Search Results (99)

Class III alcohol dehydrogenase (ADH3), primarily localized in the liver and kidney, contributes to alcohol metabolism during chronic alcohol consumption (CAC). However, its role in kidney function remains unclear. This study investigated renal morphological changes associated with ADH3-mediated alcohol metabolism. Nine-week-old male wild-type (WT) and ADH3-deficient (Adh3^-/-) mice were administered 10% ethanol for 1 month. Histological analyses were performed using periodic acid–Schiff (PAS) staining and electron microscopy. Serum biochemical parameters were also assessed. In WT mice, CAC induced an increase in cuboidal parietal epithelial cells (PECs) in Bowman’s capsule, along with elevated testosterone levels in both serum and urine. Adh3^-/- mice showed increased PECs even in the control group, with similarly elevated serum testosterone in both control and ethanol-treated groups. These findings suggest that ADH3 is involved in testosterone metabolism, and that that metabolism is suppressed by CAC because ADH3 shifts toward ethanol metabolism. The resulting testosterone elevation may contribute to PEC proliferation. An increase in PECs observed even in Adh3^-/- control mice may also be caused by the lack of testosterone metabolism via ADH3. Thus, renal ADH3 may protect kidney structure through testosterone metabolism, but its role may be disturbed by CAC. This study highlights the role of ADH3 in the relationship between physiological steroid metabolism and alcoholic pathological abnormality in the kidney. Full article

The creation of transgenic chickens holds significant promise for the agricultural and biotechnological sectors, offering potential improvements in disease resistance and production efficiency. The preferred method for generating gene-edited chickens involves the genetic manipulation of primordial germ cells (PGCs), making the identification and isolation of these cells a growing focus of research. PGCs are the precursors to sperm and oocytes, responsible for transmitting genetic material to the next generation. In humans, PGCs are characterized by their large size, round nuclei, and refractive lipids in the cytoplasm, and can be identified using periodic acid–Schiff (PAS) staining and the surface marker stage-specific embryonic antigen 1 (SSEA1). Similarly, chicken PGCs express SSEA1, but their most specific marker is the chicken vasa homologue (CVH), the avian equivalent of the RNA-binding factor gene vasa. However, SSEA1, along with other known surface markers, does not bind to all PGCs or lacks specificity, while CVH, although highly specific to PGCs, is intracellular and unsuitable for isolating viable cells. This study aims to develop an antibody targeting a PGC surface marker with the same specificity as CVH. Despite the importance of identifying surface markers for PGC characterization, to date, such reagents are limited. To address this, whole chicken PGCs were injected into mice, leading to the generation of a panel of monoclonal antibodies. One antibody was found to bind cultured chicken PGCs and showed reduced expression upon differentiation with retinoic acid, indicating its specificity to PGCs. Immunoprecipitation followed by mass spectrometry identified the antigen as myosin heavy chain-like (MYH9) protein. The antibody, αMYH9, was further characterized and shown to bind circulating PGCs and embryonic gonadal PGCs (Hamburger Hamilton (H-H) stage 30, embryonic day 6.5–7). Whilst our primary aim was to determine the binding to PGCs, further investigation is required to determine potential binding to somatic cells. In conclusion, this study provides the characterization of a surface marker for chicken PGCs, with significant implications for advancements in avian genetic preservation, agriculture, and biotechnology. Full article

This study investigated the proportions and clinicopathological presentations of oral candidal lesions in type 2 diabetes mellitus (DM) patients attending the Diabetic Clinic at Teaching Hospital Peradeniya; Sri Lanka. A descriptive cross-sectional study was conducted on 355 DM patients aged over 18 years who had been receiving treatment for at least one year. Clinical photographs and periodic acid–Schiff (PAS)-stained cytological specimens confirmed diagnoses. Oral candidal lesions were found in 17.6% of patients; with Denture Stomatitis (4.0%), Erythematous Candidiasis (3.4%), Pseudomembranous Candidiasis (3.1%), and Chronic Hyperplastic Candidiasis (2.8%) being the most common types. Notably; all lesions were identified as incidental findings. Erythematous Candidiasis was more frequently noted among individuals older than 60 years (p = 0.041); while Denture Stomatitis was more common with higher glycemic levels (>140 mg/dL) (p = 0.045). Males were significantly more susceptible to oral candidal lesions (p = 0.002); except for Pseudomembranous Candidiasis and Denture Stomatitis; which were more frequent in females. Smoking (p = 0.005) and betel quid chewing (p = 0.008) were also identified as significant risk factors. Binary logistic regression revealed that males (OR = 3.160) and denture wearers (OR = 2.348) had a higher likelihood of developing oral candidal lesions. Despite the relatively low prevalence; routine oral examinations are recommended for early detection and management; ensuring better oral health in this at-risk population. Full article

Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet combined with aerobic exercise in hindlimb-unloaded mice on muscle fiber remodeling and metabolic adaptation. Methods: Seven-week-old male C57BL/6J mice were randomly divided into six groups: normal diet control (NC), normal diet with hindlimb unloading (NH), normal diet with hindlimb unloading and exercise (NHE), ketogenic diet control (KC), ketogenic diet with hindlimb unloading (KH), and ketogenic diet with hindlimb unloading and exercise (KHE). During the last two weeks of intervention, hindlimb unloading was applied to simulate microgravity. Aerobic exercise groups performed moderate-intensity treadmill running (12 m/min, 60 min/day, and 6 days/week) for 8 weeks. Body weight, blood ketone, and glucose levels were measured weekly. Post-intervention assessments included the respiratory exchange ratio (RER), exhaustive exercise performance tests, and biochemical analyses of blood metabolic parameters. The skeletal muscle fiber-type composition was evaluated via immunofluorescence staining, lipid deposition was assessed using Oil Red O staining, glycogen content was analyzed by Periodic Acid–Schiff (PAS) staining, and gene expression was quantified using quantitative real-time PCR (RT-qPCR). Results: Hindlimb unloading significantly decreased body weight, induced muscle atrophy, and reduced exercise endurance in mice. However, the combination of KD and aerobic exercise significantly attenuated these adverse effects, as evidenced by increased proportions of oxidative muscle fibers (MyHC-I) and decreased proportions of glycolytic fibers (MyHC-IIb). Additionally, this combined intervention upregulated the expression of lipid metabolism-associated genes, including CPT-1b, HADH, PGC-1α, and FGF21, enhancing lipid metabolism and ketone utilization. These metabolic adaptations corresponded with improved exercise performance, demonstrated by the increased time to exhaustion in the KHE group compared to other hindlimb unloading groups. Conclusions: The combination of a ketogenic diet and aerobic exercise effectively ameliorates simulated microgravity-induced skeletal muscle atrophy and endurance impairment, primarily by promoting a fiber-type transition from MyHC-IIb to MyHC-I and enhancing lipid metabolism gene expression (CPT-1b, HADH, and PGC-1α). These findings underscore the potential therapeutic value of combined dietary and exercise interventions for mitigating muscle atrophy under simulated microgravity conditions. Full article

On the beach of Linosa Island (Italy), 43 loggerhead sea turtle (Caretta caretta) unhatched eggs were recovered from nests, formalin-fixed and necropsied. The tissue samples were stained with hematoxylin-eosin (HE), Grocott, von Kossa, periodic acid-Schiff (PAS), and Movat pentachrome stains. Histologically, vacuolar degeneration (100.0%) and increased numbers of melanomacrophages (18.6%) in the liver, and edema (14.0%) in the lungs were observed. Twenty-five kidneys (58.1%) showed deposition of blue amorphous material with HE staining, which also appeared PAS-positive and black with von Kossa staining, allowing a diagnosis of calcium oxalate, confirmed by transmission electron microscopy (TEM). The hepatic lesions may be indicative of toxicosis, infection, or a defense mechanism. A statistically significant association between the nest position and renal oxalosis (renal calcium oxalate deposition) was observed. Renal oxalosis was probably due to the exceptionally high summer temperatures, which were statistically higher compared to the temperatures recorded in the previous two years. Full article

Since epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were introduced in 2004, various driver gene mutations have been identified in non-small cell lung cancer, particularly adenocarcinoma, where mutations are typically mutually exclusive. EGFR and Kirsten rat sarcoma viral oncogene (KRAS) mutations are most prevalent in Japan, with routine testing now standard. However, hematoxylin and eosin staining often fails to detect mutations, except in cases such as ALK fusion lung cancer. We report a 76-year-old non-smoking Japanese woman diagnosed with adenocarcinoma confirmed as KRAS G12D/S-positive. Histological features, including thanatosomes (hyaline globules), nuclear pleomorphism, and cytoplasmic clearing, may aid in identifying mutations. Numerous thanatosomes were identified, some containing nuclear dust. Thanatosomes revealed periodic acid–Schiff reactivity with diastase resistance, fuchsinophilia with Masson’s trichrome stain, and dark blue-black color with Mallory’s PTAH stain. This is the first report linking thanatosomes in KRAS-mutant pulmonary adenocarcinoma to apoptosis via cleaved caspase-3 staining. Full article

