Periprostatic fat adipokine expression is correlated with prostate cancer aggressiveness in men undergoing radical prostatectomy for clinically localized disease.

OBJECTIVES: To investigate the relationship between periprostatic adipose tissue (PPAT) adipokine expression and prostate cancer (PCa) aggressiveness using both pathological features of radical prostatectomy (RP) and multiparametric magnetic resonance imaging ( MRI) variables. PATIENTS AND METHODS: Sixty-nine men were recruited to assess immunohistochemical expression of tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) of periprostatic fat of RP specimens. Per cent immunopositivity was quantified on scanned slides using the Aperio Positive Pixel Count algorithm for PPAT TNFα, VEGF and androgen receptors. Periprostatic fat volume (PFV) was segmented on contiguous T1 -weighted axial MRI slices from the level of the prostate base to apex. PFV was normalized to prostate volume (PV) to account for variations in PV (normalized PFV = PFV/PV). MRI quantitative values (Kep , Ktrans and apparent diffusion coefficient) were measured from the PCa primary lesion using Olea Sphere software. Patients were stratified into three groups according to RP Gleason score (GS): ≤6, 7(3 + 4) and ≥7(4 + 3). RESULTS: The mean rank of VEGF and TNFα was significantly different between the groups [H(2) = 11.038, P = 0.004] and [H(2) = 13.086, P = 0.001], respectively. Patients with stage pT3 had higher TNFα (18.2 ± 8.95) positivity than patients with stage pT2 (13.27 ± 10.66; t [67] = -2.03, P = 0.047). TNFα expression significantly correlated with Ktrans (ρ = 0.327, P = 0.023). TNFα (P = 0.043), and VEGF (P = 0.02) correlated with high grade PCa (GS ≥ 7) in RP specimens and also correlated significantly with upgrading of GS from biopsy to RP histology. CONCLUSIONS: The expression levels of TNFα and VEGF on immunostaining significantly correlated with aggressivity of PCa. As biomarkers, these indicate the risk of having high grade PCa in men undergoing RP.

The Apoptotic, Oxidative and Histological Changes Induced by Different Diameters of Sphere Gold Nanoparticles (GNPs) with Special Emphasis on the Hepatoprotective Role of Quercetin.

Purpose: Gold nanoparticles (GNPs) as pharmaceutical and drug delivery tools exhibited harmful effects on human health and other living species. Quercetin (Qur) reveals various pharmacological effects specially antioxidant, anti-inflammatory and antiapoptotic. This study is directed to investigate hepatotoxicity of GNPs, in addition, to assess the impact of Qur in mitigating the toxicological effects of GNPs. Methods: Groups of rats were treated with or without sphere GNPs (10, 20 and 50 nm) and Qur (200 mg/kg b.wt.). Blood and liver samples from euthanized rats were subjected to biochemical, hematological, histopathological, and immunohistochemical investigations. Results: In comparison with 20 and 50 nm treated groups, the 10 nm GNPs significantly increased serum hepatic enzymes, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin. These 10 nm GNPs were associated with oxidative stress and markedly decreased antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD). Immunohistochemically, 10 nm GNPs expressed intense positive signals in nuclei of hepatocytes when stained with anti-caspase-3 antibody confirming extensive apoptosis. Pre-cotreatment with Qur decreased all tested hepatic enzymes and increased serum level of antioxidant enzymes compared to 10 nm GNPs. Qur treatment strongly exhibited anti-Ki67 antibody (proliferative marker) indicating high proliferation of hepatic parenchyma. Histopathologically, 10 nm GNPs revealed diffuse hydropic degenerations, severe sinusoidal congestion, coagulative necrosis, sever steatosis and diffuse hemosiderosis within the hepatic parenchyma. Qur treatment ameliorated most of these pathological effects. Conclusion: The smaller diameters of GNPs induce potential oxidative stress, cytotoxic, and apoptotic effects in hepatic tissues rather than larger ones. In addition, Qur demonstrated a significant prophylactic role against hepatotoxicity of GNPs.

Acrylamide-targeting renal miR-21a-5p/Fibrotic and miR122-5p/ inflammatory signaling pathways and the role of a green approach for nano-zinc detected via in silico and in vivo approaches.

