The corrective role of superparamagnetic iron oxide nanoparticles for the genes controlling hypothalamus-pituitary-testis-axis in male obesity-associated secondary hypogonadism.

Background: Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields. Aim: In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). Methods: 42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMC-SPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments. Results: The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitary-testicular-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25-50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. Conclusion: CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms.

Antagonistic Effect of Zinc Oxide Nanoparticles Dietary Supplementation Against Chronic Copper Waterborne Exposure on Growth, Behavioral, Biochemical, and Gene Expression Alterations of African Catfish, Clarias gariepinus (Burchell, 1822).

The harmful impact of waterborne copper (Cu) as a common abiotic stressor in aquatic environments has gained much more interest. The present study aimed to investigate the utilization of zinc oxide nanoparticles (ZnONPs) dietary supplementation to mitigate the chronic toxicity of Cu in African catfish (Clarias gariepinus). Two hundred and forty fish (92.94 ± 0.13 g) were assigned into six groups for 60 days. Control (C), ZnONPs20, and ZnONPs30 groups were fed on basal diets fortified with 0, 20, and 30 mg kg-1 ZnONPs without Cu exposure. Cu, Cu + ZnONPs20, and Cu + ZnONPs30 groups were exposed to Cu at a dose of 10 mg L-1 and fed on basal diets fortified with 0, 20, and 30 mg kg-1 ZnONPs, respectively. The results revealed that the Cu-exposed fish experienced abnormal clinical signs and behavioral changes. The growth indices and acetylcholine esterase activity were significantly decreased (P < 0.05) in the Cu group. Meanwhile, hepatorenal and serum stress indices (P < 0.05) were significantly elevated with chronic Cu exposure. In addition, a higher expression of stress (P < 0.05) (heat shock protein 60 and hypoxia-inducible factor-1 alpha) and apoptotic-related genes (C/EBP homologous protein, caspase-3, and Bcl-2 Associated X-protein) with down-regulation (P < 0.05) of the anti-apoptotic-related genes (B-cell lymphoma 2 and proliferating cell nuclear antigen) was noticed in the Cu-exposed fish. Histopathological alterations in the gills, liver, kidney, and spleen were markedly reported in the Cu-exposed group. The dietary supplementation with ZnONPs significantly alleviated the negative impacts of chronic waterborne-Cu exposure on growth performance, physiological changes, gene expression, and tissue architecture, especially at 30 mg kg-1 diet level. In particular, the inclusion of ZnONPs at the 30 mg kg-1 diet level produced better outcomes than the 20 mg kg-1 diet. Overall, ZnONPs could be added as a feed supplement in the C. gariepinus diet to boost the fish's health and productivity and alleviate the stress condition brought on by Cu exposure.

Effect of dietary intervention with Capsicum annuum extract on growth performance, physiological status, innate immune response, and related gene expression in Nile tilapia.

The red pepper (Capsicum annuum) has gained great attention recently because of its biological and pharmacological characteristics. The present approach aimed to evaluate the effects of C. annuum alcoholic extract (CAE) supplementation on Nile tilapia (Oreochromis niloticus) growth performance, physiological status, some metabolic, immune, and regulatory genes expression, and resistance against Streptococcus agalactiae infection. Fish (22.26 ± 0.19 g) were assigned to four treatments (five replicates, each with 10 fish replicate-1) and fed tested diets for 60 days. The experimental diets were supplemented with CAE at 0, 0.4, 0.8, and 1.6 g kg-1, expressed as CAE0, CAE0.4, CAE0.8, and CAE1.6, respectively. The findings exhibited that CAE dietary supplementation improved growth performance, feed utilization, elevated growth hormone level, and digestive enzyme activities (amylase and protease), and lowered leptin hormone in a level-dependent manner. Boosting the mRNA expression of the transporter proteins (solute carrier family 15 member 2 and solute carrier family 26 member 6) and insulin-like growth factor-1 genes with a decrease in the myostatin gene expression was noticed in the CAE-fed groups. The innate immune (serum bactericidal activity %, complement 3, and phagocytic activity %) and antioxidant (glutathione peroxidase and total antioxidant capacity) parameters were significantly (p < 0.05) improved, and the serum malondialdehyde level was significantly decreased by CAE dietary inclusion. A marked upregulation in the mRNA expression of interleukins (il-1ß, il-6, il-8, and il-10), transforming growth factor-ß, glutathione peroxidase, and glutathione synthetase genes were observed in CAE-fed groups. Dietary CAE decreased the cumulative mortalities after the challenge with S. agalactiae by 20, 13.33, and 10% in CAE0.4, CAE0.8, and CAE1.6, respectively, compared to the control (40%). Overall, dietary supplementation with CAE could improve growth performance and physiological status, and modulate the expression of several regulatory genes in Nile tilapia. The recommended level of CAE is 1.6 g kg-1 to augment growth and health status.

