 7, and 19. Total leukocyte count (TLC) and differential leukocyte count (DLC) were measured in blood samples using an automatic hematology analyzer. Ear tissues were analyzed for mRNA expression levels of IL-4 and IL-13 via reverse transcription quantitative polymerase chain reaction (RT-qPCR), and molecular docking studies were performed to evaluate the binding affinity of geraniol to these cytokines. Histopathological examination using hematoxylin and eosin staining was conducted on ear and dorsal skin tissues to assess eosinophil and mast cell infiltration, as well as epidermal thickness. The results demonstrated that both oral and topical geraniol significantly alleviated AD-like symptoms. Geraniol treatment led to a reduction in DLC and TLC levels in the blood, as well as downregulation of IL-4 and IL-13 expression in ear tissue. In silico studies revealed that geraniol exhibited moderate binding affinities of -4.5 kcal/mol with IL-4 and -4.9 kcal/mol with IL-13. Histopathological analysis indicated a reduction in epidermal thickness and infiltration of mast cells and eosinophils in geraniol-treated mice.In conclusion, geraniol effectively alleviated atopic dermatitis in mice by reducing clinical scores, inflammatory cell infiltration, epidermal thickening, and regional downregulation of IL-4 and IL-13 mRNA expression. The in silicodocking studies support the hypothesis of a potential Th2-modulatory effect of geraniol.

Levistolide A induces endoplasmic reticulum stress-triggered apoptosis via ATF6 in triple-negative breast cancer.

The jujube (Ziziphus jujuba Mill.) is a significant economic fruit tree, valued for its nutritional and medicinal properties. However, advances in functional genomics are hindered by the lack of an efficient transformation system. To overcome the limitations of conventional explant, we established a fruit-pulp-derived, callus-based Agrobacterium-mediated transformation system using fruit-pulp harvested 50 days after pollination. Through orthogonal experimental design, 6-benzylaminopurine and 2,4-dichlorophenoxyacetic acid were identified as key regulators for inducing high-quality, friable callus in two jujube genotypes, 'JZ60' and 'LWCZ'. This system revealed significant genotype-specific variation in auxin requirements for callus proliferation and in differential antibiotic sensitivity. Transformation efficiency, as evaluated by fluorescence screening, was primarily determined by acetosyringone concentration and the binary vector architecture. The results revealed that the compact pCY (kanamycin resistance) vector achieved higher transformation efficiency (up to 77.8%) than pCAMBIA1301, whereas the pCAMBIA1301 (hygromycin resistance) vector enabled more uniform transgene expression. Integration and expression of the ZjCBF3 transgene were confirmed by polymerase chain reaction (PCR), reverse transcription quantitative PCR, and green fluorescent protein fluorescence assays. This study established a fruit-pulp-based callus transformation system for jujube, providing a rapid platform for its functional genomic studies.

The global burden of tick-borne viral diseases (TBVDs) has significantly increased in recent decades, emerging as a critical public health priority due to their diverse pathogenic profiles, severe disease outcomes, and therapeutic challenges. Within the expanding landscape of tick-borne pathogens, the Orthonairovirus genus has gained particular scientific attention for its members' zoonotic capacity and clinical virulence. Orthonairoviruses are arboviruses that infect humans and animals, posing a serious threat for the spread of zoonotic diseases. Huangpi tick virus 1 (HpTV-1), a member of the genus Orthonairovirus, has been detected in ticks. Haemaphysalis longicornis collected in 2023 from Central China were pooled for RNA-seq and reverse transcription quantitative polymerase chain reaction (RT-qPCR) screening. Genomes were assembled and viruses isolated in suckling mice and Vero E6. Replication kinetics, mouse pathogenesis, and 223 livestock sera were assessed. In the present study, we isolated HpTV-1 from Haemaphysalis longicornis in Central China. Viral genome and phylogenetic analyses placed HpTV-1 in a distinct clade close to the Songling and Tamdy viruses within the Nairoviridae family. In vitro experiments demonstrated that HpTV-1 infects a wide range of animal and human cell lines. Importantly, all infected C57BL/6 mice survived without overt signs of severe disease while developing only minor pathological lesions in specific organs (liver, spleen, and lungs). Serological surveys revealed HpTV-1 antibodies, including neutralizing antibodies, in 16.1% of the goats, suggesting that HpTV-1 can infect livestock. These findings suggest that HpTV-1 is an Orthonairovirus capable of infecting animals, highlighting its potential risk and the need for enhanced surveillance and research, particularly in Central China and other endemic regions.

