New insights on testicular cancer prevalence with novel diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. RECENT FINDINGS: Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. CONCLUSION: TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

Effects of ginger extract and/or propolis extract on immune system parameters of vaccinated broilers.

Newcastle disease (ND), avian influenza (AI, H5N8), and infectious bronchitis (IB) are important diseases in the poultry industry and cause significant losses. Vaccination is the most practical method for controlling infectious diseases. To reduce vaccination costs and several disorders in poultry farms, using herbal water supplements for immunomodulation with vaccination is critical to improving or preventing some conditions in the poultry industry. However, drinking water supplementation of ginger extract (GE)/propolis extract (PE) alone/in combination may increase broilers' humoral and cellular immunity due to the immunomodulatory effects of ginger and propolis. This protocol aimed to see how GE/PE alone or in combination improved the immunity, immune organ gene expression, and histology of the immune organs of broilers for 35 d after vaccination against NDV, H5N8, IBV, and IBDV. The chicks were dispensed into 5 groups according to GE and/or PE with vaccination. The control group was offered normal drinking water without any supplements or vaccinations. The GE group was supplemented with ginger extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The GE+PE group was supplemented with GE (0.5 mL/L drinking water) and PE (0.5 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The PE group was supplemented with propolis extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The fifth group was the vaccinated untreated group. This experiment showed the immunomodulatory properties of GE and/or PE against 3 common diseases, NDV, AI, and IB, in broiler chicken farms for 35 d applied to a vaccination program. Thus, ginger extract and propolis extract supplementation in drinking water increased antibody titer, INF, IL10, and IL2 and TLR3 gene expression in the bursa of Fabricius, thymus, and spleen, respectively, as well as cellular immunity as indicated by increased CD3, CD4, and CD8 in the bursa of Fabricius, thymus, and spleen, respectively, with normal lymphocytes in the medulla of the bursa, thymus, and spleen. In conclusion, propolis extracts alone or with GE improved all of the metrics mentioned above without harming the histology of the immune organs.

Biophysical, histological, and bioaccumulation properties of Tilapia muscle affected by water pollution with heavy elements and microbes at the El-Rahawy drain in Egypt.

The leakage of sewage and agricultural drains has led to the contamination of freshwater branches with toxic heavy elements. This raises concerns about their toxic effects on aquatic ecosystems, especially on fish. Tilapia is regarded as an important protein source in Egypt and many other countries. The biophysical, nutritional, and histological aspects of water pollution in the El-Rahawy and Al-Qatta locations of the Nile on Nilotic tilapia muscle were evaluated by assessing the level of contamination of Nilotic tilapia fish. The current study showed that water of the Rosetta branch water was polluted with a very high level at El-Rahawy Drain discharge (RD) location, and with a high level at Al-Qatta (Q) location, while El-Rahawy (R) location was polluted with a lower level. The study traced the pollution effects on Tilapia (Nilotic) muscles in the previous locations. Bioaccumulation factor (BAF) showed a high value of all heavy metals in Tilapia muscle at the Q and R locations. Contrary to what was expected, discharge (RD) location contamination caused BAF increment of heavy metals in Tilapia muscles at upstream R location. All these results were compared with measured dielectric parameters of Tilapia muscle samples in the frequency range (0.02-1000) kHz. There was an increase in conductivity (σac), dielectric constant (ε'), dielectric loss (ε″), penetration depth (dp), and dissipated power (PD) values of Tilapia muscle, with increasing pollution level. The values of permittivity at low and high frequencies (ε's & ε'∞) for Tilapia muscle decreased by increasing pollution. Finally, the variation of these parameters, based on that proportionality relationship, can be considered as a physical indicator for fish contamination affected by their environment pollution, although these parameters need further studies in a controlled (qualitatively and quantitatively) polluted media.

Vitamin D regulates insulin and ameliorates apoptosis and oxidative stress in pancreatic tissues of rats with streptozotocin-induced diabetes.

