Histopathological Alterations Research Articles

A combinational threat of micro- and nano-plastics (MNPs) as potential emerging vectors for per- and polyfluoroalkyl substances (PFAS) to human health.

Micro- and nano-plastics (MNPs) and per- and polyfluoroalkyl substances (PFAS) are prevalent in ecosystems due to their exceptional properties and widespread use, profoundly affecting both human health and ecosystem. Upon entering the environment, MNPs and PFAS undergo various transformations, such as weathering, transport, and accumulation, potentially altering their characteristics and structural dynamics. Their interactions, governed by factors like hydrogen bonding, hydrophobic interactions, Van der Waals forces, electrostatic attractions, and environmental conditions, can amplify or mitigate their toxicity toward human health within ecological conditions. Several studies demonstrate the in vivo effects of PFAS and MNPs, encompassing growth and reproductive impairments, oxidative stress, neurotoxicity, apoptosis, DNA damage, genotoxicity, immunological responses, behavioral changes, modifications in gut microbiota, and histopathological alterations. Moreover, in vitro investigations highlight impacts on cellular uptake, affecting survival, proliferation, membrane integrity, reactive oxygen species (ROS) generation, and antioxidant responses. This review combines knowledge on the co-existence and adsorption of PFAS and MNPs in the environment, defining their combinedin vivoandin vitroimpacts. It provides evidence of potential human health implications. While significant research originates from China, Europe, and the USA, studies from other regions are limited. Only freshwater and marine organisms and their impacts are extensively studied in comparison to terrestrial organisms and humans. Nonetheless, detailed investigations are lacking regarding their fate, combined environmental exposure, mode of action, and implications in human health studies. Ongoing research is imperative to comprehensively understand environmental exposures and interaction mechanisms, addressing the need to elucidate these aspects thoroughly.

Tempol mitigates inflammation, oxidative stress, and histopathological alterations of cadmium-induced parotid gland injury in rats

Cadmium (Cd) is a potent environmental pollutant that causes functional and structural damage to the salivary glands. Tempol (TEM) has powerful antioxidant activity that can potentially preserve organ function. Aims: This study was designed to investigate the protective effects of TEM on Cd-induced toxicity in rat parotid salivary glands. Materials and methods: Twenty-four adult Wistar male rats were randomly assigned to four equal groups: control, TEM (27.5 g/100 ml), Cd (0.6 g/100 ml), and TEM plus Cd (at the same doses). All treatments were dissolved in distilled water and administered subcutaneously four times a week for four weeks. Parotid gland tissues were isolated and subjected to molecular and histo-biochemical assessments. Key findings: TEM exerted a prophylactic effect against Cd-induced toxicity in the parotid glands by controlling inflammation through the downregulation of toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/ interleukin-1 beta mRNA expression, upregulation of aquaporin-5 mRNA expression, improvement of the oxidant/antioxidant status in the parotid gland, mitigation of endoplasmic reticulum stress, and repair of the associated histological and ultrastructural abnormalities. Significance: TEM protects against Cd-induced toxicity in the parotid glands of rats, attributable at least in part to its anti-inflammatory and antioxidant properties, as well as its ability to inhibit ER stress and facilitate glandular repair. However, the protective effects of TEM did not reach the levels observed in the control group. TEM could be a promising clinical candidate for protecting the salivary glands, particularly in high-risk groups such as workers exposed to Cd and cigarette smokers.

The impact of diabetes mellitus on tendon pathology: a review.

Diabetes is one of the most common metabolic diseases worldwide, leading to complications, mortality, and significant healthcare expenditures, which impose a substantial social and financial burden globally. A diabetic environment can induce metabolic changes, negatively affecting tendon homeostasis, leading to alterations in biomechanical properties and histopathology. Numerous studies have investigated the mechanisms through which diabetes exerts pathological effects on tendons, including increased free radical production, oxidative stress, inflammatory responses, deposition of advanced glycation end products (AGEs), and microvascular changes. These metabolic changes damages tendon structure, biomechanics, and tendon repair processes. The proliferation of tendon stem cells decreases, apoptosis increases, and abnormal differentiation, along with abnormal expression of myofibroblasts, ultimately lead to insufficient tendon repair, fibrosis, and remodeling. Although researches unveiling the effects of diabetes on tendinopathy, fibrosis or contracture, and tendon injury healing are growing, systematic understanding is still lacking. Therefore, this review summarizes the current research status and provides a comprehensive overview, offering theoretical guidance for future in-depth exploration of the impact of diabetes on tendons and the development of treatments for diabetes-related tendon diseases.

