Low frequency sinusoidal electromagnetic fields promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells by modulating miR-34b-5p/STAC2.

Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis.

Upregulation of hsa-miR-141-3p promotes uterine cervical carcinoma progression via targeting dual-specificity protein phosphatase 1.

We aimed to explore the aberrant expression status of hsa-miR-141-3p and dual-specificity protein phosphatase 1 (DUSP1) and their relative mechanisms in uterine cervical carcinoma (UCC).Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was conducted to detect the expression of hsa-miR-141-3p. Immunohistochemical (IHC) staining was performed to examine the expression of DUSP1 in UCC. Gene chips and RNA-seq datasets were also obtained to assess the expression level. Integrated standardized mean difference (SMD) was calculated to evaluate the expression status of hsa-miR-141-3p in UCC tissues comprehensively. DUSP1-overexpression and hsa-miR-141-3p-inhibition HeLa cells were established, and CCK-8, transwell, wound healing, cell cycle, and apoptosis assays were implemented. The targets of hsa-miR-141-3p were obtained with online tools, and the combination of hsa-miR-141-3p and DUSP1 was validated via dual-luciferase reporter assay. Single-cell RNA-seq data were analyzed to explore hsa-miR-141-3p and DUSP1 in different cells. An integrated SMD of 1.41 (95% CI[0.45, 2.38], p = 0.0041) with 558 samples revealed the overexpression of hsa-miR-141-3p in UCC tissues. And the pooled SMD of -1.06 (95% CI[-1.45, -0.66], p < 0.0001) with 1,268 samples indicated the downregulation of DUSP1. Inhibition of hsa-miR-141-3p could upregulate DUSP1 expression and suppress invasiveness and metastasis of HeLa cells. Overexpression of DUSP1 could hamper proliferation, invasion, and migration and boost apoptosis and distribution of G1 phase. The dual-luciferase reporter assay validated the combination of hsa-miR-141-3p and DUSP1. Moreover, the targets of hsa-miR-141-3p were mainly enriched in the MAPK signaling pathway and activated in fibroblasts and endothelial cells. The current study illustrated the upregulation of hsa-miR-141-3p and the downregulation of DUSP1 in UCC tissues. Hsa-miR-141-3p could promote UCC progression by targeting DUSP1.

Glomus Tumor of the Left Second Toe Distal Phalanx: A Case Report and Review of Literature.

Introduction: Glomus tumors are rare, benign neoplasms that originate from glomus bodies. While usually occurring in the subungual regions of the fingers, glomus tumors are seldom found in the foot, although rare reports have been made of glomus tumors in the hallux and even fewer in the lesser toes. We describe a reported case of a glomus tumor occurring in the distal phalanx of the left second toe that was initially missed on imaging studies, resulting in delayed diagnosis and surgical treatment. To the best of our knowledge, this represents one of the first few cases of glomus tumor reported in the lesser toes. Case Report: A 34-year-old Chinese female presented with pain in the left second toe occurring for several years. Initial assessment and radiological investigations came back negative for abnormalities, resulting in delayed treatment. Upon second opinion of the MRI scans, a 0.2 × 0.2 × 0.2 cm well-defined round enhancing high T2-weighted signal focus within the germinal matrix of the left second toe subungual region was found, suggestive of a glomus tumor. Surgical exploration was offered, which found a skin-colored lesion, which was resected using a transungual approach. The final histology of the excised mass showed perivascular proliferation of uniform cells which contained round to ovoid nucleus with small nucleolus and pale eosinophilic cytoplasm, confirming glomus tumor. Conclusion: Glomus tumors are rarely found in the foot, with even fewer reports in the lesser toes. Their rare occurrence in these regions reduces diagnostic suspicion for these tumors, delaying diagnosis and treatment for patients. This case report highlights the difficulty in diagnosing glomus tumors, even with adequate radiological investigations, and showcases the need for careful scrutinization of imaging. As this presentation is extremely uncommon, we hope that this case report increases suspicion of glomus tumors as a differential diagnosis for toe pain to ensure early treatment and alleviation of symptoms for patients.

RNA-Seq transcriptome profiling of Nile rat livers reveals novel insights on the anti-diabetic mechanisms of Water-Soluble Palm Fruit Extract.

