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High-fat (HF) diets are often used in aquaculture as a nonprotein energy source, resulting in lower feed costs and nitrogen emissions. However, high-fat diets have a deleterious influence on aquatic species' metabolic and immunological functioning. Thereby, bile acid (BA) is proposed to relieve the lipid metabolism dysfunction, oxidative stress, and malnutrition caused by HF. In this study, Nile tilapia (4.97 ± 0.34 g) were distributed in six groups in triplicates and stocked in fifteen 100 L plastic tanks. Fish offered six isonitrogenous test diets for 60 days: the control (6 % fat) without BA (LF) and five HF (12 % fat) diets supplemented with BA at 0, 0.05, 0.1, 0.15, and 0.2 g/kg. The results indicated that the HF diet lowered growth, feed efficiency, and survival rates. Furthermore, the fish-fed high-fat diet demonstrated reduced digestive enzyme activity (lipase and amylase), growth hormone (GH), and antioxidative responses (SOD, CAT, and GPx). The intestine of tilapia-fed HF showed also impaired histomorphological features such as reduced villi length and width. However, supplementation of BA in HF diets improved intestinal and villi architecture. The HF diet without BA supplementation revealed massive hepatic steatosis pancreatic vascular congestion and a high necrotic pancreatic cells number. While supplementing BA in HF diets enhanced pancreatic architecture and decreased necrotic hepatocytes. Fish-fed HF diet also showed increased total cholesterol, triglycerides, glucose, ALP, and AST levels as well as the malondialdehyde level (MDA). On the other hand, fish-fed LF and HF/BA diets showed improved growth performance, lipase and amylase, GH, SOD, CAT, and GPx, and intestinal histo-morphology and reduced glucose, leptin, and MDA levels. Dietary BA at 0.15–0.2 g/kg improved the digestion, and antioxidative capacity. In conclusion, dietary BA is required to mitigate the negative impacts of high-fat diets on Nile tilapia growth performance, general health, and antioxidative response.

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.

Abstract Chronic immobilization stress plays a key role in several neuropsychiatric disorders. This investigation assessed the possible ameliorative effect of chia seed oil (CSO) against the neurodisturbance-induced in rats by chronic immobilization. Rats were randomly allocated into control, CSO (1 ml/kg b.wt./orally), restrained (6 h/day), CSO pre-restraint, and CSO post-restraint for 60 days. Results revealed a significant reduction in serum corticosterone level, gene expression of corticotrophin-releasing factor, pro-inflammatory cytokines, and oxidative biomarkers in restrained rats treated with CSO. The histopathological findings revealed restoring necrosis and neuronal loss in CSO-treated-restraint rats. The immunohistochemical evaluation revealed a significant reduction in the immuno-expression of caspase-3, nuclear factor kappa B, interleukin-6, and cyclooxygenase-2 (COX-2), and an elevation of calbindin-28k and synaptophysin expression compared to non-treated restraint rats. The molecular docking showed the CSO high affinity for several target proteins, including caspase-3, COX-2, corticotropin-releasing hormone binding protein, corticotropin-releasing factor receptors 1 and 2, interleukin-1 receptor types 1 and 2, interleukin-6 receptor subunits alpha and beta. In conclusion, CSO emerges as a promising candidate against stress-induced brain disruptions by suppressing inflammatory/oxidative/apoptotic signaling pathways due to its numerous antioxidant and anti-inflammatory components, mainly α-linolenic acid. Future studies are necessary to evaluate the CSO therapeutic impacts in human neurodisturbances.

Abstract The reproductive activity of the male dromedary camel (Camelus dromedarius) as a seasonal breeder is affected by various seasonal changes that reflect on the reproductive performance. In the current study, we explored a differential cellular localization of lectins in eight dromedary camel testes utilizing lectin histochemistry (LHC). The glycoconjugates’ localizations were detected within the testicular tissue utilizing 13 biotin-labeled lectins (PNA, ConA, LCA, RCA120, GS IB4, WGA, BPL, DBA, ECA, PHA-E4, UEA-1, PTL-II, and SBA) distributed into six sets. The cellular structures revealed diverse lectins distribution that may reflect various glycoproteins’ structures and their compositional modifications during spermatogenesis. Some of the investigated lectins were restricted to acrosomes of spermatids that will help study different stages during the spermatogenic cycle of dromedary camel, particularly PNA, and ECA. The statistical analysis showed a marked positive correlation between the response intensity of various lectins and the breeding season (P

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.

