Search Results (1,769)

Constipation is a prevalent gastrointestinal disorder that significantly impairs quality of life. While pharmacological agents such as loperamide are widely used to induce constipation in experimental models, there is increasing interest in natural alternatives for alleviating intestinal dysfunction. In this study, we investigated the laxative effects of soybean powder fermented by Bacillus subtilis DKU_09 in a loperamide-induced rat model of constipation. The probiotic strain was isolated from cheonggukjang, a traditional Korean fermented soybean paste, and its identity was confirmed through 16S rRNA sequencing. Fermented soybean powder was characterized morphologically via scanning electron microscopy and chemically via HPLC to assess its isoflavone content. Rats were administered loperamide (5 mg/kg) for four days to induce constipation and were then treated with fermented soybean powder at doses of 100, 200, or 300 mg/kg. No pharmacological laxatives (e.g., PEG) were used as a positive control; instead, values from the treatment groups were compared with those from the loperamide-only constipation group. Key outcomes of fecal output, water content, colonic fecal retention, and gastrointestinal transit ratio were measured. The fermented product significantly improved stool frequency and moisture content, reduced colonic fecal retention, and restored gastrointestinal transit in a dose-dependent manner. Notably, the 300 mg/kg group demonstrated nearly complete recovery of fecal parameters without affecting body weight. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. These findings suggest that Bacillus subtilis-fermented soybean powder exerts synergistic laxative effects through the combined action of probiotic viability and fermentation-enhanced bioactive compounds such as aglycone isoflavones. This study supports the potential use of fermented soybean-based nutraceuticals as a natural and safe intervention for constipation and gastrointestinal dysregulation. Full article

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Introduction: Finger injuries are common in pediatric patients and typically heal well with conservative management. However, rare fracture patterns involving significant displacement and physeal injury, such as the one described in this case, require specialized surgical intervention to ensure proper healing and prevent long-term complications. Case Presentation: A 12-year-old left-hand-dominant female presented with pain, swelling, and deformity at the distal interphalangeal (DIP) joint following hyperextension of the left fifth digit. Initial radiographs revealed a volar displaced intra-articular fracture with physis involvement, confirmed by computed tomography (CT) imaging. Conservative management with closed reduction and splinting failed to achieve adequate alignment. Surgical intervention was performed via a dorsal approach, utilizing ORIF with K-wire fixation to restore joint congruity and ensure anatomic alignment. Outcomes: Postoperative follow-up demonstrated satisfactory healing, maintained reduction, and resolution of pain with no complications. The patient regained functional use of the digit with minimal stiffness, and the growth plate remained uninvolved during the recovery period. Discussion: This case underscores the importance of advanced imaging, early referral, and tailored surgical intervention for rare mallet fractures involving volar displacement and physeal injury. ORIF provided reliable stabilization and optimal outcomes in this complex case. Conclusions: Volar displaced Salter–Harris III fractures of the DIP joint are rare and challenging injuries in pediatric patients. This case highlights the role of ORIF in achieving successful outcomes and emphasizes the importance of precise reduction and stabilization to prevent long-term complications. Full article

Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical stress on adjacent or opposing teeth. This study aimed to investigate the association between the increased number of dental implants and the incidence of cracked teeth following the introduction of implant insurance. Methods: A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul St. Mary’s Dental Hospital. Patients who underwent molar crown restorations between 2014 and 2022 were included. The incidence and clinical features of cracked teeth were compared before (2014–2015) and after (2016–2022) the introduction of implant insurance. Statistical analyses assessed differences in symptom presentation, pulp status, and treatment outcomes. Results: Among 5044 molars restored with crowns, 1692 were diagnosed with cracks. The incidence of cracked teeth significantly increased after NHI coverage for implants (25.5% vs. 32.6%, p < 0.001). Cases after insurance implementation showed fewer signs and symptoms at initial presentation (67.4% vs. 50.0%, p < 0.001), reduced irreversible pulpitis (37.2% vs. 25.8%, p < 0.001), and increased preservation of pulp vitality (46.9% vs. 57.8%, p < 0.001). These shifts may reflect changes in occlusal adjustment practices and earlier clinical intervention. Conclusions: The findings suggest a temporal link between increased implant placement and the rising incidence of cracked teeth. Implant-induced occlusal changes may contribute to this trend. Careful occlusal evaluation and follow-up are essential after implant placement, and further prospective studies are warranted to confirm causality and refine prevention strategies. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Heavy metal pollution represents a pervasive environmental challenge that significantly exacerbates the ever-increasing crisis of antimicrobial resistance and the capacity of microorganisms to endure and proliferate despite antibiotic interventions. This review examines the intricate relationship between heavy metals and AMR, with an emphasis on the underlying molecular mechanisms and ecological ramifications. Common environmental metals, including arsenic, mercury, cadmium, and lead, exert substantial selective pressures on microbial communities. These induce oxidative stress and DNA damage, potentially leading to mutations that enhance antibiotic resistance. Key microbial responses include the overexpression of efflux pumps that expel both metals and antibiotics, production of detoxifying enzymes, and formation of protective biofilms, all of which contribute to the emergence of multidrug-resistant strains. In the soil environment, particularly the rhizosphere, heavy metals disrupt plant–microbe interactions by inhibiting beneficial organisms, such as rhizobacteria, mycorrhizal fungi, and actinomycetes, thereby impairing nutrient cycling and plant health. Nonetheless, certain microbial consortia can tolerate and detoxify heavy metals through sequestration and biotransformation, rendering them valuable for bioremediation. Advances in biotechnology, including gene editing and the development of engineered metal-resistant microbes, offer promising solutions for mitigating the spread of metal-driven AMR and restoring ecological balance. By understanding the interplay between metal pollution and microbial resistance, we can more effectively devise strategies for environmental protection and public health. Full article

Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article

Classical Hodgkin lymphoma (cHL) is a biologically and clinically unique malignancy characterized by rare Hodgkin and Reed–Sternberg (HRS) cells surrounded by a dense and diverse inflammatory infiltrate. These malignant cells actively reshape the tumor microenvironment (TME) through metabolic reprogramming and immune evasion strategies. This review synthesizes current knowledge on how metabolic alterations contribute to tumor survival, immune dysfunction, and therapeutic resistance in cHL. We discuss novel therapeutic approaches aimed at disrupting these processes and examine the potential of combining metabolic interventions with immune-based strategies—such as immune checkpoint inhibitors (CPIs), epigenetic modulators, bispecific antibodies, and CAR-T/CAR-NK cell therapies—which may help overcome resistance and enhance anti-tumor responses. Several agents are currently under investigation for their ability to modulate immune cell metabolism and restore effective immune surveillance. Altogether, targeting metabolic vulnerabilities within both tumor and immune compartments offers a promising, multifaceted strategy to improve clinical outcomes in patients with relapsed or refractory cHL. Full article

Situated in the southern hilly-mountain belt of China’s “Three Zones and Four Belts Strategy”, Gannan region is a critical ecological shelter belt for the Ganjiang River. Decades of intensive mineral extraction and irrational agricultural development have rendered it into an ecologically fragile area. Consequently, multiple restoration initiatives have been implemented in the region over recent decades. However, it remains unclear how relationships among ecosystem services have evolved under these interventions and how future ecosystem management should be optimized based on these changes. Thus, in this study, we simulated and assessed the spatiotemporal dynamics of five key ESs in Gannan region from 1990 to 2020. Through integrated correlation, clustering, and redundancy analyses, we quantified ES interactions, tracked the evolution of ecosystem service bundles (ESBs), and identified their socio-ecological drivers. Despite a 31% decline in water yield, ecological restoration initiatives drove substantial improvements in key regulating services: carbon storage increased by 6.9 × 10¹² gC while soil conservation rose by 4.8 × 10⁸ t. Concurrently, regional habitat quality surged by 45% in mean scores, and food production increased by 2.1 × 10⁵ t. Critically, synergistic relationships between habitat quality, soil retention, and carbon storage were progressively strengthened, whereas trade-offs between food production and habitat quality intensified. Further analysis revealed that four distinct ESBs—the Agricultural Production Bundle (APB), Urban Development Bundle (UDB), Eco-Agriculture Transition Bundle (ETB), and Ecological Protection Bundle (EPB)—were shaped by slope, forest cover ratio, population density, and GDP. Notably, 38% of the ETB transformed into the EPB, with frequent spatial interactions observed between the APB and UDB. These findings underscore that future ecological restoration and conservation efforts should implement coordinated, multi-service management mechanisms. Full article

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracaseiL21 (L. paracaseiL21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracaseiL21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracaseiL21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracaseiL21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracaseiL21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Background and Clinical Significance: Traumatic dental injuries, particularly complicated crown fractures of permanent incisors, are common in adolescents, with maxillary central incisors most frequently affected due to their prominent position. These injuries, often resulting from sports or accidents, require prompt management to prevent complications such as pulp necrosis or infection, which can compromise long-term prognosis. Fragment reattachment offers a conservative, esthetically favorable approach when the fractured segment is intact, with outcomes comparable to composite restorations. This case report underscores the importance of timely intervention and advanced restorative techniques in pediatric dentistry. Case Presentation: A 16-year-old male presented with a complicated crown fracture of the upper left central incisor sustained during a soccer game. The fracture extended subgingivally with pulp exposure. The patient preserved the fragment in saline. Treatment involved fragment reattachment using a dentin bonding agent and flowable composite resin, followed by single-visit root canal therapy due to delayed presentation (48 h). A glass fiber post was placed to reinforce the restoration due to significant coronal loss. Three years of follow-up visits (1, 3, 6, 12, 24, and 36 months) revealed no clinical or radiographic complications, with the tooth remaining asymptomatic and functional. Conclusions: This case underscores the effectiveness of fragment reattachment when combined with meticulous technique and long-term monitoring. Full article

Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article