Fenpropathrin provoked kidney damage via controlling the NLRP3/Caspase-1/GSDMD-mediated pyroptosis: The palliative role of curcumin-loaded chitosan nanoparticles.

This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN for 60 days. Then, serum renal damage products were assessed. Total antioxidant capacity, reactive oxygen species, interleukin 1ß (IL-1ß), malondialdehyde, NF-κB P65, cleaved-Caspase-1, and Caspase-8 were estimated in kidney homogenates. The cleaved Caspase-3 and TNF-α immunoexpression and pyroptosis-related genes were determined in renal tissues. The results showed that CU-CS-NPS significantly repressed the FPN-induced increment in kidney damage products (urea, uric acid, and creatinine). Moreover, the FPN-associated hypo-proteinemia, renal oxidative stress and apoptotic reactions, and impaired renal histology were considerably repaired by CU and CU-CS-NPs. Additionally, compared to FPN-exposed rats, CU, and CU-CS-NPs-treated rats had considerably lower immunoexpression of cleaved Caspase-3 and TNF-α in renal tissue. The pyroptosis-related genes NLRP3, GSDMD, IL-18, Caspase-3, Caspase-1, IL-1ß, Caspase-8, TNF-α, and NF-κB dramatically upregulated by FPN exposure in the renal tissues. Yet, in CU and CU-CS-NPs-treated rats, the gene above expression deviations were corrected. Notably, CU-CS-NPs were superior to CU in preventing oxidative damage and inflammation and regulating pyroptosis in the renal tissues of the FPN-exposed group. The results of the present study conclusively showed the superior favorable effect of CU-CS-NPs in counteracting renal impairment linked to environmental pollutants.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Time-dependent expression of high-mobility group box-1 and toll-like receptors proteins as potential determinants of skin wound age in rats: Forensic implication.

The skin wound age determination in living subjects is an imperative task for forensic experts. In this study, we investigated the time-dependent expression of high-mobility group box-1 (HMGB1) and toll-like receptors 2 and 4 (TLR2 and 4) in rat skin wounds using real-time PCR and seek their forensic potentials during the skin wound repair process. In addition, the levels of serum pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)), as well as nitric oxide (NO) production, were measured. The wound tissue and serum samples were collected after 30 min, 2 h, 6 h, 12 h, 1 day, 3 days, 5 days, and 7 days after incision. As a control (zero time), skin specimens and blood samples were collected without incision. The results reveal that the HMGB1, TLR2, and TLR4 expression levels were increased in a time-dependent manner until the first day where the peak level was achieved for the three tested genes compared with the zero time. On the 7th day, the statistical significance was lost for TLR2 and TLR4 but persisted for HMGB1. The serum TNF-α, IL6, and NO levels peaked within 30 min and 1st and 3rd day after injury, respectively. On the 7th day after incision, no significant differences exist in the TNF-α serum level compared to the control group, but the statistical significance persisted for IL6 and NO. It was apparent that the analyzed genes in the wound tissues showed higher R2 values rather than the serum biochemical indicators. Of note, a strong positive correlation was evident between the HMGB1 and that of TLR2 and TLR4 relative expression as well as IL-6 serum level. Conclusively, based on the observed changes in the analyzed markers in wound tissues and serum and R2 values obtained from mathematical models established to determine the wound age, the relative expression of HMGB1, TLR2, and TLR4 could be a reliable indicator for wound age determination in living subjects. Further investigation of these markers and mathematical models in human tissues is necessary.

The synbiotic mixture of Bacillus licheniformis and Saccharomyces cerevisiae extract aggravates dextran sulfate sodium induced colitis in rats.