Introduction: Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health. Methods: This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an In silico preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10 mg/kg b.wt.), ACR (20 mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A. Results: ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.

Design and Optimization of Sesamol Nanosuspensions to Potentiate the Anti-Tumor Activity of Epirubicin against Ehrlich Solid Carcinoma-Bearing Mice.

There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.

Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles.

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels.

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Cytodifferentiation of pinealocytes (I and II) and astrocyte types of mature male sheep epiphysis cerebri with special emphasis on the presence of neuronal and pigmented-like cells.

Background: The epiphysis cerebri (pineal gland) is a small-sized, photo neuroendocrine organ in the brain of most vertebrates. Their effect is through secretion of melatonin, a serotonin-derived hormone which is stimulated by darkness and inhibited by light and modulates the circadian rhythm; light and dark cycle like a biological clock, sleep patterns (sleep-wake cycle), and sexual development. Aim: This study aimed to identify and differentiate the different cell types filling the pineal gland parenchyma of mature male sheep. Methods: Pineal glands were collected and sliced parasagitally then processed histologically for light and electron microscopic examinations. Results: Two main cell types; pinealocytes and astrocytes were recognized within the gland parenchyma. Pinealocytes were the chief parenchymatus cells that occupied the largest volume of the gland and were classified according to the nuclear pictures (activity status) into two subtypes; pinealocytes I (pale subtype, active) and II (dark subtype, inactive). Astrocyte neuroglial cells had cytoplasmic processes which form a huge supportive framework between the pinealocytes and clarified two types; type I were elongated cells with elongated snake shaped nucleus and type II were smaller in size, with oval nuclei. Another marginal cell type was identified as a neuron-like cell which appeared larger in size than others and distributed sporadically, has eccentric oval nucleus with prominent nucleoli and single, long cytoplasmic process that branched at its terminal forming T-shaped process looks like pseudo unipolar neuron. Moreover, aggregations of pigment granules were markedly observed in the intercellular spaces and also near the blood capillaries. With transmission electron microscope (TEM) a special characteristic feature of pinealocytes; synaptic ribbons were recognized that appeared as bands of electron-dense material with several synaptic spherules; vesicles adjacent to its surface helping in the multivesicular release. Conclusion: The gland parenchyma revealed two main cell types; pinealocytes and astrocytes. Each one was subdivided into two subtypes; I and II. The first one was classified according to their nuclear pictures (activity status) and the second one was according to their shape, size, and cytoplasmic processes. Other cell types were also identified as neuronal and pigmented-like cells in the pineal matrix.

Cytodifferentiation of Wulzen's cone of mature male sheep hypophysis cerebri with special emphasis on its parenchymal correlations with the adjacent pars distalis, pars intermedia and pars nervosa.

Background: Hypophysis cerebri is considered the master endocrine gland as it plays a critical role in influencing and controlling the vitality of other endocrine organs via several hormones secretion. Aim: The present study was performed to clarify the localization of Wulzen's cone (WC) within sheep hypophysis and cytodifferentiation of the glandular cells filling cone parenchyma with particular emphasis on the cone correlations with adjacent pars distalis (pd), pars intermedia (pi), and pars nervosa (pn). Methods: Pituitaries were collected and processed histologically, then subjected to different combinations of special stains; Br-AB- OFG., PFA-AB-PAS-OG., PAS-Orange G., Orange G- Acid Fuchsin- Light Green, Bielschowsky technique, Masson's trichrome & Gomori's reticulin. Results: A sagittal section through the pituitaries revealed a well-developed cone of glandular cells protruding from the pi like a tongue plate towards the hypophyseal cleft in the neighborhood of the pd and behind the pn. Resembling the pd, various glandular cells were distinguished in the cone; chromophobes and chromophils of acidophils & basophils. The cone is mainly formed from acidophils intermingled with the chromophobes. Meanwhile, basophils were primarily localized at the most anterior & posterior parts of the cone. In front of the cone, pd were localized, resembling a wing-shaped and filled with several categorized glandular cells; chromophobes and chromophils. Upper to the cone, pi were localized and composed mainly of weakly basophilic cuboidal or polygonal cells arranged in parallel cords or follicles. Behind the cone, pn was localized as a ventral outpouching of the brain floor-like water drop. Unlike the cone, it was devoid of any glandular secretory cells or nerve cells but consisted mainly of unmyelinated nerve fibers, herring bodies, and pituicytes. Conclusion: WC is present and well-developed in sheep adenohypophysis. Various glandular cells were distinguished, filling the cone, chromophobes, and chromophils of acidophils & basophils that were typically similar to the glandular cells of pd but with different distributions.

