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Impact of Obesity on Response Rate for Biological Agents in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Cohort Studies
Get PDFBackground: Existing evidence suggests that obesity has an impact on the onset and development of rheumatoid arthritis (RA) and may also affect the response of patients to different treatments. However, findings from previous studies are controversial. This study aims to obtain evidence-based medical information on the influence of obesity on the response rate of biological agents in patients with RA through a systematic review and meta-analysis. Methods: A search was performed on Pubmed, Medline, Web of Science, Scopus, and Cochrane Library from their inception to June 2023. Studies that met the inclusion criteria were enrolled. A meta-analysis was used to evaluate remission, response, good European League Against Rheumatism (EULAR) response, moderate EULAR response, retention rate, and clinical disease activity index (CDAI). Subgroup analysis was carried out to identify sources of heterogeneity and sensitivity analysis was performed. Results: A total of 15 articles met the inclusion criteria and four biological disease-modifying antirheumatic drugs (bDMARDs) were included. The meta-analysis showed that the odds of reaching good EULAR response or achieving CDAI were lower in obese than in non-obese patients treated with bDMARDs. Subgroup analysis revealed significant differences between the two groups. Remission, good EULAR response and retention rate were lower in the obese group than in non-obese patients treated with tumor necrosis factor inhibitors (TNFi). However, there was no significant difference between patients receiving abatacept and tocilizumab treatment. Sensitivity analysis and publication bias confirmed that the results were highly reliable and stable. Conclusions: Obesity affects the clinical response rate of RA patients receiving TNF inhibitors (TNFi), but it does not have an adverse effect on abatacept and tocilizumab. This suggests that when choosing biological agents for RA patients, the impact of obesity should be considered. Further research is needed to validate these findings
SIRT1 Activation Reduces LPS-Induced Human Middle Ear Epithelial Cell Injury via Promoting Autophagy
No full textBackground: Otitis media (OM) is a prevalent pervasive illness among the pediatric population. Research on sirtuin 1 (SIRT1), a deacetylase sensitive to nicotinamide adenine dinucleotide (NAD(+)), has increasingly identified its pivotal role in various inflammatory conditions. Our study aims to elucidate the role of SIRT1 in inflammatory injury in OM and its potential action mechanism. Methods: Human middle ear epithelial cells (HMEECs) were stimulated with lipopolysaccharide (LPS) to establish in vitro models of OM. Western blot was used to assess SIRT1 expression. Following the addition of SIRT1 activator SRT1720, with or without the autophagy inhibitor 3-Methyladenine (3-MA), the Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell viability. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay was used to assess cell apoptotic levels. Enzyme-linked immunosorbent assay (ELISA) was used to estimate inflammatory levels and dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining was used to estimate reactive oxygen species (ROS) activity. Western blot was used to analyze the content of apoptosis-, inflammatory response-, autophagy-, and nuclear factor-kappaB (NF-κB) signaling-associated proteins. Results: SIRT1 expression was attenuated in LPS-treated HMEECs (p < 0.05). SRT1720 pretreatment significantly enhanced cell viability (p < 0.05), attenuated apoptosis (p < 0.05), suppressed the inflammatory response (p < 0.05), and reduced ROS production (p < 0.05). Additionally, it inhibited NF-κB signaling (p < 0.05) while inducing autophagy (p < 0.05) in HMEECs exposed to LPS in a concentration-dependent manner. Furthermore, 3-Methyladenine (3-MA) partially counteracted the suppressive effects of SRT1720 in LPS-induced viability loss, apoptosis (p < 0.05), inflammatory response (p < 0.05), NF-κB signaling activation (p < 0.05), and ROS generation (p < 0.05) in HMEECs. Conclusions: In summary, the activation of SIRT1 may mitigate the inflammatory response in LPS-induced HMEECs through the modulation of apoptosis, inflammatory signaling, and autophagic processes
Influence of Hemodialysis on Cardiac Function and Structure, Oxidative Stress, and Life Quality in Patients with Diabetic Nephropathy
