Significant Histological Changes Research Articles

Iron/Copper/Phosphate nanocomposite as antimicrobial, antisnail, and wheat growth-promoting agent

BackgroundOne of the current challenges is to secure wheat crop production to meet the increasing global food demand and to face the increase in its purchasing power. Therefore, the current study aimed to exploit a new synthesized nanocomposite to enhance wheat growth under both normal and drought regime. The effectiveness of this nanocomposite in improving the microbiological quality of irrigation water and inhibiting the snail’s growth was also assessed.ResultsUpon the employed one-step synthesis process, a spherical Fe/Cu/P nanocomposite was obtained with a mean particle size of 4.35 ± 1.524 nm. Cu2+, Fe2+, and P4+ were detected in the dried nanocomposite at 14.533 ± 0.176, 5.200 ± 0.208, and 34.167 ± 0.203 mg/ml concentration, respectively. This nanocomposite was found to exert antibacterial activity against Escherichia coli and Salmonella typhi. It caused good inhibition percent against Fusarium oxysporum (43.5 ± 1.47%) and reduced both its germination rate and germination efficiency. The lethal concentration 50 (LC50) of this nanocomposite against Lanistes carinatus snails was 76 ppm. The treated snails showed disturbance in their feeding habit and reached the prevention state. Significant histological changes were observed in snail digestive tract and male and female gonads. Drought stress on wheat’s growth was mitigated in response to 100 and 300 ppm treatments. An increase in all assessed growth parameters was reported, mainly in the case of 100 ppm treatment under both standard and drought regimes. Compared to control plants, this stimulative effect was accompanied by a 2.12-fold rise in mitotic index and a 3.2-fold increase in total chromosomal abnormalities.ConclusionThe finding of the current study could be employed to mitigate the effect of drought stress on wheat growth and to enhance the microbiological quality of irrigation water. This is due to the increased efficacy of the newly synthesized Fe/Cu/P nanocomposite against bacteria, fungi, and snails. This methodology exhibits potential for promoting sustainable wheat growth and water resource conservation.

Effect of Blend of Metanil Yellow and Tartrazine on Different Organs of Albino Rat

Background: Tartrazine and metanil yellow are organic azo dyes widely used in food products, drugs, and cosmetics. The present study was conducted to evaluate the toxic effect of these food colors on the liver, and kidneys of albino rats. The study also evaluates the protective effect of quercetin as an antioxidant against the toxic effect of these food colors. Methods: Eighty adult albino rats were divided into 8 groups. Control group, 3 groups were treated with a blend of tartrazine and metanil yellow in 3 doses of 25, 50, and 75 mg/kg for 30 days by gavage, one positive control group was treated with quercetin 50 mg/kg for 30 days, and three groups were treated with the blend of tartrazine and metanil yellow plus 50 mg/kg of quercetin. At the end of the experiment, serum samples were collected to evaluate liver and kidney functions. Liver, kidney samples were fixed in 10% formalin and routinely prepared for paraffin sectioning and staining for histopathological examination. Results: The study showed a significant elevation of liver and kidney function after treatment with the food color blend. Also, a significant improvement in liver and kidney function was observed after treatment with quercetin. Histopathological examination showed mild to moderate changes in the liver and kidney which improved after quercetin treatment. Conclusion: The current sub-chronic study concluded that a blend of tartrazine and metanil yellow caused significant biochemical and histological changes in different organs of albino rats. Therefore, prolonged consumption of these substances leads to adverse effects on human health. Also, quercetin is vital in protecting the body against the toxic effects of food color blends.

The Possible Protective Effect of Taurine on Bisphenol: Induced Structural Changes on the Cerebral Cortex of Rats: Histological and Immunohistochemical Study.

Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions. This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods. 35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/ three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100mg/kg/day and BPH (100 mg/kg/ three times/week). BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase-3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results. Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.

Determining optimal ALT cut-off values for predicting significant hepatic histological changes in patients with normal ALT in the grey zone of chronic hepatitis B virus infection.

We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.

Impacts of pyraclostrobin on intestinal health and the intestinal microbiota in common carp (Cyprinus carpio L.)