Nelumbo nucifera synthesized selenium nanoparticles modulate the immune-antioxidants, biochemical indices, and pro/anti-inflammatory cytokines pathways in Oreochromis niloticus infected with Aeromonas veronii.

Bacterial infection is considered one of the major issues in fish culturing that results in economic losses. Metal nanoparticles are a cutting-edge and effective disease management and preventive strategy because of their antibacterial ability. In this investigation, the selenium nanoparticles were prepared by a biological method using Nelumbo nucifera leaves extract. The in-vitro antibacterial activity of N. nucifera synthesized selenium nanoparticles (NN-SeNPs) was tested against Aeromonas veronii. A treatment assay was conducted on 210 Oreochromis niloticus (average body weight: 27 ± 2.00 g). A preliminary approach was conducted on 90 fish for determination of the therapeutic concentration of NN-SeNPs which was found to be 4 mg/L. Fish (n = 120) were categorized into four groups for 10 days; G1 (control) and G2 (NN-SeNPs) were non-challenged and treated with 0 and 4 mg/L NN-SeNPs, respectively. While, G3 and G4 were infected with 2 × 106 CFU/mL of A. veronii and treated with 0 and 4 mg/L NN-SeNPs, respectively. NN-SeNPs exhibited an inhibition zone against A. veronii with a diameter of 16 ± 1.25 mm. The A. veronii infection increased the hepato-renal biomarkers (alanine and aspartate aminotransferases and creatinine) than the control group. An oxidative stress was the consequence of A. veronii infection (higher malondialdehyde and hydrogen peroxide levels with lower glutathione peroxidase superoxide, dismutase, and catalase activity). A. veronii infection resulted in lower immunological biomarker values (immunoglobulin M, lysozyme, and complement 3) with higher expression of the inflammatory cytokines (interleukin-1ß and tumor necrosis factor-ɑ) as well as lower expression of the anti-inflammatory cytokines (interleukin-10 and transforming growth factor-ß). Therapeutic application with 4 mg/L NN-SeNPs prevented the disease progression; and modulated the hepato-renal function disruptions, oxidant-immune dysfunction, as well as the pro/anti-inflammatory cytokines pathway in the A. veronii-infected fish. These findings suggest that NN-SeNPs, employed as a water therapy, can safeguard fish from the harmful effects of A. veronii and serve as a promising antibacterial agent for sustainable aquaculture.

Potential role of dietary Boswellia serrata resin against mancozeb fungicide-induced immune-antioxidant suppression, histopathological alterations, and genotoxicity in Nile tilapia, Oreochromis niloticus.

