Histological Lesions Research Articles

Effect of atorvastatin on lipopolysaccharide-induced lung inflammation and hypoxia in mice; modulation of HIF-1α, CINC and MIP-2

Background Acute lung injury is a crucial pathological state, particularly in some severe infectious respiratory illnesses, distinguished by acute inflammation, pulmonary edema, hypoxia, and neutrophil recruitment. Cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) play a vital role in neutrophil recruitment. Objective Here, we validated the potential repressing effect of atorvastatin on acute lung injury induced by lipopolysaccharide (LPS) in mice. Materials and methods Mice were injected with LPS (250 μg/kg; i.p.) daily for 7 days, and atorvastatin (25 and 50 mg/kg; orally) daily along with LPS. Results Atorvastatin ameliorated oxidative stress as evidenced by increased reduced glutathione (GSH) and nuclear factor-erythroid 2 related factor 2 (Nrf2) levels and decreased malondialdehyde (MDA) levels. Additionally, it lessened inflammatory biomarkers including tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), CINC, and MIP-2, as well as hypoxia biomarker hypoxia-inducible factor–1α (HIF-1α). Moreover, atorvastatin slowed the progression of lung tissue histological lesions. Conclusion Collectively, the present study suggests that, atorvastatin effectively protects against LPS-induced acute lung injury through inhibition of oxidative stress, inflammation, hypoxia, and neutrophil recruitment.

Interspecies transcriptome profiles of human T cell activation and liver inflammation in a xenogeneic graft-versus-host disease model

BackgroundXenogeneic transplantation induces acute graft-versus-host disease (aGvHD) and subsequent vital organ damage. Herein, we aimed to examine hepatic damage associated with aGvHD using histopathology and gene expression profiles. MethodsA xenografic GvHD model was established by engrafting human peripheral blood mononuclear cells (PBMCs) into immunodeficient NOD-scid IL2Rγnull (NSG) mice after busulfan conditioning. NSG mice were assigned to groups treated with saline (S group) or a combination of busulfan and PBMCs (BP group). Histological lesions and RNA sequencing analysis of gene profiles in the BP group (GvHD model) were compared with those in the P group. ResultsPredominant T cell subsets (95 %) in the blood of the BP group were identified as cytotoxic CD8+ T cells (56 %) and helper CD4+ T cells (31 %). Symptoms of aGvHD, including hepatocyte necrosis, bile duct hyperplasia, and human T cell infiltration, were observed. Gene expression analysis revealed upregulation of Th1 and Th2 cell differentiation (STAT4, IL4R, and NFACT1), T cell receptor signaling pathway (CD226 and GBP1), IL-1 pathway (CCL3, NAIP, and IRAK4), cell cycle (CDCA5, CDCA8, MCM5, KNL1, BUB1B, FBXO5, and CENPE) in human cells. In mouse cells, Il1a, Ifngr, Tnfrsf, and Il6ra genes (cytokines or their receptors) and Icam, Vcam, and Endra genes (adhesion molecules) were upregulated, whereas genes related to chromosome condensation (H2ac and H2bc) and fatty acid/steroid metabolism (Fasn, Rdh, and Scd) were downregulated. Interspecies gene network analysis revealed that activated human T cells are associated with liver damage through inflammatory and metabolic pathways, accompanied by increased mouse cell adhesion molecules and cytokines. ConclusionOur findings offer valuable insights into the pathophysiology and biomarkers of aGvHD and may contribute to the development of novel therapeutics.