Background/Objectives: Acinic cell carcinoma (ACC) is a rare lung neoplasm that can affect both children and adults as a parenchymal or endobronchial mass. It is histologically similar to this kind of tumor described in salivary glands, but with a different immunophenotype. In general, it poses a reduced degree of malignancy, with indolent growth and a favorable prognosis, with exceptionally rare cases associated with recurring disease or lymph node metastases. Methods: When clinicians are facing puzzling symptomatology in their patients, the main role of the multidisciplinary team in their review of oncological cases is to recommend imagistic-guided biopsies. Tissues samples were routinely processed, stained with hematoxylin-eosin (HE) and periodic acid–Schiff (PAS), and submitted to complementary immunohistochemistry tests. Results: Histopathological reports were consistent for lung ACC with regional lymph node involvement and remote metastases. Oncological therapies followed. Conclusions: Postponements of the presentation to the doctor at the onset of symptoms, as well as a lack of periodic health control for people insured by national health insurance companies, often lead to medical, human and financial complications that are difficult to manage. The pathologist involved in the discussion of oncological cases brings his expertise in solving cases, certifying the evolution of tumors considered less aggressive, such as in the case of lung ACCs. Full article

Hemolytic-uremic syndrome (HUS) is a systemic complication of an infection with Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli, primarily leading to acute kidney injury (AKI) and microangiopathic hemolytic anemia. Although free heme has been found to aggravate renal damage in hemolytic diseases, the relevance of the heme-degrading enzyme heme oxygenase-1 (HO-1, encoded by Hmox1) in HUS has not yet been investigated. We hypothesized that HO-1, also important in acute phase responses in damage and inflammation, contributes to renal pathogenesis in HUS. The effect of tamoxifen-induced Hmox1 gene deletion on renal HO-1 expression, disease progression and AKI was investigated in mice 7 days after HUS induction. Renal HO-1 levels were increased in Stx-challenged mice with tamoxifen-induced Hmox1 gene deletion (Hmox1^R26Δ/Δ) and control mice (Hmox1^lox/lox). This HO-1 induction was significantly lower (−43%) in Hmox1^R26Δ/Δ mice compared to Hmox1^lox/lox mice with HUS. Notably, the reduced renal HO-1 expression was associated with an exacerbation of kidney injury in mice with HUS as indicated by a 1.7-fold increase (p = 0.02) in plasma neutrophil gelatinase-associated lipocalin (NGAL) and a 1.3-fold increase (p = 0.06) in plasma urea, while other surrogate parameters for AKI (e.g., periodic acid Schiff staining, kidney injury molecule-1, fibrin deposition) and general disease progression (HUS score, weight loss) remained unchanged. These results indicate a potentially protective role of HO-1 in the pathogenesis of Stx-mediated AKI in HUS. Full article

Meagre (Argyrosomus regius) is one of the fast-growing species considered for sustainable aquaculture development along the Mediterranean and Eastern Atlantic coasts. The emergence of Systemic Granulomatosis (SG), a disease marked by multiple granulomas in various tissues, poses a significant challenge in meagre aquaculture. In the current study, we investigate the association of Mycobacterium spp. and SG in offshore aquaculture facilities in Sardinia, Italy. A total of 34 adult seemingly healthy meagre were arbitrarily collected and analyzed, combining histological, microbiological, molecular, metagenomics, and in situ techniques to investigate the presence of pathogens. Ziehl–Neelsen (ZN), periodic acid–schiff (PAS), and Giemsa stains were performed for the detection of acid-fast bacteria, common parasites, and fungi within granulomas, respectively. Granulomas were detected in 91% (31/34) of fish. The affected organs were kidney (88%), liver (47%), heart (41%), intestine (17.6%), and brain (5%). Acid-fast staining, along with Mycobacterium spp. specific quantitative PCR (qPCR), in situ hybridization (ISH) assay, and microbiological analyses showed negative results for the detection of Mycobacterium spp. and other bacteria implicated in granuloma formation. However, PCR amplification and sequencing of the 65-kDa heat shock protein gene revealed the presence of M. chelonae in 13% of both formalin-fixed and frozen liver tissues. Bacterial isolation failed to detect nontuberculous mycobacteria (NTM) and other bacteria typically associated with granulomas. Consistently, the use of an M. chelonae-specific probe in ISH failed to identify this bacterial species in granulomas. Collectively, results do not support the role of M. chelonae in the development of granulomas and suggest rejecting the hypothesis of a potential link between NTM and SG. Full article

