Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study.

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1ß, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

Ameliorative Potential of Bone Marrow-Derived Mesenchymal Stem Cells Versus Prednisolone in a Rat Model of Lung Fibrosis: A Histological, Immunohistochemical, and Biochemical Study.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown origin with limited treatment options and poor prognosis. The encouraging findings from preclinical investigations utilizing mesenchymal stem cells (MSCs) indicated that they could serve as a promising therapeutic alternative for managing chronic lung conditions, such as IPF. The objective of this study was to compare the efficiency of bone marrow-derived MSCs (BM-MSCs) versus prednisolone, the standard anti-inflammatory medication, in rats with bleomycin (BLM)-induced lung fibrosis. Four groups were created: a control group, a BLM group, a prednisolone-treated group, and a BM-MSCs-treated group. To induce lung fibrosis, 5 mg/kg of BLM was administered intratracheally. BLM significantly increased serum levels of pro-inflammatory cytokines and oxidative stress markers. The disturbed lung structure was also revealed by light and transmission electron microscopic studies. Upregulation in the immune expression of alpha-smooth muscle actin, transforming growth factor beta-1, and Bax was demonstrated. Interestingly, all findings significantly regressed on treatment with prednisolone and BM-MSCs. However, treatment with BM-MSCs showed better results than with prednisolone. In conclusion, BM-MSCs could be a promising approach for managing lung fibrosis.

Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study.

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant. Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001). Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.

Investigation and drug design for novel molecules from natural products as inhibitors for controlling multiple myeloma disease using in-silico tools.

Multiple myeloma (MM) is a disease that causes plasma cell growth in the bone marrow and immune globulin buildup in blood and urine. Despite recent advances in MM therapy, many still die due to its high mortality rate. A study using computational simulations analyzed 100 natural ingredients from the SANC database to determine if they inhibited the IgH domain, a known cause of multiple myeloma. Natural component Diospyrin inhibited the IgH enzyme with the best binding energy of -10.3 kcal/mol and three carbon-hydrogen bonds, followed by Parviflorone F complex with a binding energy of -10.1 kcal/mol and two conventional-hydrogen bonds. As a result, the Molecular Dynamic simulation was used to test the stability of the two complexes. During the simulation, the Diospyrin molecule dissociated from the protein at roughly 67.5 ns, whereas the Parviflorone F molecule stayed attached to the protein throughout. The latter was the subject of the investigation. The analysis of the production run data revealed that the Parviflorone F molecule exhibits a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The analysis of the production run data revealed that the Parviflorone F molecule exhibited a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The root mean square deviation (RMSD) plots for both the protein and complex showed a stable and steady average value of 4.4 Å for the first 82 nanoseconds of manufacture. As a result, the average value increased to 8.3 Å. Furthermore, the components of the binding free energy, as computed by MM-GBSA, revealed that the mean binding energy of the Parviflorone F molecule was -23.88 kcal/mol. Finally, after analyzing all of the examination data, Parviflorone F was identified as a powerful inhibitor of the IgH domain and hence of the MM disease, which requires further in-vivo conformation.Communicated by Ramaswamy H. Sarma.

Baicalin and lung diseases.

Studies focusing on natural products have been conducted worldwide, and the results suggest that their natural ingredients effectively treat a wide range of illnesses. Baicalin (BIA) is a glycoside derived from the flavonoid baicalein present in Scutellaria baicalensis of the Lamiaceae family. Interestingly, BIA has been shown to protect the lungs in several animal models used in numerous studies. Therefore, we fully analyzed the data of the studies that focused on BIA's lung protective function against various injuries and included them in this review. Interestingly, BIA exhibits promising effects against acute lung injury, lung fibrosis, pulmonary embolism, and lung remodelling associated with COPD, LPS, and paraquat insecticide. BAI exhibits anticancer activity against lung cancer. Additionally, BIA potently attenuates lung damage associated with infections. BIA primarily exerts its therapeutic effects by suppressing inflammation, oxidative stress immune response, and apoptosis pathways. Nrf2/HO-1, PI3K/Akt, NF-κB, STAT3, MAPKs, TLR4, and NLRP3 are important targets in the pulmonary therapeutic effects of BIA on different lung disease models. Consequently, we recommend using it in future potential clinical applications, its contribution to treatment guidelines, and translating its promising effects to clinical practice in lung diseases.