This study was established to look into the toxicological consequences of chronic exposure to a fungicide (mancozeb; MAZ) on the immune-antioxidant response, gene expressions, hepato-renal functions, and histological pictures of Nile tilapia (Oreochromis niloticus). Additionally, the effectiveness of Indian frankincense resin extract (IFRE) to mitigate their toxicity was taken into account. Fish (n =240; average body weight: 22.45 ± 2.21 g) were randomized into four groups for eight weeks in six replicates (control, IFRE, MAZ, and IFRE + MAZ), where ten fish were kept per replicate. The control and IFRE groups received basal diets that included 0.0 and 5 g/kg of IFRE without MAZ exposure. The MAZ and IFRE+MAZ groups received the same diets and were exposed to 1/10 of the 96-h of LC50 of MAZ (1.15 mg/L). The outcomes displayed that MAZ exposure resulted in a lower survival rate (56.67 %) and significantly decreased levels of immune-antioxidant variables (antiprotease, complement3, phagocytic activity, lysozyme, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to the control group. The MAZ-exposed fish showed the greatest levels of lipid peroxide (malondialdehyde), alkaline phosphatase, alanine amino-transferase, and stress indicators (cortisol and glucose). Additionally, histopathological alterations, including vacuolation, severe necrosis, degeneration, and mononuclear cell infiltrations in the hepatic, renal, and splenic tissues resulted, besides a reduction in the melanomacrophage center in the spleen. A down-regulation of immune-antioxidant-associated genes [toll-like receptors (TLR-2 and TLR-7), nuclear factor kappa beta (NF-κß), transforming growth factor-beta (TGF-ß), phosphoinositide-3-kinase regulatory subunit 3 gamma b (pik3r3b), interleukins (IL-1ß and IL-8), glutathione synthetase (GSS), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] were the consequences of the MAZ exposure. Remarkably, the dietary inclusion of IFRE in MAZ-exposed fish augmented the immune-antioxidant parameters, including their associated genes, decreased stress response, and increased survival rate (85 %) compared with the MAZ-exposed fish. Moreover, dietary IFRE improved hepato-renal function indices by preserving the histological architecture of the hepatic, renal, and splenic tissues. The insights of this study advocate the use of an IFRE-dietary addition to protect Nile tilapia from MAZ toxicity, which provides perspectives for future implementations in enhancing fish health for sustainable aquaculture.

The Antiproliferative Activity of Adiantum pedatum Extract and/or Piceatannol in Phenylhydrazine-Induced Colon Cancer in Male Albino Rats: The miR-145 Expression of the PI-3K/Akt/p53 and Oct4/Sox2/Nanog Pathways.

Colon cancer is one of the most common types of cancer worldwide, and its incidence is increasing. Despite advances in medical science, the treatment of colon cancer still poses a significant challenge. This study aimed to investigate the potential protective effects of Adiantum pedatum (AP) extract and/or piceatannol on colon cancer induced via phenylhydrazine (PHZ) in terms of the antioxidant and apoptotic pathways and histopathologic changes in the colons of male albino rats. The rats were randomly divided into eight groups: control, AP extract, piceatannol (P), PHZ, PHZ and AP treatments, PHZ and P treatments, PHZ and both AP and P, and PHZ and prophylaxis with both AP and P. The results demonstrated that PHZ induced oxidative damage, apoptosis, and histopathological changes compared to the control group. However, the administration of AP or P or AP + P as therapy or prophylaxis significantly ameliorated these changes and upregulated the colonic mir-145 and mRNA expression of P53 and PDCD-4 while downregulating the colonic mRNA expression of PI3K, AKT, c-Myc, CK-20, SOX-2, OCT-4, and NanoG compared to the PHZ group. These findings suggest that the candidate drugs may exert their anti-cancer effects through multiple mechanisms, including antioxidant and apoptotic activities.

Melatonin Mitigates Cisplatin-Induced Ovarian Dysfunction via Altering Steroidogenesis, Inflammation, Apoptosis, Oxidative Stress, and PTEN/PI3K/Akt/mTOR/AMPK Signaling Pathway in Female Rats.

Ovarian damage and fertility impairment are major side effects of chemotherapy in pre-menopausal cancer patients. Cisplatin is a widely used chemotherapeutic drug. The present study was designed to assess the ameliorative effects of melatonin as an adjuvant for fertility preservation. Thirty-two adult female Wistar rats were divided randomly into four equal groups: Control, Melatonin, Cisplatin (CP) treated, and CP + Melatonin treated. The cisplatin-treated group showed decreased body and ovarian weights, decreased serum E2 and AMH, increased serum LH and FSH, reduced ovarian levels of SOD, CAT, GSH, and TAC, and increased ovarian MDA. The histopathological examination of the cisplatin-treated group showed deleterious changes within ovarian tissue in the form of damaged follicles and corpus luteum, hemorrhage, and inflammatory infiltrates with faint PAS reaction in zona pellucida, increased ovarian collagen deposition, and marked expression of caspase-3 immune reaction in granulosa and theca cells, stroma, and oocytes. Alongside, there was a significant downregulation in the mRNA expression of steroidogenic enzymes, IL10, AMPK, PI3K, AKT, mTOR, and PTEN, while TGF-ß1, IL1ß, IL6, TNF-α, NF-Kß, P53, p38-MAPK, JNK, and FOXO3 mRNA expressions were upregulated in cisplatin-treated rats' ovarian tissue. Coadministration of cisplatin-treated rats with melatonin reversed these changes significantly. In conclusion, melatonin's antioxidant, anti-inflammatory, and anti-apoptotic activities could modulate ovarian disturbances induced by cisplatin and preserve fertility.