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools.Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models.Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection.Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of β-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis.

Heat stress (HS) is still the essential environmental agent influencing the poultry industry. Research on HS in poultry has progressively acquired growing interest because of increased attention to climate alteration. Poultry can survive at certain zone of environmental temperatures, so it could be considered homoeothermic. In poultry, the normal body temperature is essential to enhance the internal environment for growth, which is achieved by normal environmental temperature. Recently, many studies have revealed that HS could cause mitochondrial dysfunction in broilers by inducing redox dysfunction, increasing uncoupling protein, boosting lipid and protein oxidation, and oxidative stress. Moreover, HS diminished the energy suppliers supported by mitochondria activity. A novel strategy for combating the negative influences of HS via boosting the mitochondria function through enrichment of the diets with mitochondria enhancers was also described in this review. Finally, the current review highlights the mitochondria dysfunction induced by HS in broilers and attempts to boost mitochondria functionality by enriching mitochondria enhancers to broiler diets.

Abstract Background Propolis extracted from beehives has been conferred with natural antimicrobial and antioxidant properties. Hence, it has been recommended as a wound healing therapy. This study investigated the additive value of nanotechnology to the herbal extract, (propolis rebuts), after which we examined its efficacy in wound healing. Methods Propolis nanostructured lipid carriers (NLCs) were first prepared using the emulsion-evaporation-solidification method at three concentrations. Then, we compared their flavonoid and phenolic contents and phenolic contents. Their antioxidant, antibacterial, and antifungal effects were also investigated after which, the skin regenerative capacity of propolis-NLCs was assessed using full-thickness skin wounds in rabbits. Results This study showed that propolis-NLCs had increased the phenolic and flavonoid contents compared to the raw propolis extract (EXTR) (9-fold and 2-fold, respectively). This increase was reflected in their antioxidant activities, which dramatically increased by 25-fold higher than the propolis-EXTR. Also, propolis-NLCs exhibited a 2-fold higher potent inhibitory effect than propolis-EXTR on Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacterium (Salmonella spp.), and fungus (Candida albicans) microbes (p

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4’s genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4’s connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4’s carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.

ABSTRACT: The alimentary tract in chickens plays a crucial role in immune cell formation and immune challenges, which regulate intestinal flora and sustain extra-intestinal immunity. The interaction between pathogenic microorganisms and the host commensal microbiota as well as the variety and integrity of gut microbiota play a vital role in health and disease conditions. Thus, several studies have highlighted the importance of gut microbiota in developing immunity against viral infections in chickens. The gut microbiota (such as different species of Lactobacillus, Blautia Bifidobacterium, Faecalibacterium, Clostridium XlVa, and members of firmicutes) encounters different pathogens through different mechanisms. The digestive tract is a highly reactive environment, and infectious microorganisms can disturb its homeostasis, resulting in dysbiosis and mucosal infections. Avian influenza viruses (AIV) are highly infectious zoonotic viruses that lead to severe economic losses and pose a threat to the poultry industry worldwide. AIV is a challenging virus that affects gut integrity, disrupts microbial homeostasis and induces inflammatory damage in the intestinal mucosa. H9N2 AIV infection elevates the expression of proinflammatory cytokines, such as interferon (IFN-γ and IFNα) and interleukins (IL-17A and IL-22), and increases the proliferation of members of proteobacteria, particularly Escherichia coli. On the contrary, it decreases the proliferation of certain beneficial bacteria, such as Enterococcus, Lactobacillus and other probiotic microorganisms. In addition, H9N2 AIV decreases the expression of primary gel-forming mucin, endogenous trefoil factor family peptides and tight junction proteins (ZO-1, claudin 3, and occludin), resulting in severe intestinal damage. This review highlights the relationship among AIV, gut microbiota and immunity in chicken.

