Search Results (2,099)

Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article

Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1 mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

Malignant gastric outlet obstruction (MGOO) is a serious complication arising from advanced gastric or pancreatic head cancer, significantly impairing patients’ quality of life by disrupting oral intake and inducing severe gastrointestinal symptoms. With benign causes such as peptic ulcer disease on the decline, malignancies now account for 50–80% of gastric outlet obstruction (GOO) cases globally. This review outlines the pathophysiology, evolving epidemiology, and treatment modalities for MGOO. Therapeutic approaches include conservative management, endoscopic stenting, surgical gastrojejunostomy (GJ), stomach partitioning gastrojejunostomy (SPGJ), and endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While endoscopic stenting offers rapid symptom relief with minimal invasiveness, it has higher rates of re-obstruction. Surgical options like GJ and SPGJ provide more durable palliation, especially for patients with longer expected survival. SPGJ, a modified surgical technique, demonstrates reduced incidence of delayed gastric emptying and may improve postoperative oral intake and survival compared to conventional GJ. EUS-GE represents a promising, minimally invasive alternative that combines surgical durability with endoscopic efficiency, although long-term data remain limited. Treatment selection should consider patient performance status, tumor characteristics, prognosis, and institutional resources. This comprehensive review underscores the need for individualized, multidisciplinary decision-making to optimize symptom relief, nutritional status, and overall outcomes in patients with MGOO. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article

Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal that SW exhibits rapid absorption but demonstrates low oral bioavailability due to the first-pass effect. Pharmacological studies have demonstrated that SW possesses a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective activities. Our analysis demonstrates that SW exerts remarkable therapeutic potential across multiple pathological conditions through coordinated modulation of key signaling cascades, including Nrf2/HO-1, NF-κB, MAPK, PI3K/Akt, and PPAR pathways. This comprehensive review systematically consolidates current knowledge on SW’s pharmacokinetic characteristics, toxicity, diverse biological activities, and underlying molecular mechanisms based on extensive preclinical evidence, establishing a scientific foundation for future drug development strategies and potential clinical applications of the potential natural lead compound. Full article

Curcumin is widely recognized for its various pharmacological properties, including antioxidant, anti-inflammatory, and anti-tumor activities. Nevertheless, the development of curcumin as a therapeutic agent is impeded by its limited oral bioavailability, which stems from its chemical instability, poor aqueous solubility, and rapid degradation. This study aimed to develop granule formulations incorporating poly(N-isopropylacrylamide)-grafted hyaluronic acid or HA-g-pNIPAM to enhance dissolution and protect curcumin from degradation. Three formulations were developed: F10 (HA-g-pNIPAM physically mixed with curcumin), F10 Encap (curcumin encapsulated within HA-g-pNIPAM), and F11 (curcumin granules without HA-g-pNIPAM). The stability results showed that F10 Encap effectively maintained curcumin content throughout the study period, retaining approximately 94% of its initial concentration by day 30, compared to 70% from F11 (p < 0.05) at 30 °C and 75% relative humidity. All dried curcumin granules exhibited excellent flowability, as determined by the angle of repose measurements. All three formulations exhibited a consistent particle size distribution across replicates, with a peak in the 150–180 μm size range. The sustained release observed for F10 Encap and F10 after the initial burst suggested that the HA-g-pNIPAM provided a controlled release mechanism, ensuring continuous curcumin dissolution over 240 min in gastric and intestinal conditions. These findings suggested that HA-g-pNIPAM improved dissolution and stability of curcumin. Full article