The role of hesperidin as a cardioprotective strategy against doxorubicin-induced cardiotoxicity: The antioxidant, anti-inflammatory, antiapoptotic, and cytoprotective potentials.

Background: Doxorubicin (DOX), an anthracycline antibiotic, is a powerful chemotherapeutic agent effective against multiple types of cancer, particularly lung, breast, bladder and hematologic neoplasia (lymphomas and leukemia). However, its therapeutic usage is restricted by its known cardiotoxicity, which is associated with the production of oxidative stress. Enhancing antioxidant capacity represents a promising approach to mitigate DOX-induced cardiotoxicity. Hesperidin (HES), a citrus bioflavonoid, possesses several pharmacological effects, such as anti-inflammatory and antioxidant characteristics. Aim: This study was designed to evaluate the cardiotoxicity of DOX and assess the possible cardioprotective role of HES. Methods: Groups of Wistar rats were either treated with DOX (4 mg/kg. bw., once a week for five consecutive weeks, intraperitoneally) or received co-treatment with HES (100 mg/kg. bw./day in distilled water, 5 days in a week for five consecutive weeks, administered orally). Heart and blood samples were obtained for histological, immunohistochemical, and biochemical assessments. Results: DOX administration resulted in severe cardiotoxicity, as evidenced by significant elevations in cardiac biomarkers, including Troponin I (CTnI), Creatine kinase (CK-Total), Creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), and Aspartate aminotransferase (AST). DOX also elevated pro-inflammatory cytokines, such as Interferon γ (IFN-γ), Interleukin 1ß (IL-1ß), and Tumor necrosis factor α (TNF-α). Furthermore, DOX-induced oxidative stress and substantially reduced the levels of antioxidant enzymes, including Glutathione peroxidase (GPX), Superoxide dismutase (SOD), and Catalase (CAT). Histopathologically, DOX caused severe Zenker's necrosis, cardiomyocyte disarray, sarcoplasmic vacuolizations, cardiomyocyte congestion, and inflammatory cell infiltration. Immunohistochemically, DOX exhibited extensive apoptosis, as indicated by strong positive immuno-localization against anti-caspase-3 antibody. In contrast, co-treatment with HES protected cardiac tissues against cardiotoxicity of DOX, as indicated by the amelioration of histological abnormalities and the normalization of biochemical values. Conclusion: We can conclude that DOX induces severe cardiotoxicity characterized by oxidative stress, inflammation, pathological alterations, and apoptosis. Co-treatment with HES demonstrates significant cardioprotective effects by virtue of its potent anti-inflammatory, antioxidant, cytoprotective, and antiapoptotic characteristics.

Green Synthesized Zinc Oxide Nanoparticles Using Moringa olifera Ethanolic Extract Lessens Acrylamide-Induced Testicular Damage, Apoptosis, and Steroidogenesis-Related Gene Dysregulation in Adult Rats.