This study was designed to evaluate the potential therapeutic efficacy of vitamin D (Vit D) in averting the harmful effects of type 2 diabetes mellitus (T2D). Forty male Wistar rats were allotted into four groups: (1) the control, (2) Vit D, (3) streptozotocin (STZ), and (4) STZ + Vit D groups. Rats co-treated with Vit D had significantly (p < 0.05) decreased levels of cortisol; proinflammatory cytokines, including interleukin-6 (IL-6); and malondialdehyde (MDA). Meanwhile, the levels of insulin significantly (p < 0.05) increased, whereas the activity of the antioxidant system, including glutathione (GSH), superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC), significantly (p < 0.05) decreased. Histopathological examination revealed the destruction of beta cells in the islets of Langerhans in rats with diabetes. Meanwhile, immunoexpression revealed an increase in the immunoreactivity of caspase-3 and endothelial nitric oxide synthase and a reduction in the immunoreactivity of insulin in rats with diabetes. In conclusion, Vit D ameliorated the harmful biochemical impact of diabetes mellitus, probably by increasing insulin secretion and sensitivity, ameliorating ß-cell function, and decreasing cortisol levels; also, the anti-inflammatory effect of Vit D reduces the number of proinflammatory cytokines (e.g., IL-6) and increases the activity of the antioxidant system, such as GSH, SOD, TAC, and catalase while reducing lipid peroxidation enzymes (e.g., MDA).

Biochemical, molecular and cytological impacts of alpha-lipoic acid and Ginkgo biloba in ameliorating testicular dysfunctions induced by silver nanoparticles in rats.

Silver nanoparticles (AgNPs) are commonly utilized in medicine. However, they have negative effects on the majority of organs, including the reproductive system. AgNPs were reported to be able to reach the testicular tissues due to their nano size, which allows them to pass through blood-testicular barriers. The goal of this study was to see if alpha-lipoic acid (LA) or Ginkgo biloba (GB) might protect adult rat testes after intraperitoneal injection of AgNPs. Forty male healthy adult Wister albino rats were randomly assigned to four groups: control, AgNPs-intoxicated group intraperitoneally injected AgNPs 50 mg/kg b.w, 3 times a week; LA + AgNPs group intoxicated with AgNPs and orally gavaged with 100 mg LA/kg b.w; and GB + AgNPs group injected with AgNPs and orally given GB extract 120 mg/kg b.w for 30 consecutive days. Biochemical changes (testosterone, ACP, and prostatic acid phosphatase), oxidative indices, mRNA expression of proapoptotic (BAX) and anti-apoptotic (BCL-2) biomarkers, histological, and immunohistochemical changes in testicular tissues were investigated. Significant decrease in serum testosterone level and elevation in ACP and PACP enzyme activity in AgNPs-treated rats. As well, there were lowering in tGSH, GSH GR, GPx, and elevation in MDA and GSSG values. AgNPs-exposed rats expressed downregulation of testicular thirodexin-1 (Txn-1), transforming growth factor-1ß (TGF-1ß), anti-apoptotic (BCL-2), and upregulaion of proapoptotic biomarkers (BAX) mRNA expressions. Strong positive action to BAX and lowering the action of Ki-67 antibody were observed. Because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with LA or GB could be beneficial in reducing the harmful effects of AgNPs on the testicles.

Role and mechanism(s) of incretin-dependent therapies for treating diabetes mellitus.

Diabetes mellitus (DM) is a worldwide ailment which leads to chronic complications like cardiac disorders, renal perturbations, limb amputation and blindness. Type one diabetes (T1DM), Type two diabetes (T2DM), Another types of diabetes, such as genetic errors in function of ß-cell and action of insulin, cystic fibrosis, chemical-instigated diabetes or following tissue transplantation), and pregnancy DM (GDM). In response to nutritional ingestion, the gut may release a pancreatic stimulant that affects carbohydrate metabolism. The duodenum produces a 'chemical excitant' that stimulates pancreatic output, and researchers have sought to cure diabetes using gut extract injections, coining the word 'incretin' to describe the phenomena. Incretins include GIP and GLP-1. The 'enteroinsular axis' is the link between pancreas and intestine. Nutrient, neuronal and hormonal impulses from intestine to cells secreting insulin were thought to be part of this axis. In addition, the hormonal component, incretin, must meet two requirements: (1) it secreted by foods, mainly carbohydrates, and (2) it must induce an insulinotropic effect which is glucose-dependent. In this review, we clarify the ability of using incretin-dependent treatments for treating DM.

2, 3-Dimethylsuccinic acid and fulvic acid attenuate lead-induced oxidative misbalance in brain tissues of Nile tilapia Oreochromis niloticus.