18F-fluorocholine PET/CT imaging in primary hyperparathyroidism after negative or inconclusive cervical ultrasonography and 99mTc-MIBI scintigraphy.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder characterized by one or more hyperfunctioning parathyroid glands. Definitive surgical treatment demands precise preoperative localisation of hyperfunctioning parathyroid tissue. The purpose of our study is to assess the value of 18F-fluorocholine positron emission tomography (PET/CT) in preoperative localisation of hyperfunctioning parathyroid glands in patients with biochemically confirmed pHPT and negative or inconclusive cervical ultrasonography and 99mTc-MIBI scintigraphy. Our study included 167 patients with biochemically confirmed pHPT and negative or inconclusive cervical ultrasonography and 99mTc-MIBI scintigraphy. In our study 18F-fluorocholine PET/CT detection rate was 92.81% (155/167) with 182 lesions identified. Overall sensitivity, specificity, accuracy, and positive predictive value (PPV) on a per-lesion analysis were 100%, 75%, 95.33%, and 94.74%. Ninety (90/95) lesions were 18F-fluorocholine PET/CT true positive. A total of 86 patients underwent surgical procedures in which 95 histological lesions were removed. Histology revealed 60 adenomas, 25 hyperplasias, 5 lesions described as inconclusive parathyroid tissue, benign lymph node tissue in 4 lesions and 1 false-positive lesion was follicular thyroid adenoma. After surgery, all patients had PTH serum values measured (15min after extirpation or during immediate postoperative recovery). Mean PTH serum values in patients with successful surgery decreased by an average of 62.54% (preoperative PTH 14.74 ± 8.54pmol/L to 6.3 ± 6.8pmol/L). 18F-fluorocholine PET/CT is an accurate, fast, and highly sensitive method for identifying the localization of overactive parathyroid glands in patients with primary hyperparathyroidism.

Impact of age on surgical excision margins for vulvar squamous cell carcinomas: A multicenter study by the francogyn group

IntroductionVulvar cancer is a rare cancer, it most often affects older women, with tumours of more advanced size and stage than in younger patients. The first-line treatment for vulvar cancer is surgery. Current European and American guidelines recommend negative histological margins. As tumor size is greater in older patients, the aim of this study was to assess the impact of patient age on surgical excision margins in squamous cell carcinomas of the vulva. Material and methodThis was a retrospective multicenter observational study. A descriptive analysis of the population was performed and a univariate analysis was performed according to patient age. Survival data were plotted using the Kaplan-Meier method and compared using a log rank test. Survival was analyzed using a Cox model to calculate the Hazard Ratio. ResultsAmong the 547 patients included, there were 206 patients <65 years and 341 ≥ 65 years, including 135 ≥ 80 years. Median postoperative histological lesion size and interquartile range was greater in patients ≥65 years (30 mm [18–45] versus 26 mm [14–34], p < 0.001). Patients ≥65 years of age more often benefited from radical total vulvectomy (n = 103 (28.8 %) versus n = 44 (20.4 %), p = 0.03). However, negative surgical excision margins were identical between the 2 groups (n = 180 (87.4 %) versus n = 286 (83.9 %), p = 0.21). Revision surgery was performed more frequently in patients <65 years. Recurrence-free survival was better in patients aged <65 years (HR = 0.60; CI95 % (0.45–0.82), p = 0.001). ConclusionDespite larger tumour size, age is not a factor influencing the achievement of negative excision margins in squamous cell carcinomas of the vulva, at the cost of more radical surgery.

Predictive value of residual active histologic lesions on renal flare in lupus nephritis patients with clinical remission

Abstract Background Renal flare in lupus nephritis (LN) is a crucial contributing factor to poor kidney outcomes. This study aimed at evaluating the predictive value of residual active histologic lesions on renal flare in proliferative LN patients with clinical remission. Methods We retrospectively enrolled LN patients with class III/IV±V (biopsy 1) who had undergone a protocol repeat biopsy (biopsy 2) at 7.3 (IQR: 6.5, 8.4) months after induction therapy with clinical remission and experienced renal flare within 3 years or had been followed up for at least 3 years without renal flare after biopsy 2 with maintenance therapy from two kidney units in China. Results A total of 114 eligible patients were included, 28 (24.6%) of whom developed a renal flare. Activity index (AI) at biopsy 2 was significantly associated with LN flare (P &amp;lt; 0.0001). If AI&amp;gt;1, the OR for LN flare was 23.1 (95%CI, 5.1-103.8, P&amp;lt;0.001). For patients with partial clinical remission compared with those with complete clinical remission, the OR for LN flare was 3.0 (95%CI: 1.1-8.3, P=0.029). Multivariate analysis showed that anti-dsDNA positivity, presence of cellular/fibrocellular crescent and endocapillary hypercellularity at biopsy 2 were independent risk factors for LN flare. When residual active histologic lesions were added to clinical variables, the area under the curve (AUC) of the prediction model for LN flare significantly increased and the misclassification rate significantly decreased. Conclusions Renal flare in LN patients with clinical remission is strongly associated with the residual active histologic lesions.