ABSTRACT: Prevention of necrotic enteritis (NE), caused by Clostridium perfringens (C. perfringens), is one of the most important goals to improve the profitability of broiler chickens. This work aimed to compare the efficacy of 2 antibiotic alternatives including a postbiotic (dry feed additive and aqueous nonviable Lactobacillus (L.) species fermentation) and a probiotic (dry feed additive and aqueous Bacillus (B.) subtilis and B. lischeniformis mixture) with an antibiotic (amoxicillin in water) against NE. Four hundred, day-old broiler chicks were divided into 8 equal groups (Gs), n = 50 each (5 replicates; 10 each). Chickens of G1 (postbiotic dry-feed additive), G2 (postbiotic and antibiotic in drinking water), G3 (postbiotic dry and aqueous), G4 (probiotic dry-feed additive), G5 (probiotic and antibiotic in drinking water), G6 (probiotic dry and aqueous), and G7 (nontreated) were orally inoculated with a toxigenic C. perfringens type A on the d 19 to 21 of age and predisposed with 3X coccidial vaccine for induction of NE. However, chickens of G8 were kept nontreated or challenged. The severity of NE signs was markedly decreased in G3 in comparison with other challenged treatment groups, and the mortality rates were 22%, 10%, 16%, 22%, 12%, 20%, and 36% in Gs 1, 2, 3, 4, 5, 6, and 7, respectively. The best significant (P ≤ 0.05) feed conversion ratio was detected in G3 (1.51), G6 (1.54), and G2 and G8 (1.61). In addition, the European production efficiency factor was significantly (P ≤ 0.05) improved in G3 (279.33) and G2 (266.67), but it was decreased in G7 (177.33) when compared with G8 (339.33). An improvement in intestinal and hepatic pathology and liver function tests, as well as a significant (P ≤ 0.05) decrease in bacterial counts were observed in Gs 2, 5, 3, 6, 1, and 4, respectively in comparison with G7. Immunologically, the highest significant (P ≤ 0.05) hemagglutination inhibition antibody titers for Newcastle disease virus vaccine were in Gs 1 and 3 (6.4 log2). In conclusion, the combined feed and water postbiotic treatment demonstrated promising results in ameliorating the severity of NE and improving the hepatic and the immune status of broiler chickens when compared with the commonly used probiotic and antibiotic.

L-theanine (γ-Glutamylethylamide) is a nonprotein water soluble amino acid (AA) mostly found in leaves of Camellia sinensis (green tea). This is a key component of green tea and is considered as the most abundant form of total AAs in green tea (i.e., about 50%). L-theanine is an exclusive taste ingredient of tea producing an attractive flavor and aroma in tea. It has biological effects such as antioxidant, growth promoter, immune booster, anti-stresser, hepatoprotective, antitumor, antiaging, antimicrobial, anti-inflammatory, and antianxiety activities that are worth noticing. It could reduce the oxidative impairment by reducing the synthesis of reactive oxygen species, oxidative parameters, and lipid damage as well as increasing the activity of antioxidant enzymes. The oral ingestion of L-theanine enhanced γδ T-cell proliferation. Therefore, it is being considered an essential compound of green tea that has the ability to improve immune function. The L-theanine can be used as a potential treatment for hepatic injury and immune-related liver diseases via the downregulation of the inflammatory response through the initiation of nitric oxide synthesis and glutathione production which are likely to be critical for the control of hepatic diseases as well as for the improvement of immune function. In addition, it could be used as a best natural feed additive with a potent antistressor by decreasing the levels of corticosterone, dopamine, and noradrenaline. After systematically reviewing the literature, it is noticed that most studies were carried out on mice, pig, human, and butterfly; while dietary supplementation studies of L-theanine in animal and poultry especially among broilers are very limited because of less awareness of this AA. So, the aim of this review is to encourage the veterinarian and poultry researchers to conduct more research at the molecular level about this AA to expose its more beneficial effects and its mechanism of absorption for potential use of this unique green tea AA in poultry nutrition.

Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

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.

In aquaculture, fish are stressed with several factors involved in impacting the growth rate and health status. Although Nile tilapia can resist brackish water conditions, hypoxia status may impair the health condition of fish. Nile tilapia were exposed to salinity water at 0, 10, and 20‰ for four weeks then the growth behavior was checked. The results showed meaningfully lowered growth rate, feed utilization, and survival rate when fish kept in 20‰ for four weeks. Then fish were subdivided into six groups (factorial design, 2 × 3) in normoxia (DO, 6 mg/L) and hypoxia (DO, 1 mg/L) conditions for 24 h. High salinity (10 and 20‰) combined with hypoxia stress-induced inflammatory features in the intestines, gills, and livers of fish. The activities of SOD, CAT, and GPX were increased in the intestines, gills, and livers of fish grown in 10 and 20‰ and exposed with hypoxia stress. Fish grown in 20‰ and stressed with hypoxia had the highest ALT, AST, and ALP levels (p

Doxorubicin (Dox) induces senescence in numerous cancer cell types, but these senescent cancer cells relapse again if they are not eliminated. On this principle, we investigated the apoptotic effect of thymoquinone (TQ), the active ingredient of Nigella sativa seeds and costunolide (COS), the active ingredient of Costus speciosus , on the senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells to rapidly eliminate the senescent cancer cells. The senescence markers of Sen-HCT116 and Sen-MCF7 were determined by a significant decrease in bromodeoxyuridine (BrdU) incorporation and significant increases in SA-β-gal, p53, and p21 levels. Then proliferative, Sen-HCT116, and Sen-MCF7 cells were subjected to either TQ (50 µM) or COS (30 µM), the Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), caspase 3 mRNA expression and its activity were established. Results revealed that TQ significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ, MCF7 + TQ, and MCF7 + Dox5 + TQ compared with their corresponding controls. COS significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ and MCF7 + Dox5 + TQ compared with their related controls. Also, TQ and COS were significantly increased caspase 3 activity and cell proliferation of Sen-HCT116 and Sen-MCF7. The data revealed a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.

While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated by utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF which was conjugated to RST, forming core shell nanohybrids into which HK was physically loaded, followed by cross linking using genipin. The crosslinked HK-loaded PMT–ALG/LF–RST nanohybrids exhibited a fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an eight-fold decrease in the IC50 compared to the free drug combination, in addition to showing an enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for an effective breast tumor suppression.

There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.

Quercetin was fed to groups of broiler chickens at concentrations of 200, 400, and 800 ppm, and a control group was supplemented with a basal diet. Results revealed that quercetin dietary supplementation numerically improved the growth performance traits and significantly increased (p < 0.05) the European production efficiency factor (EPEF) in the 200 ppm group. The total coliforms and Clostridium perfringens were decreased (p < 0.05) in quercetin-supplemented groups. Conversely, Lactobacillus counts were increased (p < 0.05), due to improvement of the gut microbiota environment in quercetin-supplemented groups. Moreover, the mRNA expression of intestinal Cu/Zn-superoxide dismutase (SOD1), glutathione peroxidase (GSH-Px) and nutritional transporters, including glucose transporter 2 (GLUT2), peptide transporter 1 (PEPT1), and fatty acid synthase (FAS) genes, were significantly upregulated in quercetin-supplemented groups. Quercetin enhanced intestinal morphometry. We can suggest quercetin supplementation in broiler chickens by levels between 200 and 400 ppm to enhance their development and gut environment.

In the present study, fish were exposed to sub-lethal doses of CuONPs (68.92 ± 3.49 nm) (10 mg/L, 20 mg/L, and 50 mg/L) for a long exposure period (25 days). Compared to the control group (0.0 mg/L CuONPs), a significant dose-dependent elevation in blood urea and creatinine values, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase enzyme activities were evident in CuONPs-exposed groups (p < 0.05). Fish exposure to 50 mg/L CuONPs significantly upregulated the transcription of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin 12, and interleukin 8), heat shock protein 70, apoptosis-related gene (caspase 3), and oxidative stress-related (superoxide dismutase, catalase, and glutathione peroxidase) genes in liver and gills of the exposed fish in comparison with those in the control group (p < 0.05). Moreover, varying histopathological injuries were noticed in the hepatopancreatic tissues, posterior kidneys, and gills of fish groups correlated to the tested exposure dose of CuONPs. In summary, our results provide new insights and helpful information for better understanding the mechanisms of CuONPs toxicity in Nile tilapia at hematological, molecular levels, and tissue levels.