Sigma-1 receptor modulation by fluvoxamine ameliorates valproic acid-induced autistic behavior in rats: Involvement of chronic ER stress modulation, enhanced autophagy and M1/M2 microglia polarization

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. While, fluvoxamine (FVX) is an antidepressant and widely prescribed to ASD patients, clinical results are inconclusive and the mechanism of FVX in the management of ASD is unclear. This study determined the potential therapeutic impact of FVX, a sigma-1 receptor (S1R) agonist, against the valproic acid (VPA)-induced model of autism. On gestational day 12.5, Wistar pregnant rats were given a single intraperitoneal (i.p.) injection of either VPA (600 mg/kg) or normal saline (10 mL/kg, vehicle-control). Starting on postnatal day (PND) 21 to PND 50, FVX (30 mg/kg, P·O. daily) and NE-100, (S1R) antagonist, (1 mg/kg, i.p. daily) were given to male pups. Behavior tests and histopathological changes were identified at the end of the experiment. In addition, the cerebellum biomarkers of endoplasmic reticulum (ER) stress and autophagy were assessed. Microglial cell polarization to M1 and M2 phenotypes was also assessed. FVX effectively mitigated the histopathological alterations in the cerebellum caused by VPA. FVX enhanced sociability and stereotypic behaviors in addition to its noteworthy impact on autophagy enhancement, ER stress deterioration, and controlling microglial cell polarization. The current investigation confirmed that the S1R agonist, FVX, can lessen behavioral and neurochemical alterations in the VPA-induced rat model of autism.

Repositioning Canagliflozin for Mitigation of Aluminium Chloride-Induced Alzheimer's Disease: Involvement of TXNIP/NLRP3 Inflammasome Axis, Mitochondrial Dysfunction, and SIRT1/HMGB1 Signalling.

Background and Objectives: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. Due to failure of the traditional drugs to produce a complete cure for AD, the search for new safe and effective lines of therapy has attracted the attention of ongoing research. Canagliflozin is an anti-diabetic agent with proven efficacy in the treatment of neurological disorders in which mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy play a pathophysiological role. Elucidation of the potential effects of different doses of canagliflozin on AD induced by aluminium chloride in rats and exploration of the molecular mechanisms that may contribute to these effects were the primary objectives of the current study. Materials and Methods: In a rat model of AD, the effect of three different doses of canagliflozin on the behavioural, biochemical, and histopathological alterations induced by aluminium chloride was assessed. Results: Canagliflozin administered to aluminium chloride-treated animals induced dose-dependent normalisation in the behavioural tests, augmentation of the antioxidant defence mechanisms, inhibition of TXNIP/NLRP3 inflammasome signalling, modulation of the SIRT1/HMGB1 axis, interference with the pro-inflammatory and the pro-apoptotic mechanisms, and restoration of the mitochondrial functions and autophagy in the hippocampal tissues to approximately baseline values. In addition, canagliflozin exhibited an interesting dose-dependent ability to repress aluminium chloride-induced histopathological changes in the brain. Conclusions: The effects of canagliflozin on oxidative stress, mitochondrial functions, inflammatory pathways, and autophagy signals may open new gates towards the mitigation of the pathologic features of AD.

Organoids Research for Colorectal Cancer: Promising Approach for Precision Medicine, their Applications and Future Perspectives

Background: Organoids are three-dimensional (3D) constructs designed to emulate the complexity and functionality of organs in the body. Organoids have recently been used as powerful instruments for modeling and investigating several diseases, including colorectal cancer. Colorectal cancer is caused by altering colonic epithelial cells, which produce adenomas and carcinomas. Objective: The objective of present study was to investigate impact of organoids on colorectal cancer and their therapeutic outcome in cancer research. Organoids can be grown from stem cells in vitro, which closely resemble the structure and function of the organ they are derived from. They have been used in a variety of research applications, including disease modeling, drug screening, and personalized medicine. Organoids have allowed researchers to understand better the mechanisms underlying colorectal cancer initiation, progression, and resistance to therapy. Methods: The literature review was surveyed, and keywords related to cancer management, organoids, modelling, personized medicine, 3D structures were screened for colorectal cancer management were screened in SCI-hub, SCOPUS, WOS, and ABC Journals. Results: The findings of studies suggested that organoids derived from patient tumors can recapitulate the histopathology and genetic alterations of the original tumor, making them a valuable tool for personalized medicine. Conclusion: Organoids have been used to develop high-throughput drug screening assays and investigate the tumor microenvironment's contribution to colorectal cancer progression. In this review, we summarize recent advances in the use of organoids to study colorectal cancer and discuss their potential applications in the clinic.