Evaluation of Hematological, inflamatory and Histopathological Changes in Doxorubicin Induced Heart Failure Rats Receiving Sardinella maderensis Oil as Protective Measure

Objective: Current studies suggest that fish oil may have cardioprotective effects. The objective of this study was to evaluate the hematological, inflammatory markers, and histopathological changes in doxorubicin induced heart failure rats receiving Sardinella maderensis fish oil. Materials and Methods: Sardine fish was purchased from Congelcam, and oil extracted using the standard Bligh and Dyer protocol. The oil quality indices (acide value, iodine value, peroxide value, anisidine value and Totox value) were measured using standard AOAC methods To test the biochemical activities of the oil, 36 male wistar rats weighing between 150g to 180g were purchased. The animals had food and water ad libitum throughout the experimental period (28 days). They were divided into six groups of six rats each: G1 (normal group), G2 (negative control), G3 (Positive control; gemfibrozil 100 mg/kg), G4 (Test group I; fish oil 250 mg/kg), G5 (Test group II; fish oil 500 mg/kg), G6 (Test Group III; fish oil 1000 mg/kg). G1 rats received distilled water, G2 to G6 rats received DOX 2.5mg/kg on days 13, 16, 19, 22, 25, 28 for a cumulative dose of 15 mg/kg. On the 29th day, the rats were anaesthetized, sacrificed and blood samples collected to assess serum cytokine levels and hematological parameters. Organs were also collected for histopathological analysis. Results: Results showed that DOX administration significantly decreased (p&lt;0.001) hematological parameters WBC, RBC, Hb, hematocrit, platelets, monocytes, granulocytes, MCV, MCH and MCHC in the negative group compared to the normal group. Serum levels of inflammatory cytokines increased significantly (p&lt;0.001) in the negative group TNF-α (352.7), INF-δ (364.17), IL-1β (323.91), IL-6 (479.88) and IL-10 (397.91) compared to the normal group. However, pre-treatment with fish oil in the test groups significantly increased (p&lt;0.05) hematological parameters (WBC, RBC, Hb, hematocrit, platelets, monocytes, granulocytes, MCV, MCH) compared to the negative group. Serum levels of inflammatory cytokines in the test groups decreased significantly (p&lt;0.05) especially those in test group III; TNF-α (184.85), INF-δ (145.15), IL-1β (152.81), IL-6 (321.58) and IL-10 (230.33). Histological lesions identified in the heart, liver, and kidney tissues of the negative control rats were significantly attenuated in all the test groups receiving fish oil. Conlusion: Animals receiving fish had improved hematological parameters, decreased levels of inflammatory cytokines and improved organ histology. These findings demonstrate therefore that Sardinella maderensis oil could have cardio-protective effects on human health.

Zoonotic Dirofilaria sp. “hongkongensis” in subcutaneous nodules from dogs and cats, Hong Kong SAR

BackgroundDirofilaria sp. “hongkongensis” is a putative Dirofilaria species, initially identified in subcutaneous nodules in humans in Hong Kong and in other South and Southeast Asian regions. While it differs genetically from the better-known zoonotic species, Dirofilaria repens and Dirofilaria immitis, information on the lesions caused by Dirofilaria sp. “hongkongensis” in the hosts as well as on its biology is scarce. This study documents for the first time the presence of this filarioid nematode in subcutaneous nodules in dogs and cats in Hong Kong, where it was originally described in human patients, therefore providing evidence for the zoonotic nature of this parasite.MethodsRecords of Veterinary Diagnostic Laboratory of City University of Hong Kong were searched between 2019 and 2024 for histological reports of possible filarioid-associated lesions. Tissue samples were collected by excisional surgical biopsy and processed with routine paraffin techniques. Selected slides were stained using various staining techniques [i.e., hematoxylin and eosin, periodic acid–Schiff (PAS), Grocott methenamine silver (GMS) or Ziehl–Neelsen (ZN) and Gram stain]. DNA from formalin-fixed paraffin-embedded tissue were extracted, submitted to conventional polymerase chain reaction (cPCR) and sequencing (i.e., cox1 and 12S rRNA genes) and phylogenetic analyzed.ResultsA total of five subcutaneous nodules from four cats and one from a dog with histopathology suggestive of filariosis were selected. The presence of Dirofilaria sp. “hongkongensis” was morphologically and molecularly confirmed in one dog and one cat. Both histopathological presentation and phylogenetic analysis enabled classification of this species close to D. repens and within the subgenus Nochtiella. In the remaining three cases, one showed histological evidence of aberrant nematode migration, while non-parasitic causes were identified in the other two.ConclusionsThis study provides the first evidence of Dirofilaria sp. “hongkongensis” in subcutaneous nodules in cats and dogs. The histology of clinical lesions of this filarioid species herein described is closely related to those caused by D. repens. Overall, this species should be considered in differential diagnoses of subcutaneous lesions in both animals and humans in the region.Graphical

Polysaccharides from Cordyceps cicadae Ameliorate Reproductive Impairments in Male Mouse through the Hypothalamic-Pituitary-Testicular Axis.