Lead has long been known as neurotoxic and immunotoxic heavy metal in human and animals including fish, whereas, 2, 3-dimethylsuccinic acid (DMSA) and fulvic acid (FA) are well-known biological chelators. The present investigation was carried out to assess the potential chelating and antioxidant effects of dietary supplementation with DMSA and FA against lead acetate (Pb)-induced oxidative stress in Nile tilapia, O. niloticus. One-hundred and eighty apparently healthy O. niloticus fish (30 ± 2.5 g) were allocated into six equal groups. The first group was fed on basal diet and served as control, while the second group was fed on DMSA-supplemented basal diets at levels of 30 mg/kg diet; the third group was fed on FA-supplemented basal diet at level of 0.3 mg/kg diet; the forth, fifths, and sixth groups were exposed to 14.4 mg Pb /L water (1/10 LC50) and feed on basal diet only, basal diet supplemented with DMSA (0.3 mg/kg diet), or basal diet supplemented with FA (0.3 mg/kg diet), respectively. Antioxidant and lipid peroxidative status, activity of glucose 6-phosphate dehydrogenase (G6PD), and lactate dehydrogenase (LDH) as well as the histopathologic findings were evaluated in brain tissues, while the Pb residues were evaluated in liver, muscles, and brain tissues. The results of the present study showed that DMSA and FA decreased malondialdehyde (MDA) and Pb residue in tissues of Pb-exposed fish and improved the histologic picture and brain contents of glutathione (GSH), glutathione-s-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), G6PD, LDH, and total antioxidant capacity (TAC). It could be concluded that DMSA and FA supplementation exhibited potential neuroprotective effect against Pb-induced oxidative brain damages in O. niloticus through improvement of antioxidant status of the brain tissue.

Natural Ghee Enhances the Biochemical and Immunohistochemical Reproductive Performance of Female Rabbits.

The reproductive effects of several dietary fats (margarine, ghee, and olive oil) on female rabbits were studied. For that purpose, 40 mature female rabbits were designed into four groups of ten rabbits each. Group I was given a control diet, Group II received 10% margarine, Group III received 10% ghee, and Group IV received 10% olive oil; after two months, all rabbits were sacrificed. Lipid profile and reproductive hormones levels were assayed in serum besides ovarian antioxidant enzyme and lipid peroxidation. Furthermore, ovarian tissue was examined using hematoxylin−eosin staining and immunohistochemistry of estrogen, follicle-stimulating hormone (FSH), luteinizing hormone (LH) receptor, and caspase 3. Our data revealed that the margarine significantly (p < 0.05) increased lipid profile and malondialdehyde (MDA) level, which decreased in olive oil and ghee compared to the control. In addition, serum FSH and estrogen (estradiol (E2)) were significantly (p < 0.05) decreased in the group treated with margarine. Furthermore, there was a significant decrease in ovarian superoxide dismutase (SOD) and catalase activity in the margarine-treated group. In contrast, SOD and MDA showed a significant (p > 0.05) increase in the olive oil and ghee- treated group compared to the control group. At the same time, there was a significant increase in serum FSH and (estradiol (E2)) in the ghee and olive oil groups, respectively, compared to the control. The margarine feed group showed moderate immunoreaction of estrogen, FSH, LH receptor, and strong caspase 3, while ghee and olive oil showed strong immunoreaction of estrogen, FSH, LH receptor, and mild immunoreaction of caspase 3 in ovarian tissue. Photomicrograph of rabbit ovarian tissue showed vacuolation in small and growing follicles in the margarine group but appeared normal in ghee and the olive oil-treated group. In conclusion, based on these results, olive oil and ghee have a strong capability of enhancing lipid profile, antioxidant status, and female hormonal functions.

Proanthocyanidin alleviates doxorubicin-induced cardiac injury by inhibiting NF-kB pathway and modulating oxidative stress, cell cycle, and fibrogenesis.

