Histological Examination Research Articles

Interrogating the Antiobesity Efficacy of Flacourtia Inermis Roxb. Fruits in High Fat Diet-induced Obese Rats

Background Flacourtia inermis Roxb. (Salicaceae) is an underutilized edible fruit known for its antioxidant-rich bioactive compounds. This study explores the antiobesity potential of F. inermis ethanolic fruit extract (FF2) in a high-fat diet (HFD) induced obesity model using Wistar albino rats. Materials and Methods Wistar albino rats were randomly assigned into five groups (n = 6). Group 1 served as the normal control and received a normal diet (ND), while Groups II–V were induced with obesity by being fed an HFD for 10 weeks. Group II acted as the obese control, receiving 100% HFD throughout the study. Groups III, IV, and V also received HFD throughout the study but were supplemented with Orlistat (30 mg/kg b.w), and FF2 extract at doses of 200 mg/kg, and 400 mg/kg, respectively, from week 11 until week 15. Treatment impact of FF2 on body weight, body mass index (BMI), serum lipid levels, glucose levels, liver function parameters, and histopathological evaluations of liver and adipose tissue were investigated. Results The study unveiled that F. inermis fruits exerted potent antiobesity effects, with FF2 treatment (at 200 mg/kg and 400 mg/kg) substantially decreasing body weight gain and BMI in comparison to the HFD group. Supplementation of FF2 alongside an HFD reduced body weight gain, glucose levels, and serum lipid profile. Both doses of FF2 counteracted the adverse effects induced by HFD, with lower triglycerides (TG), total cholesterol, and LDL cholesterol levels, and higher HDL cholesterol levels in the treated groups compared to the positive control. Additionally, FF2 extract showed dose-dependent improvements in serum lipid and glucose levels, as well as, hepatic profile, indicated by decreased AST, ALP, and ALT levels, suggesting potential benefits in managing dyslipidemia, hyperglycemia, and liver health associated with obesity. Histological examination of white adipose tissue provided further evidence of the antiobesity effect. Conclusion The study highlights FF2’s therapeutic potential in managing obesity and associated metabolic disorders. Further investigations into FF2’s mechanisms and clinical application are essential for its development as an antiobesity therapeutic agent in functional food formulations.

The Protective Effects of Citrulline on Testicular Injury Induced by Torsion and Detorsion in Adult Male Rats: An Experimental Study

Background: Testicular torsion is a critical urological emergency that can lead to testicular ischemia and significant tissue damage. Citrulline, a supplement known for enhancing cellular metabolism and mitigating oxidative stress and inflammation, has been explored for its protective effects against testicular injury resulting from torsion and detorsion in rat models. Methods: This study involved 42 Wistar rats, divided into six groups: Sham, torsion/detorsion (T/D), and four groups receiving varying doses of Citrulline (300, 600, 900 mg/kg) and vitamin E (20 mg/kg). A surgical procedure was performed to induce torsion by rotating the left testicle for 4 hr, followed by reperfusion. Daily oral administration of the supplements continued for one week post-surgery. Assessments included oxidative stress markers, apoptosis, inflammation, pathology, and sperm parameters. Statistical analysis was conducted using GraphPad Prism. Results: Citrulline administration at doses of 600 and 900 mg/kg significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Additionally, it increased glutathione (GSH) levels and decreased protein carbonyl levels at the 900 mg/kg dose. The expression of interleukin-6 (IL-6) decreased at 900 mg/ kg, tumor necrosis factor-alpha (TNF-α) levels dropped at 600 and 900 mg/kg, and the pro-apoptotic factor Bax was reduced at all doses. Sperm analysis showed improved sperm count and motility at the 900 mg/kg dose. Histological examination revealed significant positive effects of Citrulline on testicular tissue. Conclusion: Citrulline effectively lowers oxidative stress, inflammation, while enhancing sperm quality and pathological outcomes. These results indicate that Citrulline has potential as a therapeutic agent for testicular torsion.