Cordyceps cicadae polysaccharides have received attention due to their potential in treating hyperglycemia and enhancing renal function. The beneficial effect of the purified C. cicadae polysaccharides fraction (CCP-1) on the reproductive impairments and spermatogenesis dysfunction of immunocompromised mice is unavailable and is studied herein. The study establishes a GC-1 spg cell apoptosis model induced by TNF-α+SM-164 (TS) and male mouse reproductive injury model induced by cyclophosphamide (CTX), and then intervened by CCP-1. CCP-1 improves the viability of GC-1 spg cell and inhibits cells apoptosis induced by TS in vitro. CCP-1 enhances sperm quality and spermatogenesis function, as well as ameliorating the histological lesions in the hypothalamus, testicular, and kidney. CCP-1 elevates gonadotropin-releasing hormone (GnRH) level that secreted by the hypothalamus, and increases the levels of follicle stimulating hormone (FSH) and luteizing hormone (LH) in the anterior pituitary stimulated by GnRH, and promotes the secretion of testosterone (T) by testis. Moreover, CCP-1 could protect the reproductive system by activating reproductive regulatory pathway such as SCF/C-kit pathway and inhibiting apoptotic signaling pathway such as Bax/Caspase-3 pathway. These results manifest that CCP-1 could serve as a natural promising reproductive system protective supplement for ameliorating CTX biotoxicity.

Effect of vitamin C injections on exercise muscular performance and biochemical parameters in Trichinella spiralis-infected mice.

Trichinella spiralis is a worldwide intestinal nematode that can parasitize the striated muscles of its hosts at the larval stage. This study aims to evaluate potential of vitamin C for treating trichinellosis-related pathological problems in the infected muscles of mice. Thirty CD1 male Albino mice were divided into three groups (10 mice per group). Negative and positive control groups (0.9% NaCl) and the infected vitamin C group (10 mg/kg body weight). Two weeks post-infection, each group was intraperitoneally injected daily for two weeks with Vitamin C or saline. The performance of the muscles was assessed both before and after the treatment. After dissection, constant parts of striated muscles were removed for further assays. The scoring of the histological changes of infected muscles was carried out. In addition to muscle malondialdehyde levels, superoxide dismutase and catalase activities were measured for the oxidative and antioxidant states. Creatine kinase and aspartate aminotransferase were also measured in tissues to reflect the degree of muscular damage. Vitamin C enhances the weakness of the muscular performance resulting from the infection. Vitamin C was able to repair some of the histological lesions that resulted from the infection. Trichinellosis caused severe changes in the biochemical markers in positive control animals. Muscle damage biomarkers and, besides, oxidative and antioxidant conditions were greatly ameliorated in infected vitamin C animals. Summing up, vitamin C can be used as a complementary drug due to its efficiency in improving pathogenesis following a trichinellosis infection. The supplement also must be tested in the intestinal stage of infection after showing promising results in the muscular stage.

Development of a MALDI-TOF MS model for differentiating haemorrhagic septicaemia-causing strains of Pasteurella multocida from other capsular groups