Vinpocetine mitigates methotrexate-induced duodenal intoxication by modulating NF-κB, JAK1/STAT-3, and RIPK1/RIPK3/MLKL signals.

OBJECTIVES: Methotrexate (MTX) is an antimetabolite agent widely used to manage a variety of tumors and autoimmune diseases. Nonetheless, MTX-induced intestinal intoxication is a serious adverse effect limiting its clinical utility. Inflammation and oxidative stress are possible mechanisms for MTX-induced intestinal toxicity. Vinpocetine (VNP) is a derivative of the alkaloid vincamine with potent anti-inflammatory and antioxidant effects. The current study investigated the protective intestinal impact of VNP in attenuating MTX-induced intestinal intoxication in rats. MATERIALS AND METHODS: VNP was administered orally in a dose of 20 mg/kg, while MTX was injected intraperitoneal in a dose of 20 mg/kg. RESULTS: VNP administration attenuated drastic histological changes induced by MTX and preserved both normal villus and crypt histology. VNP significantly attenuated oxidative injury by upregulating intestinal Nrf2 and HO-1 expression. VNP attenuated inflammation by reducing MPO, NO2-, TNF-α, and IL-1ß levels mediated by downregulating NF-κB, NDAPH-oxidase, IRF3, p-JAK-1, and p-STAT-3 expressions. Moreover, VNP potently counteracted intestinal necroptosis by effectively downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins. CONCLUSION: Therefore, VNP may represent a promising approach that can attenuate intestinal toxicity in patients receiving MTX.

Nrf2/HO-1 as a therapeutic target in renal fibrosis.

Chronic kidney disease (CKD) is one of the most prevalent chronic diseases and affects between 10 and 14 % of the world's population. The World Health Organization estimates that by 2040, the disease will be fifth in prevalence. End-stage CKD is characterized by renal fibrosis, which can eventually lead to kidney failure and death. Renal fibrosis develops due to multiple injuries and involves oxidative stress and inflammation. In the human body, nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the expression of antioxidant, anti-inflammatory, and cytoprotective genes, which prevents oxidative stress and inflammation damage. Heme oxygenase (HO-1) is an inducible homolog influenced by heme products and after exposure to cellular stress inducers such as oxidants, inflammatory chemokines/cytokines, and tissue damage as an outcome or downstream of Nrf2 activation. HO-1 is known for its antioxidative properties, which play an important role in regulating oxidative stress. In renal diseases-induced tissue fibrosis and xenobiotics-induced renal fibrosis, Nrf2/HO-1 has been targeted with promising results. This review summarizes these studies and highlights the interesting bioactive compounds that may assist in attenuating renal fibrosis mediated by HO-1 activation. In conclusion, Nrf2/HO-1 signal activation could have a renoprotective effect strategy against CKD caused by oxidative stress, inflammation, and consequent renal fibrosis.

Influence of dietary mannan-oligosaccharides supplementation on hematological characteristics, blood biochemical parameters, immune response and histological state of laying hens.

This study aimed to determine the influence of dietary mannan-oligosaccharides (MOS) on the immune system, hematological traits, blood biochemical parameters, and histological state of laying hens. At 34 wk of age, The Mandarah chicken strain's 120 laying hens and 12 cocks were divided into 4 groups, each with 30 hens and 3 cocks. The first group performed as a control group, which nourished on a basal diet. The second, third, and fourth experimental groups received 0.1, 0.2, and 0.5 g/kg of MOS and a base diet, respectively. Birds obtained MOS at numerous doses significantly (P ˂ 0.05) raised serum levels of immunoglobulin Y (IgY), immunoglobulin M (IgM), and avian influenza (AI) antibodies compared to control birds. Furthermore, adding MOS at a level of 0.1 g/kg diet significantly improved the immune response of the control group. Additionally, compared to the control group, treated birds with MOS at various dosages did not significantly enhance hematological parameters such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin, and hematocrit. Compared to control birds, birds fed MOS at all levels exhibited considerably lower serum cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values. Also, compared to other treated birds, MOS-treated birds displayed improved histological examination of the small intestine, isthmus, and testis compared to the control group, particularly in birds fed MOS at 0.1 and 0.2 g/kg diet. It could be concluded that using MOS at 0.1 or 2 g/kg diet can successfully improve the physiological performance and overall health of laying hens.