Immune-antioxidant trait, growth, splenic cytokines expression, apoptosis, and histopathological alterations of Oreochromis niloticus exposed to sub-lethal copper toxicity and fed thyme and/or basil essential oils enriched diets.

Two experiments were conducted in this study, using 250 Oreochromis niloticus (O. niloticus) (average weight 30.28 ± 0.27 g). The first experiment was conducted to investigate the 96-h lethal concentration 50 (LC50) of copper chloride (CuCl2) using the probit analysis, seventy fish was divided into seven different concentration of CuCl2 (0, 22, 23, 24, 25, 26, and 27 mg/L), the accurate Cu concentrations were (1.23, 5.36, 6.02, 6.98, 7.05, 7.93, 8.12 mg/L Cu). The second experiment was conducted for investigating the effect of dietary supplementation with thyme (Thymus vulgaris, T. vulgaris) and sweet basil (Ocimum basilicum, O. basilicum) essential oils (TEO and BEO respectively) against sub-lethal Cu exposure (1/10 96-h LC50 of CuCl2). About 180 fish was divided into six groups in triplicate (10 fish/replicate, 30 fish/group). Group 1 (C) was kept as a control group with no Cu exposure and was fed the control basal diet. Group 2 (C-Cu) was fed the control basal diet and simultaneously exposed to 1/10 of the 96 h LC50 of CuCl2 (2.574 mg/L) as a sub-lethal concentration of Cu, where the realistic Cu concentration was 3.976 mg/L. Group 3 (TEO) and group 4 (BEO) were fed the diets fortified with 1%TEO and BEO, respectively without exposure to Cu. Group 5 (TEO-Cu) and group 6 (BEO-Cu) were fed the diets fortified with 1%TEO and 1%BEO, respectively, and simultaneously exposed to 1/10 of the 96 h LC50 of CuCl2 (2.574 mg/L). The growth and behavioral performance, immunological response and its related gene expression, antioxidant status, stress biomarker indicators, apoptosis biomarkers, and histopathological alteration were investigated. The results of the first experiment showed that the 96-h LC50 of CuCl2 in O. niloticus was 25.740 mg/L with lower and upper confidence limits of 25.152 and 26.356 mg/L, respectively. The results of the second experiment showed that sub-lethal Cu exposure induced growth retardation (lowered final body weight, total weight gain, and specific growth rate %), behavioral abnormalities (slower swimming activity and feeding performance), immunosuppression (lowered nitric oxide, complement-3, lysozyme, total proteins, albumin, and globulin), and lowering the hepatic antioxidant functions (higher MDA, and lower SOD, CAT, and GPx) in the exposed fish. Furthermore, alteration in the immune-related genes expression (down-regulation of IL-10 and TGF-ß and up-regulation of IL-1ß, IL-6, IL-8, and TRL-4), hepato-renal dysfunction (elevated ALT, AST, urea, and creatinine), and high levels of serum stress indicators (cortisol and glucose) were markedly evident. sub-lethal Cu toxicity induced significant up-regulation of apoptosis biomarkers involving, nuclear factor-κß (NF-κß), Bcl-2 Associated X-protein (BAX), meanwhile, the expression of B-cell lymphoma 2 (BCL2) and Proliferating cell nuclear antigen (PCNA) was remarkably down-regulated. In addition, apoptosis was also evident by histopathological investigation of branchial, hepatic, and renal sections. TEO and/or BEO dietary supplementation mitigate the destructive impacts of sub-lethal Cu exposure in O. niloticus, depending on the results of our study, it could be concluded that TEO and BEO with a 1% dietary level could be a promising antioxidant, immunostimulant, anti-stress factors, and anti-apoptosis mediators against heavy metal contaminants (Cu) in O. niloticus, providing a solution to the problem of aquatic bodies pollution, consequently aiding in the development of aquaculture industry.