Acral Peeling Skin Syndrome: A Rare Skin Disorder

Objective − We report the case of an 8-year-old girl with acral peeling skin syndrome.Case Report − A previously healthy 8-yearold girl presented with a history of flaccid bullous lesions on the plantar surface of her feet, and subsequent peeling and scarring since she was 12 months old. A biopsy of the plantar lesion was carried out and histological examination revealed an acral skin flap characterized only by the presence of an intracorneal bullous cleft, with hypogranulosis and focal parakeratosis. A genetic study was carried out, identifying two pathogenic heterozygous variants in the TGM5 gene. The clinical presentation, histological and genetic examination confirmed the diagnosis of acral peeling skin syndrome.Conclusion − Acral peeling skin syndrome is not a widely known pathology, which means that cases of acral peeling skin syndrome can be misdiagnosed as Epidermolysis bullosa simplex, especially when a genetic study is not available. Particularly in younger children, it is important not to underestimate the diagnosis of acral peeling skin syndrome, given the different prognostic implications between the two diagnoses.

Persistent Liver Injury Following Avacopan Discontinuation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Rare Case of Liver Biopsy in the Chronic Phase of Liver Injury.

Drug-induced liver injury (DILI) is a major concern associated with the use of avacopan, a new therapeutic agent for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Here, we report a rare instance of liver biopsy performed for persistent liver injury following discontinuation of avacopan in an elderly woman with microscopic polyangiitis (MPA). The patient developed cholestatic liver injury after 2 months of avacopan therapy, which led to drug cessation. Despite the discontinuation of avacopan followed by supportive care, the liver enzyme levels remained elevated, necessitating liver biopsy. Histological examination revealed residual inflammation and focal necrosis around the portal vein, indicating ongoing liver injury despite avacopan withdrawal. This case report highlights the hepatotoxic potential of avacopan, the importance of vigilant liver function monitoring, and the value of liver biopsy in the chronic phase of avacopan-induced liver injury. Further research is required to elucidate avacopan hepatotoxicity mechanisms and identify potential risk factors for DILI in patients with AAV.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report About a Patient with Cytology Negative for Malignancy

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare lymphoma primarily linked to textured breast implants. Symptoms are often non-specific (e.g., breast swelling, pain, or fluid collection). When imaging detects fluid around the implant, cytological examination is the first diagnostic approach. However, this method has limited sensitivity and may yield false-negative results. In this case, a 41-year-old woman presented with swelling, pain, and itching in her left breast six years after bilateral textured breast implant placement. Ultrasonography (US) revealed peri-implant fluid collection around the left implant. A following magnetic resonance imaging (MRI) scan ruled out an implant rupture. Due to persistent pain and the peri-implant effusion on the left side, open surgery was performed. During implant removal, the seroma was drained, and multiple suspicious masses were found on the left side. The cytology of the seroma fluid was negative and intraoperative frozen sections of the excised masses were inconclusive. A complete capsulectomy was conducted due to the suspicion of malignancy. Histological examination ultimately confirmed the diagnosis of BIA-ALCL. This case highlights the diagnostic challenges associated with this rare condition. Therefore, BIA-ALCL should always be considered in the differential diagnosis of breast implant-associated seroma.

The role of elastography in determining the risk of malignant thyroid nodules in children

IntroductionUltrasonography is fundamental method of diagnosing focal thyroid lesions. The additional element of ultrasound examination is Strain Elastography which allows for determining the degree of elasticity of the nodule while comparing it to the surrounding thyroid parenchyma. Pediatric thyroid nodules have a higher malignancy risk than in adults, warranting the consideration of fine-needle aspiration biopsy (FNAB) in children.Material and methodsA prospective data analysis of children with focal thyroid lesions treated from 2021 to 2022 was performed. The patients underwent ultrasound and elastography examinations to obtain the Strain Ratio (SR) of the nodules and were qualified for FNAB. SR was determined by the windowing method of relative strains in a semi-quantitative assessment. The FNAB score was determined on the Bethesda scale and the histological examination of the thyroid nodule was performed. The SR values were stratified in three groups: I - thyroid cancer, II - low-risk thyroid tumors, and III - benign lesion. The Kruskal-Wallis test was used to find the relation between the value of SR elastography and the malignancy, with the p value < 0.05 considered significant. The data were analyzed using the multiple comparisons test.ResultsThe 123 FNABs were performed in 100 patients. The final analysis included 119 nodules in 96 patients. In 19 cases, the nodule was malignant, in 5 cases they were low-risk tumors, and in 95 - benign lesions. A difference of the SR value between groups in the pairs of malignant and benign tumors, and malignant and low-risk tumors was revealed. Since no statistically significant difference in the level of elastography was found between benign and low-risk tumors, both groups were combined and formed a group of benign tumors. For the combined groups, the Man-Whitney test was performed, confirming that there was a statistically significant difference between the groups of malignant and benign tumors in the value of SR elastography. The cut-off point for SR for malignant tumors was >3.ConclusionsThe SR index of elastography is significantly higher in malignant nodules. and might be used to select changes with an increased risk of malignancy in thyroid ultrasound of children.