Lemongrass Essential Oil Attenuates Perfluorooctane Sulfonate-Induced Jejunal Mucosal Injury in Rat: A Histological, Immunohistochemical, and Biochemical Study.

Perfluorooctane sulfonate (PFOS) has harmful impacts on various organs, including the intestine. Lemongrass essential oil (LGEO) has anti-inflammatory, anti-oxidant, antibacterial, and immunomodulatory effects. This study investigated the impact of PFOS on the mucosa of the jejunum of rats and evaluated LGEO's protective impact. Four groups of rats were created: control, LGEO (100 mg/kg/day), PFOS (5 mg/kg/day), and LGEO-PFOS group. The agents were given orally for 28 days. Oxidative stress parameters, pro-inflammatory cytokines, and caspase-3 were measured in jejunal homogenates. Rat jejunal sections were evaluated histologically (light and electron microscopic examination) and immunohistochemically [for tumor necrosis factor-α (TNF-α), Proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), and Bcl2]. PFOS significantly elevated oxidative stress, pro-inflammatory cytokines, caspase-3, and gene expression of nuclear factor kappa B (NF-kB) and inducible nitric oxide synthetase (iNOS). The disturbed architecture of jejunal villi and crypts was demonstrated. Immunohistochemically, a significant rise in TNF-α, PCNA, and COX2 and a significant decrease in Bcl2 expression were revealed compared to control group. Further ultrastructural alterations included dilated RER, mitochondria with destroyed cristae, vacuolated cytoplasm, and shrunken condensed nuclei of enterocytes. LGEO treatment significantly reduced these harmful effects. LGEO protected against PFOS-induced jejunal damage by reducing the oxidative, inflammatory, and apoptotic impacts.

Quercetin Mitigates Oxidative Stress, Inflammation, Apoptosis, and Histopathological Alterations Induced by Chronic Titanium Dioxide Nanoparticle Exposure in the Rat Spleen.

Titanium dioxide nanoparticles (nano-TiO2) have become widespread but are accompanied by various health concerns. Quercetin (QT), a naturally occurring flavonoid in fruits and vegetables, exhibits potent antioxidant properties. This research examined the toxic impacts of nano-TiO2 on the structure and function of the spleen in adult male rats and assessed the possible protective effects of QT. A set of randomly grouped rats was established, consisting of a control group, a QT group (50 mg/kg/day), a nano-TiO2 group (300 mg/kg/day), and a QT-nano-TiO2 group. These substances were orally administered to the respective groups for 90 days. Nano-TiO2 significantly induced oxidative stress in the spleen, leading to reduced levels of serum immunoglobulins. Additionally, there was a notable increase in the expression of apoptotic markers and proinflammatory cytokines. These biochemical disturbances were accompanied by morphological changes in the spleens of rats exposed to nano-TiO2. However, coadministration of QT and nano-TiO2 effectively mitigated most nano-TiO2-induced alterations in the spleen, including apoptotic and proinflammatory responses, antioxidant imbalance, serum immunoglobulin levels, and histopathological changes. It can be concluded that QT has the potential to function as a protective agent against the detrimental impacts of nano-TiO2 on the spleen by improving the antioxidant defense mechanism and modulating the apoptotic and inflammatory responses.

Bone Marrow-Derived Mesenchymal Stem Cells and γ-Secretase Inhibitor Treatments Suppress Amyloid-ß25-35-Induced Cognitive Impairment in Rat Dams and Cortical Degeneration in Offspring.

