Background WD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored. Methods We conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and Kaplan-Meier analyses. Furthermore, the functional role of WDR76 in HCC was validated in vitro using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays. Results WDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly in ACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a role in shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities. Conclusion Our study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.
Infective endocarditis (IE) remains a severe condition associated with significant morbidity and mortality. Dental procedures involving manipulation of gingival tissue or the periapical region may cause transient bacteremia, making prevention strategies at the dental–medical interface clinically important. Current guidance emphasizes selective antibiotic prophylaxis (AP) for patients at the highest cardiac risk while prioritizing long-term oral health maintenance. This scoping review synthesizes contemporary evidence (2021–2025) and major international guidelines to clarify the relationship between invasive dental procedures (IDPs) and IE, identify patients who may benefit from AP, and outline practical prevention strategies in dental practice. A PRISMA-ScR-guided scoping review was conducted using PubMed/MEDLINE, Web of Science, and EMBASE (January 2021–October 2025), with citation tracking of key guidelines, including those from the American Heart Association (2021), European Society of Cardiology (2023), and National Institute for Health and Care Excellence. Thirty-four studies met the eligibility criteria and were included in the final evidence synthesis. The evidence base comprised international guidelines, systematic reviews, observational studies, registry analyses, and narrative reviews relevant to IE prevention and dental management. AHA and ESC recommend antibiotic prophylaxis for patients with high-risk cardiac conditions undergoing IDPs, defined as procedures involving gingival or periapical manipulation or mucosal perforation. NICE guidance does not recommend routine prophylaxis but supports individualized decision-making and informed consent. Contemporary data indicate the strongest short-term association between IDPs and IE following tooth extractions and oral surgical procedures in high-risk patients. In these groups, AP has been associated with reduced IE incidence, with estimated numbers needed to prevent one case of approximately 244 for all IDPs, 143 for extractions, and 71 for oral surgery. Evolving epidemiology underscores the need for accurate cardiac risk stratification. Prevention should focus on identifying high-risk patients, maintaining oral health, communicating procedural risks, and applying selective AP when indicated, although evidence remains largely observational.
Introduction/Objectives Inborn Errors of Immunity (IEIs) are rare disorders in which delayed diagnosis leads to significant morbidity and mortality. Early recognition depends largely on primary care and non-immunology healthcare professionals; however, data on IEI awareness in Central Asia are limited. This study assessed the awareness of IEI among healthcare professionals in Kazakhstan and identified the association with higher diagnostic preparedness. Methods A nationwide cross-sectional study was conducted from January to March 2025 using an online questionnaire distributed across multiple regions of Kazakhstan. Physicians and nurses affiliated with the immunology department were excluded. The survey was adapted from the Jeffrey Modell Foundation framework and demonstrated high internal consistency (KR-20 = 0.94). Descriptive analyses and multivariable logistic regression were performed. Results A total of 239 healthcare professionals participated (88.7% female; mean age, 38.3 ± 10.2 years). While 72.4% reported undergraduate exposure to immunology, only 30.5% received postgraduate or workplace-based training related to IEI. Overall, 40.6% of the respondents were familiar with the “10 warning signs” of IEI. Prior workplace-based training was independently associated with higher awareness (adjusted OR 12.6, 95% CI 6.43-24.65). Conclusions Awareness of IEI among non-immunology professionals in Kazakhstan remains limited. Targeted workplace-based education and continuing medical education (CME) programs may improve early recognition and referral rates.