Background/Objectives: Isatidis Folium (IF) has been used in traditional medicine for various ailments, and recent research highlights its anti-inflammatory, antiviral, and detoxifying properties. This study investigated the anti-inflammatory effects of a hydroethanolic extract of IF (EIF) on inflammasomes and colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis model C57BL/6 mice were treated with DSS, mesalamine, or EIF (200 mg/kg). Parameters such as daily disease activity index (DAI), spleen weight, colon length, and histopathology were evaluated. Intestinal fibrosis, mucin, and tight junction proteins were assessed using Masson’s trichrome, periodic acid–Schiff, and immunohistochemistry staining. RAW264.7 and J774a.1 macrophages were treated with EIF and lipopolysaccharide, with cell viability assessed via the cell counting kit-8 assay, nitric oxide (NO) production with Griess reagent, and cytokine levels with the enzyme-linked immunosorbent assay. NF-κB inhibition was analyzed using the luciferase assay, and phytochemical analysis was performed using UPLC-MS/MS. Results: EIF mitigated weight loss, reduced DAI scores, prevented colon shortening, and attenuated mucosal damage, fibrosis, and goblet cell loss while enhancing the tight junction protein occludin. The anti-inflammatory effects of EIF in RAW264.7 cells included reduced NO production, pro-inflammatory cytokines, and NF-κB activity, along with inhibition of NLRP3 inflammasome responses in J774a.1 cells. The key constituents identified were tryptanthrin, indigo, and indirubin. Conclusions: Animal studies demonstrated the efficacy of EIF in alleviating colitis, suggesting its potential for treating inflammatory diseases. Full article

This study investigated the potential of chicken byproduct hydrolysates (CBH) characterized by a mixture of low-molecular-weight peptides (<1.35 kDa) and larger peptides (<17.5 kDa) as a treatment for metabolic syndrome (MS), from a histological and histopathological point of view. This study aimed to evaluate the effects of CBH obtained using plant proteases (BP: B. pinguin, BK: B. karatas, BRO: bromelain) on the histological and histopathological analysis of the liver and kidney in an MS-induced murine model. Methods: Thirty adult male Wistar rats were randomly assigned to six groups (n = 5): (1) standard diet (STD); (2) MS with a hypercaloric diet (MS + HC); (3) CBH-BP (200 mg/kg of body weight); (4) CBH-BK (200 mg/kg of body weight); (5) CBH-BRO (200 mg/kg of body weight); (6) carnosine (CAR) 50 mg/kg of body weight. Liver and kidney samples were processed by conventional hematoxylin and eosin (H&E) histological techniques, Masson’s trichrome stain (MTS), and the periodic acid–Schiff (PAS) histochemical method. A scoring scale was used for the histopathological evaluation with scores ranging from 0 (normal tissue) to 4 (severe damage). Results: CBHs demonstrated a significant therapeutic effect (p < 0.05) on hepatic and renal morphological alterations induced by MS. Hepatic scores for lipid inclusions, vascular congestion, and cellular alteration were all reduced to below two. Similarly, renal scores for tubular degeneration, vascular congestion, and dilation of Bowman’s space were also decreased to less than two. The therapeutic efficacy of CBHs was comparable to that of the positive control, CAR (β-alanyl-L-histidine). Conclusions: CBH-BP, CBH-BK, and CBH-BRO treatments reduced morphological alterations observed in liver and kidney tissues, which is relevant since from a histological and histopathological point of view, it allows us to understand at the cellular and tissue level the effects that these treatments can have on a living organism, indicating a potential to improve organ health in people with MS. Full article

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid–Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion. Full article