Water-Soluble Palm Fruit Extract (WSPFE) has been shown to confer anti-diabetic effects in the Nile rat (NR) (Arvicanthis niloticus). Liquid and powder WSPFE both deterred diabetes onset in NRs fed a high-carbohydrate (hiCHO) diet, but the liquid form provided better protection. In this study, NRs were fed either a hiCHO diet or the same diet added with liquid or powder WSPFE. Following feeding of the diets for 8 weeks, random blood glucose levels were measured to categorize NRs as either diabetes-resistant or diabetes-susceptible, based on a cut-off value of 75 mg/dL. Livers were then obtained for Illumina HiSeq 4000 paired end RNA-sequencing (RNA-Seq) and the data were mapped to the reference genome. Consistent with physiological and biochemical parameters, the gene expression data obtained indicated that WSPFE was associated with protection against diabetes. Among hepatic genes upregulated by WSPFE versus controls, were genes related to insulin-like growth factor binding protein, leptin receptor, and processes of hepatic metabolism maintenance, while those downregulated were related to antigen binding, immunoglobulin receptor, inflammation- and cancer-related processes. WSPFE supplementation thus helped inhibit diabetes progression in NRs by increasing insulin sensitivity and reducing both the inflammatory effects of a hiCHO diet and the related DNA-damage compensatory mechanisms contributing to liver disease progression. In addition, the genetic permissiveness of susceptible NRs to develop diabetes was potentially associated with dysregulated compensatory mechanisms involving insulin signaling and oxidative stress over time. Further studies on other NR organs associated with diabetes and its complications are warranted.

Photobiomodulation Therapy in the Management of Oral Lichen Planus: A Systematic Review and Meta-Analysis.

Photobiomodulation therapy (PBMT) is a non-invasive and the latest form of therapy used in the treatment of non oncological diseases as well as cancers of various types and locations. The aim of this study was to systematically review and assess the efficacy of PBMT in managing oral lichen planus (OLP) compared to the interventions. A systematic review and meta-analysis were implemented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search using PubMed, Scopus, and Cochrane was conducted to retrieve relevant studies published until June 2023. The outcomes evaluated included the reduction in pain score and clinical severity scores (Prospero No CRD42023428626). A total of eight studies were identified for qualitative synthesis. The pooled analysis incorporating six studies revealed that there are no significant differences for both mean pain score (mean difference [MD] = 0.21, 95% confidence interval [CI] = -0.51, 0.93) as well as clinical score (MD = -0.08, 95% CI = -0.4, 0.25) between PBMT and comparison groups. Subgroup analysis based on corticosteroids as controls showed that there was no significant difference in mean reduction in pain score between PBMT and topical steroids (MD = 0.38, 95% CI = -0.54, 1.31). PBMT is as effective as other interventions in the treatment of OLP, though not superior, and can be a promising alternative treatment for cases resistant to steroids or when steroids are contraindicated. Further studies are recommended to standardize the optimal settings for the treatment of OLP.

Identification of Key lncRNAs in Gout Under Copper Death and Iron Death Mechanisms: A Study Based on ceRNA Network Analysis and Random Forest Algorithm.

This study focused on identifying potential key lncRNAs associated with gout under the mechanisms of copper death and iron death through ceRNA network analysis and Random Forest (RF) algorithm, which aimed to provide new insights into the molecular mechanisms of gout, and potential molecular targets for future therapeutic strategies of gout. Initially, we conducted an in-depth bioinformatics analysis of gout microarray chips to screen the key cuproptosis-related genes (CRGs) and key ferroptosis-related genes (FRGs). Using these data, we constructed a key ceRNA network for gout. Finally, key lncRNAs associated with gout were identified through the RF algorithm combined with ROC curves, and validated using the Comparative Toxicogenomics Database (CTD). We successfully identified NLRP3, LIPT1, and DBT as key CRGs associated with gout, and G6PD, PRKAA1, LIG3, PHF21A, KLF2, PGRMC1, JUN, PANX2, and AR as key FRGs associated with gout. The key ceRNA network identified four downregulated key lncRNAs (SEPSECS-AS1, LINC01054, REV3L-IT1, and ZNF883) along with three downregulated mRNAs (DBT, AR, and PRKAA1) based on the ceRNA theory. According to CTD validation inference scores and biological functions of target mRNAs, we identified a potential gout-associated lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis. This study identified the key lncRNA ZNF883 in the context of copper death and iron death mechanisms related to gout for the first time through the application of ceRNA network analysis and the RF algorithm, thereby filling a research gap in this field and providing new insights into the molecular mechanisms of gout. We further found that lncRNA ZNF883 might function in gout patients by regulating PRKAA1, the mechanism of which was potentially related to uric acid reabsorption in the proximal renal tubules and inflammation regulation. The proposed lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis might represent a potential RNA regulatory pathway for controlling the progression of gout disease. This discovery offered new molecular targets for the treatment of gout, and had significant implications for future therapeutic strategies in managing the gout.