This study assessed the possible protective role of green synthesized zinc oxide nanoparticles using Moringa olifera leaf extract (MO-ZNPs) in acrylamide (ACR)-induced reproductive dysfunctions in male rats. ACR (20 mg/kg b.wt/day) and/or MO-ZNPs (10 mg/kg b.wt/day) were given orally by gastric gavage for 60 days. Then, sperm parameters; testicular enzymes; oxidative stress markers; reproductive hormones including testosterone, luteinizing hormone (LH)-estradiol, and follicle-stimulating hormone (FSH) concentration; testis histology; steroidogenesis-related gene expression; and apoptotic markers were examined. The findings revealed that MO-ZNPs significantly ameliorated the ACR-induced decline in the gonadosomatic index and altered the pituitary-gonadal axis, reflected by decreased serum testosterone and FSH with increased estradiol and LH, and sperm analysis disruption. Furthermore, a notable restoration of the tissue content of antioxidants (catalase and reduced glutathione) but depletion of malondialdehyde was evident in MO-ZNPs+ACR-treated rats compared to ACR-exposed ones. In addition, MO-ZNPs oral dosing markedly rescued the histopathological changes and apoptotic caspase-3 reactions in the testis resulting from ACR exposure. Furthermore, in MO-ZNPs+ACR-treated rats, ACR-induced downregulation of testicular steroidogenesis genes and proliferating cell nuclear antigen (PCNA) immune-expression were reversed. Conclusively, MO-ZNPs protected male rats from ACR-induced reproductive toxicity by suppressing oxidative injury and apoptosis while boosting steroidogenesis and sex hormones.

Parasitological, Molecular, and Histopathological Investigation of the Potential Activity of Propolis and Wheat Germ Oil against Acute Toxoplasmosis in Mice.

Toxoplasmosis is one of the most common parasitic zoonoses that affects all vertebrates. The drugs most commonly used against toxoplasmosis have many side effects, making the development of new antiparasitic drugs a big challenge. The present study evaluated the therapeutic effectiveness of novel herbal treatments, including propolis and wheat germ oil (WGO), against acute toxoplasmosis. A total of 50 albino mice were divided into five groups: group 1 (G1) (non-infected and non-treated); group 2 (G2) (infected without treatment); group 3 (G3) (treated with propolis); group 4 (G4) (treated with WGO); group 5 (G5) (treated with a combination of propolis and WGO). The effects of the herbal substances on different organs, mainly liver, spleen, and lungs, were investigated using parasitological, molecular, and histopathological examinations. The results of parasitological examination demonstrated statistically significant (p < 0.05) differences in the parasitic load between treated groups (G3, G4, and G5) compared to the control positive group (G2). These differences were represented by a significant reduction in the parasite load in stained tissue smears from the liver obtained from the animals treated with propolis (G3) compared to the parasite load in the positive control group. Similarly, animals (G4) treated with WGO exhibited a significant reduction in the parasite load versus the positive control group, while the lowest parasite load was found in G5, treated with propolis and WGO. Quantification of the parasite burden through molecular methods (PCR) revealed similar findings represented by reduction in the parasite burden in all treated groups with WGO and propolis as compared to the control group. Importantly, these previous parasitological and molecular findings were accompanied by a marked improvement in the histopathological picture of the liver, spleen, and lungs. In conclusion, propolis and WGO showed a good combination of therapeutic efficacy against acute toxoplasmosis.

Stabilization of glutathione redox dynamics and CYP2E1 by green synthesized Moringa oleifera-mediated zinc oxide nanoparticles against acrylamide induced hepatotoxicity in rat model: Morphometric and molecular perspectives.

The terrible reality is that acrylamide (AA) is a common food contaminant found in a wide variety of commonly consumed foods. This research involves the advancement of a more dependable technique for the bio-fabrication of zinc oxide nanoparticles (ZNPs) through the green method using Moringa Oleifera extract (MO-ZNPs) as an efficient chelating agent for acrylamide (AA). The effects of AA on glutathione redox dynamics, liver function, lipid profile, and zinc residues in Sprague Dawley rats are investigated. Finally, the microarchitecture and immunohistochemical staining of Caspase-3 and CYP2E1 were determined in the liver tissue of rats. Four separate groups, including control, MO-ZNPs (10 mg/kg b. wt), AA (20 mg/kg b. wt), and AA + MO-ZNPs for 60 days. The results revealed a suppressed activity of glutathione redox enzymes (GSH, GPX,and GSR) on both molecular and biochemical levels. Also, AA caused elevated liver enzymes, hepatosomatic index, and immunohistochemical staining of caspase-3 and CYP2E1 expression. MO-ZNPs co-treatment, on the other hand, stabilized glutathione-related enzyme gene expression, normalized hepatocellular enzyme levels, and restored hepatic tissue microarchitectures. It could be assumed that MO-ZNPs is a promising hepatoprotective molecule for alleviating AA-induced hepatotoxicity. We witnessed changes in glutathione redox dynamics to be restorative. Glutathione and cytochrome P450 2E1 play crucial roles in AA detoxification, so maintaining a healthy glutathione redox cycle is necessary for disposing of AA toxicity.