Aquilegia oxysepala is a characteristic wildflower of Northeast China, which has great application potential owing to its unique floral morphology and strong adaptability. The R2R3-MYB is one of the largest transcription factor families and has important roles in anthocyanin biosynthesis. A total of 90 AoMYBs were identified from A. oxysepala and divided into 29 subfamilies via phylogenetic analysis. Using bioinformatics methods, a systematic analysis was conducted on the physicochemical properties, gene structures, conserved motifs, and other characteristics of these genes. Based on the transcriptomic data of A. oxysepala and A. oxysepala f. pallidiflora across different floral developmental stages, 32 differentially expressed genes (DEGs) belonging to the R2R3-MYB family were screened, and their expression patterns were analyzed. The results indicated that AoMYB32 and AoMYB34 were significantly upregulated only at the pre-anthesis stage (PrA) in A. oxysepala, whereas their expression levels remained relatively low in A. oxysepala f. pallidiflora during the same stage. Correlation network analysis indicated that AoMYB34 was positively correlated with six functional genes associated with anthocyanin synthesis, namely PAL-2, C4H, 4CL, CHS, F3′5′H, and ANS. Reverse transcription quantitative PCR (RT-qPCR) validation revealed that AoMYB32 and AoMYB34 exhibited significant upregulation at the PrA stage in A. oxysepala, while their expression showed no obvious fluctuations across the entire flowering period in A. oxysepala f. pallidiflora. In summary, it is postulated that AoMYB32 and AoMYB34 are candidate genes associated with flower color variation formation of A. oxysepala. This study provides a theoretical basis and genetic resources for deciphering the mechanism of flower color formation and facilitating flower color improvement breeding in A. oxysepala.

Dental caries demineralises the enamel and dentine of the teeth, and as infection progresses it can lead to pulpal inflammation, infection and severe pain. To determine and compare the level of mRNA expression of Toll-like receptors ((TLR)-2, TLR-4 and TLR-9), tumour necrosis factor (TNF)-α, interleukins ((IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23) as well as markers of dentinogenic (dentine matrix protein (DMP)-1, dentine sialophosphoprotein (DSPP)), regulatory (nuclear factor-kappa B (NF-κB1), mitogen activated protein kinase (MAPK1)), proliferative (mitogen activated protein kinase (MKi)) and stemness (sex determining region Y-box2 (SOX2)) between non-carious and carious dental pulp tissues. This study undertook a comprehensive analysis of inflammatory markers including TLR-2, TLR-4, TLR-9, TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23, as well as markers of dentinogenic DMP-1, DSPP, NF-κB1, MAPK1, proliferative MKi and stemness SOX2 processes in healthy and carious pulp tissues using quantitative real-time reverse-transcription polymerase chain reaction. We found higher levels of TLR-2, TLR-4, IL-6, IL-8, IL-17A, IL-23A, along with NF-κB1 and MKi67 in the carious pulps (p < 0.05). The concurrent upregulation of IL-17A and IL-23A may suggest the activation of the IL-23/IL-17 signalling axis in the carious pulps, a point underreported in the literature. These findings highlight the crucial role of the immune system in pulpal inflammation and potential implications in developing targeted molecular treatments, supporting the need for further translational research.

To assess the therapeutic relevance of BRIP1 in gastric cancer (GC), we examine its functional role in conferring resistance to anoikis within GC cells and elucidate the oncogenic signaling pathways modulated by BRIP1. By integrating the Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases with Least Absolute Shrinkage and Selection Operator (LASSO) regression, a novel risk score to stratify GC patients based on prognosis was generated, and a significantly differentially expressed gene, BRIP1, was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression associated with apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT) was quantified via RT-qPCR and Western blot (WB). 5-Ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assays were conducted to quantify proliferative activity. The protein level in axillary tumor tissues of nude mice was detected by immunohistochemistry (IHC). We established an eight-gene anoikis-related prognostic risk assessment model (DUSP1, VCAN, P3H2, TXNIP, BRIP1, FGD6, GPX3, and RLN2) for GC. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Among these genes, BRIP1 showed significant differential expression between tumor and normal tissues, as well as normal gastric mucosal epithelial cells and GC cells. Mechanistically, BRIP1 conferred anoikis resistance to GC cells by suppressing the generation of reactive oxygen species (ROS). We found that the PI3K inhibitor LY294002 counteracted BRIP1-driven oncogenic effects, which was evidenced by restored expression of key regulators governing apoptosis, cell cycle progression, and EMT, in addition to suppressed proliferation in GC cells. BRIP1 is postulated to function upstream of the PI3K/Akt signaling cascade. This study establishes a risk scoring model and identifies BRIP1 as a potential prognostic marker for GC.

