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LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function.

BACKGROUND: Lipopolysaccharide (LPS) endotoxin stimulates pro-inflammatory pathways and is a key player in the pathological mechanisms involved in the development of endometritis. This study aimed to investigate LPS-induced DNA methylation changes in bovine endometrial epithelial cells (bEECs), which may affect endometrial function. Following in vitro culture, bEECs from three cows were either untreated (0) or exposed to 2 and 8 μg/mL LPS for 24 h. RESULTS: DNA samples extracted at 0 h and 24 h were sequenced using reduced representation bisulfite sequencing (RRBS). When comparing DNA methyla

The Crosstalk between Nrf2 and TGF-β1 in the Epithelial-Mesenchymal Transition of Pancreatic Duct Epithelial Cells.

Nrf2 and TGF-β1 both affect tumorigenesis in a dual fashion, either by preventing carcinogen induced carcinogenesis and suppressing tumor growth, respectively, or by conferring cytoprotection and invasiveness to tumor cells during malignant transformation. Given the involvement of Nrf2 and TGF-β1 in the adaptation of epithelial cells to persistent inflammatory stress, e.g. of the pancreatic duct epithelium during chronic pancreatitis, a crosstalk between Nrf2 and TGF-β1 can be envisaged. By using premalignant human pancreatic duct cells (HPDE) and the pancreatic ductal adenocarcinoma cell line

Ultraviolet solid-state laser (213-nm) photorefractive keratectomy. In vivo study.

BACKGROUND: The pulsed ultraviolet 213-nm solid-state laser has been demonstrated as an alternative to the gas argon-fluoride 193-nm excimer laser for photorefractive keratectomy (PRK). The authors studied the clinical course and histopathologic changes occurring in rabbit corneas after PRK with a 213-nm solid-state laser. METHODS: The 213-nm output of neodymium:YAG frequency-quintupled laser was used to create 5-mm optical zone ablations in seven pigmented rabbit corneas. The radiant exposure was 250 mJ/cm2 delivered through a computer-controlled scanning delivery system with a spot size of

Microarchitecture of the human endometrium by scanning electron microscopy: menstrual desquamation and remodeling.

Twenty-two hysterectomy specimens were collected over a period of two decades in order to investigate the morphological sequence of menstrual desquamation and its consecutive remodeling of the endometrium. The technique used was described earlier by H. Ludwig and H. Metzger (1976). Scanning electron microscopy is the only way to illustrate and describe the microarchitecture of the endometrial surface. At the beginning of the menstrual bleeding, glandular stumps surviving the desquamation of the layer functionalis stick out from the debris at the top of the basal layer. Fibrin mesh formation, t

Rapid signalling pathway activation by androgens in epithelial and stromal cells.

Estradiol rapidly activates Src as well as the Src-dependent pathway in human mammary cancer-derived MCF-7 cells, in human prostate cancer-derived LNCaP cells and in Cos cells transiently expressing hERs [EMBO J. 15 (1996) 1292; EMBO J. 17 (1998) 2008]. In addition, estradiol immediately stimulates, yes, an ubiquitous member of the Src kinase family, in human colon carcinoma-derived Caco-2 cells [Cancer Res. 56 (1996) 4516]. Progestins and androgens activate the same pathway in human mammary and prostate cancer-derived cells [EMBO J. 17 (1998) 2008; EMBO J. 19 (2000) 5406]. We observed that es

Bisphosphate nucleotidase 1 promotes progression and docetaxel resistance in triple-negative breast cancer via STUB1-mediated destabilization of LIMA1.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer without effective targeted therapies. Integrative analysis of transcriptomic and proteomic datasets of TNBC in our center revealed that bisphosphate nucleotidase 1 (BPNT1), a member of inositol monophosphatase superfamily with poorly characterized functional and mechanistic roles in human cancer, was abnormally upregulated in TNBC and its high expression was associated with poor patient prognosis. Loss- and gain-of-function assays revealed that BPNT1 acted as a novel oncogenic driver to promote TNBC cell proli

Postbiotics: a promising tool in personalized medicine approach for the inflammatory disorders.

Epidemiological studies indicate that modern lifestyle choices are closely linked to the global rise in chronic inflammatory diseases. While considerable research has explored the role of the microbiome in inflammation, a definitive causal relationship has yet to be established. Intestinal epithelial cells (IECs) play a critical role in maintaining a protective barrier that prevents the translocation of harmful molecules and pathogens. Any disruption or compromise to the integrity of these cells can impair this barrier function, facilitating the entry of potentially harmful substances and micr

Ligustilide activates cGAS-STING to chemoprevent tobacco carcinogen-induced lung tumorigenesis.

Lung cancer is a malignant tumor of the bronchial mucosa or glands, with the fastest increasing incidence and mortality rates. In this study, we elucidated for the mechanism of prevention of tobacco-specific nitrosamine (NNK)-induced lung carcinogenesis by Ligustilide (LIG), an active ingredient of traditional Chinese medicine (TCM), through activation of the cGAS-STING innate immune pathway. In the NNK-treated A/J mouse model, LIG (10/40 mg/kg) intervention significantly ameliorated lung histopathological injury, restored body weight, and down-regulated pro-inflammatory factor IL-6 and IL-1β

Toxic Epidermal Necrolysis Mimicking Severe Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Diagnostic Challenge.

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and ou

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… The first signs of re-epithelialization were observed between days +50 and +55 post-transplant ( Figure 7 ). Progressive improvement followed, with near-complete re-epithelialization achieved by day +65 ( Figure 8 ). …

PRMT5-mediated arginine methylation of HSP90AA1 drives esophageal squamous cell carcinoma progression.

Dysregulated HSP90AA1 chaperone activity is a hallmark of multiple cancers; however, its post-translational regulation in esophageal squamous cell carcinoma (ESCC) remains poorly defined. Here, we defined PRMT5-dependent symmetric dimethylation of HSP90AA1 at arginine 182 (R182) as a critical molecular switch driving ESCC progression. HSP90AA1 physically interacted with PRMT5, and genetic or pharmacological inhibition of PRMT5 markedly reduced HSP90AA1 R182 methylation, accompanied by suppression of epithelial-mesenchymal transition (EMT) programs. HSP90AA1 depletion significantly impaired ESC

Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.

Midkine (MDK) is an oncofetal, heparin-binding cytokine that is re-expressed across diverse cancers and correlates with aggressive disease and treatment resistance. This review synthesizes current evidence on MDK as a coordinator of tumor-intrinsic signaling and microenvironmental remodeling. We summarize MDK structural features, extracellular matrix interactions, and receptor systems that mediate MDK signaling, highlighting LRP1 and PTPRZ1 with context-dependent participation of ALK, nucleolin and integrins. Downstream, MDK engages MAPK, PI3K-AKT, STAT3 and NF-κB pathways to promote tumor cel

Hepatocyte Plasticity in Liver Health and Disease: Zonation, Regeneration, Lineage Conversion, and Hepatic Malignancy.

Hepatocytes are highly specialized epithelial cells that maintain liver metabolic homeostasis, yet they also display remarkable plasticity in response to physiological demands, injury, disease, and oncogenic stress. In this review, we propose hepatocyte plasticity as an integrative framework that links homeostatic metabolic zonation, injury‑ and disease‑induced zonal remodeling and regeneration, hepatobiliary lineage conversion, and zonally biased malignant transformation. We first delineate homeostatic liver zonation as the baseline spatial architecture that constrains, rather than itself con

Identification of 3-cyanoquinolines as broad-spectrum inhibitors of Monkeypox virus and other sexually transmitted pathogens.

Sexually transmitted infections (STIs) remain a major global health concern, contributing significantly to morbidity and facilitating the co-transmission of other pathogens. Recent outbreaks of Monkeypox virus (MPXV) have further underscored the urgent need for broad-spectrum antiviral agents effective against emerging and re-emerging sexually transmissible viruses. We report here the design and synthesis of a series of 3-cyanoquinoline-based Src inhibitors to evaluate their antimicrobial efficacy against sexually transmitted pathogens. Among them, compound 7d demonstrated potent inhibitory ac

Boron-Containing Nanoenzyme for Effective Treatment of Melanoma through Boron Neutron Capture Therapy Combined with Catalytic Therapy.

Boron neutron capture therapy (BNCT) is a re-emerging field to achieve precision treatment of malignant tumors with its unique biotargeting and heavy-ion effects, and combination therapy could effectively improve the therapeutic efficacy of BNCT. Herein, a tumor-targeted boron-containing nanozyme was prepared to achieve the combination of BNCT and catalytic therapy for the effective treatment of melanoma. Notably, the boron-containing nanoenzyme exhibited strong peroxidase-like catalytic activity, had skin melanoma cell selectivity, and could undergo a catalytic reaction within the tumor cells

Detection and isolation of viable cancer cells mediated by spytag and spycatcher using conditionally replicative adenovirus and magnetic microbeads.

Circulating tumor cells (CTCs) are critical biomarkers for cancer diagnosis, prognosis, and therapy monitoring, but their rarity and reliance on surface markers limit detection and isolation. While conditionally replicative adenoviruses (crADs) enable tumor-selective targeting, their use has been limited to fluorescence-based detection without robust isolation of viable cells. To overcome this, we developed a crAD-based platform integrating SpyTag/SpyCatcher technology with SpyCatcher-decorated magnetic microbeads for marker-independent CTC detection and isolation. The engineered adenovirus (C

Clinical, Histopathological and Immunohistochemical Aspects of Digital Papillary Adenocarcinoma: A Case Report and Literature Review.

Digital papillary adenocarcinoma (DPA) is a rare malignant eccrine tumor. A 62-year-old female presented with a subcutaneous nodular 1.5cm-mass in the thumb. Macroscopically, a poorly circumscribed mass containing cystic and solid components was observed. Microscopically, epithelial neoplasm consisting of tubular-cystic structures with back-to-back arrangements was observed. The lining epithelium was composed of cuboidal/columnar cells with mild atypia, with micropapillary extensions. Immunohistochemistry revealed double-layered neoplastic epithelium containing two different types of cells: ba

Adaptive patterning of vascular network during avian skin development: Mesenchymal plasticity and dermal vasculogenesis.

A vasculature network supplies blood to feather buds in the developing skin. Does the vasculature network during early skin development form by sequential sprouting from the central vasculature or does local vasculogenesis occur first that then connect with the central vascular tree? Using transgenic Japanese quail Tg(TIE1p.H2B-eYFP), we observe that vascular progenitor cells appear after feather primordia formation. The vasculature then radiates out from each bud and connects with primordial vessels from neighboring buds. Later they connect with the central vasculature. Epithelial-mesenchymal

Z-shaped incision without epithelial resection in pterygium surgery.

AIM: To introduce a novel surgical technique using a Z-shaped incision without epithelial resection in ophthalmic pterygia. METHODS: This was a prospective study. During pterygium surgery, all proliferative tissues were separated from the cornea and conjunctiva without resection of the tissues. The unaffected conjunctiva was incised in a Z-shape. The upper (or lower) conjunctival flap was sutured to the lower (or upper) normal conjunctiva on the limbal sclera, while the proliferative tissue was sutured to the upper conjunctiva (or lower) near the fornix. RESULTS: Ten patients with pterygia w

Genomic Evolution and Recombination Dynamics of Human Adenovirus D Species: Insights from Comprehensive Bioinformatic Analysis.

Human adenoviruses (HAdVs) can infect various epithelial mucosal cells, ultimately causing different symptoms in infected organ systems. With more than 110 types classified into seven species (A-G), HAdV-D species possess the highest number of viruses and are the fastest proliferating. The emergence of new adenovirus types and increased diversity are driven by homologous recombination (HR) between viral genes, primarily in structural elements such as the penton base, hexon and fiber proteins, and the E1 and E3 regions. A comprehensive analysis of the HAdV genome provides valuable insights into

Reconstruction of complex plantar forefoot defects using free tissue flaps combined with contralateral instep thick skin grafts.

PURPOSE: To evaluate the clinical efficacy of using free tissue flap combined with contralateral instep thick plantar skin in reconstructing complex plantar forefoot defects. METHODS: During the past 8 years, 15 patients, aged 25-60 years, with defects in the soft-tissue and composite bone of the forefoot were treated. Their defects were caused by trauma. These defects were all located on the plantar forefoot. The free tissue flaps transposed to reconstruct defects were anterolateral thigh flaps, groin flaps, and latissimus dorsi flaps. Flap size varied in width 4-cm and length (6-16 cm). The