Sakuranetin reduces inflammation and chondrocyte dysfunction in osteoarthritis by inhibiting the PI3K/AKT/NF-κB pathway.

Osteoarthritis (OA) is a prevalent degenerative disease that impairs limb function, and its pathogenesis is closely related to inflammation. Sakuranetin (SK) is a cherry flavonoid phytoalexin with potent anti-inflammatory, anti-oxidant, and ant-ifungal properties. In recent studies, flavonoid and phytoalexin-related medicines have shown promise in the treatment of OA. However, the effects of SK on chondrocyte inflammation and the chondrogenesis process have remained unexplored, as have its functions in OA treatment. This study sought to confirm the therapeutic effects of SK in the OA rat model and reveal the potential mechanisms for protecting chondrocytes. The relevant mechanisms of SK were analyzed by network pharmacology analysis. Chondrocytes were subjected to IL-1ß intervention to simulate an inflammatory environment and received SK treatment. Then, anabolism, catabolism, and inflammatory markers were detected by western blot, qPCR, elisa, and immunofluorescence. Chondrogenic ability was evaluated by micromass and 3D culture assays. The rats were treated with destabilization of the medial meniscus (DMM) surgery to establish an OA model and SK intra-articular injections subsequently. Histological staining, immunohistochemistry, and micro-CT were performed to analyze the structural and morphological changes of cartilage and subchondral bone. In chondrocytes, IL-1ß treatment reduced chondrogenic ability, promoted catabolism, and exacerbated inflammation by triggering the PI3K/AKT/NF-κB pathway, whereas SK treatment partially rescued these negative effects. In vivo, SK treatment effectively alleviated the degeneration of cartilage and subchondral bone, thereby delaying the progression of OA. In summary, SK alleviates chondrocyte inflammation and promotes chondrogenesis by inhibiting the PI3K/AKT/NF-κB pathway, thereby improving OA progression.

Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis.

OBJECTIVE: Despite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified. METHODS: This study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR-A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC-1) culture to examine the direct effect of TTR-A97S protein on endothelial cells. RESULTS: In ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC-1 culture in which the expression of collagen IV was upregulated after exposure to TTR-A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p-selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv. INTERPRETATION: Microangiopathy with thromboinflammation is characteristic of advanced-stage ATTRv nerves, which provides an add-on mechanism and therapeutic target for nerve degeneration.

Amelioration Effects and Regulatory Mechanisms of Different Tea Active Ingredients on DSS-Induced Colitis.

The potential biological function of tea and its active components on colitis has attracted wide attention. In this study, different tea active ingredients including tea polyphenols (TPPs), tea polysaccharides (TPSs), theabrownin (TB), and theanine (TA) have been compared in the intervention of dextran sulfate sodium (DSS)-induced colitis in mice. Specifically, TPP showed the greatest effect on colitis since it reduced 60.87% of disease activity index (DAI) compared to that of the DSS-induced colitis group, followed by the reduction of 39.13% of TPS and 28.26% of TB on DAI, whereas there was no obvious alleviative effect of TA on colitis. TPP, TPS, and TB could regulate the composition and abundance of gut microbiota to increase the content of short-chain fatty acids (SCFAs) and enhance intestinal barrier function. Further evidence was observed that TPP and TPS regulated the activation of Nrf2/ARE and the TLR4/MyD88/NF-κB P65 pathway to alleviate the colitis. Results of cell experiments demonstrated that TPP showed the greatest antiapoptosis and mitochondrial function protective capability among the tea ingredients via inhibiting the Cytc/Cleaved-caspase-3 signaling pathway. In summary, the superior anticolitis activity of TPP compared to TPS and TB is primarily attributed to its unique upregulation of the abundance of Akkermansia and its ability to regulate the mitochondrial function.