This study investigated the potential mechanism(s) and the signaling pathway(s) underlying the prophylactic effect of proanthocyanidin extract (PE) against doxorubicin (DOX)-induced cardiotoxicity in rats. A total of 32 male albino rats were randomly allocated into four groups. Control rats were orally administrated normal saline. Rats in the second group were orally administrated PE (50 mg/kg bw/once daily) for 4 weeks. Rats in the third group were intraperitoneally injected with DOX (10 mg/kg on Days 3, 9, 15, and 21 of the experiment). Rats in the fourth group were injected with DOX and PE simultaneously for 4 weeks. DOX significantly augmented the levels of serum heart damage biomarkers. In addition, histopathology indicated that DOX-induced cardiac tissue injury upregulated the expression of fibrogenic factors, alpha smooth muscle actin (α-SMA), transforming growth factor ß1 (TGF- ß1), and p16INK4A . Downregulation of cell proliferation markers, cyclin-dependent kinase-4 (CDK4), and retinoblastoma (Rb) was also observed. Furthermore, DOX-induced oxidative and inflammatory stress resulted in increased cardiac malondialdehyde (MDA), protein carbonyl (PC), interleukin-2 (IL-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Decreased cardiac glutathione (GSH) levels and enzyme activity of catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) were observed. Treatment of DOX-induced rat cardiotoxicity with PE normalized serum parameters for the aforementioned parameters and alleviated cardiac tissue structure. Furthermore, reduced cardiac tissue α-SMA and TGF-ß1, and increased CDK4 and Rb protein expression, along with the amelioration of oxidative and inflammatory effects were observed. PE attenuates DOX-induced cardiomyocyte inflammation possibly by attenuating the nuclear factor kappa-B (NF- kB) signaling pathway. These results indicate that PE may be useful as a preventative agent against DOX-induced cardiac toxicity.

Spirulina platensis Alleviated the Oxidative Damage in the Gills, Liver, and Kidney Organs of Nile Tilapia Intoxicated with Sodium Sulphate.

The current study aimed at assessing the recuperative roles of dietary Spirulina platensis on the antioxidation capacity of Nile tilapia (Oreochromis niloticus) exposed to sodium sulphate for eight weeks. In brief, fish were allocated into four groups with three triplicates per group, where a group fed on a commercial basal diet served as control, a group was intoxicated with sodium sulphate (SS) 5.8 mg/L, another group was fed a diet supplemented with 1% S. platensis (SP), and the last group was fed 1% SP and concomitantly intoxicated with 5.8 mg/L sodium sulphate (SP/SS). Tissue antioxidative indices of each fish were measured as follows: glutathione peroxidase (GSH-Px) activity in muscles, catalase (CAT) and superoxide dismutase (SOD) activities in gills, and total antioxidant capacity (T-AOC) in the liver and kidney. Moreover, the expression of hepatic SOD, GSH-Px, and glutathione-S-transferase (GST) genes was also determined. It was found that tissue CAT, SOD, and GSH-Px activities as well as the T-AOC levels were significantly decreased in the SS group (p < 0.05). Moreover, there was a significant downregulation of hepatic SOD, GSH-Px, and GST genes in SS-exposed fish (p < 0.05). Interestingly, simultaneous dietary supplementation with SP provided a marked attenuation of the tissue antioxidative parameters when compared with the SS and control groups. To conclude, the present study exemplifies that dietary SP supplementation could be a beneficial abrogation of SS-induced tissue oxidative stress in the exposed fish.

Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway.

OBJECTIVES: This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300 mg/kg body weight. After 4 weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin. KEY FINDINGS: The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression. CONCLUSION: The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy.

Sidr honey abrogates the oxidative stress and downregulates the hyaluronic acid concentration and gene expression of TGF-ß1 and COL1a1 in rat model of thioacetamide-induced hepatic fibrosis.

Liver fibrosis is a major health concern, which might progress to cirrhosis. To date, treatment trials rely mainly on the removal of the causative factor. The current study investigated the potential ameliorative role of sidr honey on thioacetamide (TAA)-induced liver fibrosis in rats. Forty-eight Wistar albino rats were equally allocated into four groups: control; sidr honey (5g/kg body weight (BW), orally); TAA (200 mg/kg BW, IP three times weekly/15 weeks); and sidr honey plus TAA at the same dose and administration rout. Rats co-treated with sidr honey plus TAA revealed significant reduction in hepatic malondialdehyde, hyaluronic acid (HA), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, direct bilirubin, and hepatic mRNA expression of transforming growth factor (TGF)-ß1 and collagen type I alpha 1 chain (COL1a1) compared to TAA-exposed rats. In addition, the hepatoprotective potential of sidr honey was indicated via improvement of histopathologic picture of hepatocytes and upregulation of total antioxidant capacity, reduced glutathione, catalase, glutathione peroxidase, superoxide dismutase, total protein, and albumin compared to TAA-treated rats. In conclusion, daily administration of sidr honey (5 g/kg BW) is a promising natural antioxidant and fibrosuppressive agent that could ameliorate liver fibrosis via downregulation of fibrosis genes including TGF-ß1 and COL1a1 and HA and via enhancement of antioxidant system.