Background Gastric cancer is a deadly disease with poor prognosis and unfavorable therapeutic outcomes. It is known that a major cause of treatment failure for gastric cancer is related to tumor heterogeneity. However, it is difficult to assess heterogeneity, as the composition of tumors is dynamic and cancer treatments reshape cell diversity and gene/protein expression profiles. Objective We utilized gastric cancer patient-derived tumor organoids to monitor tumor heterogeneity and the impacts of chemotherapy (FLOT and FOLFOX) on cancer stem cells (LGR5 and CD133) and cancer immune checkpoint molecules (MHC-I and PD-L1). Methods Six tumor organoids were established from different patients or different regions of the same tumor. The tumor organoids were used to investigate the real-time profiles of cancer stem cell marker expression and cancer immune checkpoint molecule expression after chemotherapy treatment. Tumor suppression was monitored by the propidium iodide assay and measurements of tumor organoid diameter. Expression levels of cancer stem cell markers and immune checkpoint molecules were analyzed by flow cytometry. Results Growth of all tumor organoids could be suppressed by chemotherapy. However, diverse impacts of FLOT and FOLFOX were observed in terms of the expression profiles of cancer stem cell markers and cancer immune checkpoint molecules. In particular, tumor organoids from different patients exhibited distinct expression profiles for cancer stem cell markers and immune checkpoint molecules after treatment with the same chemotherapeutic regimen. Similar observations were made with tumor organoids derived the same patient but different tumor regions. Conclusion Our findings demonstrated that spatial and temporal tumoral heterogeneity can be observed after treatment with chemotherapy, suggesting that repeated monitoring of tumor characteristics may be essential for clinical decision making. In addition, sampling of multiple sites at multiple time-points might be important when evaluating the impacts of chemotherapy on cancer stem cells markers and immune checkpoint molecules.
Persistent neurological symptoms such as cognitive impairment, fatigue, and neuropsychiatric disturbances are increasingly reported in patients with long COVID, with chronic neuroinflammation and neuronal injury proposed as potential contributors. To characterize inflammatory and neuroinjury-related biomarker patterns, we conducted a case-control study including 325 participants recruited at King Chulalongkorn Memorial Hospital between January 2022 and December 2023, comprising 265 individuals with persistent neurological symptoms following COVID-19 infection and 60 asymptomatic COVID-19 participants who did not develop long COVID symptoms. Blood samples were analysed for inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, IFN-α, IL-4) using multiplex immunoassays, and for neuroinflammatory and neurodegenerative biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, and beta-amyloid peptides (Aβ40, Aβ42) using SIMOA and ELISA platforms. Among 265 participants with complete data (critical = 7, severe = 22, moderate = 79, mild = 157), patients with severe and critical COVID-19 exhibited significantly higher concentrations of IL-6, IL-1β, TNF-α, and IL-8, together with elevated NfL, GFAP, and phosphorylated tau181 levels, and reduced Aβ42/40 ratios. Strong positive correlations between neurodegenerative biomarkers and pro-inflammatory cytokines were observed in critically ill patients, whereas these associations were weak or absent in mild and moderate cases. Older age was also associated with greater disease severity and increased risk of persistent neurological complications. These findings indicate that individuals with persistent neurological symptoms following COVID-19, particularly those with a history of severe or critical disease, exhibited higher inflammatory and neuroinjury-related biomarker levels, while blood-based biomarkers such as NfL, GFAP, and phosphorylated tau181 may serve as minimally invasive tools for characterizing neurological involvement and identifying patients at risk of long-term neurological sequelae.
Atherosclerosis (AS) is a chronic inflammatory disorder of the medium and large arteries, characterized by lipid accumulation within the arterial wall and a sustained inflammatory milieu, and it remains a leading cause of cardiovascular morbidity and mortality worldwide. Glycolysis and neutrophil extracellular traps (NETs) are both involved in the initiation and progression of AS in part through effects on endothelial function, platelet activation, lipid metabolism, and the inflammatory microenvironment. This article reviews the roles of NETs and glycolysis in AS, elucidates the mechanisms underlying NETosis, and discusses the association between glycolysis and NETosis. Finally, the article discusses the potential value of glycolytic inhibitors in the treatment of AS, with the aim of providing new perspectives for the diagnosis and treatment of AS and related cardiovascular diseases.
