Diabetic foot ulcer (DFU) is a severe complication of diabetes, characterized by chronic, difficult‑to‑heal foot wounds. It has been hypothesized that miR‑222‑3p may influence wound healing via the regulation of angiogenesis. To elucidate the underlying mechanism, experimental investigations were conducted in vitro using human dermal microvascular endothelial cells (HMEC‑1) and in vivo in a mouse model of streptozotocin‑induced diabetes. Methylglyoxal (MGO), a glycolytic intermediate, is known to contribute to diabetic vascular complications. The results demonstrated that MGO‑treated HMEC‑1 cells exhibited an increased expression of miR‑222‑3p and impaired microvascular endothelial cell function. The overexpression of miR‑222‑3p in MGO‑treated HMEC‑1 cells further suppressed cell proliferation, migration and tube formation, while it enhanced apoptosis. Moreover, the upregulation of miR‑222‑3p reduced the expression of apelin (APLN), and dual‑luciferase reporter assays confirmed APLN as a direct downstream target of miR‑222‑3p. The silencing of APLN markedly impaired HMEC‑1 cell function. Notably, both the exogenous supplementation with Apelin‑13 and the overexpression of APLN significantly reversed endothelial dysfunction caused by the upregulation of miR‑222‑3p. In vivo, in both normal and diabetic mice, the elevated expression of miR‑222‑3p in skin wounds reduced APLN levels in the peri‑wound tissue and impaired wound healing. However, the overexpression of APLN or the inhibition of miR‑222‑3p with an antagomiR reversed this impairment. Collectively, these results suggest that miR‑222‑3p impairs microvascular endothelial cell function by targeting APLN, thereby contributing to delayed wound healing in diabetic skin.

Oral pigmentation in childhood ranges from common constitutional variants to less frequent reactive, local, medication-related, vascular, genetic, endocrine, and neoplastic disorders. Overlapping clinical appearances can create diagnostic uncertainty, especially when adult-oriented approaches are applied to children. This narrative review presents a pediatric-focused framework for initial evaluation based on five domains: onset and evolution; focal, multifocal, or diffuse distribution; color and surface morphology; blanching or compressibility; and medication, dental, family, environmental, and systemic clues. Longstanding, symmetric, diffuse brown pigmentation without symptoms usually favors constitutional melanin pigmentation. Multifocal lentigines with gastrointestinal, endocrine, skeletal, or family-history findings should prompt targeted evaluation for an underlying syndrome. Blue-gray lesions adjacent to a restoration or trauma site suggest exogenous pigment, whereas red-blue compressible lesions raise concern for a vascular process and should not undergo blind biopsy. Oral melanoacanthoma is an important benign mimic because it may enlarge rapidly and appear clinically alarming. New or changing focal lesions, particularly those showing nodularity, ulceration, spontaneous bleeding, marked asymmetry, irregular borders, color variegation, or diagnostic uncertainty, warrant prompt specialist assessment and histopathologic evaluation when indicated. Pediatric evidence remains limited and consists largely of observational studies, case reports or series, and extrapolation from adult literature; accordingly, the proposed pathway is an evidence-informed clinical aid rather than a validated prediction rule. A structured history-first approach can support appropriate reassurance, targeted referral, and timely biopsy while minimizing unnecessary intervention for convincingly benign pigmentation.