Protective Effects of Ascorbic Acid Against Cadmium-Induced Toxicity in the Placenta and Fetus of Rats.

This study aimed to determine the protective role of l-ascorbic acid in a pregnant rat model of cadmium-induced toxicity. Cadmium is a toxic heavy metal that can seriously harm placenta and fetus tissue in pregnant women. Forty-two healthy female Wistar albino rats (250-300 g weight and 14-16 weeks) were randomly distributed into six equal groups (n = 7): control, cadmium 1 mg (CD1), cadmium 5 mg (CD5), ascorbic acid (AA), CD1+AA, CD5+AA. Cadmium was administered to pregnant rats by oral gavage every other day, and/or AA (200 mg) was administered every day. At the end of pregnancy (Day 21), blood, placenta, and fetuses were collected from rats. The results indicated that cadmium-induced oxidative stress by increasing the level of MDA and by decreasing the levels of GSH, SOD, and CAT activity in the serum of maternal. However, AA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). Cadmium (5 mg/kg) exposure significantly increased creatinine levels compared to AA and CD1+AA groups (p < 0.05). In addition, AA (200 mg/kg) significantly attenuated cadmium-induced histopathological alteration in the placental and fetal tissues. In conclusion, AA may prevent cadmium toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat tissues and alleviates histopathological changes.

Avocado Oil Alleviates Oxidative Stress and Improves Biochemical and Histopathological Alterations in Diabetic Rats

Avocado Oil Alleviates Oxidative Stress and Improves Biochemical and Histopathological Alterations in Diabetic Rats

Immediate Diagnosis of Breast Carcinoma on Core Needle Biopsy Using Ex Vivo Fluorescence Confocal Microscopy: Feasibility in a One-Stop Breast Clinic Workflow.

In the one-stop breast clinic setting, breast cytology traditionally provides immediate diagnosis of carcinoma. Fluorescence confocal microscopy (FCM) is an emerging optical technique enabling ex vivo analysis of breast biopsies in real-time. This study represents the first proof of concept for integrating FCM imaging into the routine workflow of breast core needle biopsies (CNB) at Gustave Roussy's one-stop breast clinic. Fifty women with breast masses underwent consecutive enrollment. Biopsies were stained with acridine orange and fast green, followed by imaging using the Vivascope 2500M-G4 (FCM). Interpretation was conducted by two pathologists in real time (PT1) or postoperatively (PT2). Concordance with definitive histology, the duration of the FCM protocol, and its impact on conventional histopathology, immunohistochemistry, and FISH analyses were evaluated. In our study of 50 biopsies, a concordant diagnosis of malignancy was performed using FCM on the malignant cases at definitive histology in 93.5% (29/31 cases) and in 90.3% (28/31 cases) according to PT1 and PT2, respectively. When the FCM suspicious cases were added, FCM identified 100% (31/31 cases) and 96.7% (30/31 cases) of the malignant cases according to PT1 and PT2, respectively. A notable false positive case was identified as a complex sclerosing lesion. The median time for sample preparation (including tissue reception) was 5 min, while the median time for imaging acquisition with interpretation was 3 min for PT1, but 1 min required for interpretation alone by PT2. Histopathological alterations were not more prevalent in FCM-imaged biopsies compared to conventionally treated biopsies. The immunophenotyping and molecular assessment of tissue were preserved after FCM protocol. FCM shows promise as a new histological method for the immediate diagnosis of breast carcinoma on core needle biopsies in a one-stop clinic setting, while also preserving tissue specimens for final histology.