Moringa Oleifera Leaf Extract Repairs the Oxidative Misbalance following Sub-Chronic Exposure to Sodium Fluoride in Nile Tilapia Oreochromis niloticus.

The potential antioxidant property of Moringa oleifera (MO) has been the recent focus of an increased number of studies. However few studies investigated its antioxidative ability against sodium fluoride-induced redox balance breakdown in Oreochromis niloticus. Thus, this study evaluates the effects of MO against the oxidative stress induced by sub-chronic exposure to sodium fluoride (NaF). A total of 264 fish (40 ± 3 g BW) were used to calculate the 96 hr-LC50 of NaF and perform the sub-chronic exposure study. 96 hr-LC50 of NaF was calculated as (61 mg/L). The 1/10 dose of the calculated 96 hr-LC50 (6.1 mg/L) was used to complete the sub chronic exposure for eight weeks. Fish were divided into four groups (n = 51; three replicates each); control, non-treated group; NaF group (exposed to NaF 6.1 mg/L); MO group (treated with 1% MO of diet); and NaF+MO (exposed to NaF 6.1 mg/L and treated with 1% MO of diet). The results revealed that the sub-chronic exposure to NaF (6.1 mg/L) was substantially increased malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) in the gills, liver, kidney, and muscle tissue in a time-dependent manner. In addition, a significant reduction in mRNA expression of GST in the liver was reported following NaF exposure. On the contrary, dietary supplementation of MO to NaF-exposed fish resulted in a significant reduction in MDA levels, and a significant elevation of SOD, CAT, GSH, GPx, and TAC activities in a time-dependent manner, in addition to significant elevation of GST mRNA expression in liver tissue. It could be concluded that a 1% MO (w/w) ration is a promising antioxidant plant that may successfully use to interfere with the oxidation processes induced by NaF in various tissues of Oreochromis niloticus.

Effects of Liquid Yucca Supplementation on Nitrogen Excretion, Intestinal Bacteria, Biochemical and Performance Parameters in Broilers.

This study was done to determine the impacts Yucca schidigera supplementation to drinking water on the excretion of nitrogen, and subsequently the level of ammonia, intestinal bacterial count, hematological and biochemical parameters, and some performance parameters. A total of 270 one-day old Cobb 500 chicks were equally divided into three groups (90 chicks/group). The first control group (G1) was fed on the basal diets without any yucca supplementation. The 2nd and 3rd groups (G2 and G3) were fed on basal diets with Yucca Plus liquid®, at an 8 h/day supplementation rate of 0.5, and 1 mL/L to drinking water, respectively. The chicks that received yucca showed significant decreases in litter nitrogen content, when compared to controls. The chicks that received liquid yucca had reduced counts of total bacteria (TBC) (p < 0.05), Escherichia coli, and a non-significant increase in the number of lactic acid producing bacteria. They also showed increased activity of antioxidant enzymes, increased levels of immunoglobulins M and G, and decreased levels of lipid peroxidation biomarkers, without a harmful effect on liver and kidney function. The chicks that received yucca showed a better feed conversion ratio. In conclusion, the use of natural additives is necessary to decrease nitrogen losses, feed cost, and environmental pollution; without adverse impacts on animal performance. Liquid supplementation of saponins is valuable for the performance, gut health, and welfare of broiler chickens.

Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats.

Oxidative stresses intensify the progression of diabetes-related behavioural changes and testicular injuries. Graviola (Annona muricata), a small tree of the Annonaceae family, has been investigated for its protective effects against diabetic complications, oxidative stress, and neuropathies. This study was planned to investigate the effects of graviola on behavioural alterations and testicular oxidative status of streptozotocin (STZ; 65 mg/kg)-induced diabetic rats. Forty adult male Wistar rats were equally allocated into four groups: control (received normal saline 8 ml/kg orally once daily), diabetic (received normal saline orally once daily), graviola (GR; received 100 mg/kg/day; orally once daily), and diabetic with graviola (Diabetic+GR; received 100 mg/kg/day; once daily). Behavioural functions were assessed using standard behavioural paradigms. Also, oxidative statuses of testis were evaluated. Results of behavioural observations showed that diabetes induced depression-like behaviours, reduction of exploratory and locomotor activities, decreased memory performance, and increased stress-linked behaviours. These variations in diabetic rats were happened due to oxidative stress. Interestingly, treatment of diabetic rats with graviola for four weeks alleviated all behavioural changes due to diabetes. Also, rats in graviola-treated groups had greater testicular testosterone and estradiol levels compared with diabetic rats due to significant rise in testicular acetyl-CoA acetyltransferase 2 expression. In the same context, graviola enhanced the antioxidant status of testicular tissues by significantly restoring the testicular glutathione and total superoxide dismutase that fell during diabetes. In addition, Graviola significantly decreased the expression of apoptotic (Bax) and inflammatory (interleukin-1ß) testicular genes. In conclusion, these data propose that both the hypoglycemic and antioxidative potential of graviola are possible mechanisms that improve behavioural alterations and protect testis in diabetic animals. Concomitantly, further clinical studies in human are required to validate the current study.