BACKGROUND: Uncertain effects of probiotics and/or prebiotics have been reported in experimental and clinical colitis. This study aims to examine the effects of a synbiotic combination comprising Bacillus licheniformis DSM 17236 and Saccharomyces cerevisiae cell wall extract on dextran sulfate sodium (DSS)-induced colitis in Sprague Dawley rats. METHODS: Acute colitis was induced in rats by oral administration of DSS 3.5% for 7 days. Fifty rats were divided equally into five groups; one control group and the other groups were induced with colitis and treated with or without the tested synbiotic, mixed with diet, for 28 days and sulfasalazine (100 mg/kg) via intragastric tube once daily for 14 days. RESULTS: Symptomatically, the synbiotic administration raised the disease activity index (DAI) to comparable scores of the DSS group, specially from the 2nd to 7th days post DSS intoxication. It also induced a significant (p < 0.05) amplification of WBCs, myeloperoxidase (MPO), malondialdehyde (MDA), nuclear factor kappa B (NF-kB) expression and proinflammatory cytokines tumor necrosis factor alpha (TNFα), interferon gamma (INFγ), and interleukin-1 beta (IL-1ß) while depressed the antioxidant enzymes glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) when compared with the DSS and control groups. The DSS intoxicated and Synbiotic+DSS groups showed desquamations of the covering epithelium, noticeable diffuse leukocytic infiltrations, sever catarrhal enteritis, ischemic colitis with diffuse coagulative necrosis of the entire colonic mucosa. Contrarily, sulfasalazine proved to be effective in the reduction of the tested inflammatory markers and the pathological degenerative changes of the DSS ulcerative colitis. CONCLUSION: The examined synbiotic did not ameliorate but aggravated the DSS-induced colitis, so it should be subjected to intensive experimental and clinical testing before their use in animals and human.

Ligand-based design and synthesis of N'-Benzylidene-3,4-dimethoxybenzohydrazide derivatives as potential antimicrobial agents; evaluation by in vitro, in vivo, and in silico approaches with SAR studies.

Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4h, and 4i showed the most promising antibacterial and antifungal activities. Moreover, compounds 4h and 4i being the broader and superior members regarding their antimicrobial effects were selected to be further evaluated via in vivo testing using biochemical analysis and liver/kidney histological examination. Additionally, molecular docking was carried out to attain further deep insights into the synthesised compounds' binding modes. Also, ADMET studies were performed to investigate the physicochemical/pharmacokinetics features and toxicity parameters of the synthesised derivatives. Finally, a structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future. HighlightsA series of new N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised targeting the multidrug efflux pump (MATE) guided by the pharmacophoric features of the co-crystallized native inhibitor of the target protein.The newly synthesised compounds were assessed through in vitro, in vivo, and in silico approaches.Using the agar well diffusion assay, the antibacterial activities of the synthesised compounds were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas, their antifungal activities were screened against C. albicans.The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the synthesised compounds were investigated on variable microbial species.Compounds (4h and 4i) -as the broader and superior members regarding their antimicrobial effects- were further evaluated via in vivo testing using bio-chemical analysis and liver/kidney histological examination.A molecular docking study and ADMET in silico studies were performed.A structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.

Histological and biochemical studies on effect of Sofosbuvir (Sovaldi) on adult male albino rat kidney.

Sofosbuvir (sovaldi) is the backbone of many anti-HCV drugs. We aimed to demonstrate the effect of sofosbuvir on the adult male albino rat kidney. Sixty adult male albino rats were used. The animals were divided equally into 2 main groups (I and II), and each group was divided equally into 3 subgroups (A, B, and C). In group I (control group), each rat was gavaged 0.5 ml distilled water daily for 4 weeks. In group II (sofosbuvir treated group), each albino rat was gavaged 0.5 ml distilled water containing 7.2 mg sofosbuvir daily for 4 weeks. The rats were sacrificed at the end of the 4th week (subgroups IA and IIA), 6th week (subgroups IB and IIB), and 8th week (subgroups IC and IIC) from the start of the treatment. The kidneys were used for histological study while blood samples were used for biochemical study. The obtained data were statistically analyzed. Sofosbuvir (sovaldi) induced pathological changes that gave the criteria of acute Kidney injury in the adult male albino rats. The pathological changes were confirmed by elevation of serum level of urea and creatinine. After 2 and 4 weeks of drug withdrawal, the kidney incompletely recovered. We concluded that sofosbuvir induced criteria of acute tubular injury in the kidney of the adult male albino rats. This renal injury was proved by histological and biochemical studies. These insults were incompletely reversible after the end the treatment.

Nifuroxazide Mitigates Angiogenesis in Ehlrich's Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling.

Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich's mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich's solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-ß, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.

Movement Disorders Due to Selective Basal Ganglia Lesions with Uremia.

BACKGROUND: Basal ganglia (BG) lesions are rarely reported in patients with uremia and may manifest by movement disorders. However, their exact incidence and pathogenesis have not been extensively studied. This study aimed to determine the frequency, types, risk variables (clinical, laboratory, and imaging), and manifestations of BG lesions with uremia and patients' neurologic outcomes. METHODS: This observational study included 70 adults (mean age: 45.87 ± 3.36 years; duration of uremia: 5.5 ± 1.5 years). They underwent extensive evaluations (clinical, laboratory, and neuroimaging) and had prospectively evaluated clinically every 3 months for 2 years. Repeated magnetic resonance imaging (MRI) brains were done to patients with movement disorders and correlated with their neurologic outcomes. RESULTS: BG lesions were found in 15 patients (21.4%) and 6 (8.6%) had movement disorders [Parkinsonism (n = 4), choreo-dystonia (n = 1) and dystonia (n = 1)] after the onset of uremia (mean = 10 months). There were no characteristic risk variables that distinguished patients with movement disorders from those without. Five developed movement disorders prior to the period of the study and one was de novo. The majority was females and had diabetes and higher frequencies of abnormal renal dysfunction, metabolic derangements, and white matter hyperintensities in MRIs. Movement disorders persisted in all patients despite the resolution of neuroimaging in three patients. CONCLUSIONS: There is no clear threshold for renal failure to result in movement disorders due to BG lesions. The clinical outcome is variables depending on each patient's comorbidities and complications. Persistent neuronal damage (due to uremic toxins/metabolic/nutritional and ischemic/microvascular factors) has been suggested as the cause of poor neurologic outcomes.

Effect of hexavalent chromium exposure on the liver and kidney tissues related to the expression of CYP450 and GST genes of Oreochromis niloticus fish: Role of curcumin supplemented diet.

The present study evaluated the adverse effects of the hexavalent chromium (Cr (VI)) at sub-lethal concentrations and the ameliorative potential of curcumin (CUR) over a sub-chronic exposure period on Oreochromis niloticus. Fish were exposed to Cr (VI) (4.57 mg/L) and CUR (0.02% in diet or 200 mg/kg diet), individually or in combination for 60-days. The growth rate during the period of experiment, condition factor, body composition, hepatosomatic index (HSI), hematological parameters, oxidative stress, apoptotic and DNA damage, branchial, hepato- and nephrotoxicity were estimated in this study. Moreover, the changes in mRNA expression of Cytochromes (CYP450) and glutathione S-transferase (GST) in kidney and liver tissues were assessed by qRT-PCR. Additionally, the concentration of metallothionine in the liver, histological investigation, and lesion scoring to the branchial, hepatic, renal and gill tissues were applied. The results revealed that Cr (VI) exposure caused a significant decline in most hematological variables and growth rate with down-regulation of CYP450 and GST expression. Histologically, Cr (VI) induced diverse forms of cell injury, vascular, and inflammatory alterations with upregulation of caspase-3 and downregulation of Bcl2 expression in the examined tissues. Additionally, it elevated the levels of serum MDA and 8-hydroxy-2' -deoxyguanosine than control. CUR-supplementation resulted in a significant improvement in most indices, amelioration of histological alterations and up-regulation of CYP450 and GST expression. These results may conclude that dietary supplements with CUR could be useful for modulation of the growth with protective effects to the branchial, hepatic, and renal tissues in response to Cr (VI) exposure, thereby presenting a promising feed additive for Nile tilapia in aquaculture.

Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation.

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl ßeta-cyclodextrin (HPß-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer-Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.

Food Yellow4 reprotoxicity in relation to localization of DMC1 and apoptosis in rat testes: Roles of royal jelly and cod liver oil.

Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4 mL/kg), the RJ group (300 mg/kg), the FY4 group (500 mg/kg b.w.), and the co-treated groups (FY4 + CLO or FY4 + RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.

Fenpropathrin induces testicular damage, apoptosis, and genomic DNA damage in adult rats: Protective role of camel milk.