Pyraclostrobin (PYR) is a strobilurin fungicide that is commonly used in agriculture, and its use in agriculture may lead to an increase in its residue in the aquatic environment and may have a deleterious influence on the intestinal health of aquatic creatures. Here, common carp were chronically exposed to PYR (0, 0.5, or 5.0 μg/L) for 30 d to determine its effect on the physical and immunological barrier and intestinal microbiota in the intestine. PYR exposure caused significant histological changes; altered the mRNA expression levels of occludin, claudin-2, and zonula occludens-1 (ZO-1); induced oxidative stress in the common carp intestine; and increased the serum D-lactate and diamine oxidase (DAO) levels. Moreover, PYR significantly increased the protein expression levels of tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and IL-6 while decreasing the level of transforming growth factor beta (TGF-β). Further studies revealed that PYR significantly reduced lysozyme (LZM) and acid phosphatase (ACP) activities as well as complement 3 (C3) and immunoglobulin M (IgM) levels. Furthermore, PYR decreased gut microbial diversity while increasing the abundance of pathogenic bacteria such as Aeromonas and Shewanella, causing an intestinal microbial disturbances in common carp. These results imply that PYR has a negative impact on fish intestinal health and may pose serious health risks to fish by disrupting the intestinal microbiota, physical barrier, and immunological barrier in common carp.

Skin irritation assessment and potential mechanism of Capparis spinosa L. fruits

Ethnopharmacological relevanceIn China, Capparis spinosa L. fruits (CSF) are often used topically in Uyghur folk medicine in treating rheumatic diseases with remarkable efficacy. However, it has noticed severe skin irritation after a short time application with high dose of CSF, which limited long-term clinical use. To date, there is almost no research related to skin irritation of CSF.Aim of the study: This study was intended to perform the first systematic assessment of morphological and histological changes in skin after stimulation with CSF. Furthermore, potential irritant components in CSF and related mechanisms were explored by in vitro transdermal techniques, network pharmacology, molecular docking, and experimental validation. Materials and methodsSkin changes after single and multiple stimulations with CSF were observed and subjected to skin irritation response scoring, irritation strength assessment, and histopathological analysis. In addition, in vitro transdermal technology, liquid chromatography-mass spectrometry (LC-MS) method, network pharmacology, molecular docking, and experimental validation were used to further exploit underlying skin irritant components and possible mechanisms of action. ResultsCSF induced significant morphological (erythema and edema) and histological (epidermal thickening and inflammatory infiltration) changes in skin of mice, which were similar to the clinical presentation of irritation contact dermatitis (ICD). The ethyl acetate fraction of CSF (CFEAF) was the main source of CSF-induced skin irritation. Kaempferol, flazin, and gallic acid were potential major irritant compounds. Moreover, CFEAF, kaempferol, flazin, and gallic acid could increase the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-17A (IL-17A) to promote skin inflammation. The potential mechanism of CSF-induced skin irritation may be activation of the nuclear factor kappa-B (NF-κB) signaling pathway, including phosphorylation of NF-κB p65 (p65) and nuclear factor-kappa B inhibitor alpha (IκBα). ConclusionKaempferol, flazin, and gallic acid are potential skin irritant components from CSF. Altogether, they induce skin irritation responses through promoting the release of the inflammatory factors TNF-α and ICAM-1, as well as activating the NF-κB signaling pathway. In addition, IL-17A may be an important pro-inflammatory factor in skin irritation.

Liver-Derived Ketogenesis via Overexpressing HMGCS2 Promotes the Recovery of Spinal Cord Injury.

