Fungal metabolites serve as a prolific source of structurally diverse bioactive compounds with significant potential for skin health and pigmentation regulation. In this study, two diastereomers of 11-hydroxycurvularin (compounds 1 and 2) and curvularin (compound 3) were isolated from Curvularia intermedia and evaluated for their anti-melanogenic and immunomodulatory effects. The diastereomeric mixture of 11-hydroxycurvularins (HC mix) exhibited superior anti-melanogenic activity in α-MSH-stimulated B16F10 melanoma cells, surpassing the efficacy of the individual diastereomers, the parent compound 3, and the positive control arbutin, without inducing cytotoxicity. Mechanistically, the HC mix exerted dual regulatory effects by inhibiting tyrosinase enzymatic activity and downregulating the transcription of core melanogenic genes (Tyr, Tyrp1, and Tyrp2). Furthermore, the HC mix attenuated LPS-induced reactive oxygen species (ROS) production and selectively regulated inflammatory gene expression in RAW 264.7 macrophages and primary murine splenocytes, downregulating IL-1β and IL-6 while upregulating TGF-β. These findings highlight that hydroxyl substitution at C-11 is critical for enhancing biological potency. Collectively, the HC mix represents a potential candidate for managing pigmentary and inflammatory skin disorders, warranting further validation in human models.

Osteoradionecrosis (ORN) is a severe late complication of head and neck radiotherapy, often refractory to conventional treatment. Photobiomodulation therapy (PBMT) and photodynamic therapy (PDT) have shown regenerative, analgesic, and antimicrobial effects. This report aims to describe the non-invasive management of extensive mandibular ORN with intra- and extraoral fistulas using a combined PBMT-PDT protocol.

A 72-year-old man previously treated with chemoradiation for laryngeal carcinoma developed chronic mandibular ORN after third molar extraction, complicated by a pathologic fracture, persistent suppuration, and failure of surgery, hyperbaric oxygen, antibiotics, and curettage. Clinical evaluation revealed intra- and extraoral suppurative fistulas and radiographic bone sequestration. A conservative regimen was initiated, consisting of weekly PBMT and PDT sessions following chlorhexidine irrigation. Over approximately one year (50 sessions), the patient reported progressive pain relief and reduced analgesic use. Complete closure of both fistulas was achieved, with recovery of soft-tissue sensitivity and radiographic resolution of sequestration. No adverse effects occurred, and the planned surgical debridement was canceled.

Combined PBMT and PDT promoted complete resolution of extensive, refractory mandibular ORN using a fully non-invasive approach. This case highlights the synergistic potential of dual phototherapy as a safe and effective alternative when surgery is contraindicated or declined. Further studies are warranted to clarify underlying mechanisms and optimize treatment parameters.

Pulmonary embolism is a common and potentially life-threatening acute condition encountered in clinical practice. Neuroendocrine tumors are heterogeneous neoplasms characterized by diverse biological behaviors, and patients with poorly differentiated or advanced neuroendocrine tumors may have an increased risk of developing venous thromboembolism. We report the case of a 60-year-old female who experienced acute chest discomfort and was diagnosed with pulmonary embolism. Comprehensive evaluation revealed no evidence of lower limb thrombosis, autoimmune or hematologic disorders, or other identifiable causes. The emboli resolved following anticoagulant therapy. Seventeen months later, the patient developed upper abdominal pain and underwent a colonoscopy, which revealed a lesion approximately 20 cm proximal to the terminal ileum. Histopathological and immunohistochemical analyses confirmed a grade-1 neuroendocrine tumor. ¹⁸F-octreotide positron emission tomography-computed tomography demonstrated increased tracer uptake in the terminal ileum and multiple hepatic foci, consistent with an ileal neuroendocrine tumor with liver metastases. The patient received intramuscular octreotide acetate microspheres (20 mg every 4 weeks) and remained clinically stable during follow-up. This case underscores the importance of considering occult malignancy in older patients presenting with unprovoked pulmonary embolism. Small intestinal neuroendocrine tumors may remain clinically silent for extended periods and should be included in the differential diagnosis when common etiologies have been excluded.