Amivantamab is an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) antibody. Lazertinib is an EGFR tyrosine kinase inhibitor with central nervous system penetration. Used in combination, this targeted therapy is effective in treating non-small cell lung cancer (NSCLC). However, it has been associated with severe dermatologic adverse reactions. A 61-year-old woman with a history of EGFR-mutated NSCLC with brain metastases on amivantamab-lazertinib therapy presented for follow-up with drainage from her scalp incision after undergoing a right parietal craniotomy and mass excision five months prior. The patient denied constitutional and neurologic symptoms, but reported yellow staining on her pillow. Examination initially demonstrated yellow fibrinous exudate and hair matting along the surgical incision. Computed tomography (CT) of the head revealed overlying scalp swelling and minimal extra-axial dural thickening over the prior right parietal craniotomy site with stable intracranial metastatic lesions. Due to concern for dehiscence, her biologic therapy was paused, and she was taken to the operating suite where no evidence of infection, delayed healing, or wound dehiscence was noted. A 10 × 5 cm area of patchy granulation tissue and ulceration was observed along the right parietal scalp. Biopsy revealed granulation tissue and multinucleated giant cells and was negative for tumor. Given the risk of malignant progression with all targeted therapy paused, the patient was restarted on amivantamab monotherapy. Following disease progression two months later, she was transitioned to carboplatin and etoposide. EGFR is widely expressed in skin keratinocytes and intimately involved in epithelial differentiation. Therapies targeting EGFR, such as amivantamab plus lazertinib, are associated with adverse dermatologic reactions, ranging from dry skin to severe scalp ulceration, which can interrupt treatment, contribute to poorer clinical outcomes, and reduce quality of life. Standard of care includes limiting sun exposure and avoiding alcohol-based topical agents. The use of daily prophylactic antibiotics, such as oral doxycycline, topical clindamycin, chlorhexidine wash, and ceramide moisturizer, may significantly reduce the risk of adverse skin reactions. Implementation of this multicomponent regimen reduced the rate of severe scalp reactions from 26% to 10% relative to the standard of care, with sustained benefit observed for at least six months.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, frequently cause gastric injury, often characterized by ulceration. This study investigated the comparative gastroprotective effects of white quinoa and tri-color quinoa (a combination of red, black, and white varieties) in mitigating indomethacin-induced gastric damage in male rats. Thirty-six male rats were divided into dietary groups and administered quinoa-supplemented diets for 21 days before gastric injury was induced using indomethacin. Biochemical markers, including TNF-α and IL-6, were assessed, and molecular docking was employed to examine the interactions of quinoa-derived compounds, such as procyanidin B2 and cinchonain IB, with target proteins Atp4a, COX-2, and NF-κB. Tri-color quinoa demonstrated greater efficacy than white quinoa, reducing mucosal necrosis by 83%, attenuating oxidative stress, and significantly enhancing anti-inflammatory markers (p < 0.05). Furthermore, bioactive compounds showed strong binding affinities (-7.1 to -8.9 kcal/mol) to target proteins through hydrogen and hydrophobic interactions. Histological examination confirmed superior protection for the tri-color group, displaying near-normal mucosa (lesion score 0.4 vs. 2.4) and minimal submucosal edema. In conclusion, tri-color quinoa provides more effective protection against NSAID-induced gastric injury than white quinoa, likely due to its enhanced phytochemical profile and broader range of plant-derived compounds that collectively reduce inflammation and preserve gastric mucosal integrity.

Oral formulations of aminosalicylates are widely used in the treatment of ulcerative colitis (UC), but their efficacy is limited by low absorption and bioavailability due to first-pass metabolism and gastric degradation. pH-sensitive hydrogels were formulated for colon-targeted, delayed drug release to address this concern. Moreover, molecular docking was conducted to evaluate the binding affinity between β-cyclodextrin (oligomer) and balsalazide disodium. 15 formulations were developed using a Box-Behnken design in Design-Expert® 11, varying the concentrations of cross-linker, oligomer, and monomer while keeping the initiator constant. Hydrogels were developed via free radical polymerization using N,N-methylene bisacrylamide (MBA), β-cyclodextrin, potassium persulfate (KPS), and acrylic acid. Formulations were evaluated for swelling behavior, drug release, entrapment efficiency, porosity, and sol-gel fraction. The hydrogels exhibited maximum swelling at pH 7.2 (3783.4%) and a low sol fraction (10%), achieving 96% drug entrapment. FTIR suggested no interaction between the drug and excipients used. DSC and SEM analyses revealed stable thermal behavior and porous morphology. Molecular docking confirmed promising binding between balsalazide disodium and β-cyclodextrin. In vitro release studies showed sustained drug release for up to 8 hours, with kinetic modeling best fitting the Hixson-Crowell model, indicating drug release by change in geometry, surface area, and swelling of the hydrogel matrix. In the current research work, the optimized pH-sensitive hydrogel providing an effective sustained-release system for balsalazide disodium has been successfully developed, exhibiting promising pH-responsive drug-release characteristics.