Infections with human herpesviruses are known to be associated with oral lesions and other oral complications. For example, herpes simplex virus 1 (HSV-1) is the causative agent for cold sores. Kaposi’s sarcoma-associated herpesvirus (KSHV) causes oral Kaposi’s sarcoma (KS) and other oral complications among immunocompromised patients, such as HIV-positive individuals. Novel antiviral strategies are needed to effectively treat oral infections caused by HSV-1 and KSHV, given the limitations of current FDA-approved anti-HSV-1 and anti-KSHV therapies. Nucleic acid-based gene-interfering molecules, such as antisense oligonucleotides, ribozymes, and small interfering RNA (siRNA), are promising gene-targeting agents for therapeutic applications. Ribozymes derived from the catalytic RNA subunit of RNase P in Escherichia coli represent a novel class of RNA-based gene targeting molecules for degrading target mRNAs and modulating gene expression. Methods have been developed to engineer RNase P ribozymes that more effectively suppress gene expression. In this review, we summarize the recent advances in using RNase P ribozymes to block the expression of HSV-1 and KSHV genes and inhibit the infection of HSV-1 and KSHV. Moreover, we discuss the potential of engineered RNase P ribozymes as therapeutics to treat infections and associated diseases caused by HSV-1 and KSHV in the oral cavity.
Cancer has become a major global health crisis and the second leading cause of death worldwide. With over 270 different types, it is estimated to claim 13 million lives by 2030. The complex pathophysiology of cancer, with its diverse genetic, epigenetic, and biochemical pathways, complicates the diagnostic criteria. Therapeutic approaches such as surgical interventions, radiotherapy, chemotherapy, and immunotherapy have been developed. However, the treatment is still challenging due to higher costs, toxicity, off-target effects, and comorbid conditions. Over the decades, liposomes, based on their particle size, surface charge, lipid composition, and lamellarity, have been explored for different therapeutic modalities for other cancers. They offer unique advantages, including improved drug efficacy, controlled site-specific release, enhanced cellular uptake, reduced systemic toxicity, and greater capacity to overcome tumor-induced resistance mechanisms. Researchers have explored liposomal treatment modalities for breast, lung, adenocarcinoma, ovarian, liver, fibrosarcoma, glioblastoma, and brain cancers. The tumor targeting drugs, for example, doxorubicin and paclitaxel, are delivered at the tumor microenvironment (TME) by passive and active transport, utilizing both the enhanced permeability and resistance (EPR) effect and cellular targets, for example, receptors, proteins, and organelles, in response to physical stimuli, for example, temperature, pH, fluid pressure, and nutrient and metabolic regulation. However, liposomes also face several limitations, including endosomal entrapment, heterogeneous targeting, suboptimal uptake by antigen-presenting cells (APCs), and storage instability. This review focuses on the advancements in liposomal nanocarriers for targeted cancer therapy. It emphasizes the evolution of their formulations to overcome potential limitations, making them highly tumor-specific and effective.
Introduction: Breast cancer (BC) is a major global health issue. Combination therapies using chemical compounds have shown potential benefits, including reduced toxicity, slowed cancer cell growth, and improved treatment outcomes, compared to single-drug treatments. Objectives: This study investigates the synergistic effects of doxorubicin (DOX) and Zm-093, a novel sulfonamide derivative with unique properties that offer potential advantages over existing sulfonamide compounds, including enhanced solubility and improved bioavailability, on apoptosis induction in BC cell lines. Methods: Zm-093 was synthesized, and its structure was confirmed through Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. Cell viability was assessed using the MTT assay, while the combination index (CI) was calculated with Compusyn software to evaluate the synergistic interaction between DOX and Zm-093 in MCF-7 cells. The apoptotic effects of these compounds were further analyzed using western blotting, flow cytometry, and TUNEL assays. Results: Notably, the combined treatment of DOX and Zm-093 at concentrations of 0.36 µM and 14.5 µM resulted in a 57% reduction in Bcl-2 expression compared to the control group. In contrast, expressions of pro-apoptotic proteins Bax and tBid, as well as caspase-3, increased significantly by 2.4, 3.3, and 5.7 times, respectively. Flow cytometry and TUNEL assay results indicated that the combination therapy significantly enhanced early apoptosis while minimizing necrosis. Conclusion: These findings confirm that DOX and Zm-093 exhibit synergistic effects on apoptotic pathways in MCF-7 cells, highlighting the potential of Zm-093 as a novel therapeutic agent with improved efficacy and reduced toxicity compared to existing sulfonamide compounds.