Leukemia represents a heterogeneous and refractory hematological malignancy, with current clinical therapies, including conventional chemotherapy, targeted therapy, and hematopoietic stem cell transplantation, still limited by drug resistance, off-target toxicity, and poor efficacy against high-risk subtypes. Indole/azaindole is a privileged heterocyclic scaffold in medicinal chemistry with versatile structural modification potential and inherent antileukemic bioactivity. Rational hybridization of indole/azaindole with diverse pharmacophores has become a core strategy for developing novel antileukemic agents, thereby enabling synergistic efficacy, reversal of drug resistance, and reduced toxicity. This review systematically summarizes the research progress of indole-based hybrids and closely related indole bioisosteres (azaindole hybrids) with antileukemic activity from 2021 to the present. Distinct from previous descriptive reviews, we stratified all candidate compounds by evidence hierarchy: in vitro antiproliferative activity, molecular mechanistic validation, and in vivo preclinical efficacy. This work focuses on structure-activity relationships (SARs), multi-target mechanisms, and preclinical pharmacological characteristics of indole- and azaindole-based antileukemic hybrids, aiming to provide targeted guidance for the rational design and clinical translation of novel indole- and azaindole-based antileukemic drugs.

Lung adenocarcinoma (LUAD) is among the most common cancers and a leading cause of cancer-related deaths. The histone variant H2A.Z has two isoforms (H2A.Z1 and H2A.Z2) encoded by distinct paralogs. Increasing numbers of evidence have demonstrated that H2A.Z1 and H2A.Z2 play a critical role in the pathogenesis of various cancers. Nevertheless, the precise biological functions and underlying mechanisms of H2A.Z in LUAD remain unclear.

The levels of H2A.Z expression in LUAD were evaluated using immunohistochemistry (IHC) and western blot assays. To investigate the biological role of H2A.Z2 in LUAD cells, both in vitro and in vivo experiments were conducted. To evaluate gene expression alterations and predict downstream pathways, transcriptome sequencing was performed. To validate that E2F transcription factor 1 (E2F1) regulates H2A.Z2 expression, dual luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were used.

Herein, we demonstrated high expression pattern of H2A.Z in LUAD tissues and its correlation with adverse clinical outcomes. Functionally, we indicated that H2A.Z2 exerts an oncogenic function in driving LUAD cell proliferation and metastasis. Mechanistically, analysis based on transcriptome sequencing suggested the influence of H2A.Z2 on the JAK-STAT pathway. Rescue experiments revealed that H2A.Z2 promotes LUAD progression by modulating STAT5B. Furthermore, we identified E2F1 as an activator that binds to the H2A.Z2 promoter to drive its transcription, thereby providing a novel mechanism of H2A.Z2 dysregulation.

In conclusion, our findings revealed a novel E2F1/H2A.Z2/STAT5B axis accelerating LUAD malignance, suggesting its potential as a promising target for diagnostic and therapeutic interventions in LUAD.

Chronic atrophic gastritis (CAG) is a well-recognized precursor of gastric cancer (GC). Spasmolytic polypeptide-expressing metaplasia (SPEM) is a key intermediate state during this process, representing a reparative response to gastric mucosal injury, and may promote the development of malignancy under persistent inflammation. Recent studies have suggested that SPEM is not a static lesion but a dynamic and heterogeneous process regulated by epithelial injury, oxyntic atrophy, and chronic inflammation. This review summarizes current knowledge on cellular plasticity, lineage dynamics, and molecular mechanisms underlying SPEM formation and progression in CAG. We focus on recent advances in oxyntic atrophy, immune cell and inflammation, as well as oxidative stress in gastric epithelial remodeling, and highlight emerging evidence implicating ferroptosis, a regulated form of iron-dependent lipid peroxidation, in gastric mucosal inflammation and SPEM development. By integrating classical models of GC with recent mechanistic insights, we aim to discuss the role of SPEM in CAG-associated GC risk and to identify potential therapeutic targets related to oxyntic atrophy, inflammation, and ferroptosis. These emerging findings offer new perspectives for future research aiming at risk stratification and precision prevention.

With the increasing global burden of cancer, traditional chemotherapy is limited by issues such as high toxicity and poor targeting, making the development of new therapeutic strategies an urgent priority. As natural bioactive macromolecules, herbal polysaccharides have become a hotspot in antitumor research due to their multi‑target effects, low toxicity, and excellent biocompatibility. The present review summarizes recent advances in the mechanisms of plant polysaccharides in antitumor activity and their applications in drug delivery systems. It highlights their synergistic antitumor effects through multiple pathways, including regulation of the immune microenvironment, induction of programmed cell death, modulation of the microbiota‑immune axis, and inhibition of angiogenesis and metastasis. These compounds significantly enhance the efficacy of chemotherapy and immunotherapy while reversing drug resistance. Novel formulations such as polysaccharide‑based nano‑delivery systems, selenium‑modified complexes and gel platforms have further improved drug targeting, stability, and immunomodulatory efficacy, providing a solid theoretical foundation and innovative directions for integrated traditional Chinese and Western medicine in cancer treatment.

To compare long-term incisional hernia (IH) risk between Pfannenstiel and supraumbilical muscle-sparing transverse extraction sites following minimally invasive colon cancer surgery with standardised fascial closure. Reported according to the IDEAL framework (Stage 4).