No full textBackground: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease throughout the world. Currently, hemodialysis (HD) and peritoneal dialysis (PD) are widely applied in treating patients with DN. Objective: The present research is dedicated to investigating the impact of hemodialysis on heart function and structure, oxidative stress, and inflammatory factor levels of DN patients. Methods: The data of 100 cases of DN patients (between 2021 and 2022 in our hospital) with normal left ventricular systolic function were collected. These patients were randomly divided into two groups: the observation group (48 cases of DN patients that underwent HD) and the control group (52 cases of those subjected to PD). Echocardiography was employed to evaluate the changes in cardiac function and structure of DN patients in both groups. The enzyme-linked immunosorbent assay (ELISA) and oxidative stress commercial assay kits were used to measure the levels of inflammatory factors and oxidative stress markers in the serum of both groups of patients. Additionally, the nutritional status and occurrence of complications during HD were observed and recorded in both groups. The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) were used to evaluate the social-psychological status of patients. The simplified comfort state scale and the 36-item short-form health survey (SF-36) were used to assess the comfort and quality of life of patients, respectively, before and after hemodialysis care. Results: Compared to the control group, the observation group of patients with DN showed more significant cardiac structural and functional impairments, as well as elevated levels of inflammatory markers and oxidative stress. Meanwhile, compared to the control group, the observation group of patients exhibited significantly higher levels of anxiety and depression. Moreover, the patients reported significantly decreased comfort and quality of life (p < 0.05). Conclusions: Compared to peritoneal dialysis, hemodialysis reduces the quality of life for DN patients and may not be the optimal choice for DN patients
The Role of Somatostatin in Alzheimers Disease: Modulation of NLRP3-Mediated Microglial Pyroptosis via the MDM2/DPP4/Sirt1 axis
No full textBackground: The progression of Alzheimers disease (AD) is closely linked to microglial pyroptosis. This study investigated the impact of somatostatin (SST) on microglial pyroptosis in AD and elucidated the underlying mechanisms. Methods: In-vitro AD cell models were established through sequential stimulation with 100 ng/mL lipopolysaccharide and 10 μM amyloid-β protein fragment 1-42 (Aβ1-42). The model cells which were transfected with or without silencing transformed mouse 3T3 cell murine double minute 2 (MDM2) or/and sirtuin 1 (Sirt1) overexpression plasmid, underwent SST treatment. Pro-inflammatory cytokines (interleukin 1β (IL-1β), interleukin 18 (IL-18)) were quantified using enzyme-linked immunosorbent assay, followed by the determination of lactate dehydrogenase (LDH) release. Intracellular Aβ1-42 deposition, NOD-like receptor family protein 3 (NLRP3)-mediated pyroptosis, and the MDM2/dipeptidyl peptidase 4 (DPP4)/Sirt1 axis were assessed using propidium iodide staining, immunofluorescence staining, and Western blot. The interaction between MDM2 and DPP4 was validated through ubiquitination analysis. Results: SST upregulated MDM2 and Sirt1 levels, leading to MDM2 ubiquitination and subsequent degradation of DPP4 in BV2 cells. Moreover, SST downregulated IL-1β and IL-18 levels, LDH release, Aβ1-42 deposition, and the expressions of DPP4, NLRP3, N-gasdermin D (N-GSDMD), and caspase-1 in AD model cells (p < 0.001). These effects were reversed by MDM2 silencing (p < 0.001). However, Sirt1 overexpression counteracted the effects of MDM2 silencing on SST-treated model cells by reducing pro-inflammatory cytokine production, LDH release, Aβ1-42 deposition, and NLRP3-mediated pyroptosis (p < 0.001). Conclusion: SST activates the MDM2/DPP4/Sirt1 axis to inhibit NLRP3-mediated microglial pyroptosis and thereby alleviates AD. This discovery presents a promising strategy for AD therapy
Capsaicin Alleviates Ankylosing Spondylitis in Mice: A Study on the NLRP3/Caspase-1/GSDMD Pyroptosis Pathway and Intestinal Barrier Repair
No full textBackground: Cell pyroptosis and dysbiosis of the gut microbiota are closely related to the pathogenesis of Ankylosing Spondylitis (AS). Capsaicin, an active component in chili peppers, has demonstrated anti-inflammatory and antioxidant potential. This study aims to explore the therapeutic effects of capsaicin on a mouse model of AS and its underlying mechanisms. Methods: The AS mouse model was established and divided into control, AS model, capsaicin-treated, and sulfasalazine (positive control drug) treated groups. Cytokines in serum were detected by Enzyme-Linked Immunosorbent Assays (ELISA). The activation status of pyroptosis-related proteins and the nuclear factor kappa-B (NF-κB) pathway in spinal joint tissues were analyzed by Western blot. The function of the intestinal mucosal