Exploring the regulatory mechanism of tRNA-derived fragments 36 in acute pancreatitis based on small RNA sequencing and experiments.

BACKGROUND: Acute pancreatitis (AP) is a disease featuring acute inflammation of the pancreas and histological destruction of acinar cells. Approximately 20% of AP patients progress to moderately severe or severe pancreatitis, with a case fatality rate of up to 30%. However, a single indicator that can serve as the gold standard for prognostic prediction has not been discovered. Therefore, gaining deeper insights into the underlying mechanism of AP progression and the evolution of the disease and exploring effective biomarkers are important for early diagnosis, progression evaluation, and precise treatment of AP. AIM: To determine the regulatory mechanisms of tRNA-derived fragments (tRFs) in AP based on small RNA sequencing and experiments. METHODS: Small RNA sequencing and functional enrichment analyses were performed to identify key tRFs and the potential mechanisms in AP. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to determine tRF expression. AP cell and mouse models were created to investigate the role of tRF36 in AP progression. Lipase, amylase, and cytokine levels were assayed to examine AP progression. Ferritin expression, reactive oxygen species, malondialdehyde, and ferric ion levels were assayed to evaluate cellular ferroptosis. RNA pull down assays and methylated RNA immunoprecipitation were performed to explore the molecular mechanisms. RESULTS: RT-qPCR results showed that tRF36 was significantly upregulated in the serum of AP patients, compared to healthy controls. Functional enrichment analysis indicated that target genes of tRF36 were involved in ferroptosis-related pathways, including the Hippo signaling pathway and ion transport. Moreover, the occurrence of pancreatic cell ferroptosis was detected in AP cells and mouse models. The results of interference experiments and AP cell models suggested that tRF-36 could promote AP progression through the regulation of ferroptosis. Furthermore, ferroptosis gene microarray, database prediction, and immunoprecipitation suggested that tRF-36 accelerated the progression of AP by recruiting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) to the p53 mRNA m6A modification site by binding to IGF2BP3, which enhanced p53 mRNA stability and promoted the ferroptosis of pancreatic follicle cells. CONCLUSION: In conclusion, regulation of nuclear pre-mRNA domain-containing protein 1B promoted AP development by regulating the ferroptosis of pancreatic cells, thereby acting as a prospective therapeutic target for AP. In addition, this study provided a basis for understanding the regulatory mechanisms of tRFs in AP.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

OBJECTIVES: Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. METHODS: We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS: Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS: We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Introduction: Body status, categorized as sarcopenia or obesity and assessed using body mass index and body composition, affects the outcome of bladder cancer patients. However, studies comparing disease progression, recurrence, or overall survival in patients with non-muscle-invasive bladder cancer (NMIBC) with different body compositions are lacking. Therefore, we conducted a retrospective study to identify the impact of body composition, sarcopenia, and obesity on the oncological prognosis of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) with Bacillus Calmette-Guerin (BCG) intravesical instillation (IVI). Methods: Patients with NMIBC who had undergone TURBT with adjuvant IVI with BCG from March 2005 to April 2021 were included. Body composition parameters were evaluated using computed tomography images of the third lumbar vertebrae and further categorized by sarcopenia and obesity. Oncological outcomes including recurrence-free survival (RFS), progression-free survival, and overall survival (OS) after treatment were analyzed. Results: A total of 269 patients were enrolled. Subcutaneous adipose tissue (SAT) density was a significant predictor of RFS, whereas psoas muscle density was a significant predictor of OS in the multivariate analysis. Patients with sarcopenia but without obesity tolerated significantly fewer BCG IVIs than patients without sarcopenia or obesity. Patients with sarcopenia had poorer RFS and OS than those without sarcopenia. In contrast, patients with obesity had better OS than those without obesity. Discussion: Body composition parameters, including SAT density and psoas muscle density, emerged as significant predictors of OS and RFS, respectively. Hence, our findings indicate that body composition is a helpful measurement to assess the oncological outcomes of patients with NMIBC.

State-of-the-art review of theabrownins: from preparation, structural characterization to health-promoting benefits.