ISG15 is a type I interferon (IFN-I)-inducible ubiquitin-like protein that restrains IFN-I signaling. Classical ISG15 deficiency is thought to cause disease mainly by disrupting USP18 stabilization, which leads to sustained IFN-I signaling and interferon-driven autoinflammation. Whether patient-derived C-terminal ISG15 variants can impair IFN-I negative feedback through altered C-terminal functional presentation has remained unclear.

Observational studies have frequently reported an association between primary biliary cirrhosis (PBC) and inflammatory bowel disease (IBD). In this study, we leveraged summary-level data from genome-wide association studies (GWAS) to conduct a two-sample bidirectional Mendelian randomization (MR) analysis, with the primary objective of investigating the genetic causal relationship between PBC and IBD, comprising ulcerative colitis (UC) and Crohn's disease (CD). Additionally, a validation analysis was performed by repeating the bidirectional MR framework, alternately defining PBC and IBD as the exposure and outcome variables to confirm the directionality of the observed associations. A comprehensive panel of sensitivity analyses was implemented to test the robustness of the findings. We first examined the genetic causality at the subtype level. In the forward MR, PBC exerted a significant positive causal effect on UC (P < 0.001, OR 95% CI = 1.081 [1.037-1.127]) and on CD (P = 0.002, OR 95% CI = 1.136 [1.047-1.232]). In the reverse MR, only UC showed a significant negative causal influence on PBC (P > 0.003, OR 95% CI = 0.788 [0.672-0.924]), whereas no significant effect was detected from CD on PBC (P = 0.431, OR 95% CI = 0.956 [0.856-1.068]). We then extended the analysis to the overall IBD phenotype. The forward MR demonstrated a significant positive genetic relationship between PBC on IBD (P < 0.001, OR 95% CI = 1.076 [1.042-1.110]). Conversely, the reverse MR did not support a causal effect of IBD on PBC (P = 0.357, OR 95% CI = 0.898 [0.714-1.129]). The robustness of all these findings was confirmed by comprehensive sensitivity analyses, which showed no evidence of heterogeneity, horizontal pleiotropy, or undue influence from individual instrumental variables. Our MR analysis demonstrates that PBC serves as a genetic determinant of IBD as a whole and of UC/CD separately, whereas reverse causation is limited to a protective effect of UC on PBC. This direction-dependent and subtype-specific causal architecture provides novel insights into the shared etiological pathways between PBC and IBD.

Homeostasis of the intestinal mucosal barrier microenvironment is contingent upon the coordinated interplay among mechanical, chemical, and immunological barriers. Recent studies have demonstrated that protein S-palmitoylation, a dynamic and reversible lipid modification, holistically reprograms the intestinal mucosal barrier microenvironment. This is achieved by modulating the membrane localization of tight junction proteins (Claudins and ZO proteins) and E-cadherin/catenin complexes, the secretion and anchoring of MUC2, as well as the membrane recruitment and signaling activation of receptors such as TLR4, NOD2, and NLRP3. Dysregulation of this modification not only drives barrier collapse and chronic inflammation in inflammatory bowel diseases (IBD), such as ulcerative colitis, but also exacerbates pathological progression by modulating the phenotypic remodeling of innate immune cells, including macrophages and neutrophils. Targeting the palmitoylation cycle-including ZDHHC acyltransferases, depalmitoylases (APTs and PPTs), or upstream metabolic enzymes like FASN-using either the broad-spectrum inhibitor 2-BP or selective inhibitors (ML348 and Palmostatin B), has shown promise in preclinical models restore barrier function and attenuate intestinal inflammation. However, it is important to emphasize that the therapeutic potential of these agents in IBD is currently supported primarily by in vitro and animal studies, and their clinical efficacy and safety remain to be established. This review systematically proposes a conceptual framework for the "reprogramming of the intestinal mucosal barrier microenvironment by S-palmitoylation." By integrating current evidence spanning from molecular modifications to barrier functions and from mechanistic insights to therapeutic strategies, we aim to provide novel molecular targets and a theoretical foundation for the development of mucosal healing therapies that are independent of traditional immunosuppression.