Myxoid Solitary Fibrous Tumor of the Nasal Vestibule: An Unusual Histological Subtype in the Head and Neck Region.

Solitary fibrous tumors (SFTs) are mesenchymal neoplasms associated with the characteristic NAB2::STAT6 gene fusion. They frequently occur in extra-thoracic sites and are not uncommon in the head and neck (HN) region. Myxoid SFT is a rare morphological subtype of SFT, the features of which overlap with those of other myxoid-appearing tumors, making the diagnosis challenging. We describe the distinctive histopathological and immunohistochemical features of myxoid SFT that occurred in a 32-year-old man with a recurrent swelling in the nasal vestibule. Histological examination showed a nodular tumor composed of short spindle-shaped cells in an abundant myxoid stroma. Nuclei were ovoid, with minimal pleomorphism. Occasional intervening slender vascular channels were present; staghorn vasculature was absent. Tumor cells were diffusely immunopositive for STAT6, CD34, and BCL2, while S100, SOX10, EMA, ER, and CD10 were negative, confirming the diagnosis of myxoid SFT. Thus, myxoid SFTs are unusual in the HN, with potential for misdiagnosis. Due to their propensity for local recurrence if incompletely excised, a high index of suspicion is required to include them in differential diagnosis of myxoid mesenchymal neoplasms occurring at this location. STAT6 is a reliable immunohistochemical marker that aids in diagnosis, reducing the necessity for molecular testing.

BN SO14 - Evaluation of local cholecystectomy service and outcomes (Local Data for GECKO study)

Abstract Background Cholecystectomy is a common procedure performed for different biliary pathologies. Patients have their procedure as elective, emergency, or prioritised bases (Hot Gall bladder service). Method GECKO is a prospective, international, observational collaborative cohort study Consecutive patients undergoing cholecystectomy, between 23rd Oct – 19th Nov 2023 with follow-up at 30-day and one-year postoperatively Results Over a 4-week period , 38 cholecystectomies were performed, with 47.5% of patients having prior cholecystitis or cholangitis and multiple admissions. Half of the surgeries occurred within 6 months, and the longest wait was 13 months. Procedures were split equally between elective and emergency cases. Indications included acute cholecystitis (13), biliary colic (11), and others. All surgeries were laparoscopic, with 2 subtotal cholecystectomies. Complications included bile or stone spillage (12) and bleeding (7). Postoperative follow-up showed 16 patients discharged within 24 hours, 3 readmissions, and a 37% complication rate. No bile leaks or CBD injuries were reported. Conclusion Emergency and hot cholecystectomy services not only cut down waiting lists but also reduce costs of reoccurring admissions and treatments, with no significant associated complications. Selective gall bladder histological examination may help cost reduction with no significant recognised risks in the literature.

A clinical case of skin lymphocytoma in a young woman

A 25-year-old woman came to consult a dermatovenerologist. The woman complained of a rapidly progressing painless lump on the right wing of her nose which developed after photo-rejuvenation treatment and the development of herpetic infection.in the place of a previous lipoma removed by radio wave surgery. The clinical picture was characterized by a solitary disc-shaped plaque, 2 cm in size, bluish-reddish-brownish in color, of a doughy consistency, significantly protruding above the skin surface, with clear borders and a smooth, shiny surface. There was a complex differential diagnostics, the final diagnosis was confirmed by the results of a histological examination, which revealed changes characteristic of lymphocytoma. The patient was treated with aminoquinoline preparations and topical glucocorticosteroids and rapid positive dynamics with complete regression of the skin pathological process was observed. A clinical case of skin lymphocytoma that occurred after several successive trigger factors such as lipoma formation and removal, photo rejuvenation procedures, and herpes infection is presented in the article. This is a fairly rare disease that does not have a pathognomonic clinical picture, so it is difficult to differentiate and diagnose it. The results of a pathomorphological examination are essential for the diagnosis. A positive effect with a complete regression of skin changes can quickly occur if treated correctly.

Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium-Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats.

Mesenchymal stem cells-derived exosomes (MSCs-EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs-EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4-weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ-diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic-treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H2O2) inflammatory (IL-6, TNF-α, and TGF-β), and apoptotic (P53, BAX, caspase-3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority.

Abstract 4145821: Serial Vascular Responses of Balloon-expandable Stent with Biodegradable Film-type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study)

Introduction and Background: Arterial dissection during endovascular therapy rarely occurs but can be lethal. A significant blood volume extravasation during coronary artery interventions is related to the very high mortality (20-30%). In this hyperacute emergent clinical situation, covered stents have been considered as a primary measure to prevent further serious arterial events. A fabric-based covered graft stents yield poor clinical outcomes. To overcome these challenges, the balloon-expandable stent with biodegradable film-type graft for treating arterial dissection was invented. Research Questions and Objectives: A novel balloon-expandable stent with biodegradable film graft for overcoming these issues would be valid for efficacy and safety in a rabbit iliac artery dissection model. Method and Approach: Eighteen iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0 x 24 mm). Subsequently, twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year. Results and Data: There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2weeks, 26.1 at 1month, 29.7 at 3months, 49.2 at 9months, and 51.0 at 1year), along with mild peri-strut inflammatory response (Grade: 1-2 at mid-term and 0-1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2weeks, 12.3 at 1month, 14.2 at 3months, 25.1 at 9months, and 26.6 at 1 year). Conclusion: The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model. Future human studies are warranted to validate these findings and elucidate the clinical outcomes of the study.

Abstract 4124354: Transplantation of vascularized cardiac microtissue derived from human iPS cells improves impaired electrical conduction capacity in a porcine myocardial injury model

Background: To realize efficient regenerative medicine using human iPS cell (hiPSC)-derived cardiac tissue, it is necessary to achieve electrical synchronization between the graft and the host heart and to improve conduction disturbances in the impaired heart. In this study, we aimed to demonstrate that the transplantation of hiPSC-derived vascularized cardiac tissue can improve these conduction disturbances using a porcine myocardial injury model. Methods: We prepared cell sheet-shaped vascularized cardiac microtissue (VCM) by seeding cardiomyocytes, endothelial cells, and vascular mural cells differentiated from hiPSCs onto temperature-responsive culture plates and thickening them using dynamic rocking culture. We induced myocardial injury (MI) via epicardial cryoablation in immunosuppressed crown minipigs and transplanted the VCMs immediately after MI induction, covering the cryoinjury-induced MI area. The pigs underwent epicardial electroanatomic mapping under sinus rhythm and epicardial pacing, both immediately before and one week after MI induction, while using amiodarone. Differences in myocardial voltages and conduction velocities were assessed between VCM and sham groups (N=3 in each group). After electroanatomic analysis, the hearts were harvested and subjected to histological examination. Results: One week after MI induction, mean voltages at the MI site decreased in both groups during sinus rhythm, remote site pacing, and combined remote and MI site pacing (11.05 to 1.74 mV, 14.26 to 3.44 mV, and 15.61 to 3.67 mV, respectively, in the VCM group; and 8.72 to 2.70 mV, 19.64 to 3.64 mV, and 14.66 to 1.96 mV, respectively, in the Sham group). Mean voltages at the remote site also decreased in both groups during the same conditions (12.57 to 4.53 mV, 10.61 to 3.38 mV, and 19.56 to 5.85 mV, respectively, in the VCM group; and 8.75 to 6.03 mV, 14.15 to 5.79 mV, and 13.67 to 6.23 mV, respectively, in the Sham group). The mean conduction velocity between the remote and MI sites was numerically higher in the VCM group compared to the Sham group (2.84 m/s vs. 1.74 m/s, respectively). Histological examination confirmed that in the VCM transplantation group, the VCM remained intact, completely covering the MI area. Conclusions: The transplantation of VCM showed a tendency to improve conduction disturbances in the porcine MI model. This suggests that the graft may synchronize with the host and function mechanically after cell transplantation.