Epithelioid angiosarcoma (EA) is a malignant tumor of endothelium origin that most commonly arises in the deep soft tissues of extremities but may occasionally be primary in skin, adrenal gland, and bone. A 72-year-old male presented with a painless enlargement of his thyroid for more than 10 days before hospitalization. A walnut-sized mass in the right thyroid was found simultaneously by palpation and Color Doppler Ultrasound. After a total thyroidectomy was performed, a mass with a size of 4.5 cm × 3.5 cm was found at the lower pole of the right thyroid gland. Histologically, the tumor was diffusely distributed in a sheet-like pattern, with tumor cells being epithelioid. There was extensive coagulative necrosis while no components of papillary carcinoma, follicular carcinoma and insular poorly differentiated carcinoma were noticed. CD31 and vimentin were positive for immunostaining. The diagnosis of primary epithelioid angiosarcoma of right thyroid was then given to the patient. Eleven months after the operation, the patient died from brain metastasis. It is suggested that primary epithelioid angiosarcoma of thyroid, as an extremely rare tumor, have no characteristic clinical manifestations, laboratory and imaging examinations, and the diagnosis mainly depend on its unique clinical pathological features. Although extensive surgical resection is the preferred treatment, the prognosis is still very poor.
Objective: To identify key RNA-binding proteins (RBPs) associated with breast cancer (BRCA) prognosis and to construct an RBP-based prognostic scoring model and clinical nomogram. Additionally, to explore the functional role of RPL9 in BRCA cell proliferation and apoptosis. Introduction: Breast cancer is a molecularly heterogeneous malignancy in which posttranscriptional dysregulation contributes significantly to tumor progression. RNAbinding proteins regulate multiple steps of RNA metabolism and have emerged as promising prognostic biomarkers and therapeutic targets in BRCA. Methods: RNA-sequencing data and clinical information of BRCA patients were obtained from TCGA. Differential expressions, Cox, and LASSO regression analyses were performed to identify prognosis-related RBPs and establish a risk scoring model. A clinical nomogram integrating the model with clinicopathological features was generated. Tumor mutational burden (TMB), tumor immune microenvironment (TIME), and immune checkpoint expression were analyzed between risk groups. Functional assays, including CCK-8 proliferation and flow cytometry–based apoptosis analyses, were conducted in BRCA cell lines to determine the role of RPL9. Results: Nine prognosis-related RBPs were identified and used to construct the RBPbased prognostic scoring model, which effectively predicted 3-, 5-, and 9-year survival outcomes. The model remained robust in an external validation cohort. A clinical nomogram based on the model showed strong predictive performance. High-risk patients displayed higher TMB, lower immune scores, reduced CD8⁺ T-cell infiltration, and decreased immune checkpoint expression. RPL9 was markedly downregulated in BRCA tissues and cells, and RPL9 overexpression inhibited cell proliferation and significantly increased apoptosis, supporting its tumor-suppressive role. Conclusion: We identified and constructed a 9-RBP based scoring model and a clinical prognostic nomogram for accurately predicting the survival probability and assessing the tumor microenvironment of patients with BRCA. Moreover, our findings firstly demonstrated that RPL9 downregulation correlated with poor clinical outcomes and functionally drives tumor cell proliferation, establishing it as a potential therapeutic target and prognostic biomarker for BRCA.