The current investigation assessed the impacts of sub-lethal concentrations of silicon dioxide nanoparticles (SiO2NPs) on hepato-renal functions, histopathological characteristics, and gene transcription in gills and liver of Nile tilapia juveniles. Fish were exposed to 20, 40, and 100 mg/L of SiO2NPs for 3 weeks. Pairwise comparisons with the control group showed a significant dose-dependent elevation in serum ALP, ALT, and AST enzyme activities as well as blood urea and creatinine levels in SiO2NP-intoxicated groups. Exposure to 100 mg/L SiO2NPs significantly upregulated expression of HSP70, TNF-α, IL-1β, and IL-8 genes in the gills as compared to the control group. Moreover, exposure to 100 mg/L SiO2NPs significantly upregulated the expression SOD, HSP70, IL-1β, IL-8, and TNF-α genes in the hepatic tissues as compared to the control group. Exposure of fish to 20 mg SiO2NPs/L significantly increased the mRNA expression levels of IL-12 in both the gills and liver tissues. Notably, all tested SiO2NP concentrations significantly upregulated the transcription of CASP3 gene in gills and liver of Nile tilapia as compared to the control group. Interestingly, varying histopathological alterations in renal, hepatopancreatic, and branchial tissues were observed to be correlated to the tested SiO2NP concentrations. In conclusion, our results provide additional information on the toxic impacts of SiO2NPs in Nile tilapia at the hematological, tissue, and molecular levels.

Insects could be a potential replacement of protein-rich ingredients in poultry diets. Among these insects, black soldier fly (BSF), Hermetia illucens, has a high content of protein and fat, which reinforces the potential of using it in poultry feed formulation and makes it one of the most promising insect species for commercial production. Protein content as well as amino acid profile in H. illucens larvae is comparable to those in many protein-rich feedstuffs such as fish meal and soybean meal. BSF can convert organic wastes into a precious source of nutrients, such as proteins, lipids, and chitin, which contribute to reducing the environmental burden and pollution potential arising from organic waste accumulation. This review emphasizes the significance of this insect as a “green” technology in the extremely variable recycling of organic waste and generates a sustainable protein source as well as the importance of its use as a substitute of protein-rich feedstuff in poultry feed manufacturing.

Fipronil (FIP) is an insecticide commonly used in many fields, such as agriculture, veterinary medicine, and public health, and recently it has been proposed as a potential endocrine disrupter. The purpose of this study was to inspect the reproductive impacts of FIP and the possible protective effects of cerium nanoparticles (CeNPs) on male albino rats. Rats received FIP (5 mg/kg bwt; 1/20 LD50), CeNPs (35 mg/kg bwt) and FIP+CeNPs per os daily for 28 days. Serum testosterone levels, testicular oxidative damage, histopathological and immunohistochemical changes were evaluated. FIP provoked testicular oxidative damage as indicated by decreased serum testosterone (≈60%) and superoxide dismutase (≈50%), glutathione peroxidase activity (≈46.67%) and increased malondialdehyde (≈116.67%) and nitric oxide (≈87.5%) levels in testicular tissues. Furthermore, FIP induced edematous changes and degeneration within the seminiferous tubules, hyperplasia, vacuolations, and apoptosis in the epididymides. In addition, FIP exposure upregulated interleukin-1β (IL-1β), nitric oxide synthase 2 (NOS), caspase-3 (Casp3) and downregulated the Burkitt-cell lymphomas (BCL-2), inhibin B proteins (IBP), and androgen receptor (Ar) mRNA expressions Casp3, nitric oxide synthase (iNOS), ionized calcium-binding adapter molecule 1(IBA1), and IL-1β immunoreactions were increased. Also, reduction of proliferating cell nuclear antigen (PCNA), mouse vasa homologue (MVH), and SOX9 protein reactions were reported. Interestingly, CeNPs diminished the harmful impacts of FIP on testicular tissue by decreasing lipid peroxidation, apoptosis and inflammation and increasing the antioxidant activities. The findings reported herein showed that the CeNPs might serve as a supposedly new and efficient protective agent toward reproductive toxicity caused by the FIP insecticide in white male rats.