Alzheimer's disease (AD) is the most frequent cause of age-related neurodegeneration and ensuing cognitive impairment. Progressive deposition of extracellular amyloid beta (Aß) aggregates (plaques) and intracellular hyperphosphorylated Tau protein (p-Tau) are the core pathological markers of AD but may precede clinical symptoms by many years, presenting a therapeutic window of opportunity. Females are more frequently afflicted by AD than males, necessitating evaluation of novel treatments for the female population. The current study examined the protective efficacies of intravenous bone marrow-derived mesenchymal stem cells (BM-MSCs) and oral gamma-secretase inhibitor-953 (GSI-953) during pregnancy on cognitive impairment in rat dams and neurodegeneration in offspring induced by intracerebroventricular injection of Aß25-35 prior to pregnancy. The Aß25-35 (AD) group exhibited significant (P < 0.001) impairments in the Y-maze and novel object recognition test performance prior to conception. Histological analysis of the offspring cortex revealed substantial dendritic shrinkage and activation of microglial cells, while neurochemical analysis demonstrated significant increases in the proinflammatory cytokine interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). In contrast, BM-MSC or GSI-953 treatment of dams following Aß25-35 injection significantly (P < 0.001) reduced the number and size of activated microglial cells, markedly increased dendrite length, and reversed proinflammatory cytokine elevations in offspring. Moreover, BM-MSC or GSI-953 treatment reversed the Aß25-35-induced amyloid precursor protein and p-Tau elevations in the offspring brain; these changes were accompanied by upregulation of the brain-derived neurotrophic factor and downregulation of glycogen synthase kinase-3ß in the serum and brain. Treatment with BM-MSCs or GSI-953 also reversed Aß25-35-induced elevations in different gene expressions in the neonatal cortex. Finally, treatment of dams with BM-MSCs or GSI-953 prevented the Aß25-35-induced disruption of newborn brain development. Thus, BM-MSC and GSI-953 treatments have broad-spectrum effects against Aß25-35-induced brain pathology, including the suppression of neural inflammation, restoration of developmental plasticity, and promotion of neurotrophic signaling.

Umbelliferone potentiates intestinal protective effect of Lactobacillus Acidophilus against methotrexate-induced intestinal injury: Biochemical and histological study.

Intestinal injury is a common adverse effect of methotrexate (MTX) therapy, limiting its clinical use. Despite oxidative stress and inflammation being the most embedded mechanism of injury, pharmacological agents that exhibit antioxidant and anti-inflammatory impacts could prevent such toxicities. This study aimed to assess the enteroprotective effect of lactobacillus acidophilus (LB) and/or umbelliferone (UMB) against MTX-induced intestinal injury. Histologically, pretreatment with LB, UMB, or their combinations preserve the intestinal histological structure and mucin content with superior effect in combination therapy. In addition, oral pretreatment with UMB, LB, or their combinations significantly restored oxidant/antioxidant status, as evidenced by the upregulation of Nrf2, SOD3, HO-1, GSH, and GST levels concurrent with a decline in MDA contents. Besides, they suppressed the inflammatory burden by inhibiting STAT3, MPO, TLR4, NF-κB, TNF-α, and IL-6 levels. Moreover, LB, UMB, or their combinations significantly upregulated Wnt and ß-catenin expression. Notably, pretreatment with the combination therapy is superior to monotherapy in protecting rats' small intestines from MTX-induced enteritis. In conclusion, combined pretreatment with LB and UMB could be a novel therapeutic regimen for conditions of intestinal injury induced by MTX via restoring oxidant/antioxidant balance and suppressing inflammatory burden.

Polystyrene microplastic particles induced hepatotoxic injury via pyroptosis, oxidative stress, and fibrotic changes in adult male albino rats; the therapeutic role of silymarin.