Dietary Salvia officinalis leaves enhances antioxidant-immune-capacity, resistance to Aeromonas sobria challenge, and growth of Cyprinus carpio.

The current perspective is a pioneer to assess the efficacy of Salvia officinalis leave powder (SOLP) on growth, intestinal enzymes, physiological and antioxidant status, immunological response, and gene expression of Common carp (Cyprinus carpio). We also looked into fish resistance after being challenged with Aeromonas sobria, a pathogenic zoonotic bacteria. Fish (N = 120) were fed four different experimental diets in triplicate for 8 weeks. The control diet (SOLP0 - without SOLP); meanwhile, the other three diets included SOLP of 2, 4, and 8 g kg-1 concentrations (SOLP2, SOLP4, and SOLP8), respectively. Findings demonstrated that fish fed SOLP4 and SOLP8 diets had better growth performance and improved digestion by noticeable enhancing lipase and amylase enzymes activity than other groups. Additionally, the antioxidant (superoxide dismutase and glutathione peroxidase) and immune activities (immunoglobulin M, nitric oxide, and antiprotease) clarified a significant increase (p < 0.05) in SOLP4 and SOLP8 groups. Enriched diets with SOLP4 and SOLP8 exhibited better expression of splenic genes (IL-1ß, IL-6, IL-10, TLR-2, and SOD), intestinal genes (Slc26a6) and (PepT1 or Slc15a1), and muscular genes (IGF-1 and SOD), while MSTN was down-regulated. After 8 weeks of the experimental trial, C. carpio challenged by A. sobria exhibited the highest cumulative mortality (66.67%), while SOLP8-dietary intervention showed the best results in enhancing the fish resistance against A. sobria by lessening mortalities to 13.33% followed by SOLP4 diet (20%). The outcomes indicate that the expression of splenic, muscular, and intestinal genes confirm the efficacy of SOLP on enhancing growth, digestion, and immune-antioxidant status, and recommend the potential use of SOLP especially at 4 g kg-1 level as a valuable natural economic diet additive in C. carpio culture for sustaining aquaculture.

The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria.

Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGFß), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-ß, EGF-ßr, VEGF-ß, and FGF-ß), inflammatory cytokine expression (IL8, TNFα, NFKß, IL1ß, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

Immune-antioxidant trait, Aeromonas veronii resistance, growth, intestinal architecture, and splenic cytokines expression of Cyprinus carpio fed Prunus armeniaca kernel-enriched diets.

Currently, the intervention of plant by-products in the fish diet has gained tremendous attention owing to the economic and high nutritious value. The current study is a pioneer attempt to incorporate the apricot, Prunus armeniaca kernel powder (PAKP) into the Common carp, Cyprinus carpio diets, and assess its efficacy on growth, digestion, intestinal morphology, immunity, antioxidant capacity, and splenic cytokines expression, besides the antibacterial role against Aeromonas veronii infection. Apparently healthy fish (N = 120) with an initial body weight of 24.76 ± 0.03g were allotted in 12 glass aquaria (60 L) and randomly distributed into four groups (triplicates, 10 fish/aquarium). The control group (PAKP0) was fed a basal diet without additives. The second, third, and fourth groups were provided PAKP diets with various concentrations (2.5 (PAKP2.5), 5 (PAKP5), and 10 g kg-1 (PAKP10)) respectively. After 60 days (feeding trial), sub-samples of the fish (12 fish/group) were intraperitoneally injected with 1 × 107 CFU mL-1 of A. veronii. Results revealed that body weight gain, feed conversion ratio, and specific growth rates were significantly augmented in the PAKP10 group in comparison to the other groups. The dietary inclusion of PAKP at all concentrations boosted the digestive capacity and maintained the intestinal morphology (average villus length, villus width, and goblet cells count) with a marked improvement in PAKP10. Moreover, fish fed on PAKP10 followed by PAKP5 then PAKP2.5 diets had noticeably elevated values of immunological biomarkers (IgM, antiprotease, and lysozyme activity) and antioxidant capabilities (the total antioxidant capacity, superoxide dismutase, and reduced glutathione) as well as significant up-regulation of immune and antioxidant-related genes (TGF-ß2, TLR-2, TNF-α, IL-10, SOD, GPx, and GSS). Fourteen days post-infection with A. veronii, the highest relative percentage survival of fish was observed in PAKP10 (83.33%), followed by PAKP5 (66.67%), and PAKP2.5 (50%). Our results indicated that a dietary intervention with PAKP could promise growth, digestion, immunity, and protect C. carpio against A. veronii infection in a dose-dependent manner. This offers a framework for future application of such seeds as a growth promotor, immune-stimulant, and antioxidant, besides an alternative cheap therapeutic antibacterial agent for sustaining the aquaculture industry.