The liver is the major ketogenic organ of the body, and ketones are reported to possess favorable neuroprotective effects. This study aims to elucidate whether ketone bodies generated from the liver play a critical role in bridging the liver and spinal cord. Mice model with a contusive spinal cord injury (SCI) surgery is established, and SCI induces significant histological changes in mice liver. mRNA-seq of liver tissue shows the temporal changes of ketone bodies-related genes, β-hydroxybutyrate dehydrogenase (BDH1) and solute carrier family 16 (monocarboxylic acid transporters), member 6 (SLC16A6). Then, an activated ketogenesis model is created with adult C57BL/6 mice receiving the tail intravenous injection of GPAAV8-TBG-Mouse-Hmgcs2-CMV- mCherry -WPRE (HMGCS2liver ) and mice receiving equal AAV8-Null being the control group (Vectorliver ). Then, the mice undergo either a contusive SCI or sham surgery. The results show that overexpression of HMG-CoA synthase (Hmgcs2) in mice liver dramatically alleviates SCI-mediated pathological changes and promotes ketogenesis in the liver. Amazingly, liver-derived ketogenesis evidently alleviates neuron apoptosis and inflammatory microglia activation and improves the recovery of motor function of SCI mice. In conclusion, a liver-spinal cord axis can be bridged via ketone bodies, and enhancing the production of the ketone body within the liver has neuroprotective effects on traumatic SCI.

Acute and Sub-Acute Toxicity Evaluation of the Crude Methanolic Extract of Justicia schimperiana Leaf in Wistar Albino Rats.

This study evaluates the acute and sub-acute toxicity of 80% methanolic extracts of the leaves of Justicia schimperiana in Wistar albino rat models. Dried powdered leaves of Justicia schimperiana were macerated in 80% methanol. The experiment was conducted in accordance with the Organization for Economic Co-operation and Development guideline 423 for acute and 407 for sub-acute toxicity testing. A single dose of 5000 mg/kg extract was orally administered to three female rats for the acute toxicity study. The plant extract was administered orally for 28 days in daily dosages of 250, 500, and 1000 mg/kg for the sub-acute study. Animals in a control group were given distilled water. A total of 40 rats (5 rats/group/sex) were used for the sub-acute toxicity testing. Daily food intake and weekly body weight measurements were done. The rats were sacrificed at the end of the 28-day treatment period for hematological, biochemical, and histopathological tests. One-way analysis of variance and Kruskal-Wallis tests were employed for the analysis. The single-dose oral administration of the plant resulted in no deaths or serious morbidity. The median lethal dose was >5000 mg/kg. The 28-day oral treatment of the plant extract had no significant effect on general behavior, food intake, organ weight, biochemical parameters, or the majority of the hematological markers, with the exception of the decrease in hemoglobin and hematocrit in the 1000 mg/kg extract-treated groups compared to the controls. Both sexes experienced significant weight increases at all dosage levels. With the exception of minor alterations in a few of the organs, no significant histological change was identified. It is concluded that the single-dose and repeated-dose 28-day oral administration of the methanolic leaf extract of Justicia schimperiana is relatively safe.

Significant histological changes are not rare in indeterminate‐phase chronic hepatitis B patients with hepatitis B e antigen‐negative and normal alanine aminotransferase levels

AbstractBackground & ObjectivesThe degree of liver injury in indeterminate chronic hepatitis B (CHB) infection patients with Hepatitis B e antigen(HBeAg)‐negative and persistently normal alanine aminotransferase (PNALT) levels is yet unclear. Therefore, we aimed to assess liver histological changes in such patients by liver biopsy and explore possible predictors.MethodsOverall, 711 HBeAg‐negative CHB patients with PNALT levels who underwent liver biopsy from January 2017 to June 2022 were included in this retrospective study. The relationships between histological changes and predictors were assessed by smooth curve fitting and multivariate logistic regression analysis models. Data were also analyzed using American Association for the Study of Liver Disease (AASLD) modified alanine aminotransferase (ALT) criteria.ResultsThe proportion of significant histological changes in the indeterminate phase was higher than that in the inactive phase (53.97% vs. 41.33%). The adjusted odds ratios (aORs) of significant necroinflammation and histological changes for the indeterminate phase were 2.05 and 1.43, respectively, when compared with the inactive phase by multivariate logistic regression analyses. Significant histological changes in the‐phase were positively associated with age, ALT, Aspartate aminotransferase (AST), Hepatitis B surface antigen (HBsAg), and Hepatitis B virus (HBV) DNA levels but negatively correlated with platelet (PLT) levels. HBV DNA ≥5 log10 U/L and PLT <200 × 109/L were independent predictive factors for assessing histological changes in indeterminate‐phase patients. Similar analysis findings were obtained using the two sets of modified ALT criteria.ConclusionsSignificant histological changes are not rare in indeterminate‐phase CHB patients and are higher than in the inactive phase, regardless of the ALT criteria. Histological investigation is strongly suggested for intermediate stage patients with HBV DNA >5 log10 U/L or PLT <200 × 109/L and antiviral therapy should be considered for such patients.