Pasteurella multocida capsular types A, D, and F cause disease in many animal hosts, including bovine respiratory disease in cattle, which is one of the most globally significant animal diseases. Additionally, P. multocida capsular types B and E cause haemorrhagic septicaemia, a devastating disease primarily of cattle, water buffalo, and bison that develops rapidly with high mortality. Haemorrhagic septicaemia mostly occurs in developing countries and has potential to emerge elsewhere in the world. The diagnosis of haemorrhagic septicaemia currently requires recognition of compatible gross or histologic lesions and serotyping or molecular characterization of strains. In this study, we performed genomic characterization of 84 P. multocida strains, which were then used to develop and validate a matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) biomarker-based method for differentiating non-haemorrhagic septicaemia strains of P. multocida from haemorrhagic septicaemia-causing strains. Haemorrhagic septicaemia strain types B:2,5, E:2,5, and B:3,4 were used to maximize diversity. Three automated classification models were generated and then used to develop an assisted model, which utilized two peaks (6419 and 7729 m/z) to accurately differentiate non-haemorrhagic septicaemia-causing strains from haemorrhagic septicaemia-causing strains of P. multocida. The assisted model performed with 98.2 % accuracy for non-haemorrhagic septicaemia strains, 100 % accuracy for classic B:2,5 and E:2,5 strains, and 84.4 % accuracy for combined haemorrhagic septicaemia-causing strains (B:2,5, E:2,5, and B:3,4) with an overall accuracy of 96.9 %. Our results suggest that MALDI-TOF MS may be used to routinely screen P. multocida isolated from diagnostic cases for initial identification of haemorrhagic septicaemia-causing strains, and to determine whether additional characterizations are warranted.

Evaluation of Tissue Tropism and Horizontal Transmission of a Duck Enteritis Virus Vectored Vaccine in One-Day-Old Chicken.

Herpesvirus of turkey (HVT) recombinant vector vaccines are widely used in the poultry industry. However, due to limitations in loading multiple foreign antigens into a single HVT vector, other viral vectors are urgently needed. Since chickens lack maternal immunity to duck enteritis virus (DEV), vector vaccines using DEV as a backbone are currently under study. Even though a recently developed DEV vector vaccine expressing the influenza hemagglutinin H5 of highly pathogenic avian influenza (DEV-H5) induces highly detectable anti-HA antibodies, safety issues hamper further vaccine development. In this work, tissue affinity and horizontal transmission in 1-day-old chickens were systematically evaluated after DEV-H5 vector vaccine inoculation. Sixty percent of DEV-H5-inoculated chickens died between day 2 and day 7 post-inoculation. The displayed clinical signs consisted of lethargy, anorexia, and diarrhea, and virus was shed in feces. Gross and/or histological lesions were recorded in the kidney, heart, intestine, liver, lung, and spleen. Moreover, DEV-H5 replication in intestinal cells caused an increment in interferon-α expression, while occluding junction proteins and ZO-1 expression were significantly upregulated. As a control, birds inoculated with a commercial recombinant turkey herpesvirus expressing the VP2 protein of the infectious bursal disease virus (HVT-VP2) vector vaccine showed neither clinical signs nor mortality. Overall, while the HVT-VP2 vaccine demonstrated complete safety in 1-day-old chickens, our potential DEV-H5 vaccine requires further attenuation for consideration as a vector vaccine candidate in chickens.

Intracranial inoculation rapidly induces Nipah virus encephalitis in Syrian hamsters.

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.

A histopathological study in road-killed European badgers (Meles meles) from the English midlands with isolation of novel non-tuberculous atypical mycobacteria

European badgers (Meles meles) play an important role in the epidemiology of bovine tuberculosis (caused by Mycobacterium bovis) in England, but little is known about the prevalence of atypical mycobacteriosis. Badgers are also known to be infected by other infectious agents, and the relationship between mycobacteriosis and concomitant infections needs further investigation. Overall, 88 badger carcasses from the Midlands of England collected between July 2016-August 2017 were selected for histopathological examination based on the degree of autolysis (mild), mycobacterial culture results and a balanced sex ratio. Mycobacteria were cultured from 44 badgers, of which 31 were mycobacteria belonging to the M. tuberculosis complex (MTBC) (based on IS6110 PCR and Hsp64 and/or rRNA PCR and sequencing) and 13 were non-tuberculous atypical mycobacteria (NTM). Mycobacteria were not cultured from the remaining 44 animals. Histologically, the most common findings were silica-laden macrophages (85%), granulomas (53%), sarcocystosis (47%), nephritis (31%), portal/periportal hepatitis (26%), ulcerative dermatitis (18%). Culturable mycobacteriosis was associated with higher prevalence of granulomas (p < 0.001) and lower prevalence of hepatitis (p = 0.003). NTM (M. nonchromogenicum, M. avium complex, M. hassiacum, M. malmoense, M. vaccae.) infections were associated with granulomatous pneumonia, and M. malmoense was associated with pyogranulomatous and ulcerative dermatitis. In conclusion, this study describes, for the first time, histological lesions associated with NTM in badgers, the histomorphology of which was similar to those caused by MTBC. In addition, the negative relationship between mycobacteriosis and periportal hepatitis may indicate a complex relationship between mycobacteriosis and other diseases, as previously observed with tuberculosis.