Objective: To explore whether circulating plasma proteins have potential causal effects on gout risk by integrating genome-wide association study (GWAS) data with protein quantitative trait loci (pQTL) information, aiming to identify candidate proteins and pathways for therapeutic targeting. Introduction: Despite advances in gout pathophysiology, personalized therapies and validated drug targets remain limited. We conducted an exploratory Mendelian randomization (MR) analysis to assess whether circulating plasma proteins show evidence consistent with potential causal effects on gout risk, integrating GWAS with pQTL data to prioritize proteins and pathways for follow-up. Methods: We applied an integrated genetics framework combining proteome-wide MR, reverse MR, Bayesian colocalization, and sensitivity analyses. Plasma pQTL datasets were obtained from Zheng et al. and deCODE Genetics; gout GWAS were from UK Biobank and the FinnGen R12 study. Primary inference used inverse-variance weighting (IVW) with MR-Egger and complementary sensitivity tests. Colocalization used Bayesian methods; reverse MR evaluated potential reverse causation. Where available, findings were checked in external datasets. Analyses followed STROBE-MR guidance and were implemented in R with standard MR/colocalization packages. Results: Five circulating proteins (FN1, PLAU, CPQ, SPOCK2, and FAM213A) met the predefined discovery threshold. Reverse Mendelian randomization provided no evidence supporting reverse causality from gout to protein levels, while Steiger directionality tests supported the protein-to-gout causal orientation. Bayesian colocalization indicated moderate to strong evidence of shared genetic signals for PLAU, FAM213A, and FN1, whereas the evidence for CPQ and SPOCK2 was comparatively weak. In the independent replication analysis, genetically predicted higher levels of PLAU and CPQ were directionally associated with an increased risk of gout, while higher FN1 levels showed a consistent protective association. Nevertheless, effect estimates and precision varied across datasets, and the overall findings should be interpreted as exploratory rather than confirmatory. Conclusion: This exploratory, assumption-dependent MR work nominates five circulating proteins as hypothesis-generating candidates for gout risk and potential therapeutic targeting. Given method assumptions and cross-dataset heterogeneity, functional validation and independent replication are required to clarify mechanisms, confirm targetability, and assess translational relevance.
The spectrum of pathological conditions affecting the nasopharynx includes infections, congenital anomalies, and tumoral lesions, particularly angiofibroma, nasopharyngeal carcinoma, and lymphoma. Hypertrophy of adenoid tissue is a frequent phenomenon in children, but it is less common in the adult population. With this case report, we wanted to point out the importance of rhinological and otological manifestations of adenoid hypertrophy in adult patients. A 48-year-old man presented with impaired hearing in both ears, difficulty breathing through the nose, impaired sense of smell, hyponasal speech, and occasional scanty bleeding from the right side of the nose. After taking detailed data, the diagnostics included a classic ENT examination, endoscopy of the nasal cavity and nasopharynx, audiological diagnostics, allergy tests, computerized tomography of the paranasal sinuses and the skull base, and serological analysis for viruses and protozoa. A soft tissue lesion that filled the entire nasopharynx was surgically removed, and the pathohistological analysis indicated B-cell small lymphocytic lymphoma (SLL) with polyclonal plasma cell differentiation. Serological analyses showed that it was a human immunodeficiency virus (HIV)-positive patient, who also had a high blood titer of IgG to the Epstein-Barr virus. The patient was admitted to another institution for oncology treatment under the supervision of an infectious disease specialist. Although rare, malignant transformation of nasopharyngeal lymphoid tissue is possible. B-cell SLL with polyclonal plasma cell differentiation represents a minority of malignancies originating from the nasopharynx, and there are limited data regarding epidemiologic and treatment outcomes. Early recognition and thorough evaluation are essential to distinguish benign enlargement from more serious conditions.
OBJECTIVE:To evaluate the safety and effectiveness of isoniazid preventive therapy (IPT) in pregnant women living with HIV (WLWH) through a systematic review and meta-analysis. INTRODUCTION:Isoniazid preventive therapy (IPT) is recommended for preventive treatment of tuberculosis in high risk groups. However, evidence on its role in pregnant WLWH remains scarce. METHODS:We performed a systematic review and meta-analysis to pool randomized controlled trials (RCTs) as well as non-randomized studies (NRS) where IPT was administered to pregnant WLWH (PROSPERO ID: CRD42024618836). PubMed, Embase, and Cochrane Central databases were searched for relevant articles, until November 15, 2024. Statistical analysis was performed using R Software v4.4.1 and a random-effects model was applied to pool risk ratios (RRs) along with 95% confidence intervals. RESULTS:Five studies with a total of 45,402 patients (mean age = 30 years) were included. The risk of maternal mortality was significantly decreased in pregnant WLWH exposed to IPT compared with the control group (RR 0.42; 95% CI 0.20-0.92; p = 0.03). However, the risks of other outcomes including composite adverse pregnancy outcome (RR 0.90; 95% CI 0.56-1.43; p = 0.66), prematurity (RR 0.86; 95% CI 0.46-1.60; p = 0.63), low birthweight (RR 0.99; 95% CI 0.69-1.42; p = 0.95), very low birthweight (RR 1.28; 95% CI 0.39-4.23; p = 0.55), congenital anomalies (RR 1.48; 95% CI 0.59-3.75; p = 0.41), and hepatotoxicity (RR 0.99; 95% CI 0.71-1.37; p = 0.93) were comparable between the two groups. CONCLUSION:IPT in pregnant WLWH significantly reduces maternal mortality without increasing adverse pregnancy outcomes. These findings support the continued use of IPT during pregnancy, with careful monitoring for hepatotoxicity, and highlight its potential role as an important maternal health intervention in high TB/HIV burden regions.