Assessment of the physicochemical and sensory characteristics of fermented camel milk fortified with Cordia myxa and its biological effects against oxidative stress and hyperlipidemia in rats.

Natural feed additives and their potential benefits in production of safe and highly nutritious food have gained the attention of many researchers the last decades. Cordia myxa is a nutrient-dense food with various health benefits. Despite this fact, very limited studied investigated the physicochemical and sensory impacts of incorporation of fermented camel milk with Cordia myxa and its biological effects. The current study aimed to assess the physical, chemical, and sensory characteristics of fermented camel milk (FCM) fortified with 5, 10, and 15% Cordia myxa pulp. The study demonstrated that fortification of camel milk efficiently enhanced protein, total solids, ash, fiber, phenolic substance, and antioxidant activity. When compared to other treatments, FCM supplemented with 10% Cordia myxa pulp had the best sensory features. In addition, FCM fortified with 10% Cordia myxa pulp was investigated as a potential inhibitor of hypercholesterolemia agents in obese rats. Thirty-two male Wistar rats were split into two main groups including normal pellet group (n = 8) served as negative control group (G1) and a group of hyperlipidemic animals (n = 24) were feed on a high-fat diet (HFD). Hyperlipidemic rats group (n = 24) were then divided into three subgroups (8 per each); second group or positive control (G2) which include hyperlipidemic rats received distilled water (1 mL/day), the third group (G3) involved hyperlipidemic rats feed on FCM (10 g/day) and the fourth group (G4) included hyperlipidemic animals feed on 10 g/day FCM fortified with 10% of Cordia myxa pulp by oral treatment via an intestinal tube for another 4 weeks. In contrast to the positive control group, G4 treated with Cordia myxa showed a substantial decrease in malondialdehyde, LDL, cholesterol, triglycerides, AST, ALT, creatinine, and urea levels, while a significant increase in HDL, albumin, and total protein concentrations. The number of large adipocytes decreased while the number of small adipocytes increased after consumption of fortified FCM. The results indicated that fermented milk fortified with Cordia myxa pulp improved the functions of the liver and kidney in hyperlipidemic rats. These results demonstrated the protective effects of camel milk and Cordia myxa pulp against hyperlipidemia in rats.

Palliative effect of Moringa olifera-mediated zinc oxide nanoparticles against acrylamide-induced neurotoxicity in rats.

Repeated acrylamide (ACR) exposure in experimental animals and humans causes variable degrees of neuronal damage. Because of its unique features, several green synthesized nanomaterials are explored for neuromodulatory activity. Hence, this study investigated the effect of green synthesized zinc oxide nanoparticles using Moriga olifera leaves extract (MO-ZnONP) against acrylamide (ACR)-induced neurobehavioral and neurotoxic impacts in rat. Forty male Sprague Dawley rats were distributed into four groups orally given distilled water, MO-ZnONP (10 mg/kg b.wt), ACR (20 mg/kg b.wt), or MO-ZnONP + ACR for 60 days. Gait quality and muscular, motor, and sensory function were assessed. Acetylcholinesterase (AChE), dopamine, catalase, malondialdehyde (MDA), and Zn brain contents were determined. Brain histopathology and immunohistochemical localization of the amyloid-ß protein and abnormal Tau were performed. The results revealed that MO-ZnONP significantly reduced ACR-induced sensory dysfunctions, hind limb abnormality, and motor deficits. Additionally, the ACR-induced increase in dopamine and AChE were significantly supressed by MO-ZnONP. Besides, MO-ZnONP significantly restored catalase and Zn content but reduced increased MDA brain content resulting from ACR. Furthermore, the ACR-induced neurodegenerative changes and increased amyloid-ß and phosphorylated Tau immunoexpression was significantly abolished by MO-ZnONP. Conclusively, MO-ZnONP could be used as a biologically effective compound for mitigating ACR's neurotoxic and neurobehavioral effects.