barrier was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Additionally, the composition of the gut microbiota was analyzed. Results: Capsaicin inhibited tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-17A in the serum of AS mice and increased IL-10 (p < 0.01). In the spinal joint tissues, capsaicin effectively inhibited pyroptosis-related proteins such as NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD) (p < 0.01), thus reducing cell pyroptosis. Furthermore, capsaicin inhibited the activation of the NF-κB pathway (p < 0.01), improved the function of the intestinal mucosal barrier, increased levels of beneficial probiotics such as Lactobacillus and Bifidobacterium (p < 0.001), and decreased levels of harmful bacteria including Enterococcus faecalis (p < 0.05) and Escherichia coli (p < 0.001). Conclusion: This study confirms that capsaicin alleviates inflammation and pathological damage in AS mice by inhibiting the pyroptosis pathway, repairing the intestinal barrier, and regulating the composition of the gut microbiota
Antidiabetic, Anti-Inflammatory, Anthelminthic, Cytotoxic, Thrombolytic, Antidiarrheal, and Antipyretic Activity of Dipterocarpus turbinatus Leaves: In Vitro, In Vivo and Computational Insights
No full textBackground: Dipterocarpus turbinatus is a well-known ethnomedicinal plant species. Traditionally, it has been used to treat various medical ailments, including diabetes, diarrhea, tuberculosis, leprosy, ringworm, gonorrhea, ulcers, skin infections, wounds, and burns. This study aimed to assess the pharmacological properties of the methanol extract of D. turbinatus (MEDT) obtained from leaves, specifically focusing on its potential antidiabetic, anti-inflammatory, anthelminthic, cytotoxic, thrombolytic, antidiarrheal, and antipyretic properties. Methods: In this study, castor oil-induced diarrhea, gastrointestinal transit, and castor oil-induced enteropooling mice models were used to examine the antidiarrheal potential of MEDT. The alpha-amylase inhibition assay was employed to investigate its antidiabetic attributes. Moreover, human blood samples were analyzed using a rapid clot analysis method to evaluate their thrombolytic properties. Furthermore, the anti-inflammatory attributes of MEDT were assessed using bovine serum albumin and egg albumin denaturation assays. The Brewers yeast technique was used to evaluate the pyretic potential of MEDT in mouse models. The chemical composition of MEDT was analyzed using gas chromatography-mass spectrometry (GC-MS) analysis. Furthermore, a docking analysis of selected phytochemicals in MEDT was performed using BIOVIA and Schrödinger Maestro (v11.1) methods. Additionally, the absorption, distribution, metabolism, and excretion/toxicity (ADME/T) properties of these compounds were investigated utilizing online tools. Results: The phytochemical analysis of the MEDT revealed the presence of diverse phytoconstituents such as flavonoids, alkaloids, glycosides, steroids, phytosterols, and resins. MEDT significantly inhibited alpha-amylase in a concentration-dependent manner, with a minimal inhibitory concentration required to inhibit 50% of enzyme activity (IC50) value of 38.40 μg/mL. Furthermore, MEDT significantly exhibited cytotoxicity, as evidenced by the median lethal dose (LC50) value of 439.25 μg/mL. Compared to streptokinase, the thrombolytic activity was statistically significant (p < 0.001). Additionally, the anthelmintic experiment revealed that exposure to MEDT led to a significant reduction in the duration of paralysis and the time to death in a dose-dependent manner. Furthermore, in pyrectic-induced mice, MEDT at 200 and 400 mg/kg doses resulted in a significant decrease in pyrexia. Moreover, GC-MS analysis enabled the detection of 31 compounds in MEDT. Interestingly, the binding predictions showed that 3-azabicyclo[3.2.2]nonane interacted favorably with 1A5H and 1ERR and that 8,11,14-Eicosatrienoic acid (Z,Z,Z)- showed potential interactions with 1SA0 which might mediate their anthelmintic and antidiabetic properties. Conclusion: Taking into account the above findings and the ethnomedicinal importance of D. turbinatus, further research is needed to isolate and describe the phytoconstituents that underpin its purported biological effects
STAT3 Up-Regulation Reverses the Effect of NCOR1 on the Hindrance of Osteoclastogenesis