Fenpropathrin (FNP) is a member of the synthetic pyrethroids. Herein, the present study was conducted to investigate, for the first time, the potentially harmful effects of FNP on the reproductive system of male rats. In addition, the prophylactic or concurrent influence of camel milk (CM) was assessed. Adult male rats were divided into five groups; control, vehicle control (oil), CM (2ml/rat/day), FNP (15mg/kg bwt/60 days), CM/FNP (prophylaxis) and FNP /CM (co-treated) groups. Sperm morphology, count, serum testosterone (TES), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), superoxide dismutase (SOD), testicular enzymes, and comet assay analysis were estimated. In addition, histopathology, the ultrastructure of testicular tissue and apoptosis were evaluated. Reduced body weight and gonadosomatic index were observed in the FNP exposed group. TES, LH, FSH were markedly declined following FNP treatment. SOD and TAC concentrations were reduced while PC and TBARS were significantly elevated in FNP group indicating oxidative stress. Furthermore, FNP induced DNA damage and apoptosis in the testis which was evidenced histopathologically and by electron microscope examination. CM significantly counteracted FNP reprotoxic effects, particularly at the prophylactic routine (CM/FNP) than the co-exposure (FNP/CM) one. Conclusively, these findings verified that CM could be a potential candidate therapy against FNP reprotoxic impacts.

Aß inhibits SREBP-2 activation through Akt inhibition.

We previously demonstrated that oligomeric amyloid ß42 (oAß42) inhibits the mevalonate pathway impairing cholesterol synthesis and protein prenylation. Enzymes of the mevalonate pathway are regulated by the transcription factor SREBP-2. Here, we show that in several neuronal types challenged with oAß42, SREBP-2 activation is reduced. Moreover, SREBP-2 activation is also decreased in the brain cortex of the Alzheimer's disease (AD) mouse model, TgCRND8, suggesting that SREBP-2 may be affected in vivo early in the disease. We demonstrate that oAß42 does not affect enzymatic cleavage of SREBP-2 per se, but may impair SREBP-2 transport from the endoplasmic reticulum (ER) to the Golgi. Trafficking of SREBP-2 from the ER to the Golgi requires protein kinase B (Akt) activation. oAß42 significantly reduces Akt phosphorylation and this decrease is responsible for the decline in SREBP-2 activation. Overexpression of constitutively active Akt prevents the effect of oAß42 on SREBP-2 and the downstream inhibition of cholesterol synthesis and protein prenylation. Our work provides a novel mechanistic link between Aß and the mevalonate pathway, which will impact the views on issues related to cholesterol, isoprenoids, and statins in AD. We also identify SREBP-2 as an indirect target of Akt in neurons, which may play a role in the cross-talk between AD and diabetes.

Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate the Pancreatic Changes of Chemically Induced Hypothyroidism by Carbimazole in Male Rats.

We induced hypothyroidism (HT) in male rats through chronic oral administration of carbimazole and then tested whether an i.v. injection of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate the HT-induced changes in pancreatic structure and function. The thyroid and pancreatic function tests, as well as total antioxidant capacity (TAC) and malondialdehyde (MDA) were estimated. The pancreatic structure was evaluated by hematoxylin and eosin (H&E) stain. Insulin protein and cleaved caspase-3 were detected immunohistochemically. The degree of apoptosis was assessed by TUNEL assay. The morphometric measurements were done by an image analyzer system and the obtained data were statistically analyzed. HT rats showed hyperglycemia associated with insulin deficiency, decreased TAC and increased MDA levels. H&E-stained sections showed that the pancreatic septa were infiltrated with acidophilic material. Some acini were vacuolated while others showed depleted acidophilia and dilated lumina. Spindle-shaped cells were accumulated within deformed islets in HT rats. The positive reaction with anti-cleaved caspase-3 was exclusively noted in the cytoplasm of islet cells with no immunostaining reaction in the acinar and ductal cells, whereas the positively stained nuclei with TUNEL were demonstrated in the islet and acinar cells. A significant increase in the apoptotic index % of both markers was detected. Injection of BM-MSCs in HT rats restored all biochemical indicators of disturbed pancreatic function to normal level and improved pancreatic structure, resulting in a clear septa and normal appearance of acini and islets. In conclusion, many of the significant structural and func tional pancreatic alterations detected in HT rats were ameliorated after the injection of BM-MSCs. These data demonstrate the ability of BM-MSCs to repair pancreatic disturbances. Further studies on humans are necessary to determine the potential clinical applications of BM-MSCs.