Biodistribution and histological analysis of iron oxide-dextran nanoparticles in wistar rats

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mgFe/kg, 45 mgFe/kg and 60 mgFe/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance.

Recurrent atypical antiglomerular basement membrane nephritis in the kidney transplant

Atypical antiglomerular basement membrane (anti-GBM) nephritis can be defined as linear GBM staining for monotypic or polytypic immunoglobulin (Ig) by immunofluorescence (IF) without a diffuse crescentic pattern. We describe the clinicopathologic features of 6 patients (18 biopsies) in this first series of recurrent atypical anti-GBM nephritis after kidney transplantation. Recurrent glomerulonephritis occurred at a mean of 3.8 months posttransplant (range 1-7 months). Three index biopsies were for clinical indication, and 3 were protocol biopsies. Glomerular histologic changes were mild, with 2 showing segmental endocapillary hypercellularity, 1 focal glomerular microangiopathy, and the others no significant glomerular histologic changes. All 6 allografts showed monotypic linear glomerular Ig staining by IF: IgG kappa (n = 2), IgG lambda, IgA kappa, IgA lambda, and IgM lambda. Follow-up biopsies were available for 5 patients and showed similar histologic and IF findings without evidence of significant progression. No patients had detectable serum anti-GBM antibody or monoclonal proteins. The mean serum creatinine level on follow-up (24-62 months posttransplant) was 1.8 (range 0.93-2.77) mg/dL; no grafts were lost to recurrent disease. This series demonstrates that monotypic atypical anti-GBM recurs in the allograft and supports the idea that this disease is due to a circulating monoclonal protein.

Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis

BackgroundUncontrolled T-cell activation plays a key role in systemic sclerosis (SSc). Arsenic trioxide (ATO) has immunological effects and has demonstrated potential in preclinical SSc models. In this study, we assessed the efficacy of ATO in Fra2 transgenic (Fra2TG) mice, which develop severe vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human SSc-associated pulmonary hypertension, therefore partially resembling to the SSc human disease.MethodsThe efficacy of ATO in Fra2TG mice was evaluated through histological scoring and determination of cell infiltration. Fibrotic changes in the lungs were assessed by measuring collagen content biochemically, using second harmonic generation to measure fibrillar collagen, and imaging via computed tomography. Cardiovascular effects were determined by measuring right ventricular systolic pressure and vessel remodeling. The mechanism of action of ATO was then investigated by analyzing lung cell infiltrates using flow cytometry and bulk RNA with sequencing techniques.ResultsAfter ATO treatment, the Ashcroft histological score was substantially decreased by 33% in ATO-treated mice compared to control mice. Other investigations of fibrotic markers showed a trend of reduction in various measurements of fibrosis, but the differences did not reach significance. Further cardiovascular investigations revealed convergent findings supporting a beneficial effect of ATO, with reduced right ventricular systolic pressure and medial wall thickness, and a significant decrease in the number of muscularized distal pulmonary arteries in ATO-treated Fra2TG mice compared to untreated Fra2TG mice. Additionally, inflammatory cell infiltration was also markedly reduced in lesioned lungs. A reduction in the frequency of CD4 + and T effector memory cells, and an increase in the percentage of CD4 + T naive cells in the lungs of ATO-treated Fra-2TG mice, was observed when compared to PBS group Fra-2Tg mice. RNA-seq analysis of ATO-treated mouse lungs revealed a downregulation of biological pathways associated with immune activity and inflammation, such as T-cell activation, regulation of leucocyte activation, leucocyte cell–cell adhesion, and regulation of lymphocyte activation.ConclusionsOur results suggest the clinical relevance of ATO treatment in SSc. Using the Fra2TG mouse model, we observed significant lung histological changes, a trend towards a decrease in various fibrotic makers, and a strong reduction in vascular remodeling. The mechanism of action of ATO appears to involve a marked counteraction of the immune activation characteristic of SSc, particularly T-cell involvement. These findings pave the way for further studies in SSc.