Onychomycosis is a common fungal nail infection that is difficult to diagnose due to its similarity to other nail conditions. Accurate identification is essential for effective treatment. The current gold standard methods include microscopic examination with potassium hydroxide, fungal cultures, and Periodic acid-Schiff biopsy staining. These conventional techniques, however, suffer from high turnover times, variable sensitivity, reliance on human interpretation, and costs. This study examines the potential of integrating AI (artificial intelligence) with visualization tools like dermoscopy and microscopy to improve the accuracy and efficiency of onychomycosis diagnosis. AI algorithms can further improve the interpretation of these images. The review includes 14 studies from PubMed and IEEE databases published between 2010 and 2024, involving clinical and dermoscopic pictures, histopathology slides, and KOH microscopic images. Data extracted include study type, sample size, image assessment model, AI algorithms, test performance, and comparison with clinical diagnostics. Most studies show that AI models achieve an accuracy comparable to or better than clinicians, suggesting a promising role for AI in diagnosing onychomycosis. Nevertheless, the niche nature of the topic indicates a need for further research. Full article

The importance of decellularized extracellular matrix (dECM) as a natural biomaterial in tissue engineering and regenerative medicine is rapidly growing. The core objective of the decellularization process is to eliminate cellular components while maximizing the preservation of the ECM’s primary structure and components. Establishing a rapid, effective, and minimally destructive decellularization technique is essential for obtaining high-quality dECM to construct regenerative organs. This study focused on human umbilical cord tissue, designing different reagent combinations for decellularization protocols while maintaining a consistent processing time. The impact of these protocols on the decellularization efficiency of human umbilical cord tissue was evaluated. The results suggested that the composite decellularization strategy utilizing trypsin/EDTA + Triton X-100 + sodium deoxycholate was the optimal approach in this study for preparing decellularized human umbilical cord dECM. After 5 h of decellularization treatment, most cellular components were eliminated, confirmed through dsDNA quantitative detection, hematoxylin and eosin (HE) staining, and DAPI staining. Meanwhile, Masson staining, periodic acid-silver methenamine (PASM) staining, periodic acid-Schiff (PAS) staining, and immunofluorescent tissue section staining results revealed that the decellularized scaffold retained extracellular matrix components, including collagen and glycosaminoglycans (GAGs). Compared to native umbilical cord tissue, electron microscopy results demonstrated that the microstructure of the extracellular matrix was well preserved after decellularization. Furthermore, Fourier-transform infrared spectroscopy (FTIR) findings indicated that the decellularization process successfully retained the main functional group structures of extracellular matrix (ECM) components. The quantitative analysis of collagen, elastin, and GAG content validated the advantages of this decellularization process in preserving and purifying ECM components. Additionally, it was confirmed that this decellularized matrix exhibited no cytotoxicity in vitro. This study achieved short-term decellularization preparation for umbilical cord tissue through a combined decellularization strategy. Full article

A prospective study on 110 patients with echinococcosis at Dr. Khuroo’s Medical Clinic, Srinagar, Kashmir, India, from March 2019 to April 2024 identified 12 cases (4 males, 8 females; mean age of 46.58 ± 11.97 years) of Alveolar echinococcosis (AE). Two patients were detected through ultrasound examinations carried out for unrelated causes; one presented with features of liver abscess, and nine had pain in the right upper quadrant for a mean period of 2.2 ± 1.79 years. All had the liver as the primary organ involved, with 15 tumor masses of a mean maximum diameter of 9.22 ± 3.21 cm and volume of 426 ± 374.61 cm³. Tumors placed centrally had invaded vessels and the biliary tract in eight patients, and those placed peripherally had invaded the liver capsule and adjacent organs in nine patients. Histologic examination of liver biopsies or resected organs revealed necrotic lesions, calcifications, and granulomatous inflammation with slender, thin-walled vesicles of bizarre configuration that stained strongly eosinophilic with periodic acid Schiff. Two patients had segmental liver resections; one was treated with liver aspiration, while the other nine with advanced disease received chemotherapy with albendazole along with praziquantel. Patients showed clinical improvement on a median follow-up of 12 months (range 1 to 60 months); however, MRI T2-weighted images and ¹⁸F-FDG-PET-CECT scans in two patients showed active disease on follow-up at one and five years, respectively. A systematic review detected 146 cases of AE in India from 1980 to April 2024. Twenty cases were from foreign countries, mostly from Central Asian republics, and 118 (93.65%) of the remaining 126 Indian patients were permanent residents of Kashmir Valley. The disease affected a population of 79,197 residing in 22 villages from 5 border districts of the valley. These villages were either high in or adjacent to the Himalayan mountain range. Disease prevalence in the affected population was 146.47/10⁵ (males 131.53/10⁵ and females 163.18/10⁵) and the incidence was 12.41/10⁵/year (males 11.16/10⁵/year and females 13.81/10⁵/year). Possible causes of the emergence of AE are discussed, and future directions for research to face this challenge arebeen identified. Full article