Could Cisplatin Loading on Biosynthesized Silver Nanoparticles Improve Its Therapeutic Efficacy on Human Prostate Cancer Cell Line and Reduce Its In Vivo Nephrotoxic Effects?

Nanotechnology is a possible solution to the drawbacks of cancer therapy because it decreases the clinical side effects of chemotherapeutic drugs and increases their clinical activity. Thus, this work compared the in vitro cytotoxic activity and in vivo side effects of cisplatin (CP) with those of CP-loaded green silver nanoparticles (CP-AgNPs). The cytotoxic activity of CP, green AgNPs, and CP-AgNPs against PC-3, a human prostate cancer cell line, was assessed using MTT assay. CP-AgNPs had a superior cytotoxic effect on PC-3 cells with a 50% inhibition of viability (IC50) of 27.05 µg/mL, followed by CP with an IC50 of 57.64 µg/mL and AgNPs with an IC50 125.4 µg/mL. To evaluate in vivo side effects, 40 male adult Wistar rats were assigned into four groups and intraperitoneally injected with normal saline (control), CP (2.5 mg/kg body weight), green AgNPs (0.1 mL/kg body weight), and CP-AgNPs (2.5 mg/kg body weight). Intraperitoneal CP injection caused a substantial reduction in erythrocyte and leukocyte counts and hemoglobin concentration and a marked increase in urea and creatinine levels and disturbed the renal oxidant/antioxidant status. Furthermore, it caused noticeable structural alterations and significant upregulation of renal Bax and caspase-3 mRNA along with a significant downregulation of B-cell lymphoma 2 mRNA expressions. The loading of CP on green AgNPs significantly relieved the CP-induced pathological alterations and considerably enhanced its therapeutic effectiveness on PC-3 cells. These outcomes reflect the possible use of CP-AgNPs as a more efficient and safer anticancer agent than free CP.

Early intervention with breast milk mesenchymal stem cells attenuates the development of diabetic-induced testicular dysfunction via hypothalamic Kisspeptin/Kiss1r-GnRH/GnIH system in male rats.

Diabetic male infertility and sub fertility are major complications that may implicate both central and peripheral pathways as well as mechanisms controlling reproduction. This study was an attempt to explore the potential effect of breast milk mesenchymal stem cells (Br-MSCs) as a therapeutic tool for diabetic induced reproductive dysfunction at molecular level. Forty-five adult male Sprague Dawely rats were divided into 3 groups (n = 15); control group, diabetic group, and Br-MSCs treated diabetic group. The homing ability of Br-MSCs in diabetic treated rat testicles was confirmed via semi-quantitative RT- PCR analysis of a human specific Gapdh mRNA expression level. Our result showed that type1 diabetic rats exerted an elevation in blood glucose level and a reduction in body weight, fasting serum insulin, FSH, LH, and total testosterone levels, relative and absolute testicular weights, sperm count, motility, and live ratio. In addition, downregulation in the hypothalamic kisspeptin-GnRH system, HPG axis and testicular steroidogenesis compared to control group was noticed. Moreover, upregulation of testicular proinflammatory and apoptotic markers relative mRNA expression compared to control group was observed. Furthermore, a decrease in testicular tissue antioxidant activity (CAT, SOD, GSH) and an increase in lipid peroxidation (MDA) compared to control group was shown. However, Br-MSCs administration restored or even exceeded the normal physiological tone in most of these parameters to the point where a potential therapeutic role for Br-MSCs in type1diabetic induced infertility can be suggested.