Anti-Inflammatory Humulene-Type Sesquiterpenoids from Asteriscus Graveolens

Objectives: Inflammation is the initial physiological reaction of the immune system to infection or irritation, leading significant risk factors for several forms of cancer. The genus Asteriscus has been observed to possess a notable abundance of sesquiterpenes with anti-inflammatory properties. This study was designed to assess the anti-inflammatory activity of the sesquiterpenoids isolated from Asteriscus graveolens. Methods: The organic extract of the Asteraceae plant A. graveolens was subjected to different chromatographic and spectroscopic techniques for isolation, purification, and identification of sesquiterpenoid contents. The isolated compounds were screened for anti-inflammatory activities in two animal models: rat paw edema and rat ear edema. Histopathological examinations as well as biochemical markers of inflammation were assessed. This was followed by in silico screening for anti-inflammatory activity. Results: Four known sesquiterpenoids were isolated from A. graveolens, including two humulene derivatives, namely, 9-oxohumula-4-en-6,15-olide (1), and 9-oxohumula-1(10)(Z),4,7(E)-trien-6,15-olide (2) and two bisabolene derivatives, identified as bisabola-2,10-dien-1-one (3) and 6- hydroxybisabola-2,10-dien-1-one (4) described. In the rat paw edema model, compound 2 showed highest activity in preventing formation carrageenan-induced paw edema. This was confirmed by histopathological examinations that indicated partial preservation of the epidermal and dermal layers. Further, the compound significantly inhibited cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) release. In the croton oil indued rat ear edema, compounds 2 and 4 significantly inhibited ear edema and protected against histopathological alterations. This was associated with prevention of myeloperoxidase (MPO) concentration in ear tissues. Molecular docking and molecular dynamic simulation indicated the affinity and docking stability of compounds 1-4 to the selected inflammatory protein. Conclusion: Phytochemical investigation of A. graveolens resulted in the isolation and characterization of four sesquiterpenes. In particular, compound 2 showed potent anti-inflammatory activity in carrageenan rat paw edema and croton oil ear edema.

Biomarker and adverse outcome pathway responses of Tubifex tubifex(sludge worm) exposed to environmentally-relevant levels of acenaphthene: insights from behavioral, physiological, and chemical structure-activity analyses.

Polycyclic aromatic hydrocarbons (PAHs), including acenaphthene, pose a significant threat to aquatic ecosystems by harming vital organisms such as benthic invertebrates. This study evaluated the impact of environmentally relevant concentrations of acenaphthene on Tubifex tubifex, focusing on sublethal acute toxicity and subchronic biomarker responses. Key biomarkers assessed included histopathological changes and the modulation of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and malondialdehyde (MDA). Additionally, the study examined structure-activity relationships and species sensitivity distribution (SSD). Concentrations exceeding the solubility threshold of acenaphthene (3.9 mg/L) triggered distinct, concentration-dependent behavioral responses in Tubifex tubifex, such as clumping, mucus secretion, and body wrinkling. Prolonged exposure exacerbated these behavioral dysfunctions, while subchronic exposure resulted in significant histopathological alterations, including epithelial hyperplasia, inflammation, edema, fibrosis, and degenerative changes. The edematic appearance of the body wall suggested a potential immune response to exposure. Furthermore, increased activities of CAT, SOD, and GST indicated oxidative stress in the worms. The study found a 1.5-fold increase in CAT and GST activity, a fivefold increase in SOD, and a striking 100-fold increase in MDA levels compared to controls, signifying an overwhelmed antioxidant defense system and potential cellular disruption. The SSD curve revealed hazard concentrations (HC50 and HC90), indicating that Tubifex tubifex exhibited lower sensitivity to acenaphthene compared to other taxa. In silico analysis and read-across models confirmed the potential of acenaphthene to induce significant oxidative stress upon exposure. The correlation between biomarker responses and structure-activity relationship analysis highlighted the aromatic nature of acenaphthene as a key factor in generating reactive metabolites, inhibiting antioxidant enzymes, and promoting redox cycling, ultimately contributing to adverse outcomes. These findings, coupled with behavioral responses and SSD curve inferences, underscore the importance of the solubility threshold of acenaphthene as a critical benchmark for evaluating its ecological impact in aquatic environments.