Neocapsular reconstruction for challenging partial nephrectomy: A feasibility study in a porcine model and recent clinical experience.

Multifocal renal masses and large central-endophytic tumors can be challenging for partial nephrectomy (PN) due to the paucity of capsule remaining after tumor removal. Our objective was to develop a neocapsule to provide tamponade and test its feasibility/safety in a porcine model. Eight live pigs (50-70 kg) underwent unclamped open right flank PN. Renal defects were 1 cm deep and had moderate ongoing venous bleeding. A 6 × 9 inch sheet of Nu-knit® was used for neocapsular reconstruction with Fibrillar™ packing to provide modest tamponade and preclude ongoing bleeding. Blood chemistry and hemoglobin (Hb) levels were drawn preoperatively and postoperative Days 3/5/8. On postoperative Day 8, euthanasia was performed, and both kidneys were inspected and analyzed for histologic changes. PN defects ranged from 1 × 1 × 1 cm to 4 × 2 × 1 cm; four pigs had PN performed in both poles and four in one pole. Neocapsular reconstruction was successful (n = 8), with no perioperative complications. Median baseline Hb was 10.4 g/dL, and median Hb postoperative Days 3/5/8 were 10.0/10.8/10.6 g/dL, respectively. Median baseline serum creatinine (SCr) was 1.9 mg/dL, and median SCr postoperative Days 3/5/8 were 1.5/1.4/1.5 mg/dL, respectively. At sacrifice, no significant hematomas were observed. Other than adjacent to the PN site, there were no significant histologic changes in the parenchyma for operative kidneys versus controls. Based on our experience, we recently performed neocapsular reconstruction safely/effectively after extensive PN for multifocal tumors and for an allograft with difficult-to-manage subcapsular hematoma. Neocapsular reconstruction after PN or capsular trauma appears feasible and safe and may be considered to reduce the risk of perioperative bleeding. However, further study will be needed to confirm the utility/efficacy of this approach.

Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage.

Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular histone H3.3, indicating potential pathogenic implications. Notably, histone H3.3 is often found hyperacetylated (AcH3.3) in the lungs of COPD patients. Despite these observations, the specific role of these acetylated histones in inducing pulmonary tissue damage in COPD remains unclear. To investigate AcH3.3's impact on lung tissue, we administered recombinant histones (rH2A, rH3.3, and rAcH3.3) or vehicle solution to mice via intratracheal instillation. After 48 h, we evaluated the lung toxicity damage and found that the rAcH3.3 treated animals exhibited more severe lung tissue damage compared to those treated with non-acetylated H3.3 and controls. The rAcH3.3 instillation resulted in significant histological changes, including alveolar wall rupture, epithelial cell damage, and immune cell infiltration. Micro-CT analysis confirmed macroscopic structural changes. The rAcH3.3 instillation also increased apoptotic activity (cleavage of caspase 3 and 9) and triggered acute systemic inflammatory marker activation (TNF-α, IL-6, MCP-3, or CXCL-1) in plasma, accompanied by leukocytosis and lymphocytosis. Confocal imaging analysis confirmed lymphocytic and monocytic/macrophage lung infiltration in response to H3.3 and AcH3.3 administration. Taken together, our findings implicate extracellular AcH3.3 in inducing cytotoxicity and acute inflammatory responses, suggesting its potential role in promoting COPD-related lung damage progression.

Systematic review with meta-analysis: Significant histological changes among treatment-naïve chronic hepatitis B patients with normal alanine aminotransferase levels by different criteria.