Salinity is a reliable issue of crop productivity loss in the world and in certain tropical and subtropical zones. However, tremendous progress in the genetic improvement of plants for salinity tolerance has been made over several decades. In light of this, halophytic plants can be used as animal feeds and have promising features because they are a good feed resource. However, the main constraint of saline pasture systems is the extreme concentration of NaCl salt in drinking water and forage plants for grazing animals. Ecological reports revealed that excess diet salt causes mortality and morbidity worldwide. Animal fed halophytic forages may have adverse effects on growth performance and reproductive function in males and females due to inducing reductions in hormone regulation, such as testosterone, FSH, LH, and leptin. It was indicated that high salt intake promotes circulating inflammatory factors in the placenta and is associated with adversative effects on pregnancy. This review focuses on the scientific evidence related to the effect of high salt intake on growth performance, spermatogenesis, sperm function, and testicular morphology changes in male animals. In addition, the review will also focus on its effect on some female reproductive features (e.g., ovarian follicle developments, placental indices, and granulosa cell function).

Retinoic acid (RA) is an indigenous metabolite and descriptive physiologically functioning constituent of vitamin A. Retinoids were documented as vital regulators for cell development and distinction, embryonic growth, and reproductive function in both male and female livestock. Previously, RA has been shown to have several positive impacts in vivo and in vitro and critically control many reproductive events, such as oocyte development, follicular growth, and early embryonic growth. In addition, RA manages apoptotic signaling and oxidative damages in cells. Recently, RA has been used widely in assisted reproductive technology fields, especially during in vitro embryo development in various mammalian species, including buffaloes, bovine, goats, sheep, pigs, and rabbits. However, the optimum concentration of RA greatly differs based on the condition of maturation media and species. Based on the obtained findings, it was generally accepted that RA enhances nuclear oocyte maturation, cleavage and maturation rates, blastocyst formation, and embryo development. As such, it possesses antioxidant properties against reactive oxygen species (ROS) and an anti-apoptotic effect through enhancing the transcription of some related genes such as superoxide dismutase, prostaglandin synthase, glutathione peroxidase, peroxiredoxins, and heme oxygenase. Therefore, the current review concludes that an addition of RA (up to 50 nM) has the potential to improve the oocyte maturation media of various species of livestock due to its antioxidant activity.

Elite camels often suffer from massive injuries. Thus, there is a pivotal need for a cheap and readily available regenerative medicine source. We isolated novel stem-like cells from camel skin and investigated their multipotency and resistance against various stresses. Skin samples were isolated from ears of five camels. Fibroblasts, keratinocytes, and spheroid progenitors were extracted. After separation of different cell lines by trypsinization, all cell lines were exposed to heat shock. Then, fibroblasts and dermal cyst-forming cells were examined under cryopreservation. Dermal cyst-forming cells were evaluated for resistance against osmotic pressure. The results revealed that resistance periods against trypsin were 1.5, 4, and 7 min for fibroblasts, keratinocytes, and spheroid progenitors, respectively. Furthermore, complete recovery of different cell lines after heat shock along with the differentiation of spheroid progenitors into neurons was observed. Fibroblasts and spheroid progenitors retained cell proliferation after cryopreservation. Dermal cyst-forming cells regained their normal structure after collapsing by osmotic pressure. The spheroid progenitors incubated in the adipogenic, osteogenic, and neurogenic media differentiated into adipocyte-, osteoblast-, and neuron-like cells, respectively. To the best of our knowledge, we isolated different unique cellular types and stem-like cells from the camel skin and examined their multipotency for the first time.