Oxidative stress, histopathological and genotoxicity of copper oxide nanoparticles in Biomphalaria alexandrina snail

AbstractHigher usage of copper oxide nanomaterials in industrial and biomedical fields may cause an increase of these nanoparticles in aquatic environments, which could have a detrimental ecological effect. Thus, the objective of this study was to evaluate the acute toxicity of copper oxide nanoparticles on the freshwater gastropod, Biomphalaria alexandrina. Transmission electron microscopy, x-ray diffraction analysis and UV–VIS spectrophotometer of CuO NPs revealed a typical TEM image and a single crystal structure with average crystallite size of approximately 40 nm also, a sharp absorption band was appeared. Following exposure to sub-lethal concentrations of CuO NPs (LC10, 15.6 mg/l and LC25, 27.2 mg/l), treated snails revealed a significant decrease (p &lt; 0.05) in total antioxidant capacity, reduced glutathione contents as well as catalase, and sodium dismutase activities were significantly declined (p &lt; 0.05) in comparison to the control group. Also, histopathological alterations were observed in the digestive gland, including ruptured and vacuolated digestive cells, and a marked increase in the number of secretory cells and the severity of the damage increased with rising concentrations. Furthermore, changes in RAPD profiles were detected in the treated snails. In conclusion, our research highlights the potential ecological impact of CuO NPs release in aquatic ecosystems and advocates for improved monitoring and regulation of CuO NPs industrial usage and disposal.

Carbenoxolone upregulates TRAIL\\TRAILR2 expression and enhances the anti-neoplastic effect of doxorubicin in experimentally induced hepatocellular carcinoma in rats

AimsThis study investigates the in vivo anticancer activity of carbenoxolone (CBX) and its role in fighting hepatocellular carcinoma (HCC) progression and alleviating resistance against doxorubicin (DOX). Moreover, the molecular mechanism of action of CBX is explored. MethodsHCC was induced in Sprague Dawley rats via biweekly administration of thioacetamide (TAA) (200 mg/kg) intraperitoneally (i.p.) for 16 weeks after administering a single dose of diethylnitrosamine (DEN) (200 mg/kg, i.p.). A prophylactic model was established by treating rats with i.p. CBX (20 mg/kg/day) for 4 weeks starting on week 13 post-TAA injection. A therapeutic model was established by treating rats with CBX, DOX, or their combination for 7 weeks following 16 weeks of TAA administration. Serum Alpha-fetoprotein (AFP) and biochemical markers of hepatic functions were assessed. Histopathological examinations of hepatic tissues were performed. Immunohistochemical and qRT-PCR analyses were applied to assess the differential expressions of TRAIL/TRAILR2, Bcl-2, TGF-β1, and caspases 3, 8, and 9. ResultsCBX markedly improved hepatic functions, reduced serum AFP levels, and alleviated TAA-induced hepatic histopathological alterations. CBX triggered apoptosis as evident by upregulating apoptotic markers: TRAIL/TRAILR2, caspases 3, 8, and 9, and downregulating the antiapoptotic protein Bcl-2. CBX downregulated TGF-β1. Interestingly, CBX/DOX combination mitigated hepatic damage and induced apoptosis in a way that surpassed DOX-only treatment. ConclusionThe current study proposes that CBX is a promising anti-tumor compound, which can work effectively under prophylactic and therapeutic modes. Interestingly, CBX enhanced the anti-tumor effect of DOX. CBX exerted these effects via, in part, stimulating TRAIL-induced apoptosis along with attenuating fibrosis.

Are Environmental Levels of Nonsteroidal Anti-Inflammatory Drugs a Reason for Concern? Chronic Life-Cycle Effects of Naproxen in Zebrafish.

The nonsteroidal anti-inflammatory drug naproxen (NPX) is among the most consumed pharmaceuticals worldwide, being detected in surface waters within the ng to μg/L range. Considering the limited chronic ecotoxicity data available for NPX in aquatic ecosystems, the present study aimed at evaluating its impact in the model organism Danio rerio, following a full life-cycle exposure to environmentally relevant concentrations (0.1 to 5.0 μg/L). An integration of apical endpoints, i.e., survival, growth, and reproduction, with gonad histopathology and gene transcription (RNA-seq) was performed to provide additional insights into the mode of action (MoA) of NPX. NPX decreased zebrafish growth and reproduction and led to histopathological alterations in gonads at concentrations as low as 0.1 μg/L. At the molecular level, 0.7 μg/L of NPX led to a disruption in gonads transcription of genes involved in several biological processes associated with reproduction, mainly involving steroid hormone biosynthesis and epigenetic/epitranscriptomic machineries. Collectively, these results show that environmentally realistic concentrations of NPX affect zebrafish reproduction and associated signaling pathways, indicating that current hazard and risk assessment data for NPX underestimate the environmental risk of this pharmaceutical.