Shikonin has been reported to regulate caudal-type homeobox 2 (CDX2)-mediated intestinal epithelial cell (IEC) differentiation, and ferroptosis has been identified a critical event during this process. However, the exact role of ferroptosis in shikonin-induced IEC differentiation remains unclear. Accordingly, the aim of this study was to elucidate the involvement of ferroptosis in CDX2-mediated IEC differentiation induced by shikonin. Real-time polymerase chain reaction, western blotting, luciferase assay, immunoprecipitation, and chromatin immunoprecipitation were used to reveal the mechanism underlying shikonin-modulated ferroptosis-dependent IEC differentiation in HT-29 and Caco-2 cells. Shikonin treatment reduced ferroptosis in IECs, as evidenced by the increased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 (cationic amino acid transporter) member 11, which enhanced CDX2 expression and improved IEC barrier function. Mechanistically, shikonin activated the protein kinase A (PKA)/cAMP-responsive element-binding protein (CREB) signaling cascade, promoting CREB binding to the GPX4 promoter and initiating GPX4 transactivation. GPX4 inhibition reversed the effects of shikonin on CDX2 expression. Endogenous pyruvate kinase isozyme M2 interacted with phosphodiesterase 4; this interaction was disrupted by shikonin, leading to the activation of PKA/CREB signaling. The findings of this study indicate that a low dose of shikonin improves IEC barrier function through GPX4-mediated inhibition of ferroptosis, highlighting its potential as a therapeutic agent for intestinal mucosal injury.
Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by damage to alveolar epithelial cells and pulmonary capillary endothelial cells. Compared with ARDS caused by other causes, the subtypes of ARDS caused by sepsis are more serious and lead to poor prognosis and higher mortality. Agmatine (AGM) is a biological metabolite of L-arginine decarboxylation, proven to ameliorate sepsis-induced acute lung injury (SALI), but the mechanism remains unclear. Therefore, this study aims to explore the role of AGM in SALI, clarify the relationship between the I 2 R/RSK2/NF-κB signaling pathway regulated by AGM and macrophage polarization, and provide a theoretical basis for the clinical treatment of SALI. Cellular and animal models of lung injury in sepsis were established with lipopolysaccharide (LPS). We conducted a series of experiments to examine the oxygenation index (OI), wet/dry ratio (W/D) of the lung, pathological changes, levels of inflammation, Apoptosis and related protein expression in different groups of mice. Finally, we found that AGM can ameliorate sepsis-induced acute lung injury by suppressing the I 2 R/RSK2/NF-κB signaling pathway and modulating polarization of alveolar macrophage.
Hepatitis C virus (HCV) infection is a major global public health problem. Although it has traditionally been linked to liver damage, several studies have demonstrated its extrahepatic impact, specifically in the oral cavity. Oral manifestations can be considered early signs of infection or contribute to clinical progression. This narrative review aims to describe the oral alterations associated with HCV, integrating the pathophysiological mechanisms and clinical implications for dental management. The most prevalent manifestations include periodontal disease, oral lichen planus, Sjögren's syndrome-like sialadenitis, and squamous cell carcinoma of the oral cavity. Recent findings suggest that HCV triggers dysbiosis of the oral microbiome, promotes exacerbated immune responses with overproduction of pro-inflammatory cytokines, and disrupts the homeostatic environment, thereby promoting the progression of inflammatory and neoplastic diseases. In addition, viral RNA has been identified in saliva and gingival crevicular fluid, which could be considered a non-parenteral route of transmission, particularly important in dental interventions. In parallel, direct-acting antiviral therapy, in addition to achieving virus elimination, could also partially correct immunological and microbial disruptions in the cavity, with favorable clinical responses. Understanding these oral alterations can guide dentists in early detection and improve systemic outcomes.