Abstract 4123630: MRPL44 Plays an Important Role in Cardiac Hypertrophy and Function

Background: Mitochondrial ribosomal large subunit 44 (MRPL44) knockout mice were embryonic lethal, for which mutations are known to cause mitochondrial infantile cardiomyopathy and hypertrophic cardiomyopathy. However, it remains unknown how MRPL44 contributes to cardiac function and hypertrophy. Aims: Our aim is to investigate the effect of MRPL44 haploinsufficiency in mice. Methods: MRPL44 haploinsufficient (MRPL44 +/- ) mice were generated. Mineralocorticoid receptor-associated hypertension mice were induced in MRPL44 +/- and wild-type (WT, MRPL44 +/+ ) mice with subcutaneous infusion of aldosterone(Aldo) and 8% NaCl food for 4 weeks after uninephrectomy. Systolic blood pressure was measured by tail cuffs every week. WB, qPCR, cardiac echo, and histological examinations were performed. RNA sequencing analysis, electron microscopy examinations and mitochondrial activity assay were performed to find differences between MRPL44 +/- and MRPL44 +/+ mice. Results: MRPL44 haploinsufficient mice spontaneously developed left ventricular hypertrophy. Heart rate, blood pressure, and cardiac systolic function were normal in MRPL44 haploinsufficient mice. MRPL44 was decreased about to 70% in MRPL44 haploinsufficient mice and mitochondrial arrangement were impaired in electron microscopic analysis. After Aldo treatment, blood pressure elevation were similar, however, MRPL44 haploinsufficient mice developed left ventricular systolic dysfunction and dilation compared with MRPL44 +/+ mice. WB showed mitochondrial electron transport chain protein complex IV expression was significantly decreased. Furthermore, mitochondrial activity assay showed MRPL44 haploinsufficient mice had a significant reduction in complex IV activity, whereas complex I and II activity were similar to MRPL44 +/+ mice. RNA sequencing analysis showed the significant changes in the expression of ribosomal subunits coded by nucleus in addition to mitochondrial ribosomal subunits. These results indicate MRPL44 plays an important role in the cardiac function of mitochondrial electron transport chain protein complexes via the expression of ribosomal protein subunits coded by both nucleus and mitochondria. Conclusion: MRPL44 haploinsufficient mice spontaneously develop left ventricular hypertrophy and shows systolic dysfunction after aldosterone treatment accompanied with oxidative phosphorylation enzyme dysfunction.

Unconventional Histopathological Features With KIAA1549::BRAF Fusion in Advanced Prostatic Adenocarcinoma.

This report delineates an intriguing example of advanced prostatic adenocarcinoma displaying distinctive histopathological characteristics associated with a KIAA1549::BRAF fusion, a genomic anomaly predominantly identified in central nervous system tumors. A 66-year-old man, presenting with acute renal failure, exhibited metastatic disease involving pelvic soft tissue, bladder, liver, and bone. Histological examination revealed a markedly unconventional morphology within the prostate, characterized by infiltrative tumor sheets exhibiting abundant vacuolated cytoplasm, hyperchromatic nuclei, and irregular nuclear membranes, distinct from typical prostatic adenocarcinoma. Immunophenotyping confirmed NKX3.1 positivity and GATA3 negativity. Molecular analysis revealed the rare KIAA1549::BRAF fusion alongside pertinent mutations in phosphatidylinositol 3-kinase, phosphatase and tensin homolog, and tumor protein 53 genes. Despite diverse therapeutic interventions targeting mitogen-activated protein kinase signaling and subsequent clinical trial enrollment, disease progression remained relentless, culminating in the patient's demise within 4 years of diagnosis. This report highlights the exceptional histopathological presentation associated with KIAA1549::BRAF fusion in prostatic adenocarcinoma, emphasizing the need for a deeper comprehension of its implications on disease behavior and therapeutic responsiveness in similar instances.

Anti-thrombotic Mechanisms of Echinochrome A on Arterial Thrombosis in Rats: In-Silico, In-Vitro and In-Vivo Studies.