CRB2 Depletion Induces YAP Signaling and Disrupts Mechanosensing in Podocytes.

Focal Segmental Glomerulosclerosis (FSGS) is a histologic lesion caused by a variety of injurious stimuli that lead to dysfunction/loss of glomerular visceral epithelial cells (i.e. podocytes). Pathogenic mutations in CRB2, encoding the type 1 transmembrane protein Crumb 2 Homolog Protein, have been shown to cause early-onset corticosteroid-resistant nephrotic syndrome (SRNS)/FSGS. Here, we identified a 2-generation East Asian kindred (DUK40595) with biopsy-proven SRNS/FSGS caused by a compound heterozygous mutation in CRB2 comprised of the previously described truncating mutation p.Gly1036_Alafs*43 and a rare 9-bp deletion mutation p.Leu1074_Asp1076del. Because compound heterozygous mutations involving the truncating p.Gly1036_Alafs*43 variant have been associated with reduced CRB2 expression in podocytes and autosomal recessive SRNS/FSGS, we sought to define the pathogenic effects of CRB2 deficiency in podocytes. We show that CRB2 knockdown induces YAP activity and target gene expression in podocytes. It upregulates YAP-mediated mechanosignaling and increases the density of focal adhesion and F-actin. Using Elastic Resonator Interference Stress Microscopy (ERISM), we demonstrate that CRB2 knockdown also enhances podocyte contractility in a substrate stiffness-dependent manner. The knockdown effect decreases with increasing substrate stiffness, indicating impaired mechanosensing in CRB2 knockdown cells at low substrate stiffness. While the mechanical activation of CRB2 knockdown cells is associated with increased YAP activity, the enhanced cell contractility is not significantly reduced by the selective YAP inhibitors K-975 and verteporfin, suggesting that multiple pathways may be involved in mechanosignaling downstream of CRB2. Taken together, these studies provide the first evidence that CRB2 deficiency may impair podocyte mechanotransduction via disruption of YAP signaling in podocytes.

Mandarin Fish Ranavirus (MRV) Infection Induced Inflammation and Histologic Lesions in the Gut of Mandarin Fish.

Mandarin fish ranavirus (MRV) is widely spread in China and causes huge economic losses to the mandarin fish (Siniperca chuatsi) aquaculture. However, the pathogenesis of MRV is still unclear. In the present study, mandarin fish were artificially infected with MRV, and then different gut compartments from diseased fish were subjected to histologic analysis by H&E staining, quantification of proinflammatory genes and MRV copies by qPCR. MRV-MCP protein expression was assessed using indirect fluorescence assay (IFA) and immunohistochemistry. Proliferation of IgM+ B cells was evaluated by indirect fluorescence assay (IFA). Then, we found that MRV infection caused serious histologic lesions along with inflammatory cell infiltration, especially in the foregut. A significant accumulation of IgM+ B cells was detected in the foregut (~6.5-fold) and hindgut (~3.3-fold), respectively. The expression of inflammation-related genes such as IL-1β, IL-6, IL-8,TNF-α, CSF1r and NCF1 was significantly upregulated in the foregut, varying from ~2.8-fold to ~11.9-fold. In addition, MRV exhibited foregut tropism, according to the investigation of viral loads and MCP protein expression. Overall, our findings indicated that MRV-induced hyperinflammation in the gut eventually led to enteritis. This study provided new insights into uncovering the pathogenesis of MRV infection.

Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps.