Influences of Chlorella vulgaris dietary supplementation on growth performance, hematology, immune response and disease resistance in Oreochromis niloticus exposed to sub-lethal concentrations of penoxsulam herbicide.

Little is known regarding the impact of penoxsulam, a fluorinated benzenesulfonamid rice herbicide, on Oreochromis niloticus (O. niloticus). Therefore, the current study was undertaken to highlight the effects of penoxsulam exposure on O. niloticus and to evaluate the advantages of Chlorella vulgaris (CV) dietary supplementation against the induced effects. The 96-h lethal concentration 50 (LC50) penoxsulam value for O. niloticus was estimated at 8.948 mg/L by probit analysis in a static bioassay experiment. Next, 360 healthy fish were randomly allocated into 6 treatment groups. The T1 group served as the negative control and was fed a basal diet. The T2 group served as the positive control and was fed a basal diet supplemented with 10% CV. The fish in the T3 and T4 groups were exposed to 1/10 the 96-h LC50 of penoxsulam (0.8948 mg/L) and were fed the basal diet alone or the basal diet supplemented with 10% CV, respectively. The fish in the T5 and T6 groups were exposed to 1/5 the 96-h LC50 of penoxsulam (1.7896 mg/L) and fed the basal diet alone or the basal diet supplemented with 10% CV, respectively. Sub-acute penoxsulam exposure significantly altered hematological indices, as well as compromised the fish's immune defense mechanisms, including the phagocytic percentage, phagocytic index, nitric oxide production, immunoglobulin M levels and lysozyme, anti-trypsin and bactericidal activities subsequently decreasing O. niloticus's resistance to the Aeromonus sobria challenge and increasing disease symptoms and the mortality rate. Furthermore, sub-chronic penoxsulam exposure markedly altered growth performance, oxidant/antioxidant status and liver status and down-regulated the expression of interleukin-1ß (IL-1ß) and tumor necrosis-α (TNF-α). Interestingly, incorporating 10% CV into the diet protects fish against sub-acute penoxsulam-induced immunotoxicity via improvement of immune responses that increases the resistance against bacterial infection. Further, it improved the growth performance, oxidant/antioxidant status, liver status and markedly up-regulated immune-related gene expression, IL-1ß and TNF-α, in the spleens of fish sub-chronically exposed to penoxsulam. These outcomes showed that dietary CV supplementation can protect the commercially valuable freshwater fish O. niloticus against penoxsulam toxicity and may be a potential feed supplement for Nile tilapia in aquaculture.

Microwave-Assisted Synthesis of some Novel Azoles and Azolopyrimidines as Antimicrobial Agents.

In this study, new derivatives of pyrazole, isoxazole, pyrazolylthiazole, and azolopyrimidine having a thiophene ring were synthesized under microwave irradiation. Their pharmacological activity toward bacteria and fungi inhibition was screened and compared to the references Chloramphenicol and Trimethoprim/sulphamethoxazole. The antimicrobial results of the investigated compounds revealed promising results and some derivatives have activities similar to the references used.

Role of serotonin and nuclear factor-kappa B in the ameliorative effect of ginger on acetic acid-induced colitis.

The current study was designed to investigate the role of serotonin (5-HT) and nuclear factor-kappa beta (NF-κB) in the ameliorative effect of ginger on acetic acid (AA)-induced colitis rat model. Colitis was induced by intra-colonic instillation of 3% AA, preceded or followed by daily administration of ginger (400mg/kg) by gavage for 5 days. Colons were assessed macroscopically and microscopically and the expression of NF-κB was evaluated by immunohistochemistry. Colonic tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), total peroxide (TP), and serum 5-HT levels were assessed. Administration of ginger ameliorated the effects of AA-induced colitis by plummeting colon weight-to-length ratio, macroscopic and microscopic scores. These effects were further supported by down-regulation of NF-κB and reduction of colonic TNF-α, IL-10, TP and serum 5-HT levels. Moreover, there were significant positive correlations between serum 5-HT and macroscopic, microscopic, immunoreactivity scores and colonic TNF-α level. In conclusion, ginger ameliorated AA-induced colitis not only through its anti-inflammatory and anti-oxidant properties, but also through the reduction of 5-HT which may contribute to the down-regulation of NF-κB-dependent TNF-α expression and the reduction of lipid peroxidation and tissue damage. In addition, the therapeutic effect of ginger was more pronounced than its preventive effect.