Arterial thrombosis is one of the most significant healthcare concerns in the world. Echinochrome A (Ech-A) is a natural quinone pigment isolated from sea urchins. It has a variety of medicinal values associated with its antioxidant, anticancer, antiviral, anti-diabetic, and cardio-protective activities. The current study aims to investigate the effect and mechanism of Ech-A to inhibit thrombus formation induced by ferric chloride in rats. Twenty-four rats were assigned into four groups (n= 6); sham and thrombotic model groups were orally administered 2% DMSO, while the other groups were treated with two dosages of Ech-A (1 and 10 mg/kg, body weight). After seven days of administration, all groups were exposed to 50% ferric chloride for 10 min, except the sham group exposure to normal saline. The molecular docking showed the free binding energies of Ech-A and vitamin K (Vit. K) with Vit. K epoxide reductase were -8.5 and -9.8 kcal/mol, which confirm the antithrombotic activity of Ech-A. The oral administration of Ech-A caused a significant increase in partial thromboplastin time, prothrombin time, clotting time, platelet count, fibrinogen levels, factor VIII, glutathione reduced, catalase, nitric oxide, and glutathione S-transferase. While white blood cells count, calcium level, and malondialdehyde concentration significantly decreased. The histological examination revealed a definite improvement in the carotid and cardiac tissues in the Ech-A groups. The study results showed that Ech-A prevented thrombosis by several mechanisms, including chelating calcium ions, increasing the NO concentration, suppressing oxidative stress, and antagonizing Vit. K.

Lack of Evidence for Transmission of Atypical H-Type Bovine Spongiform Encephalopathy Prions (H-BSE Prions) by Intracranial and Oral Challenges to Nonhuman Primates.

Bovine spongiform encephalopathy (BSE) is a prion disease in cattle caused by classical-type (C-), L-type (L-), or H-type (H-) BSE prions. While C-BSE prions are zoonotic agents responsible for variant Creutzfeldt-Jakob disease, L- and H-BSE prions are believed not to be connected to human prion diseases. However, L-BSE prions have been shown to transmit to cynomolgus monkeys (Macaca fascicularis), suggesting they may have zoonotic potential. In the present study, we examined whether H-BSE prions are transmissible to cynomolgus monkeys. The monkeys were injected intracranially (n = 2) or given orally (n = 2) with brain homogenates from a cow infected with H-BSE prions. After asymptomatic observation periods of 4-6 years, the monkeys were euthanized for autopsy. Histological examination of the brain did not reveal any pathological changes. Immunohistochemical and Western blot analyses did not detect disease-associated forms of prion protein (PrPSc) in the brain, peripheral neurons, or lymphatic tissues. The unsuccessful transmission indicates an effective barrier against the transmission of cattle H-BSE prions to cynomolgus monkeys. Based on the results obtained in this nonhuman primate model, we estimated that the potential transmission of H-BSE prions to humans is substantially lower than C- and L-BSE prions.

Pristimerin inhibits the progression of antibody-induced autoimmune arthritis

Objectives Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. Pro-inflammatory cytokines produced by various immune cells drive the chronic inflammatory processes that lead to joint damage. Many drugs are available for the treatment of RA, but a significant proportion of patients do not respond adequately to them and/or have severe adverse effects. Accordingly, there is an urgent need for new therapeutics for RA. Therefore, we tested pristimerin, a natural triterpenoid, for its anti-arthritic activity in experimental RA. Method Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice. After the onset of arthritis, mice were injected daily intraperitoneally with pristimerin or vehicle for 9 days. The severity of clinical arthritis was graded and further validated by micro-computed tomography and histological examination of the hind paws. Defined mediators of arthritogenic processes were quantified by gene expression in the spleen and further validated by immunohistochemistry of paws. Results We observed that pristimerin can effectively control arthritis progression in CAIA mice. A preliminary exploration of the mechanisms showed that pristimerin targeted key pro-inflammatory cytokines and chemokines, along with specific mediators of angiogenesis, bone remodelling, and cellular signalling, including the Notch signalling pathway. Conclusions This is the first report on pristimerin for its use in the treatment of antibody-induced arthritis and for the targeting of Notch pathway in arthritis by this triterpenoid. As pristimerin can control the effector phase of arthritis, our results are promising for the translation of this experimental therapy to RA patients.