The upper limits of normal (ULNs) of ALT are not consistent across the major international guidelines which may affect the eligibility for antiviral therapy for chronic hepatitis B (CHB). To estimate the proportions of histological changes among treatment-naïve patients with CHB within differently defined ALT ULNs. We searched PubMed and Embase up to May 15th, 2023, to identify studies of treatment-naïve CHB patients with liver biopsies. We pooled proportions of moderate to severe necroinflammation, significant fibrosis, and cirrhosis in those patients within different ALT ULNs by using random-effect models. We included 23 studies with 4010 participants. Within ALT ULN at 40 IU/L, the pooled proportions of moderate to severe necroinflammation, significant fibrosis, and cirrhosis were 33% (95% CI: 26%-42%), 32% (95% CI: 27%-38%), and 3% (95% CI: 1%-5%), respectively. Within ALT ULN at 30 IU/L for men and 19 IU/L for women, the pooled proportion of significant fibrosis remained at 30% (95% CI: 25%-34%; 432 participants). However, it was 21% (95% CI: 11%-37%; 361 participants) even in those within ALT ULN at 20 IU/L. Subgroup analyses suggested a significantly higher proportion of significant fibrosis among studies with prospective design or enrolled patients' mean age >35 or >40 years. Significant histological changes occurred in approximately 1/3 of treatment-naïve CHB patients within ALT ULN at 40 IU/L, whereas the proportion of significant fibrosis was approximately 1/5 even in those within ALT ULN at 20 IU/L.

Therapeutic role of boron on acrylamide-induced nephrotoxicity, cardiotoxicity, neurotoxicity, and testicular toxicity in rats: Effects on Nrf2/Keap-1 signaling pathway and oxidative stress

BackgroundAcrylamide (ACR) is a heat-related carcinogen used in cooking some foods as well as in other thermal treatments. The present study aims to investigate the possible protective effect of boron (BA) against ACR-induced toxicity of kidney, brain, heart, testis, and bladder tissues in rats. MethodsRats have been divided into 5 equal groups: Control (saline), ACR (38.27 mg/kg), BA (20 mg/kg), BA+ ACR (10 mg/kg + ACR), and BA+ ACR (20 mg/kg BA+ACR). Kidney tissue from rats was collected and the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of superoxide dismutase (SOD) were measured. In addition, the kidneys of these animals, as well as the brain, heart, testes, and bladder tissues were examined for possible histological changes. Total Nrf2 and Keap-1 protein expression in kidney, heart, and testis tissues was examined by immunohistochemistry. ResultsWhile significant increases in MDA levels were observed in the kidneys of rats receiving ACR alone, significant decreases in antioxidant markers (SOD and GSH) were observed. Besides, kidney, brain, heart, and testicular tissues were analyzed and damage was observed in the groups receiving ACR. However, no significant histologic changes were noted in the bladder tissue. Both dosages of BA in combination with ACR improved the changes in ACR-induced antioxidant tissue parameters. Despite the fact that MDA levels were decreased with these two dosages, histological structural abnormalities were found to be greatly improved. ConclusionOur results show that BA has a strong protective effect on ACR-induced multi-organ toxicity. The study results show that BA could be a potential element to reduce ACR toxicity to which we are often exposed.

Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

The influence of dietary Coenzyme Q10 on growth performance, antioxidant capacity and resistance against Aeromonas hydrophila of juvenile European eel (Anguilla anguilla).

The present study was conducted to investigate the effects of dietary Coenzyme Q10 (CoQ10) on the growth performance, body composition, digestive enzyme activity, antioxidant capacity, intestinal histology, immune-antioxidant gene expression and disease resistance of juvenile European eel (Anguilla anguilla). Fish were fed a diet supplemented with CoQ10 at concentrations of 0, 40, 80 and 120 mg/kg for 56 days. The results indicated that dietary CoQ10 supplementation did not significantly affect final body weight (FBW), survival rate (SR), weight gain (WG), feed rate (FR), viscerosomatic index (VSI) or hepatosomatic index (HSI) among all experimental groups. However, the highest FBW, WG and SR were found in the 120 mg/kg CoQ10 group. Dietary 120 mg/kg CoQ10 markedly improved feed efficiency (FE) and the protein efficiency ratio (PER). The crude lipids in the body and triglycerides (TG) and total cholesterol (TC) in serum were obviously lower in the 120 mg/kg CoQ10 group than in the control group. For digestive enzymes, protease activity in the intestine was markedly boosted in the 120 mg/kg CoQ10 group. The serum activities of SOD, CAT and GST in the 120 mg/kg CoQ10 group were significantly higher than those in the control group. Dietary 120 mg/kg CoQ10 efficiently enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities in the liver, while the malondialdehyde (MDA) content was significantly decreased. No significant histological changes in the liver were identified in any group. Dietary supplementation with 120 mg/kg CoQ10 improved antioxidant capacity and immunity by upregulating the expression of cyp1a, sod, gst, lysC, igma1, igmb1 and irf3 in the liver. Furthermore, the cumulative survival rate of juvenile European eel against challenge with Aeromonas hydrophila was significantly elevated in the 80 and 120 mg/kg CoQ10 supplemented groups. Conclusively, our study suggested that supplementing the diet of juvenile European eel with CoQ10 at a concentration of 120 mg/kg could promote their feed utilization, fat reduction, antioxidant capacity, digestibility, immune-antioxidant gene expression and resistance to Aeromonas hydrophila without negative effects on fish health status.