Diallyl Disulfide Mitigates Cadmium Hepatotoxicity by Attenuating Oxidative Stress and TLR-4/NF-κB Signaling and Upregulating PPARγ.

Heavy metals can cause serious health problems that affect different organs. Cadmium (Cd) is an environmental contaminant known for its toxicological consequences on different organs. Hepatotoxicity is a serious effect of exposure to Cd with oxidative stress (OS) and inflammation playing a central role. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, is known for its cytoprotective and antioxidant effects. In this study, the effect of DADS on Cd-induced inflammation, oxidative stress and liver injury was investigated. DADS was supplemented for 14 days via oral gavage, and a single intraperitoneal dose of Cd (1.2 mg/kg body weight) was administered to rats on day 7. Blood and liver samples were collected at the end of the experiment for analyses. Cd administration resulted in remarkable hepatic dysfunction, degenerative changes, necrosis, infiltration of inflammatory cells, collagen deposition and other histopathological alterations. Cd increased liver malondialdehyde (MDA) and nitric oxide (NO) (p < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 (p < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes (p < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression (p < 0.001). DADS ameliorated liver injury and tissue alterations, attenuated OS and apoptosis, suppressed TLR-4/NF-κB signaling, and enhanced antioxidants. In addition, DADS upregulated PPARγ in the liver of Cd-administered rats. DADS is effective against Cd-induced hepatotoxicity and its beneficial effects are linked to suppression of inflammation, OS and apoptosis and upregulation of PPARγ. DADS could be valuable to protect the liver in individuals at risk of Cd exposure, pending further studies to elucidate other underlying mechanism(s).

The Therapeutic Effects of Lycopene Against Experimental Giardiasis in Mice.

Giardia duodenalis is a protozoan parasite that infects approximately one billion people worldwide. In this study, the effects of lycopene on experimental giardiasis in mice were investigated by evaluating cyst shedding rate, weight changes, duodenal antioxidant status, and histopathological alteration. Ninety-five male mice aged four to six weeks were divided into six groups of 15 and one group of 5 as the negative control. All mice were infected with 2 × 105 Giardia duodenalis (B genotype) cysts except for the negative control. The treatment groups were treated with metronidazole, mixed lycopene-metronidazole, and 5, 10, and 20 mg/kg lycopene for 7 days. The mice treated with lycopene 20 and mixed lycopene-metronidazole had no cyst shedding from the 7th day of treatment. The mildest lesions were observed in the mixed lycopene-metronidazole group. Results showed that treatment with mixed lycopene-metronidazole significantly increased TAC and decreased MDA levels as compared with the positive control. It seems that the antigiardial effect of lycopene is related to its antioxidant properties. Nevertheless, direct effect of lycopene on Giardia and its probable mechanism remain to be investigated.

Effect of CCl4 on Renal Tissues of Male Mice and Prevented by Pretreatment with Bromelain Loaded with Gold Nanoparticles: Histopathological and Caspase-9 Expression Alterations

The study aimed to investigate the potential protective effect of bromelain on renal histopathological changes induced by carbon tetrachloride (CCl4) in albino mice. CCl4 is widely used in the chemical industry but is also known to cause toxicity to various organs including the brain, liver, kidneys and lungs. In this study, 49 animals were divided into 7 equal groups. The kidneys of the mice were examined to assess histopathological changes and immunohistochemical markers, specifically caspase-9. The groups that received bromelain solution coated with gold nanoparticles demonstrated greater protective effects against CCl4-induced kidney damage. The findings suggest that kidney damage induced by CCl4 may be attributed to oxidative stress, which disrupts the antioxidant defense system, enzyme function and biochemical markers. However, administration of bromelain significantly mitigated CCl4 toxicity by enhancing the antioxidant defense system and reducing the production of free radicals. Notably, the study found that a dose of 300 mg of bromelain effectively reduced CCl4-induced toxicity in rats. This highlights the potential therapeutic value of bromelain in protecting against chemical-induced kidney damage. HIGHLIGHTS The kidney damage from carbon tetrachloride can occur through oxidative stress, altering the antioxidant defense system, enzyme function, and biochemical markers. The bromelain can decreased the toxicity of CCL4. The 300 mg bromelain solution proved to be more efficacious than the 100 mg dose. GRAPHICAL ABSTRACT

Biologically informed deep neural networks provide quantitative assessment of intratumoral heterogeneity in post treatment glioblastoma.

Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf). BioNet significantly outperforms existing methods (p < 2e-26). In cross-validation, BioNet achieved AUCs of 0.80 (Pro) and 0.81 (Inf), with accuracies of 80% and 75%, respectively. In blind tests, BioNet achieved AUCs of 0.80 (Pro) and 0.76 (Inf), with accuracies of 81% and 74%. Competing methods had AUCs lower or around 0.6 and accuracies lower or around 70%. BioNet's voxel-level prediction maps reveal intratumoral heterogeneity, potentially improving biopsy targeting and treatment evaluation. This non-invasive approach facilitates regular monitoring and timely therapeutic adjustments, highlighting the role of ML in precision medicine.

Daidzein ameliorates experimental traumatic brain injury-induced neurological symptoms by suppressing oxidative stress and apoptosis.

Traumatic brain injury (TBI) causes deficits in neurological function, induces pathological changes, and increases oxidative stress. The current investigation aimed to determine Daidzein's neuroprotective potential in experimental TBI. Initially, the HT-22 cell line exposed to H2O2 underwent in vitro examination, and the results showed that Daidzein had a neuroprotective effect evident from enhanced cell viability and decreased NO generation. Using three different Daidzein doses-1 mg/kg, 5 mg/kg, and 10 mg/kg-in the in vivo experiment, the potential of Daidzein was evaluated against TBI. The neurological severity score (NSS), kondziela's screen test, and elevated plus maze showed improvements after treatment with Daidzein manifested by decreased score, enhanced motor coordination, and anti-anxiety effects. Additionally, Daidzein improved mechanical allodynia and restored the breakdown of the blood-brain barrier. The FTIR spectral analysis showed restoration of the biochemical compositional changes. Furthermore, H & E and Toluidine blue staining revealed an improvement in the histopathological alterations. The RT-qPCR revealed an increase in mRNA expression level of Nrf2, HO-1, and Bcl-2 and the downregulation of Keap-1, Bax and Cleaved caspase-3 expressions. Thus, exhibiting its antioxidant and antiapoptotic potential. The RT-qPCR also manifested a decrease in mRNA expression of GFAP and Iba-1. Further immunohistochemistry results indicated Daidzein's antioxidant and antiapoptotic properties by upregulating Nrf2 and downregulating cleaved caspase-3. Daidzein also lowered the apoptosis index and improved neuronal survival evidenced by flow cytometric analysis. In addition to this, Daidzein notably increased the antioxidant enzyme levels and decreased the oxidative stress markers. The current study's findings point to the neuroprotective potential of the phytoestrogen Daidzein as it lessened neurological abnormalities, decreased oxidative stress, and lowered proapoptotic protein expression.

Berberine attenuates ECM accumulation and the progression of acute liver failure through inhibition of NLRP3 inflammasome signalling

Acute liver failure (ALF) is a life-threatening disease, characterized by upregulated extracellular matrix deposition and inflammatory signalling, with no effective treatment options and targets. The present study was designed to investigate the preventive and therapeutic effects of berberine (BBR) and its underlying mechanism in thioacetamide (TAA)-induced ALF. Male SD rats were administered with TAA 300 mg/kg, i.p., thrice to induce ALF and pre- or post-treated with BBR. To decipher the effects of BBR LFT markers, histopathological analysis of key fibrotic and inflammatory proteins was performed. In addition, the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were assessed by ELISA. Our work showed TAA-induced ALF animals were associated with increased ALT, AST, bilirubin (LFT markers) and histopathological alterations with profuse infiltration of inflammatory cells in the liver tissue. Treatment with BBR has significantly inhibited LFT markers and histological alterations triggered by TAA. In addition, TAA animals demonstrated increased collagen accumulation and upregulated expression of TGF-β1, vimentin, and α-SMA compared to control. The excessive accumulation of collagen, TGF-β1, vimentin, and α-SMA were significantly modulated with BBR treatment. Further, the fluorescence intensity of ROS an activator of NLRP3 including the NLRP3 inflammasome, and its downstream signalling ASC, cleaved IL-1β, and other pro-inflammatory cytokines like TNF-α and IL-6 stimulated by TAA were attenuated by BBR treatment. The current work indicated that BBR significantly ameliorated TAA-induced ALF by inhibiting the extracellular matrix accumulation associated with the NLRP3/IL-1β signalling pathway and could be a viable therapeutic option to treat ALF and other fibroinflammatory diseases.