OBJECTIVE:Cannabidiol (CBD) administration (5 mg/kg) in healthy rats has been shown to significantly decrease lymphocyte subset numbers in peripheral blood without involvement of natural killer cells. The aim was to evaluate whether lymphocyte numbers also decrease in the spleen. INTRODUCTION:CBD, the major non-psychotropic compound of Cannabis sp., is an effective treatment for inflammatory and autoimmune diseases with various anti-tumor effects, but the mechanisms of its long-term actions in vivo remain unclear. METHODS:To examine the effects of CBD on lymphocyte subsets in the spleen and NK cellular cytotoxicity (NKCC), adult male Wistar rats (n = 63) were administered intraperitoneal injections of CBD (2.5 or 5 mg/kg/day) for 14 consecutive days, and lymphocyte counts were obtained using flow cytometry. NKCC in the peripheral blood and spleen was quantified using a Chromium-51 release assay. Furthermore, the effect was similar to a decrease in lymphocytes caused by treatment with the selective receptor antagonist AM630 (1 mg/kg). RESULTS:The results indicate that repeated administration of CBD at a dose of 5 mg/kg/day decreased splenic lymphocyte numbers, involving T and non-T/NK CD45RA+ lymphocytes but not NK cells. The effects of CB2 receptor antagonist were not significant, but it had a significant interaction with CBD. No changes in NKCC were observed following CBD administration. CONCLUSION:These results reveal that in healthy rats, CBD produces similar lymphopenic effects in the spleen as it does in peripheral blood without affecting NK cell counts or cytotoxicity.
The oral epithelium is a dynamic interface between host and environment, where keratinocytes not only serve as structural components but also actively modulate immune responses. Emerging research identifies IRF6 as a pivotal regulator of epithelial differentiation and immune signaling within chronic inflammatory contexts. This narrative review explores the role of IRF6 and its downstream effects in oral keratinocytes, particularly in relation to Toll-like receptor (TLR) activation, CCL5-mediated inflammation, hypoxic signaling, and the epithelial-mesenchymal transition (EMT). It proposes a mechanistic framework for understanding the progression from chronic inflammation to epithelial disruption and malignant transformation in oral mucosal disorders. Modulation of IRF6 signaling represents a promising therapeutic target for restoring epithelial integrity and halting disease progression in chronic inflammatory oral diseases. This model lays groundwork for future research integrating molecular biomarkers and immune modulation strategies in oral pathology.
OBJECTIVE:This study aimed to evaluate whether EDTA-based targeted chelation therapy can act as senomorphic in chronic kidney disease (CKD)-induced vascular calcification. INTRODUCTION:Vascular calcification, a significant complication of CKD, is induced due to osteogenic trans-differentiation and senescence of vascular smooth muscle cells (VSMCs). Senescent VSMCs contribute to inflammation and calcification via the senescence-associated secretory phenotype (SASP). Recent evidence implicates the NLRP3 inflammasome as a key mediator of inflammation and senescence in vascular calcification. We previously demonstrated that EDTA chelation therapy removes calcium deposits from arteries in the CKD model. In this study, we investigated whether EDTA also exerts senomorphic effects by reducing NLRP3 expression and vascular cell senescence in calcified aortic tissue. METHODS:We used an adenine diet-based rodent model of late-stage CKD and an ex vivo aortic ring culture model to evaluate the senotherapeutic potential of EDTA-loaded human serum albumin nanoparticles tagged with anti-elastin antibody-Flexibzumab (EDTA NPs). For validation, we performed a comparative proteomics analysis on the total proteins harvested from the abdominal aortas of the EDTA-treated and untreated animals. RESULTS:Our results show that targeted chelation therapy with EDTA NPs decreases the percentage of SA-β-gal positive senescent cells in the calcified aorta and acts as senomorphic by decreasing NLRP3 inflammasome formation, which is a primary intracellular source of senescence-associated secretory phenotype (SASP). CONCLUSION:For the first time, the current study provides proof of concept on the senotherapeutic potential of a targeted chelation therapy and its capacity to modulate SASP from the senescent cells accumulated in calcified aorta.