As far as health benefit is concerned, dark tea is one of the best beverages in the world. Theabrownins are the major ingredient contributing to the health benefits of dark tea and known as "the soft gold in dark tea." A growing body of evidence indicated that theabrownins are macromolecular pigments with reddish-brown color and mellow taste, and mainly derived from the oxidative polymerization of tea polyphenols. Theabrownins are the main active ingredients in dark tea which brings multiple health-promoting effects in modulating lipid metabolism, reducing body weight gain, attenuating diabetes, mitigating NAFLD, scavenging ROS, and preventing tumors. More importantly, it's their substantial generation in microbial fermentation that endows dark tea with much stronger hypolipidemic effect compared with other types of tea. This review firstly summarizes the most recent findings on the preparation, structural characteristics, and health-promoting effects of theabrownins, emphasizing the underlying molecular mechanism, especially the different mechanisms behind the effect of theabrownins-mediated gut microbiota on the host's multiple health-promoting benefits. Furthermore, this review points out the main limitations of current research and potential future research directions, hoping to provide updated scientific evidence for their better theoretical research and industrial utilization.

Advances in the application of computational pathology in diagnosis, immunomicroenvironment recognition, and immunotherapy evaluation of breast cancer: a narrative review.

BACKGROUND: Breast cancer (BC) is a prevalent and highly lethal malignancy affecting women worldwide. Immunotherapy has emerged as a promising therapeutic strategy for BC, offering potential improvements in patient survival. Neoadjuvant therapy (NAT) has also gained significant clinical traction. With the advancement of computer technology, Artificial Intelligence (AI) has been increasingly applied in pathology research, expanding and redefining the scope of the field. This narrative review aims to provide a comprehensive overview of the current literature on the application of computational pathology in BC, specifically focusing on diagnosis, immune microenvironment recognition, and the evaluation of immunotherapy and NAT response. METHODS: A thorough examination of relevant literature was conducted, focusing on studies investigating the role of computational pathology in BC diagnosis, immune microenvironment recognition, and immunotherapy and NAT assessment. RESULTS: The application of computational pathology has shown significant potential in BC management. AI-based techniques enable improved diagnosis and classification of BC subtypes, enhance the identification and characterization of the immune microenvironment, and facilitate the evaluation of immunotherapy and NAT response. However, challenges related to data quality, standardization, and algorithm development still need to be addressed. CONCLUSION: The integration of computational pathology and AI has transformative implications for BC patient care. By leveraging AI-based technologies, clinicians can make more informed decisions in diagnosis, treatment planning, and therapeutic response assessment. Future research should focus on refining AI algorithms, addressing technical challenges, and conducting large-scale clinical validation studies to facilitate the translation of computational pathology into routine clinical practice for BC patients.

[Retracted] TRIM16 suppresses the progression of prostate tumors by inhibiting the Snail signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by concerned readers that the western blotting data shown in Figs. 4C and 7B and D, the scratch­wound assay images shown in Figs. 5A and 6A, and certain of the cell migration and invasion assay data shown in Figs. 5B and 6B were strikingly similar to data that had previously appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 38: 1734­1742, 2016; DOI: 10.3892/ijmm.2016.2774].

Cystathionine-γ-lyase attenuates inflammatory response and pain of osteoarthritis.

The chronic articular disease osteoarthritis (OA) is characterized by osteophyte generation, subchondral bone remodeling, and cartilage deterioration. Low levels of H2S catalyzed by cystathionine-γ-lyase (CSE) encoded by Cthhas neuroprotective, cardioprotective, anti-apoptotic, and anti-inflammatory effects thus, Cth is being developed as a potential therapy for the management of the pathogenesis and symptoms of osteoarthritis. Single-cell RNA sequencing (scRNA-seq) and immunohistochemistry of human cartilage revealed that the expression of CTH was decreased in OA patients. We found that Cthoverexpression decrease IL-1ß-induced overactivation of the NF-κB signaling pathway. In vivo, Cthoverexpression relieved pain response and cartilage damage in the anterior cruciate ligament transection (ACLT) rat model. In vitro, CSE alleviated chondrocytes catabolism, inflammation, apoptosis, and senescence, and suppressed the NF-κB pathway. We postulate that CSE has therapeutic effects in suppressing inflammation and degeneration in OA and should be further investigated clinically.

Autophagy-Related Gene 4 Participates in the Asexual Development, Stress Response and Virulence of Filamentous Insect Pathogenic Fungus Beauveria bassiana.