Crohn disease (CD) is a chronic, recurrent inflammatory bowel disease. Mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as promising cell-free treatments for CD. In this study we aimed to investigate the therapeutic effect and potential mechanisms of MSC-Exos derived from induced pluripotent stem cells (iPSCs) (iPSC-MSC-Exos) in patients with colitis. iPSC-MSC-Exos were administered intraperitoneally to mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. The colonic stem cell markers Lgr5 and Bmi1, and the proliferation marker Ki-67 were assessed by immunofluorescence. Lamina propria mononuclear cells (LPMCs) were isolated from the mouse colons and analyzed by flow cytometry. Furthermore, microarray analysis was performed to identify the differential expression of micro RNAs (miRNAs) in the iPSC-MSC-Exos. iPSC-MSC-Exos with micro RNA (miR)-34a-5p overexpression (Exo-OE) or knockdown (Exo-KD) were used to treat colitis in the mice. The candidate targets of miR-34a-5p and its downstream signaling pathways were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The iPSC-MSC-Exos migrated to the inflamed colon and protected the colon stem cells against inflammatory damage, promoted epithelial cell proliferation, and decreased the infiltration of proinflammatory Th1/9/17, CD4 + tumor necrosis factor alpha (TNF-α)+, and macrophage cells while increasing anti-inflammatory T-regulatory (Treg) and B-regulatory (Breg) cells to alleviate TNBS-induced colitis in the mice. The therapeutic effect was sustained for 7 days after a single injection. MiR-34a-5p Exo-OE magnified this effect, whereas Exo-KD abolished it. The iPSC-MSC-Exos also inhibited the proliferation and migration of CD4 + LPMCs isolated from patients with CD. The miR-34a-5p expression was significantly elevated in the iPSC-MSC-Exos, which inhibited PPP2R3A expression by directly targeting its 3' untranslated region (3'-UTR). MiR-34a-5p Exo-OE significantly decreased the expression of PPP2R3A while increasing the expression of the Wingless-related integration site (Wnt) signaling ligands of β-catenin (Wnt/β-catenin signaling) and CD44. iPSC-MSC-Exos ameliorated colitis and promoted mucosal healing in a TNBS-induced CD-like model by activating Wnt/β-catenin signaling via miR-34a-5p, which targets PPP2R3A.

Previous studies have demonstrated a close association between diabetic nephropathy (DN) and lactic acid metabolism; however, the underlying mechanisms remain unclear. This study aimed to investigate the role of lactic acid metabolism-related biomarkers in the pathogenesis of DN. The DN training and validation datasets were obtained from public databases, while lactic acid metabolism-related genes (LRGs) were sourced from the literature. Using a comprehensive bioinformatics approach, we screened for potential biomarkers. Subsequent analyses included nomogram construction, functional enrichment, immune cell infiltration profiling, regulatory network mapping, drug target prediction, and molecular docking to elucidate the biomarkers' roles in DN pathogenesis. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to validate biomarker expression levels in clinical samples. Through a comprehensive analysis of bioinformatics methods, we identified two biomarkers-PTGS2 and NFE2L2-as significant candidates in DN. The nomogram demonstrated robust predictive efficacy, validating their utility. NFE2L2 and PTGS2 were positively correlated with the five signal pathways, such as hypoxia and IL2 STAT5 signaling. Both PTGS2 and NFE2L2 had the highest positive correlation with T follicular helper cells (correlation coefficient (cor) = 0.49, p<0.01, and cor = 0.54, p<0.01). Two biomarkers predicted multiple miRNAs and transcription factors (TFs), such as miR-144-3p, GATA2, and GATA3. Drug-target analysis highlighted high-affinity interactions for NFE2L2 -lagascatriol and PTGS2 -cimicoxib, further supported by molecular docking. Finally, RT-qPCR confirmed significantly elevated expression of PTGS2 and NFE2L2 in DN samples compared to controls (p<0.05), aligning with bioinformatics predictions.