Background/objectives: This study evaluated the immunoenhancing effects of Agastache rugosa extract in a cyclophosphamide-induced immunosuppressed mouse model. Methods: Jeju A. rugosa was processed via hot water extraction and 20% ethanol extraction. For immunosuppression induction, 7-week-old male BALB/c mice received intraperitoneal CPA injections (150 mg/kg, day −3; 110 mg/kg, day −1), followed by oral administration of hot water extract (ARE-W) and ethanol extract (ARE-E) at 100 and 300 mg/kg for 14 days. Oral administration of ARE-W and ARE-E was started on day 0, immediately following the final CPA injection on day −1. Immune function was assessed through body weight changes, spleen weight, NK cell activity, IFN-γ production, and splenic lymphocyte proliferation. Results: Results demonstrated that CPA treatment induced comprehensive immune dysfunction, while A. rugosa extracts significantly ameliorated these immunosuppressive conditions. Notably, ARE-W (300 mg/kg) significantly enhanced NK cell cytotoxicity against tumor cells and IFN-γ production compared to the CPA group, and effectively restored spleen weight and lymphocyte proliferation. ARE-E also exhibited dose-dependent immune function recovery; however, ARE-W showed superior efficacy across most immune parameters. Conclusions: These findings suggest that A. rugosa extract, particularly ARE-W, effectively restores immune function in immunosuppressed conditions, indicating potential application as a natural functional material for ameliorating immunosuppression caused by cancer treatment or immune diseases. Full article

Background/Objectives: Alectinib, a second-generation tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer (NSCLC), exhibits suboptimal oral bioavailability, primarily attributable to its inherently low aqueous solubility and limited dissolution kinetics. This study aimed to enhance Alectinib’s solubility and therapeutic efficacy by formulating a G4-NH2-PAMAM dendrimer complex. Methods: The complex was prepared using the organic solvent evaporation method and characterized by DSC, FTIR, dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with the G4-NH2-PAMAM dendrimer complex. Cytotoxicity against NSCLC cell line A549 was assessed using MTT assays, clonogenic assay, and scratch-wound assay. Xenograft effect was investigated in the H460 lung cell line. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: Alectinib exhibited an encapsulation efficiency of 59 ± 5%. In vitro release studies demonstrated sustained drug release at pH 6.8 and faster degradation at pH 2.5. Anticancer activity in vitro showed comparable efficacy to free Alectinib, with 98% migration inhibition. In vivo tumor suppression studies revealed near-complete tumor regression (~100%) after 17 days of treatment, compared to 75% with free Alectinib. Pharmacokinetic analysis indicated enhanced absorption (shorter Tmax), prolonged systemic circulation (longer half-life), and higher bioavailability (increased AUC) for the dendrimer-complexed drug. Conclusions: These findings suggest that the G4-NH2-PAMAM dendrimer system significantly improves Alectinib’s pharmacokinetics and therapeutic potential, making it a promising approach for NSCLC treatment. Full article

Background and Clinical Significance: Juvenile ossifying fibroma (JOF) is a rare, benign, but locally aggressive fibro-osseous neoplasm that primarily affects the craniofacial skeleton of children and adolescents. Early surgical intervention is often required due to the lesion’s rapid growth and potential for significant facial deformity. Long-term functional and esthetic rehabilitation following maxillary resection in early childhood remains a clinical challenge. Case Presentation: This case reports a unique long-term follow-up of a 22-year-old female patient who underwent partial maxillary resection at the age of five due to JOF. Initial reconstructive efforts failed, necessitating a removable prosthesis to restore function and appearance. The patient experienced persistent self-consciousness and social withdrawal during adolescence, attributed to altered facial esthetics and repeated surgical disappointment. Nevertheless, prosthetic rehabilitation significantly improved mastication, phonetics, facial symmetry, and psychological well-being. Conclusions: The enduring psychosocial and functional impact of early maxillary resection for JOF and the pivotal role of prosthodontic management in long term rehabilitation are highlighted. A multidisciplinary approach that includes psychological support is suggested. This case report is among the few reports documenting long-term prosthetic outcomes for pediatric JOF patients extending into adulthood. Full article