Development a novel nomogram model for predicting significant hepatic histological changes in chronic hepatitis B virus carriers.

A proportion of chronic hepatitis B virus (HBV) carriers with normal alanine transaminase(ALT) present with significant liver histological changes (SLHC).To construct a noninvasive nomogram model to identify SLHC in chronic HBV carriers with different upper limits of normal (ULNs) for ALT.The training cohort consisted of 732 chronic HBV carriers who were stratified into four sets according to different ULNs for ALT: chronic HBV carriers I,II,III,and IV. The external validation cohort comprised 277 chronic HBV carriers. Logistic regression and least absolute shrinkage and selection operatoranalyses were applied to develop a nomogram model to predict SLHC.A nomogram model-HBGP (based on hepatitis B surface antigen, gamma-glutamyl transpeptidase, and platelet count) demonstrated good performance in diagnosing SLHC with area under the curve(AUCs) of 0.866 (95% confidence interval [CI]:0.839-0.892)and 0.885 (95% CI:0.845-0.925) in the training and validation cohorts, respectively. Furthermore, HBGP displayed high diagnostic values for SLHC with AUCs of 0.866 (95% CI:0.839-0.892), 0.868 (95% CI:0.838-0.898), 0.865 (95% CI:0.828-0.901), and 0.853 (95% CI:0.798-0.908) in chronic HBV carriers I, II, III, and IV, respectively. Additionally, HBGP showed greater ability in predicting SLHC compared with the existing predictors.HBGP has shown high predictive performance for SLHC, and thus may lead to an informed decision on the initiation of antiviral treatment.

Identification and verification of hub genes associated with ferroptosis in ischemia and reperfusion injury during renal transplantation

Ferroptosis is involved in ischemia and reperfusion injury (IRI) of transplanted kidney. Understanding the molecular mechanisms of ferroptosis is essential to elucidate the pathogenesis of IRI. 1307 differentially expressed genes (DEGs) were obtained by GSE90861 retrieved from the GEO database. 29 ferroptosis-related DEGs were obtained from the intersection with FerrDb database, which were subjected to enrichment analysis and cytoHubba plugin for selecting the top three (IL6, ATF3 and JUN) as hub genes. Next, ROC analysis of hub genes showed good diagnostic prospects in both GSE90861 and GSE126805. Given the close link between ferroptosis and immunity, immunological analysis of CIBERSORTx revealed that the proportions of 10 cell types out of 22 immune cells in the transplanted kidney significantly changed after reperfusion. To study the relationship between IRI and ferroptosis, 15 male C57BL/6j mice were randomly divided into three groups: control (C), ischemia and reperfusion (IR), and IR + Fer-1 (IF) groups. The IRI mouse model not only developed significant histological damage changes, but also exhibited mitochondrial damage, iron accumulation, increased MDA, and decreased GSH. The ferroptosis inhibitor, Fer-1, ameliorated renal IRI, as demonstrated by rise of GPX4 and decline of TFRC, PTGS2 and ACSL4. In addition, hub genes were further confirmed by significant increase in IRI mouse model the same as the GEO database. In brief, ferroptosis-related hub genes (IL-6, ATF3 and JUN) screened were closely relevant to immune response and might be diagnostic biomarkers and therapeutic targets for IRI during renal transplantation, which could prevent renal allograft dysfunction.