No full textBackground: Osteoclast formation serves as a triggering factor during osteoarthritis (OA), therefore, our study aimed to elucidate the influence of nuclear receptor corepressor 1 (NCOR1) on osteoclast differentiation and formation. Methods: At days 0, 1, 3, or 5 of osteoclast differentiation, osteoclasts were quantified using tartrate-resistant acid phosphatase (TRAP) staining assay, and their apoptosis rate was assessed employing flow cytometry. Moreover, the protein levels of c-Src, β3-integrin, matrix metalloproteinase 9 (MMP9), NCOR1, histone deacetylase 3 (HDAC3), and signal transducer and activator of transcription 3 (STAT3) were measured by western blot analysis. Additionally, the acetylation of STAT3 during the differentiation of osteoclast precursor (OCP) cells was examined through chromatin immunoprecipitation assay. Furthermore, following the transfection of NCOR1 and STAT3 overexpression, the mechanism of NCOR1 in regulating osteoclastogenesis was determined. Results: The number of TRAP-positive cells and the protein levels of osteoclast-specific genes (MMP9, c-Src, and β3-integrin) as well as STAT3 and its acetylation were significantly increased during osteoclast differentiation. However, the protein expression levels of NCOR1 and HDAC3 were substantially decreased. Meanwhile, these outcomes were reversed with overexpression of NCOR1. Furthermore, STAT3 up-regulation reversed the hindering effect of NCOR1 on osteoclastogenesis. Conclusion: NCOR1 inhibits osteoclastogenesis by suppressing STAT3 acetylation, and this effect can be reversed by STAT3 overexpression
Liquid Chromatography-Tandem Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Head and Neck Squamous Cell Carcinomas
No full textBackground: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and one of the malignant tumors with poor prognosis. To gain insights into HNSCC, we analyzed the proteome and phosphoproteome between cancerous and paracancerous normal tissue samples using quantitative mass spectrometry. Methods: Proteins were extracted from five pairs of tumor-normal samples and digested for data-independent acquisition mass spectrometry. Subsequently, phosphopeptides were enriched using TiO2 and prepared for phosphoproteome detection. A bioinformatics analysis was then conducted to identify potential biomarkers for HNSCC. Results: A total of 1239 protein groups and 2025 phosphorylation sites were differentially expressed. Among these, KRT16, MUC21, SH3BGRL2, ASL, and METTL7A were selected as biomarkers for HNSCC. Conclusions: This study presents a comprehensive and quantitative analysis using mass spectrometry of five pairs of NHSCC samples, including five adjacent non-cancerous tissues, unveiling five potential protein biomarkers for HNSCC
Correction: Wang et al. Downregulating TUBB Inhibits Certain Biological Behaviors but Promotes Apoptosis of Triple-Negative Breast Cancer Cells. Journal of Biological Regulators and Homeostatic Agents. 2023; 37: 4249–4259.
No full textCorrection of Journal of Biological Regulators and Homeostatic Agents 2023, 37 (8) https://www.biolifesas.org/EN/10.23812/j.biol.regul.homeost.agents.20233708.416 The authors wish to make the following correction to this paper [1]: The corresponding authors email address [email protected] should be changed to [email protected]
The Potential of Cell-Free DNA in Cancer: towards Standardization and Optimization for Enhanced Diagnosis and Monitoring
No full textBackground: Cancer, characterized by the rapid and abnormal growth of cells affecting any part of the body, stands as the leading cause of death worldwide. Cell-free DNA (cfDNA) has garnered significant attention as a non-invasive liquid biopsy approach for disease detection, therapy evaluation, and prognosis. This review aims to provide a comprehensive exploration of cfDNA within the realm of oncology. It encompasses its diagnostic and therapeutic applications while identifying areas necessitating standardization and optimization. Methods: We reviewed existing literature to delve into the biological properties of cfDNA, exploring genetic and epigenetic aberrations found in various bodily fluids. Additionally, we explored its correlation with circulating tumor DNA (ctDNA). The review also encompasses preanalytical procedures and emerging technologies geared towards maximizing the complete potential of cfDNA. Results: Genetic and epigenetic markers have been identified in cfDNA across plasma, serum, and urine, presenting promising diagnostic and prognostic applications. Furthermore, ctDNA preserves genomic profiles akin to those found in corresponding tumor tissues, enabling a nuanced evaluation of tumor heterogeneity and mutation burdens. However, despite its potential, current methodologies suffer from a lack of standardization and optimization, thereby restraining the complete clinical utility of cfDNA. Conclusions: Although cfDNA stands as a compelling avenue for non-invasive early cancer diagnosis and therapy evaluation, unlocking its maximum potential requires methodological refinement and a deeper understanding of its biological characteristics. This review advocates for targeted research to standardize and optimize cfDNA analytical techniques, thereby enhancing its role in oncology