Microplastics (MPs) have become a worldwide issue because of their persistence in marine organisms, their accumulation in the food chains, and their inevitable human exposure. Silymarin is a therapeutic agent used in the treatment of multiple liver diseases. The study aimed to explore the potential therapeutic effect of 2 weeks of silymarin treatment against the effects of two sizes of 1 and 5 µm of polystyrene microplastic particles (PS-MPs) on the liver after 6 weeks of the study period. Animals were divided into negative and positive control, silymarin group (200 mg/kg), PS-MP groups of 1 and 5 µm size (0.02 mg/kg), 1 µm size PS-MPs + silymarin group, and 5 µm size PS-MPs + silymarin group, animals were treated once daily by oral gavage. The study revealed that hepatotoxicity induced by two diameters of PS-MPs with marked destructive effects of 1 µm size greater than that of 5 µm size and the effective therapeutic role of silymarin in improving PS-MPs caused hepatotoxic injury, particularly with 5 µm PS-MPs size; through regression of liver pathology (hepatic cell lysis, inflammation, fibrotic changes, and collagen deposition), restoring ultrastructure morphology (mitochondrial destruction and accumulation of lipid droplets accumulation). It improved liver function by reducing serum AST, ALT, LDH, total cholesterol, and triglycerides. It also reduced oxidative stress by reducing serum MDA, increasing TAC, down-regulation of iNOS, and up-regulation of Nrf2 and HO-1 hepatic gene expression. Furthermore, it relieved pyroptosis by negatively regulating the expression of the NLRP3, caspase-1, and IL-1ß hepatic gene expression. The results suggested silymarin's therapeutic effects in treating PS-MPs-induced hepatotoxic injury and recommended its use as a postexposure treatment for a longer duration.

Evening primrose oil attenuates oxidative stress, inflammation, fibrosis, apoptosis, and ultrastructural alterations induced by metanil yellow in the liver of rat: a histological, immunohistochemical, and biochemical study.

The food color metanil yellow (Myl) is hazardous to several body systems. Evening primrose oil (EPO) was reported to have anti-inflammatory and anti-oxidant properties. The present work investigated the impact of Myl on the hepatic structure and function of rats and evaluated the protective effect of EPO. Forty adult male rats were divided into four groups: control, EPO (5 g/kg/day), Myl (200 mg/kg/day), and EPO- Myl group. Myl significantly increased liver enzymes, advanced glycation end products (AGE), oxidative stress parameters, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS). Blood vessels in the liver were dilated and congested, with cellular infiltration around them and associated with fibrosis. The hepatocytes were vacuolated and had dark nuclei. The immunohistochemical expression of iNOS, glial fibrillary acidic protein (GFAP), and Bax was significantly elevated. Ultrastructurally, the hepatocytes showed lipid droplets, irregular condensed nuclei with widened perinuclear space, dilated rER, mitochondria with destructed cristae, and multiple vacuoles. Dilated congested blood sinusoids and collagen fiber bundles were seen between hepatocytes. Interestingly, these alterations were less pronounced in rats co-administrated with EPO and Myl. In conclusion, EPO can protect liver against the toxic effects of Myl due to its anti-inflammatory and anti-oxidant activities.

The neuroprotective effect of ginsenoside Rb1 on the cerebral cortex changes induced by aluminium chloride in a mouse model of Alzheimer's disease: A histological, immunohistochemical, and biochemical study.

Alzheimer's disease (AD) is one of the most common types of dementia among neurodegenerative disorders characterized by attention deficits and memory loss. Panax ginseng is a traditional Chinese herbal remedy that has been employed for millennia to manage dementia linked with aging and memory impairment. Ginsenoside Rb1 is one of Panax ginseng's most abundant components. The present work evaluated the neuroprotective effects of ginsenoside Rb1 on the cerebral cortex of AlCl3-induced AD in adult male albino mice. Forty male mice were alienated arbitrarily into; control group, ginsenoside Rb1 group (70 mg/kg/day), AlCl3 group (50 mg/kg/day), and ginsenoside Rb1-AlCl3 group that received ginsenoside Rb1 one hour before AlCl3. Oxidative stress parameters, Amyloid ß (Aß) and phosphorylated tau protein, and acetylcholine esterase (AChE) activity were measured. Cerebral cortex sections were evaluated histologically by light microscopic examination and immunohistochemistry. AlCl3-induced memory impairment, Aß and phosphorylated tau protein accumulation, and AChE elevation. Moreover, histopathological alterations in the cerebral cortex were reported in the form of irregular shrunken neurons and the surrounding neuropil showed vacuolation. Some neurons appeared with darkly stained nuclei, others had faintly stained ones. The synaptophysin expression was significantly decreased, while the expression of cleaved caspase-3, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) were significantly elevated. It's interesting to note that these changes were attenuated in mice pretreated with ginsenoside Rb1. Collected data indicated that ginsenoside Rb1 showed a potential neuroprotective effect against cerebral cortex changes caused by AlCl3 via suppression of Amyloid ß and phosphorylated tau protein formation, oxidative stress correction, anti-apoptotic effect, and by minimizing gliosis.