PD-L1, PD-1, FOXP3, and miR-155 are emerging as key modulators of immune evasion and progression of oral squamous cell carcinoma (OSCC). This study investigated the clinical relevance of their gene expression and variants in HPV-negative OSCC. Bulk-tissue mRNA expression was evaluated in 70 patients, while variants in PD-1 (rs36084323), PD-L1 (rs822336, rs4143815, copy number variation), FOXP3 (rs3761548, rs2232365), and miR-155 (rs767649) were assessed in 134 patients. Expression data were validated using the TCGA cohort of 222 HPV-negative OSCC cases. Low FOXP3 expression was significantly associated with tumor stage (MMA: p = 0.028, TCGA: p = 0.025) and poor overall survival (MMA: p = 0.0004, TCGA: p = 0.019) in both cohorts. Declining FOXP3 expression correlated with advancing tumor stages, and low FOXP3 expression was significantly associated with poor survival in advanced stage III–IV tumors (MMA: p = 0.001, TCGA: p = 0.015), but not early-stage tumors. High miR-155 expression was associated with recurrence (p = 0.002) and poor survival in the MMA (p = 0.007), but not TCGA cohort. MiR-155 rs767649 was associated with alcohol consumption (p = 0.018). These findings point to FOXP3 and miR-155 as potential prognostic biomarkers for HPV-negative OSCC. Stage-specific FOXP3 expression suggests a dynamic immunoregulatory role, with implications for optimizing immunotherapy timing. Further studies are warranted to resolve cellular context and stage-adapted immune interventions in HPV-negative OSCC. Full article

Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance risk stratification and guide treatment planning in OSCC patients. Methods: A retrospective study of 100 patients with confirmed OSCC treated surgically with curative intent between January 2019 and January 2024 was analyzed. Clinicopathologic variables—including tumor volume, angioinvasion, perineural invasion, lymphatic invasion, and nodal status—were evaluated. Disease-specific survival (DSS) was assessed using Kaplan–Meier estimates, Cox regression, and logistic regression models. Results: The cohort had a mean age of 62.1 years, with a 46% OS rate and 43% DSS at study end. Perineural invasion (44%) and lymphatic invasion (42%) were the most common invasive features. Kaplan–Meier analysis revealed significantly reduced DSS in patients with angioinvasion, perineural invasion, and pN+ status. Multivariate logistic regression identified perineural invasion (OR = 3.93, p = 0.0023) and pN+ status (OR = 2.74, p = 0.0284) as independent predictors of cancer-specific mortality. Tumor volume was significantly associated with lymphatic invasion but not directly with DSS. Conclusions: Perineural invasion, angioinvasion, lymph node involvement, and tumor volume are important prognostic markers in OSCC, offering critical information beyond TNM staging. Incorporating these features into risk assessment models could improve prognostic accuracy and inform more individualized treatment strategies for high-risk OSCC patients. Full article

Patients undergoing epidermal growth factor receptor inhibitor (EGFRI) therapy frequently experience dermatologic side effects, notably papulopustular rash, which impacts 50–90% of recipients. This rash typically appears on the face, chest, and back within weeks of treatment, resembling acne but stemming from distinct pathophysiological mechanisms, causing significant discomfort and reduced quality of life. Prophylactic measures and symptom-based treatment are recommended, emphasizing patient education, topical agents, and systemic therapies for severe cases. A 41-year-old female with advanced colonic mucinous adenocarcinoma developed severe acneiform rash and pruritus during EGFRI therapy with panitumumab. Initial standard treatment with oral doxycycline was discontinued after two days due to severe gastrointestinal intolerance characterized by intense nausea and dyspepsia. With limited access to dermatological consultation, treatment with rose stem cell-derived exosomes (RSCEs) provided rapid symptom relief. Significant improvement was observed within 24 h, with complete resolution of pruritus and substantial reduction in inflammatory lesions within 72 h. RSCEs demonstrate anti-inflammatory effects through the modulation of pro-inflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, while promoting fibroblast proliferation and collagen synthesis enhancement. They may represent a possible alternative to corticosteroids, avoiding associated side effects such as skin atrophy, delayed wound healing, and local immunosuppression. This case underscores the potential of innovative treatments like RSCEs in managing EGFRI-induced skin complications when standard therapies are not tolerated, particularly in healthcare systems with limited dermato-oncological resources. Full article