Autophagy is a conserved mechanism for the turnover of intracellular components. Among the 'core' autophagy-related genes (ATGs), the cysteine protease Atg4 plays an important role in the activation of Atg8 by exposing the glycine residue at its extreme carboxyl terminus. In the insect fungal pathogen Beauveria bassiana, a yeast ortholog of Atg4 was identified and functionally analyzed. Ablation of the BbATG4 gene blocks the autophagic process during fungal growth under aerial and submerged conditions. Gene loss did not affect fungal radial growth on various nutrients, but ΔBbatg4 exhibited an impaired ability to accumulate biomass. The mutant displayed increased sensitivity to stress caused by menadione and hydrogen peroxide. ΔBbatg4 generated abnormal conidiophores with reduced production of conidia. Additionally, fungal dimorphism was significantly attenuated in gene disruption mutants. Disruption of BbATG4 resulted in significantly weakened virulence in topical and intrahemocoel injection assays. Our study indicates that BbAtg4 contributes to the lifecycle of B. bassiana via its autophagic roles.

Metformin Attenuates the Inflammatory Response via the Regulation of Synovial M1 Macrophage in Osteoarthritis.

Osteoarthritis (OA), the most common chronic inflammatory joint disease, is characterized by progressive cartilage degeneration, subchondral bone sclerosis, synovitis, and osteophyte formation. Metformin, a hypoglycemic agent used in the treatment of type 2 diabetes, has been evidenced to have anti-inflammatory properties to treat OA. It hampers the M1 polarization of synovial sublining macrophages, which promotes synovitis and exacerbates OA, thus lessening cartilage loss. In this study, metformin prevented the pro-inflammatory cytokines secreted by M1 macrophages, suppressed the inflammatory response of chondrocytes cultured with conditional medium (CM) from M1 macrophages, and mitigated the migration of M1 macrophages induced by interleukin-1ß (IL-1ß)-treated chondrocytes in vitro. In the meantime, metformin reduced the invasion of M1 macrophages in synovial regions brought about by the destabilization of medial meniscus (DMM) surgery in mice, and alleviated cartilage degeneration. Mechanistically, metformin regulated PI3K/AKT and downstream pathways in M1 macrophages. Overall, we demonstrated the therapeutic potential of metformin targeting synovial M1 macrophages in OA.

Preparation, Identification and Preliminary Application of the Fenvalerate Monoclonal Antibody in Six Kinds of Dark Tea.

Fenvalerate has the advantages of a broad insecticidal spectrum, high efficiency, low toxicity and low cost, and it is widely used in agriculture, especially in tea, resulting in the accumulation of fenvalerate residues in tea and the environment, posing a serious threat to human health. Therefore, the timely monitoring of fenvalerate residue dynamics is vital for ensuring the health of humans and the ecological environment, and it is necessary for establishing a fast, reliable, accurate and on-site method for detecting fenvalerate residues. Based on the methods of immunology, biochemistry and molecular biology, mammalian spleen cells, myeloma cells and mice were used as experimental materials to establish a rapid detection method of an enzyme-linked immunosorbent assay to detect the residues of fenvalerate in dark tea. Three cell lines-1B6, 2A11 and 5G2-that can stably secrete fenvalerate antibodies were obtained by McAb technology, and their sensitivities (IC50) were 36.6 ng/mL, 24.3 ng/mL and 21.7 ng/mL, respectively. The cross-reaction rates of the pyrethroid structural analogs were all below 0.6%. Six dark teas were used to detect the practical application of fenvalerate monoclonal antibodies. The sensitivity IC50 of the anti-fenvalerate McAb in PBS with 30% methanol is 29.12 ng/mL. Furthermore, a latex microsphere immunochromatographic test strip with an LOD of 10.0 ng/mL and an LDR of 18.9-357 ng/mL was preliminarily developed. A specific and sensitive monoclonal antibody for fenvalerate was successfully prepared and applied to detect fenvalerate in dark teas (Pu'er tea, Liupao tea, Fu Brick tea, Qingzhuan tea, Enshi dark tea and selenium-enriched Enshi dark tea). A latex microsphere immunochromatographic test strip was developed for the preparation of rapid detection test strips of fenvalerate.

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. METHODS: This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). RESULTS: A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. CONCLUSIONS: Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage.