Search Results (296)

Background: As a well-known environmental hazard, ambient fine particulate matter (PM_2.5, aerodynamic diameter ≤ 2.5 µm) has been positively correlated with an increased risk of digestive system diseases, including appendicitis, inflammatory bowel disease, and gastrointestinal cancer. Additionally, PM_2.5 exposure has been shown to alter microbiota composition and diversity in human and animal models. However, its impact on goblet cells and gut mucus barrier integrity remains unclear. Methods: To address this, 8-week-old male and female interleukin-10 knockout (IL10^−/−) mice, serving as a spontaneous colitis model, were exposed to concentrated ambient PM_2.5 or filtered air (FA) in a whole-body exposure system for 17 weeks. Colon tissues from the PM_2.5-exposed mice and LS174T goblet cells were analyzed using H&E staining, transmission electron microscopy (TEM), and transcriptomic profiling. Results: The average PM_2.5 concentration in the exposure chamber was 100.20 ± 13.79 µg/m³. PM_2.5 exposure in the IL10^−/− mice led to pronounced colon shortening, increased inflammatory infiltration, ragged villi brush borders, dense goblet cells with sparse enterocytes, and lipid droplet accumulation in mitochondria. Similar ultrastructure changes were exhibited in the LS174T goblet cells after PM_2.5 exposure. Transcriptomic analysis revealed a predominantly upregulated gene expression spectrum, indicating an overall enhancement rather than suppression of metabolic activity after PM_2.5 exposure. Integrated enrichment analyses, including GO, KEGG, and GSEA, showed enrichment in pathways related to oxidative stress, xenobiotic (exogenous compound) metabolism, and energy metabolism. METAFlux, a metabolic activity analysis, further substantiated that PM_2.5 exposure induces a shift in cellular energy metabolism preference and disrupts redox homeostasis. Conclusions: The findings of exacerbated gut barrier impairment and goblet cell dysfunction following PM_2.5 exposure provide new evidence of environmental factors contributing to colitis, highlighting new perspectives on its role in the pathogenesis of colitis. Full article

Respiratory viral diseases infecting poultry lead to variable lesions in the respiratory organs, including nasal sinuses, trachea, lungs, and air sacs. Additional involvement of eyelids/conjunctiva was reported. The distribution and the intensity of lesions depend on multiple factors, including virulence, the host’s immunity, and secondary or concurrent infections. It may be challenging to detect remarkable lesions during experimental infections conducted in a controlled environment because some viruses fail to produce the intense lesions seen in field cases. This creates a challenge in developing a reliable model to study pathogenicity or vaccine efficacy experimentally. The development of the proposed histologic respiratory index (HRI) aims to help monitor the least microscopic changes that can be scored, thereby creating an objective and accurate grading of lesions in experimentally infected birds. HRI scores the changes in eyelids/conjunctiva and respiratory mucosa, including hyperplasia, metaplasia, inflammatory cellular infiltration in the submucosa, including lymphocytes and heterophils, and vascular changes (vasculitis) in nasal sinuses, trachea, and lungs. The score was validated in birds infected experimentally with avian metapneumovirus (aMPV) and low pathogenic avian influenza (LPAI-H4N6). The HRI reliably graded higher scores in the respiratory organs of experimentally infected birds compared with non-infected control ones. The HRI is the first of its type with poultry viral respiratory pathogens and it was initially proven to be a reliable in pathogenicity and vaccine trials of certain poultry respiratory viral diseases. Full article

Background and Objectives: Cardiac transplantation is currently the elective treatment choice in end-stage heart failure, and cellular rejection is a predictive factor for morbidity and mortality after surgery. We proposed an evaluation of the clinicopathologic factors involved in the mechanism of rejection. Materials and Methods: This study included 146 patients who underwent transplantation at the Institute of Cardiovascular Diseases and Transplantation in Targu Mures between 2010 and 2023, and we evaluated the function and structure of the myocardium after surgery by using endomyocardial biopsy. Results: Overall, 120 men and 26 women underwent transplantation, with an approximately equal proportion under and over 40 years old (48.6% and 51.4%). Evaluating the degree of acute cellular rejection according to the International Society for Heart and Lung Transplantation classification showed that most of the patients presented with acute cellular rejection (ACR) and antibody-mediated rejection (AMR) grade 0, and most cases of ACR and AMR were reported with mild changes (13% or 10.3% patients). Therefore, the most frequent histopathologic diagnoses were similar to lesions unrelated to rejection (45.2% of patients) and ischemia–reperfusion lesions (25.3% patients), respectively. Conclusions: Although 82.2% of the transplanted cases showed no rejection (ISHLT score 0), non-rejection-related lesion-like changes were present in 45.2% of cases, and because more of the non-rejection-related criteria could be detected, it may be necessary to adjust the grading of the rejection criteria. The histopathologic changes that characterize rejection are primarily represented by the mononuclear inflammatory infiltrate; in our study, inflammatory changes were mostly mild (71.9%), with myocyte involvement in all cases. These changes are associated with and contribute to the maintenance of the rejection phenomenon. Full article

Background and Clinical Significance: Kaposi sarcoma (KS) is a rare angio-proliferative mesenchymal tumor that predominantly affects the skin and mucous membranes but may involve lymph nodes and visceral organs. Clinically, it manifests as red-purple-brown papules, nodules, or plaques, either painless or painful, often with disfiguring potential. The diagnosis is traditionally based on clinical and histopathological evaluation, although non-invasive imaging techniques are increasingly used to support diagnosis and treatment monitoring. We report a case of HHV-8-negative Kaposi sarcoma evaluated with multiple non-invasive imaging modalities to highlight their diagnostic utility. Case Presentation: An 83-year-old man presented with multiple painful, violaceous papulo-nodular lesions, some ulcerated, on the lateral aspect of his left foot. Dermoscopy revealed the characteristic rainbow pattern. Dynamic Optical Coherence Tomography (D-OCT) allowed real-time visualization of microvascular abnormalities, identifying large serpentine and branching vessels with clearly delineated capsules. Line-field Optical Coherence Tomography (LC-OCT) showed irregular dermal collagen, vascular lacunae, and the presence of spindle cells and slit-like vessels. Histological analysis confirmed the diagnosis of Kaposi sarcoma, revealing a proliferation of spindle-shaped endothelial cells forming angulated vascular spaces, with red blood cell extravasation and a mixed inflammatory infiltrate. Conclusions: Non-invasive imaging tools, including dermoscopy, D-OCT, and LC-OCT, have emerged as valuable adjuncts in the diagnosis and monitoring of KS. These techniques enable in vivo assessment of vascular architecture and tissue morphology, enhancing clinical decision-making while reducing the need for immediate biopsy. Dermoscopy reveals polychromatic vascular features, such as the rainbow pattern, while D-OCT and LC-OCT provide high-resolution insights into vascular proliferation, tissue heterogeneity, and cellular morphology. Dermoscopy, dynamic OCT, and LC-OCT represent promising non-invasive diagnostic tools for the assessment of Kaposi sarcoma. These technologies provide detailed morphological and vascular information, enabling earlier diagnosis and more personalized management. While histopathology remains the gold standard, non-invasive imaging offers a valuable complementary approach for diagnosis and follow-up, particularly in complex or atypical presentations. Ongoing research and technological refinement are essential to improve accessibility and clinical applicability. Full article

Background/Objectives: Lumbar disc herniation (LDH) is the most common condition associated with low back pain, and it adversely impacts individuals’ health. The interplay between energy metabolism and apoptosis is critical, as the loss of viable cells in the intervertebral disc (IVD) can lead to a cascade of degenerative changes. Efferocytosis is a key biological process that maintains homeostasis by removing apoptotic cells, resolving inflammation, and promoting tissue repair. Therefore, enhancing mitochondrial energy metabolism and efferocytosis function in IVD cells holds great promise as a potential therapeutic approach for LDH. Methods: In this study, energy metabolism and efferocytosis-related differentially expressed genes (EMERDEGs) were identified from the transcriptomic datasets of LDH. Machine learning approaches were used to identify key genes. Functional enrichment analyses were performed to elucidate the biological roles of these genes. The functions of the hub genes were validated by RT-qPCR. The CIBERSORT algorithm was used to compare immune infiltration between LDH and Control groups. Additionally, we used single-cell RNA sequencing dataset to analyze cell-specific expression of the hub genes. Results: By using bioinformatics methods, we identified six EMERDEGs hub genes (IL6R, TNF, MAPK13, ELANE, PLAUR, ABCA1) and verified them using RT-qPCR. Functional enrichment analysis revealed that these genes were primarily associated with inflammatory response, chemokine production, and cellular energy metabolism. Further, we identified candidate drugs as potential treatments for LDH. Additionally, in immune infiltration analysis, the abundance of activated dendritic cells, neutrophils, and gamma delta T cells varied significantly between the LDH group and Control group. The scRNA-seq analysis showed that these hub genes were mainly expressed in chondrocyte-like cells. Conclusions: The identified EMERDEG hub genes and pathways offer novel insights into the molecular mechanisms underlying LDH and suggest potential therapeutic targets. Full article

Background and Objectives: Methotrexate (MTX) is a widely utilised pharmaceutical agent in the treatment of various malignancies and inflammatory diseases. However, its clinical utility is often constrained by its potential for hepatotoxicity. Although pyridostigmine is a well-established reversible acetylcholinesterase inhibitor, its potential therapeutic role in preventing hepatic injury remains incompletely defined. The present study aimed to investigate whether pyridostigmine provides protective effects against MTX-triggered liver damage in a rat model. Methods: Thirty-six female Wistar albino rats randomly assigned to three groups: control (n = 12), MTX + saline (n = 12), and MTX + pyridostigmine (n = 12). Hepatotoxicity was induced by a single-dose MTX injection (20 mg/kg), followed by daily oral administration of either pyridostigmine (5 mg/kg) or saline for ten consecutive days. Hepatic function markers, oxidative stress parameters, fibrosis-associated mediators, and histopathological changes were assessed. Results: Pyridostigmine significantly attenuated MTX-induced elevations in plasma alanine aminotransferase (p < 0.05) and cytokeratin-18 levels (p < 0.001), and reduced liver and plasma malondialdehyde (MDA) levels (p < 0.05). Additionally, pyridostigmine treatment resulted in reduced levels of transforming growth factor-beta (p < 0.05), bone morphogenetic protein-9 (p < 0.001), and endoglin levels (p < 0.05), as well as increased sirtuin 1 level (p < 0.05). Histopathological examination revealed that pyridostigmine treatment significantly reduced MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. Conclusions: Pyridostigmine exerted hepatoprotective effects against MTX-induced liver injury by attenuating oxidative stress, restoring SIRT1 expression, and suppressing pro-fibrotic signaling. These findings indicate that pyridostigmine may hold therapeutic potential for the prevention of MTX-associated hepatotoxicity. Full article

Plasma, an ionized gas composed of charged particles, has shown therapeutic potential in enhancing biological processes such as wound healing and tissue integration. Implants, such as silicone and human acellular dermal matrix (hADM), are commonly used in reconstructive surgery, but improving their biocompatibility and integration remains a challenge. This study investigated the effects of vacuum plasma treatment on silicone and hADM implants using an in vivo rat model. Plasma-treated and untreated implants were inserted subcutaneously, and tissue samples were collected at 1, 4, and 8 weeks post-implantation. Histological and immunohistochemical analyses were performed to assess inflammation, cellular infiltration, collagen formation (neocollagenesis), and angiogenesis. Results showed that plasma-treated silicone and hADM implants had significantly reduced capsule thickness at weeks 4 and 8 compared to untreated controls, indicating a lower chronic inflammatory response. Plasma treatment also promoted greater fibroblast infiltration and enhanced neocollagenesis within the hADM implants. Furthermore, immunohistochemical staining revealed a notable increase in blood vessel formation around and within the plasma-treated hADM implants, suggesting improved vascularization. In conclusion, vacuum plasma treatment enhances the biocompatibility and tissue integration of implants by reducing inflammation and promoting cellular and vascular responses, offering promising potential for improving outcomes in reconstructive surgery. Full article

With growing public concern about the health effects of low-dose radiation, numerous studies have demonstrated that low-dose radiation can cause damage to the immune system, making intervention measures essential. This study investigated the protective effects of silybin against low-dose radiation-induced immune system damage and its underlying mechanisms at both the cellular and animal levels. At the cellular level, CCK-8 assays, ROS measurements, and RT-qPCR analysis revealed that silybin alleviated the reduction in RAW264.7 cell proliferation, intracellular ROS levels, and inflammatory cytokine expression following low-dose radiation exposure. At the animal level, comparative analyses of post-irradiation body weight, peripheral blood cell counts, immune organ coefficients, spleen HE/IHC staining, and spleen immune cell numbers demonstrated that silybin mitigated the radiation-induced decrease in body weight, reduction in peripheral blood leukocyte counts, inflammatory cell infiltration in the spleen, decline in spleen immune cell numbers, and increase in cGAS protein-positive cells. These findings indicate that silybin exerts protective effects against low-dose radiation-induced immune system damage, potentially by regulating the cGAS signaling pathway to reduce radiation-induced cellular injury, thereby enhancing its radioprotective properties. Full article

Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular and molecular changes that occur during demyelination and remyelination, with a focus on glial cell responses, blood-brain barrier (BBB) integrity, and neuroimmune interactions. C57BL/6J mice exposed to cuprizone exhibited weight loss, sensorimotor deficits, and cognitive decline, which were reversed during remyelination. Histological and immunofluorescence analyses revealed reduced myelin protein levels, including myelin basic protein (MBP) and myelin-associated glycoprotein (MAG), and decreased oligodendrocyte populations during demyelination, with recovery during repair. The BBB permeability increases during demyelination, is associated with the decreased expression of tight junction proteins (ZO-1, Occludin), and normalizes during remyelination. Single-cell RNA sequencing revealed dynamic shifts in glial cell populations and upregulated Psap-Gpr37l1 signaling. Neuroimmune activation and oxidative stress peak during demyelination, characterized by elevated ROS, MDA, and immune cell infiltration, followed by recovery. Transcriptomic profiling revealed key inflammatory pathways (JAK-STAT, NF-κB) and hub genes associated with demyelination and repair. These findings provide insights into myelin repair mechanisms and highlight potential therapeutic targets for treating demyelinating diseases. Full article

(1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using wild-type, keratin 14-specific IL-33 transgenic, IL-18 transgenic, caspase-1 transgenic, and caspase-1 transgenic mice with IL-17AF deletion, reflecting diverse aspects of human skin inflammation. IL-36α was administered subcutaneously in five doses on alternate days across the five strains to examine cellular infiltration patterns and cytokine expression levels. (3) Results: The skin phenotype was exacerbated, accompanied by worsening edema and skin thickness in all mouse groups upon IL-36α administration. An increase in infiltrating cells was observed among innate immune cells, while lymphocyte counts, including T cells and innate lymphoid cells, did not rise. Additionally, anti-inflammatory cytokines were induced simultaneously with inflammatory cytokines and downstream cytokines of IL-36α as well. Infiltrating lymphocytes in the skin displayed a distinct Type 2 cytokine-dominant profile for innate lymphoid cells and a Type 3 cytokine-dominant profile for T helper cells and γδ T cells, contrasting with the Type 1-dominant cell profile in draining lymph nodes. Type 1, Type 2, and Type 3 cytokine dominance patterns were not affected by the administration of IL-36α. (4) Conclusions: IL-36α triggers inflammatory responses in atopic dermatitis by activating innate immunity. The infiltrating lymphocytes in the skin have different cytokine production profiles between innate lymphoid cells and T cells, as well as different patterns of cytokine production in their draining lymph nodes. Full article

Diabetes and its complications, including impaired wound healing, present a critical clinical challenge and burden for the U.S. healthcare system, with costs of over USD 13 billion annually. Hyperglycemia and chronic inflammation in diabetic wounds increase reactive oxygen species (ROS) production, inducing oxidative stress and perpetuating inflammation, which delays healing. This study investigates inflammation, oxidative stress, and the roles of cellular populations in a diabetic wound healing mouse model (db/db). Given that diabetes leads to persistent inflammation and impaired fibroblast function, we also examined how diabetes influences superoxide production in dermal fibroblasts. Blood, dermal fibroblasts, and wound tissue were collected from 12-week-old female diabetic (Db) and heterozygous (Hz) mice. Electron paramagnetic resonance (EPR) spectroscopy revealed higher superoxide levels in diabetic blood, dermal fibroblasts, and wounds compared to controls. In diabetic wounds, immunohistochemistry and flow cytometry showed increased leukocyte infiltration and reduced macrophage presence, with a higher proportion of pro-inflammatory Ly6C^hi macrophages. These results suggest that elevated superoxide production and persistent inflammation contribute to impaired fibroblast function and delayed wound healing in diabetes. By identifying the contributions of ROS and Ly6C^hi macrophages to oxidative stress and chronic inflammation, this study offers insights into therapeutic strategies. These findings highlight the importance of addressing systemic oxidative stress alongside localized inflammation to improve wound healing outcomes in diabetic patients and advance diabetic wound care strategies. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic inflammatory disorder characterized by alcohol-independent hepatic lipid accumulation, remains poorly understood in terms of PANoptosis involvement. Methods: We integrated high-throughput sequencing data with bioinformatics to profile differentially expressed genes (DEGs) and immune infiltration patterns in MASLD, identifying PANoptosis-associated DEGs (PANoDEGs). Machine learning algorithms prioritized key PANoDEGs, while ROC curves assessed their diagnostic efficacy. Cellular, animal, and clinical validations confirmed target expression. Results: Three PANoDEGs (SNHG16, Caspase-6, and Dynamin-1-like protein) exhibited strong MASLD associations and diagnostic significance. Immune profiling revealed elevated M1 macrophages, naïve B cells, and activated natural killer cells in MASLD tissues versus controls. Further experiments verified the expression of the key PANoDEGs. Conclusions: This study provides new insights for further studies on the pathogenesis and treatment strategies of PANoptosis in MASLD. Full article

Background and Objectives: Liver fibrosis, a chronic process caused by various pathogenic factors, including drug toxicity, metabolic disorders, and chronic inflammation, is associated with liver-related mortality rates worldwide. It has been established that methotrexate (MTX), a pharmaceutical agent utilised in the treatment of numerous diseases, induces hepatic fibrosis. Currently, there is still a paucity of clinically efficacious antifibrotic drugs for the management of hepatic fibrosis. Thus, the present research sought to evaluate the antifibrotic effects of baricitinib in a rat model of MTX-induced liver fibrosis through the yes-associated protein (YAP) pathway. Materials and Methods: A total of 36 Wistar rats were assigned to three groups (n = 12) randomly: a control group, an MTX-induced liver fibrosis group, and a baricitinib-treated group, which received 20 mg/kg/day of baricitinib following fibrosis induction. All treatments were administered for 10 days. Results: Biochemical analyses revealed significant increases in plasma alanine aminotransferase (ALT), cytokeratin-18 (CK-18), and malondialdehyde (MDA) levels, as well as liver transforming growth factor-beta (TGF-β), YAP1, and MDA levels, in the MTX-induced fibrosis group in comparison to the control group (p < 0.05). Notably, baricitinib addition significantly reduced these biomarkers (p < 0.05). A histopathological evaluation further confirmed a marked reduction in fibrosis, hepatic necrosis, and cellular infiltration in the baricitinib-treated group relative to the MTX-induced fibrosis group. Conclusions: Accordingly, our findings suggest that baricitinib mitigates MTX-induced liver fibrosis, potentially through its anti-inflammatory and antifibrotic effects mediated by the suppression of the YAP signalling pathway. These results highlight that baricitinib could be a potential treatment option for patients with liver fibrosis. Full article

Early and appropriate diagnosis of soft-tissue sarcomas (STSs) is hampered by their relatively low prevalence and sometimes unusual clinical appearance. It takes a comprehensive diagnostic work-up to differentiate between different types of soft-tissue sarcomas. Determining tumor margins by preoperative imaging is important, especially in order to preserve the affected limb and improve quality of life. Misjudgment of tumor margins may increase or decrease the stage of soft-tissue sarcoma and thus influence the patient’s prognosis. The applicability of conventional MRI alone for determining the tumor margin is limited. Additional information regarding the peritumoral tissue, particularly at the cellular level, can be obtained via diffusion-weighted imaging (DWI). However, there are not many publications on employing DWI to evaluate tumor margin infiltration in soft-tissue sarcoma patients. Because the immune system plays a variety of roles during oncogenesis, it can occasionally be difficult to distinguish between tumor invasion and the presence of a reactive inflammatory infiltrate. Clarifying the predictive importance of lymphocyte infiltration in soft-tissue sarcomas was the goal of this investigation. We examined the correlations between expression of CD4, CD8, and CD34 and tumor margin infiltration observed on a DWI sequence. CD4, CD8, and CD34 marker positivity was linked to soft-tissue sarcomas that were less aggressive and did not invade the tumor margins, indicating a higher survival percentage for these individuals. Full article

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article