This single-centre study included patients (Stages I-III colon adenocarcinoma, 2014-2017) undergoing laparoscopic resection via Pfannenstiel or supraumbilical incisions. Fascial closure used continuous slowly absorbable poly-4-hydroxybutyrate sutures (ratio ≥ 4:1). The primary endpoint was CT-verified IH at the extraction site at 5 years. Inverse Probability of Treatment Weighting (IPTW) adjusted for baseline covariates.

The final cohort comprised 245 patients (Pfannenstiel, n = 141; supraumbilical, n = 104). The median follow-up was 5.3 and 5.6 years, respectively. In the unadjusted analysis, the 5-year IH risk was 15.4% (95% CI: 9.5-21.3) for Pfannenstiel and 18.8% (95% CI: 11.2-26.4) for supraumbilical incisions (p = 0.49). Following IPTW adjustment, the estimated risks were 14.6% (95% CI: 8.9-20.3) and 13.6% (95% CI: 7.7-19.4), respectively (adjusted risk difference - 1.0%; 95% CI: -9.2-7.2, p = 0.81). Only two (0.8%) of the 245 patients underwent surgical hernia repair.

The IH risk seems not associated with the extractions site incision, Pfannenstiel and supraumbilical muscle-sparing transverse extraction sites, when standardised closure techniques are applied. These findings challenge the assumption that Pfannenstiel sites are inherently superior for hernia prevention. The choice of extraction site based on anastomosis technique may not be justified; instead, it should be guided by oncological requirements and procedural ergonomics rather than perceived differences in hernia risk.

Danish Patient Safety Authority (#31-1522-51).

To characterize the multimodal ultrasonographic features of lingual schwannomas and evaluate their diagnostic value in clinical practice.

This retrospective study included five patients with histopathologically confirmed lingual schwannomas treated between 2018 and 2020. All patients underwent preoperative grayscale ultrasound and Color Doppler Flow Imaging, and contrast-enhanced ultrasound (CEUS) was additionally performed in one patient. Sonographic features-including lesion location, morphology, echogenicity, posterior acoustic characteristics, capsule presence, vascularity (Adler scale), spectral Doppler parameters, and CEUS enhancement patterns-were analyzed.

All lesions (mean maximum diameter, 15.6 ± 2.7 mm) were located within the intrinsic musculature of the tongue. Grayscale ultrasound exhibited well-defined, homogeneous hypoechoic masses with posterior acoustic enhancement and oval or ellipsoid morphology. A distinct capsule was observed in three cases. Color Doppler imaging demonstrated low intralesional vascularity, with four lesions classified as Adler Grade 1 and one as Grade 2. Spectral Doppler demonstrated high-resistance arterial flow (resistive index, 0.69-0.81). In the representative case examined with CEUS, the lesion exhibited slow wash-in and slow wash-out with homogeneous centrifugal enhancement and clear delineation from surrounding tissues.

Lingual schwannomas in this series exhibited a set of recurrent ultrasonographic features that may aid preoperative diagnosis and support ultrasonography as a first-line imaging modality.

Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with limited effective therapies. Although hexokinase 2 (HK2) is upregulated in multiple cancers, its role in ESCC progression and underlying mechanisms, particularly its interaction with the mitochondrial damage pathway, remains incompletely understood.

Bioinformatic analyses and clinical specimens were used to evaluate HK2 expression in ESCC and its association with prognosis. Functional assays, including CCK-8, wound healing, Transwell, flow cytometry, ROS detection, JC-1 staining, and mitochondrial protein analyses, were performed in ESCC cells with HK2 overexpression or knockdown. Co-immunoprecipitation (CO-IP) was conducted to validate the physical interaction between HK2 and VDAC1. A subcutaneous xenograft model was used to assess the pro-tumorigenic role of HK2 in vivo.

HK2 was markedly overexpressed in ESCC and was associated with poor prognosis. Mechanistically, HK2 interacted with VDAC1 on the outer mitochondrial membrane, suppressed mitochondrial depolarization and ROS accumulation, protected mitochondrial function, and thereby promoted ESCC cell proliferation, migration, and invasion. Conversely, HK2 knockdown disrupted HK2-VDAC1-associated mitochondrial regulation, induced mitochondrial dysfunction and apoptosis, and attenuated malignant phenotypes. In vivo, HK2 overexpression promoted tumor growth, whereas HK2 knockdown significantly suppressed tumor progression.

These findings suggest that HK2 promotes ESCC progression at least partly by interacting with VDAC1, protecting mitochondrial function and reducing cell apoptosis. The HK2-VDAC1 axis may represent a potential therapeutic vulnerability in ESCC.