Effects of alginates on the growth, haematological, immunity, antioxidant and pro-inflammatory responses of rabbits under high temperature.

Heat stress (HS) is one of the most severe hurdles impacting rabbit growth, immunity, homeostasis, and productivity. Alginate oligosaccharides (AOS) have considerable beneficial effects due to their plausible antioxidant and immune-stimulatory properties. This work was planned to explore the preventive function of AOS as a new bio-feed additive against the harmful effects caused by environmental HS on growing rabbits. Rabbits were allotted in four experimental groups (25 animals in each group) and fed on a basal diet supplemented with 0.0 (AOS0), 50 (AOS50), 100 (AOS100), and 150 (AOS150) mg AOS/kg diet reared under summer conditions. Dietary AOS supplementation improved significantly (P ≤ 0.001) feed conversion rate, while both AOS100 and AOS150 significantly (P ≤ 0.001) enhanced the final body weight and body weight gain. All AOS addition significantly increased nitric oxide and lysosome activity and significantly reduced interferon-gamma (IFNγ) compared with those in the control group. Tumor necrosis factor α (TNFα), interleukin1ß (IL-1ß), myeloperoxidase and protein carbonyl levels were significantly reduced in rabbits fed diets containing AOS (100 and 150 mg/kg) compared with those in the control group under heat stress conditions. In addition, glutathione (GSH) and catalase (CAT) were significantly (P ≤ 0.001) improved with increasing AOS dietary levels compared with the control group. Still, total antioxidant capacity (TAC), malondialdehyde (MDA), hematocrit, mean corpuscular volume (MCV), eosinophils, and lymphocytes did not change. Erythrocyte's indices improved significantly (P ≤ 0.001), while neutrophils and white blood cell counts were decreased by dietary AOS inclusion. Immunological (IgM and IgG) were markedly reduced in AOS-treated groups compared with the control group. The current investigation exemplified that AOS as a novel bio-feed additive that could be an effective strategy to extenuate prejudicial effects in heat-stressed rabbits via enhancing immunity, and antioxidant defence system, further regulating the inflammation cytokines.

Impacts of synthetic androgen and estrogenic antagonist administration on growth performance, sex steroids hormones, and immune markers of male and female broilers.

The influence of synthetic androgen and estrogenic antagonists (Tamoxifen) on body characteristics and immune response of male and female broilers and the correlation between sex hormone levels were estimated in our experiment. One day old chicks were sexed, and chicks of each sex were randomly distributed on three experimental treatments; the first treatment group (TAM20) chicks were supplied with estrogenic antagonist tamoxifen citrate 20 mg/kg body weight through oral administration for four times every other day from third until ninth d; Androgen treatment chicks were injected intramuscular with veterinary androgen AD GAN@ (Boldenone Undecylenate 50 mg) 1 cm/10 kg body weight at fifth and ninth day, and the third treatment was control. Androgen treatment reported the highest feed intake with the lowest for TAM20 treatment. Concerning carcass characteristics, early androgen injection increased breast percentage significantly compared to TAM20 treatment. Androgen supplementation increased significantly comb the percentage. However, TAM20 decreased it particularly compared to control. Moreover, the percentage of comb and shanks was substantially higher for males than females. Concerning the effects of both treatments on sex hormones, androgen showed favorable effects on testosterone and estrogen compared to Tamoxifen 20 treatment. On the other hand, the administration of TAM 20 improves phagocytic activity compared to androgen administration.

Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat.

The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta's sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11-12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.

Pomegranate Pomace Extract with Antioxidant, Anticancer, Antimicrobial, and Antiviral Activity Enhances the Quality of Strawberry-Yogurt Smoothie.