Chronic expanding hematoma (CEH) is a rare condition characterized by progressive enlargement of a hematoma long after an initial hemorrhagic event and may mimic malignancy. We report a 61-year-old woman who developed a progressively enlarging left axillary mass 15 years after modified radical mastectomy followed by adjuvant chemotherapy and radiotherapy for breast cancer. The lesion became ulcerated and spontaneously bled, raising concern for locoregional recurrence. Ultrasonography demonstrated heterogeneous mixed cystic-solid lesions, while systemic evaluation revealed no evidence of distant metastatic disease. Ultrasound-guided core needle biopsy showed hemorrhage, fibrin deposition, and fibrous tissue without malignant cells but was considered inconclusive because of potential sampling limitations. Surgical excision and extensive debridement were therefore performed. The 7 × 5 × 2 cm excised specimen was extensively sampled in 20 tissue blocks and demonstrated organized hematoma, fibrosis, hemosiderin-laden macrophages, and chronic inflammatory changes, without atypical endothelial proliferation or malignant tumor cells. CEH was definitively diagnosed. Following staged wound management with vacuum sealing drainage, the axillary defect was successfully reconstructed using a pedicled scapular artery perforator propeller flap. This case emphasizes the importance of considering CEH, recurrent carcinoma, and angiosarcoma in the differential diagnosis of delayed hemorrhagic masses after breast cancer treatment and highlights the importance of adequate histopathological sampling for definitive diagnosis.

Gastrointestinal mucormycosis is a rare, life-threatening invasive fungal infection that is often diagnosed late because of nonspecific clinical and endoscopic findings. Khat or Qat (Catha edulis) leaves may harbor environmental fungi, including Mucor species, and chronic chewing may contribute to gastrointestinal mucosal injury. However, a possible association between Qat use and gastrointestinal mucormycosis has not been established. We report a case of a 60-year-old man with diet-controlled type 2 diabetes mellitus and long-standing Qat chewing who was admitted after an out-of-hospital cardiac arrest secondary to acute myocardial infarction. He had no history of malignancy, transplantation, neutropenia, or immunosuppressive therapy. Return of spontaneous circulation was achieved after 34 min of cardiopulmonary resuscitation, followed by temporary venoarterial extracorporeal membrane oxygenation. On hospital day 14, coffee-ground material was observed through the nasogastric tube, accompanied by a decline in hemoglobin from 14.0 to 9.5 g/dL. Esophagogastroduodenoscopy revealed a fungating, ulcerated lesion involving the gastric fundus and body. Histopathological examination demonstrated extensive necrosis, angioinvasion, and broad, ribbon-like, pauci-septate fungal hyphae with irregular branching, consistent with gastric mucormycosis. Intravenous liposomal amphotericin B was initiated at 8 mg/kg/day. Gastrointestinal bleeding resolved without surgery. Repeat endoscopy one month later showed marked healing, and follow-up biopsy revealed no residual fungal elements. The patient completed six weeks of antifungal therapy and achieved clinical and histopathological resolution. Fungal culture and molecular identification were not performed, precluding species-level confirmation.‏ In conclusion, this case describes gastric mucormycosis in a patient without profound immunosuppression but with severe physiological stress and chronic Qat exposure. Critical illness, gastric hypoperfusion, and mucosal disruption may have facilitated fungal invasion. Qat chewing is presented as a hypothesis-generating factor because of possible fungal contamination of leaves and repeated mucosal injury; nevertheless, causality cannot be inferred from a single case. Further microbiological and epidemiological studies are required to investigate this potential association.

Diabetic foot complications are a major cause of morbidity, disability, and amputation worldwide, yet many complications are preventable through effective self-care. Limited evidence is available on foot self-care knowledge and behaviours among adults with diabetes in Ras Al Khaimah, United Arab Emirates.