Molecular mechanisms underlying fibrosis and elastin destruction in childhood interstitial lung diseases.

OBJECTIVE: This study aimed to evaluate fibrosis and elastin destruction in childhood interstitial lung disease (chILD) patients. METHODS: Sixty patients and twenty healthy children were recruited. On admission, evaluation of chILD severity was made using Fan chILD score. Participants provided urine and blood samples. Plasma levels of transforming growth factor (TGF)-ß1, connective tissue growth factor (CCN2), soluble factor related apoptosis (sFas) and long non-coding RNAs and urinary levels of desmosine/urinary creatinine (UDes/UCr) were measured. RESULTS: In patients, clinical findings were crackles (100.00%), tachypnea (65.00%), cardiomegaly (45.00%), digital clubbing (43.30%), cough (33.00%), cyanosis (26.70%), hepatomegaly (28.30%) and wheezes (23.30%). Categorizing of the patients with Fan chILD clinical score revealed that most patients 33.30% scored (3, symptomatic with abnormal saturation/cyanosis during exercise) then 28.30% scored (5, symptomatic with clinical and echocardiographic features of pulmonary hypertension), 18.30% scored (2, symptomatic with normal room air saturations), 15.00% scored (1, asymptomatic) and 5.00% scored (4, symptomatic with abnormal room air saturation/cyanosis at rest). TGF-ß1, CCN2, sFas, lncrRNA-2700086A05Rik relative gene expression and UDes/UCr levels were higher in patients than controls (P=0.002, P=0.001, P=0.001, P=0.001, P=0.001, respectively). In patients, significant positive correlations were found between TGF-ß1 and CCN2, sFas, UDes/UCr; between CCN2 and both sFas and UDes/UCr; between UDes/UCr and sFas. Morbidity and mortality rates were 46.70% and 10.00%, respectively. CONCLUSION: Markers of fibrosis (TGF-ß1, sFas, CCN2) and elastin destruction (UDes/UCr) were increased in chILD especially in patients with long disease duration. So blockage of their pathways signals may offer novel therapeutic targets.

Increased levels of type 1 interferon in a type 1 diabetic mouse model induce the elimination of B cells from the periphery by apoptosis and increase their retention in the spleen.

BACKGROUND: The autoimmune disease type 1 diabetes mellitus (T1D) is associated with a defect in the immune response, which increases susceptibility to infection. We recently demonstrated that prolonged elevated levels of type 1 interferon (IFN) induce lymphocyte exhaustion during T1D. AIMS: In the present study, we further investigated the effect of blocking the type I IFN receptor signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile leads to the exhaustion of B cells and alteration of their distribution and functions. METHODS: T1D was induced in a mouse model by an intraperitoneal injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of mice were examined: a non-diabetic control group, a diabetic group and a diabetic group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1) blocking antibody to block type I IFN signaling. RESULTS: We observed that induction of T1D was accompanied by a marked destruction of ß cells and a reduction in the insulin levels in the diabetic group. Diabetic mice exhibited many changes, including alterations in their lipid profiles, expansion of splenic B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the insulin and lipid profiles to normal levels, subsequently restored the B cell distribution, and rescued the peripheral B cells from apoptosis. CONCLUSION: Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D.

Increased susceptibility to apoptosis and growth arrest of human breast cancer cells treated by a snake venom-loaded silica nanoparticles.

BACKGROUND: The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV), either alone or in combination with silica nanoparticles (WEV+NP), resulted in the growth arrest and apoptosis of different cancer cell lines. AIMS: In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies. METHODS: The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA. RESULTS: WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS), hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells. CONCLUSION: Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.