Valorizing the wastes of the food industry sector as additives in foods and beverages enhances human health and preserves the environment. In this study, pomegranate pomace (PP) was obtained from the company Schweppes and exposed to the production of polyphenols and fiber-enriched fractions, which were subsequently included in a strawberry-yogurt smoothie (SYS). The PP is rich in carbohydrates and fibers and has high water-absorption capacity (WAC) and oil-absorption capacity (OAC) values. The LC/MS phenolic profile of the PP extract indicated that punicalagin (199 g/L) was the main compound, followed by granatin B (60 g/L) and pedunculagin A (52 g/L). Because of the high phenolic content of PP extract, it (p ≤ 0.05) has high antioxidant activity with SC50 of 200 µg/mL, besides scavenging 95% of DPPH radicals compared to ascorbic acid (92%); consequently, it reduced lung cancer cell lines' viability to 86%, and increased caspase-3 activity. Additionally, it inhibited the growth of pathogenic bacteria and fungi i.e., L. monocytogenes, P. aeruginosa, K. pneumonia, A. niger, and C. glabrata, in the 45-160 µg/mL concentration range while killing the tested isolates with 80-290 µg/mL concentrations. These isolates were selected based on the microbial count of spoiled smoothie samples and were identified at the gene level by 16S rRNA gene sequence analysis. The interaction between Spike and ACE2 was inhibited by 75.6%. The PP extract at four levels (0.4, 0.8, 1.2, and 1.4 mg/mL) was added to strawberry-yogurt smoothie formulations. During 2 months storage at 4 °C, the pH values, vitamin C, and total sugars of all SYS decreased. However, the decreases were gradually mitigated in PP-SYS because of the high phenolic content in the PP extract compared to the control. The PP-SYS3 and PP-SYS4 scored higher in flavor, color, and texture than in other samples. In contrast, acidity, fat, and total soluble solids (TSS) increased at the end of the storage period. High fat and TSS content are observed in PP-SYS because of the high fiber content in PP. The PP extract (1.2 and 1.6 mg/mL) decreases the color differences and reduces harmful microbes in PP-SYS compared to the control. Using pomegranate pomace as a source of polyphenols and fiber in functional foods enhances SYS's physiochemical and sensory qualities.

Evaluation of Green Silver Nanoparticles Fabricated by Spirulina platensis Phycocyanin as Anticancer and Antimicrobial Agents.

Green nanotechnology has attracted attention worldwide, especially in treating cancer and drug-resistant section 6 microbes. This work aims to investigate the anticancer activity of green silver nanoparticles synthesized by Spirulina platensis phycocyanin (SPAgNPs) on two cancer cell lines: Lung cancer cell line (A-549) and breast cancer cell line (MCF-7), compared to the normal human lung cell line (A138). We also aimed to investigate the bactericidal activity against Staphylococcus aureus ATCC29737, Bacillus cereus ATCC11778, Escherichia coli ATCC8379, and Klebsiella pneumonia, as well as the fungicidal activity against Candida albicans (ATCC6019) and Aspergillus niger. The obtained SPAgNPs were spherical and crystalline with a size of 30 nm and a net charge of -26.32 mV. Furthermore, they were surrounded by active groups responsible for stability. The SPAgNPs scavenged 85% of the DPPH radical with a relative increase of approximately 30% over the extract. The proliferation of cancer cells using the MTT assay clarified that both cancer cells (A-549 and MCF-7) are regularly inhibited as they grow on different concentrations of SPAgNPs. The maximum inhibitory effect of SPAgNPs (50 ppm) reached 90.99 and 89.51% against A-549 and MCF7, respectively. Regarding antimicrobial activity, no inhibition zones occurred in bacterial or fungal strains at low concentrations of SPAgNPs and the aqueous Spirulina platensis extract. However, at high concentrations, inhibition zones, especially SPAgNPs, were more potent for all tested microorganisms than their positive controls, with particular reference to Staphylococcus aureus, since the inhibition zones were 3.2, 3.8, and 4.3 mm, and Bacillus cereus was 2.37 mm when compared to tetracycline (2.33 mm). SPAgNPs have more potent antifungal activity, especially against Aspergillus niger, compared to their positive controls. We concluded that SPAgNPs are powerful agents against oxidative stress and microbial infection.