Antidiabetic activity of Inonotus obliquus water extract in alloxan-induced diabetic mice.

The Inonotus obliquus is a medicinal mushroom that grows on mature birch trees and is commonly used in traditional medicine for various ailments. The current study aimed to explore the hypoglycemic, hypolipidemic, and pancreatic protective effects of the water extract of Mongolian natural Inonotus obliquus on alloxan-induced diabetic mice. Alloxan monohydrate (200 mg/kg) was intraperitoneally single injected into C57BL/6 mice to induce diabetes. Alloxan-induced diabetic mice were orally given the water extract of inonotus obliquus (WEIO) at doses of 500 mg/kg and subcutaneously administered with insulatard 0.6 IU for 4weeks. Subsequently, the levels of factors related to blood glucose, insulin and lipids were assessed. WEIO significantly restored body weight, reduced fasting blood glucose levels, improved glucose tolerance ability, and increased insulin levels compared to the control diabetic mice. WEIO also enhanced cholesterol transportation in the liver, correlated with increased HDL-C levels and decreased TC, TG and LDL-C levels. Histologic examinations revealed that WEIO alleviated alloxan-induced pancreatic tissue damage. Natural Mongolian I. Obliquus water extracts have an antihyperglycemic effect and enhance islet cell function in alloxan-induced diabetic mice. It is a good candidate for a hypoglycemic functional food or medicine.

Coexistence of complete intestinal tract, prostatic tissue, prostatic urethra and bladder structure in ovarian mature cystic teratoma: a case report.

Mature cystic teratomas (MCTs) of the ovary comprise tissues from all three germ layers. The coexistence of the complete intestinal tract, prostatic tissue, and bladder component within the same ovarian MCT is unprecedented. Here, we report the diagnosis and management of such a rare case. A 26-year-old woman presented with a right ovarian mass, which was later confirmed as an MCT by histopathological examination. The patient underwent a successful laparoscopic cystectomy with no evidence of malignancy or postoperative complications. Histological examination revealed that this MCT contained the complete organ structures including a lower intestinal tract and male genital tract with prostate, urethra, and bladder components, which is unusual. This case underscores the importance of understanding the pathogenesis of extensive organogenesis in MCTs and raises questions about the differentiation processes leading to such unique presentations.

Assessing the effects of cadmium on antioxidant enzymes and histological structures in rainbow trout liver and kidney

Cadmium contamination in aquatic environments poses severe risks to aquatic organisms, particularly fish, where cadmium accumulation in tissues can lead to compromised organ functionality and reproductive issues. The present study aimed to assess the effects of cadmium (Cd) exposure on key biomarkers of oxidative stress, DNA damage, apoptosis, and enzyme activity in the liver and kidney tissues of rainbow trout (Oncorhynchus mykiss). Specifically, the study measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, caspase-3 activation, acetylcholinesterase (AChE) activity, and oxidative stress indicators (ONOO−, MDA, GSH, SOD, and CAT) following exposure to three Cd concentrations (1, 3, and 5 mg/L) over three time points (24, 48, and 96 h). Tissue samples were collected post-exposure, and the analysis revealed a significant decrease in MDA levels in both tissues. GSH concentrations declined with prolonged exposure, while SOD activity increased, indicating a response to oxidative stress, contrasted by a reduction in CAT activity. An initial increase in ONOO− levels was observed at 24 h, followed by a subsequent decrease at the 48 and 96 h marks. These results suggest that cadmium induces oxidative stress in the liver and kidney tissues of fish. Cadmium exposure also significantly elevated 8-OHdG levels, signaling DNA damage, and increased caspase-3 activity, indicative of apoptosis, across all doses and time points (p < 0.05). The histological examination of liver and kidney showed tissue injury. Additionally, a negative correlation between AChE activity and exposure duration was noted, with prolonged exposure resulting in substantial AChE inhibition. Given the role of AChE in behavior regulation, these findings underscore the importance of exploring time-dependent, tissue-specific changes in AChE activity to further elucidate the mechanisms underlying cadmium-induced behavioral abnormalities.