Graviola attenuates DMBA-induced breast cancer possibly through augmenting apoptosis and antioxidant pathway and downregulating estrogen receptors.

Breast cancer is a global public health problem where it is the second most prevalent cancer. Historical cancer treatment with graviola has been reported. This study aimed to investigate the protective effects of graviola on 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat breast cancer. Fifty female Wistar rats were allocated into four groups: control group (gastro-gavaged by sesame oil), DMBA-treated group (gastro-gavaged a single dose of DMBA [50 mg/kg body mass, diluted in 1 ml sesame oil]) at the age 57 days, DMBA+G37-treated group (gastro-gavaged a single dose of DMBA [50 mg/kg body mass, diluted in 1 ml sesame oil]) at the age of 57 days plus graviola (200 mg/kg body mass) two times weekly (p.o.) at the age of 37 days till the end of the experiment, and DMBA+G57-treated group (received a single dose of DMBA [50 mg/kg body mass, diluted in 1 ml sesame oil]) plus graviola (200 mg/kg body mass) two times weekly at the age of 57 days until the end of the experiment. After the 30-week experimental period, blood samples were collected. Then, animals were sacrificed to determine the apoptotic indices, antioxidant status, and mammary gland tumor marker (CA 15-3). The DMBA upregulated the expression of one of the main anti-apoptotic genes: B-cell lymphoma protein 2 (BCL2) and estrogen receptor alpha (ER-α) gene. Moreover, it significantly increased breast lipid peroxidation and serum CA 15-3 but decreased breast antioxidant enzymatic activities (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase). Nevertheless, administration of DMBA and graviola especially DMBA+G37 induced apoptosis through at least 1.5-fold in gene expression levels of pro-apoptotic genes: BCL2-associated X protein (BAX), tumor suppressor gene (P53), and cysteinyl-aspartic acid-protease-3 (caspase-3). A critical role of P53 in the regulation of the BCL2 and BAX has been reported. These proteins can determine if the cell undergoes apoptosis or cancels the process. Once the BAX gene activates caspase-3, there is no irreversible way toward cell death. Also, graviola ameliorated the DMBA effects on antioxidant enzymatic activities and tumor marker CA 15-3. This study concludes that graviola ameliorated DMBA-induced breast cancer potentially through upregulating apoptotic genes, downregulating the ER-α gene, increasing antioxidants, and decreasing lipid peroxidation levels.

The possible neuroprotective effects of melatonin in aluminum chloride-induced neurotoxicity via antioxidant pathway and Nrf2 signaling apart from metal chelation.

Aluminum (Al) had well-identified adverse influences on the nervous system mainly through the creation of reactive oxygen species (ROS). Melatonin works as an antioxidant through the inhibition of ROS and attenuating peroxidation of lipids. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a pivotal transcription factor which controls the transcription of antioxidant enzymes. This study was conducted to determine the potential neuroprophylactic impacts of melatonin in aluminum chloride (AlCl3)-initiated neurotoxicity including potential mechanism(s) of action and relevant signaling in rats. Thirty-six male rats were distributed into 4 groups: Control; AlCl3 (50 mg/kg bwt, i.p, 3 times weekly for 3 months); melatonin (5 mg/kg bwt, i.p daily for 2 weeks before AlCl3 and sustained for the next 3 months); and melatonin with AlCl3. Neuronal alterations were histopathologically and biochemically evaluated. The neuronal antioxidant-related genes and relevant Nrf2 protein expression were determined by real-time PCR and Western blotting, respectively. The current data showed a substantial increase in brain damage biomarkers, acetylecholinesterase (AchE) activity, and malondialdehyde (MDA) content while the enzymatic antioxidant expression as glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were substantially attenuated in the aluminum-treated group, with cleared histopathological changes as inflammatory cell infiltration with neuronal degeneration. Supplementation of melatonin resulted in an obvious amelioration in all previous abnormal alteration observed in AlCl3-treated rats rather than increased Al burden and/or altered Fe and Cu homeostasis with upregulating both total and phosphorylated Nrf2 expression. Therefore, the study concluded that melatonin has a potential ability to be neuroprophylactic against Al-induced neurotoxic effect and oxidative damage in the rat brain through upregulating and instigating Nrf2 signaling apart from metal chelation.