Thymoquinone counteracts oxidative and inflammatory machinery in carrageenan-induced murine paw edema model.

Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.

Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring.

In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient's quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg/kg b.wt), and T2DM-BBR-Vild (10 mg/kg b.wt + Vild (5 mg/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK/mTOR-mediated autophagy and limiting ER stress.

Hepatic and renal toxicity following the injection of copper oxide nanoparticles (CuO NPs) in mature male Westar rats: histochemical and caspase 3 immunohistochemical reactivities.

Copper nanoparticles are widely utilized in a variety of applications, including metal catalysts, semiconductors, heat transfer fluids in machine tools, and even in antibacterial medications. Forty mature healthy Westar rats were utilized in the current investigation and grouped randomly into four groups (n = 10 rats/group). Group I (G1) was kept as a control group, but G2, G3, and G4 were intraperitoneally injected with CuO NPs with a dose (5 mg, 10 mg, 25 mg/kg body weight/day) respectively for 9 days. Rats were sacrificed; then, the livers and kidneys were dissected and subjected to histopathological and immunohistochemical examination. Our findings of G2 and G3 revealed mild to moderate degenerative changes within the hepatic parenchyma, moderate blood vessel congestions, glycogen depletion, hemosiderosis, and microvesicular steatosis (fatty changes within the hepatocytes). In addition, at the level of kidney, our examination clarified moderate degenerations of the renal corpuscles and renal tubules with moderate swelling and congestions of the glomerulus with moderate vacuolations in the renal tubules lining epithelium. On the other hand, increasing the dose of CuO NPs, the toxicity became more obvious, where the liver of G4 revealed severe necrosis of hepatocytes with completely disorganizations of the hepatic rays, loss of the hepatic architectures, severe steatosis, severe hemosiderosis, sinusoidal dilatations with congestions, as well as severe fibrous tissue proliferation with anti-inflammatory cell infiltrations specially around portal triad with hyperplasia of bile duct. Meanwhile in kidney, G4 clarified severe necrosis and atrophy of the renal corpuscles with severe damage of Bowman's capsule leading to completely disorganization and loss of normal renal cortex architectures, severe congestion of the glomerulus, severe necrosis of the renal tubules with damage and sloughing for its lining epithelium, and severe hemorrhage between renal tubules. In addition, severe and diffuse caspase 3 immunoreactivity were observed within the hepatic and renal tissues of G4. The present investigation was concluded that the CuO NPs have a potential toxicological effect on the hepatic and renal tissues that may affect their functions.-->.

A Novel Role of Galectin-3 and Thyroglobulin in Prognosis and Differentiation of Different Stages of Thyroid Cancer and Elucidation of the Potential Contribution of Bcl-2, IL-8 and TNF-α.

Thyroid cancer is among the most prevalent cancers with different types and stages. New markers are required for the prognosis and diagnosis of the disease. The present study aimed to detect the role of new markers, including galectin-3 (Gal-3) and thyroglobulin (TG), in the prognosis and staging of thyroid cancer. The study also investigated the potential apoptotic and inflammatory mechanisms involved in thyroid cancer through the determination of B-cell lymphoma 2 (Bcl-2), interleukin-8 (IL-8) and tumor necrosis factor α (TNFα) during the different stages of the cancer using a series of molecular methods. Histopathological and immunohistochemical examinations were also performed. A total of 300 subjects were classified into: 100 normal healthy subjects matched in age and sex, 100 patients with thyroid carcinoma stage I (T1N0M0) and 100 patients with thyroid carcinoma stage 2 (T2N1M1). Interestingly, the present study revealed a significant increase in the levels of TG and Gal-3 in thyroid cancer patients compared to the control group. Furthermore, the levels of Bcl-2, IL-8 and TNF-α significantly increased in the patient serum. The histopathological examination and immunohistochemical observations confirmed the molecular and hematological findings. Collectively, the present study concluded that serum TG and Gal-3 could be useful markers in the prognosis and staging of patients with thyroid cancer. Furthermore, the determination of Bax, Bcl-2, IL-8 and TNF-α levels constitute a major important marker for investigation of the mechanisms of apoptosis and inflammation in thyroid cancer. To our knowledge, this is the first study that used both galectin-3 and TG as tumor markers in the prognosis and differentiation between the different stages of cancer.