The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3years±6months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10mm. High-grade dysplasia or villous component, serrated polyps ≥10mm or with dysplasia or CRC. At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p<0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p<0.01) were independently associated with the development of advanced lesions at surveillance. Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

A Novel Deep Learning Approach for Analyzing Glomerular Basement Membrane Lesions in a Mouse Model of X-Linked Alport Syndrome

Alport syndrome is a rare kidney disease typically more severe in males due to its X-linked inheritance. However, female patients with heterozygous X-linked Alport syndrome (XLAS) can develop renal failure over time, necessitating accurate pathological assessment for effective therapy. A key pathological finding in female XLAS patients is the mosaic pattern of partial loss of α5 chains of type IV collagen. This study, using a mouse model of XLAS with a nonsense mutation (R471*) in the Col4a5 gene, analogous to human XLAS, aimed to examine the consistency of this pattern with the glomerular basement membrane (GBM) structure. A modified periodic acid-methenamine silver (PAMS) staining method was developed for clearer GBM visualization. The integrated images from COL4α5-stained fluorescence, PAMS, and low-vacuum scanning electron microscopy (LVSEM) into a single-slide section and applied supervised deep learning to predict GBM lesions. Results showed significant individual variability in urinary protein levels and histological lesions. Pathological parameters, including crescent formation, focal segmental glomerulosclerosis, and the COL4α5/α2 ratio, correlated with clinical parameters like urinary protein and plasma creatinine levels. Integrated LVSEM analysis revealed dense GBM regions corresponded to areas where COL4α5 was preserved, while coarse GBM (basket-weave lesions) occurred in COL4α5-deficient regions. These advanced techniques can enhance biopsy-based diagnosis of Alport syndrome and aid in developing AI diagnostic tools for diseases involving basement membrane lesions.

NQO1 from Litopenaeus vannamei involved in the regulation of antioxidant capacity, inflammation, and apoptosis

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a versatile FAD-dependent flavoprotein and a key regulator in the Nrf2/ARE signaling pathway. In this study, we cloned the NQO1 gene of Litopenaeus vannamei (LvNQO1) and investigated its role in immune regulation. The results showed that the LvNQO1 gene has an ORF of 987 bp, encoding 328 amino acids. The protein contains an NQO family domain. Homology and phylogenetic analysis revealed that LvNQO1 shares similarities with the NQO1 of Marsupenaeus japonicus, clustering into the same clade. LvNQO1 was expressed in 10 tissues of L. vannamei, with the highest expression in the hepatopancreas and the lowest in the intestine. After RNA interference (RNAi) of LvNQO1, the expression of antioxidant genes (SOD and GST) initially increased but then decreased after 24 h. The expression levels of Gpx and CAT decreased early on but gradually recovered. Immune-related factors (Toll4, JNK, and Hsp90) and apoptosis-related factors (Caspase3, P53, and bcl2) were upregulated. Following RNAi of LvNQO1, Vibrio harveyi challenge significantly increased the expression of immune factors (JNK and HIF1α) and apoptosis factors (Caspase3, P53, and bcl2) in the hepatopancreas. Toll 4 receptors recognized the infection, upregulated their expression, and activated an immune response. RNAi of LvNQO1 led to noticeable histological lesions and apoptosis. These findings suggest that LvNQO1 may play a role in regulating antioxidant capacity, inflammation, and apoptosis in response to Vibrio infection.

Histopathological correlations of CT-based radiomics imaging biomarkers in native kidney biopsy

BackgroundKidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade.MethodsWe included patients aged ≥ 18 years who underwent kidney biopsy and abdominal CT scan within a week before kidney biopsy. Left kidneys were three-dimensionally segmented using a deep learning model based on the 3D Swin UNEt Transformers architecture. We additionally defined isovolumic cortical regions of interest near the lower pole of the left kidneys. Shape, first-order, and high-order texture features were extracted after resampling and kernel normalization. Correlations and diagnostic metrics between extracted features and chronic histologic lesions were examined. A machine learning-based radiomic prediction model for moderate chronicity was developed and compared according to the segmented regions of interest (ROI).ResultsOverall, moderate correlations with statistical significance (P < 0.05) were found between chronic histopathologic grade and top-ranked radiomic features. Total parenchymal features were more strongly correlated than cortical ROI features, and texture features were more highly ranked. However, conventional imaging markers, including kidney length, were poorly correlated. Top-ranked individual radiomic features had areas under receiver operating characteristic curves (AUCs) of 0.65 to 0.74. Developed radiomics models for moderate-to-severe chronicity achieved AUCs of 0.89 (95% confidence interval [CI] 0.75–0.99) and 0.74 (95% CI 0.52–0.93) for total parenchymal and cortical ROI features, respectively.ConclusionSignificant historadiological correlations were identified between CT-based radiomic features and chronic histologic changes in native kidney biopsies. Our findings underscore the potential of CT-based radiomic features and their prediction model for the non-invasive assessment of kidney fibrosis.