Papaya extract upregulates the immune and antioxidants-related genes, and proteins expression in milk somatic cells of Friesian dairy cows.

Carica papaya is a perennial plant containing bioactive constituents with free radical-scavenging and immune-modulating activities. In contrast, the immune suppression is predominant in the periparturient period, where oxidative stress has a substantial impact on the mammary gland health. The aim of the experiment reported here was to determine the potential effect of C. papaya aqueous extract (CPE) on milk production traits, and expression of genes and proteins related to immune and antioxidant status in dairy milk somatic cells (MSCs). Forty Friesian dairy cows were divided equally between a control and CPE-treated groups (orally drenched 250 µg/kg bwt, once weekly a month before expected parturition and continued until 5 months post-partum). CPE did not affect milk yield or composition but upregulated the expression of ß13-defensin (DEFB13), cathelicidin 2 (CATHL2), cathelicidin antimicrobial peptide (CATHL3), hepcidin (HAMP), lysozyme (LYZ), catalase (CAT) and glutathione peroxidase (GSH-Px) in MSCs. The environmental micro-organisms did not influence the levels of the transcripts. The DEFB13, CATHL2, CATHL3, HAMP and LYZ, but not ß1-defensin (DEFB1) transcripts and proteins were constitutively expressed in MSCs obtained from pathogen-free udders. It could be concluded that CPE has immunostimulant and antioxidant activities; thereby, it could be utilized to minimize the occurrence of mastitis.

Potential role of α-lipoic acid and Ginkgo biloba against silver nanoparticles-induced neuronal apoptosis and blood-brain barrier impairments in rats.

AIMS: This study explored whether silver nanoparticles (AgNPs) can disrupt tight-junctions integrity resulted in blood-brain barrier dysfunction along with oxidative stress, pro-inflammation, and apoptosis induction. Additionally, neuroprotective activities of α-lipoic acid (LA) and Ginkgo biloba (GB) were investigated. MAIN METHODS: Forty adults rats were enrolled into; Control, AgNPs (50 mg/kg), LA (100 mg/kg) + AgNPs, and GB (120 mg/kg) + AgNPs. After 30 days, neuronal changes were assessed biochemically and histopathologically. Brain tissues oxidative indices, mRNA expression of proinflammatory cytokines and tight-junction proteins and pro-apoptotic biomarker, caspase-3 were investigated. KEY FINDINGS: AgNPs exposure enhanced lipid peroxidation (+195%) along with declines in glutathione (-43%), glutathione peroxidase (-34%), glutathione S-transferase (-31%), catalase (-43%), and superoxide dismutase (-38%) activities in brain tissues. The apparent brain oxidative damage was associated with obvious neuronal dysfunction that was ascertained by neuropathological lesions. AgNPs lowered serum acetylcholine esterase, iron and copper levels, and increased creatine phosphokinase and creatine phosphokinase-brain type activities. Following AgNPs exposure, brain silver and iron contents were increased, but the copper level was decreased. AgNPs up-regulated TNF-α (6.5-fold) and IL-1ß (8.9-fold) transcript levels, and simultaneously over-expressed the caspase-3 protein in cerebrum and cerebellum inducing cell apoptosis. Moreover, AgNPs down-regulated the transcript levels of tight-junction proteins; JP-1 (0.65-fold) and JAM-3(0.81-fold). SIGNIFICANCE: LA and relatively GB improved the serious effects of AgNPs on the blood-brain barrier function and tight-junction proteins through their antioxidants, anti-inflammatory, and anti-apoptotic efficacies. Co-treatment with LA or GB may be favorable in ameliorating the neurotoxic side effects of AgNPs.