Modulatory effect of dietary probiotic and prebiotic supplementation on growth, immuno-biochemical alterations, DNA damage, and pathological changes in E. coli-infected broiler chicks.

Avian pathogenic Escherichia coli is one of the principal causes of heavy economic losses to the poultry industry. Little is known about the underlying mechanisms, particularly the potential role of immunoglobulin A and the DNA damage, involving the beneficial effects of dietary supplementation of probiotics and prebiotics in avian colibacillosis. The current study investigated the potential effects of probiotic and prebiotic dietary supplementation on E. coli-infected broiler chicks. A total of 120 1-day-old unsexed Hubbard chicks were divided into six groups: Group 1 was considered as a negative control; Group 2 was supplemented with 1 g/kg feed of Lactobacillus plantarum; Group 3 was supplemented with amylase enzyme; Group 4 served as a positive control infected orally by E. coli O78; Group 5 was supplemented with L. plantarum from 1-day-old chicken and then infected orally with E. coli O78; and Group 6 was supplemented with amylase enzyme from 1-day old chicken and then infected orally with E. coli O78. For all examined groups, the experimental period lasted for 42 days. The E. coli-infected group revealed a decrease in body performance parameters with a significant increase in the liver enzymes and renal function tests. The same group recorded a significant decrease in serum total proteins, albumins, and globulins, and the alteration of immunological parameters, antioxidant enzymes, oxidative stress parameters, and comet assay revealed highly damaged DNA in the liver and the intestine. By histopathological examination, a series of histopathological changes in the liver, the kidney, and the intestine were observed. The infected chick pretreated with probiotics or prebiotics demonstrated an improvement in body performance parameters besides a significant decrease in the hepatic enzymes and renal function tests. We noticed that, in treated groups, there was a significant increase in serum total proteins in the serum albumin and globulin levels, immunological parameters, and antioxidant enzymes. Furthermore, DNA damage and histopathological changes within hepatic, renal, and intestinal tissues were markedly diminished in the treated groups compared with the infected group. We concluded that the adverse effects of E. coli could be modulated through the chemopreventive administration of probiotics and prebiotics.

Ameliorative Effects of Bovine Lactoferrin on Benzene-Induced Hematotoxicity in Albino Rats.

Benzene (Bz) is one of the major products of the petrochemical industry globally, which induces aplastic anemia and leukemia in humans and animals. This study aimed to investigate the modulatory effects of bovine lactoferrin (bLf) on Bz-induced hematotoxicity in albino rats. Eighty male rats were randomly divided into eight groups: corn oil group [2 mL/kg body weight (BW)], bLf groups (100, 200, and 300 mg/kg BW), Bz group (Bz 2 mL/kg BW; corn oil 2 mL/kg BW), and Bz + bLf groups (Bz 2 mL/kg BW; corn oil 2 mL/kg BW; bLf 100, 200, and 300 mg/kg BW). Hematobiochemical results exhibited marked pancytopenia, a significant decrease in total protein, albumin, α2- and γ-globulin, ferritin, serum iron, and total iron-binding capacity (TIBC), and an increase in serum bioactivities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and erythropoietin hormone levels in Bz-treated rats. Histopathological examination revealed a marked reduction in all hematopoietic cell lines in the bone marrow (BM), necrosis in the white pulp of the spleen and cytosolic hydrops, and apoptosis of hepatocytes in the Bz-treated group. Rats treated with bLf (300 mg/kg BW) revealed marked increases in total protein, albumin, α2- and γ-globulin, ferritin, serum iron, and TIBC levels and decreases both in ALP and LDH bioactivities and erythropoietin hormone levels compared with the Bz-treated group. Histopathological results were concomitant with hematobiochemical parameters in rats treated with bLf (300 mg/kg BW), almost showing restoration of the normal cellularity of BM, the architecture of red and white pulps of the spleen, and even the normal hypertrophy of hepatocytes compared with the control groups. To conclude, bLf (300 mg/kg BW) can be recommended to treat Bz-induced hematotoxicity.