Monitoring the effects of fungi isolated from archival document on model albumen silver prints.

Fungi are a common problem in the photographic collection, so the aim of this study focused on isolating and molecular identification of fungi from old albumen prints dating to an archive of Dr. Francis and belonging to the Al-Hagar Family and dating back to 1880-1890. The isolated fungi were identified according to their morphological traits and PCR sequencing. The ability of these isolates to cause deterioration was evaluated on model samples (2 × 2 cm) of albumen silver prints. The effect of these fungi on the morphology and structure of the tested samples were examined by SEM, ATR-FTIR, and chromatic alternations. Four fungal species Aspergillus sydowii, A. flavus, Talaromyces atroroseus, and Penicillium chrysogenum were identified. All isolates were able to grow on the surface of the model Albumen silver print and were capable of causing damage to the binder and able to extend their growth to the paper fibers. A. sydowii, A. flavus, and P. chrysogenum caused hydrolysis and oxidation to the albumen prints, while no significant chemical damage to the albumen was detected for the photographic sample infected with T. atroroseus. All the inoculated samples were significantly affected in terms of color change and the high-light areas have become darker. ATR-FTIR spectra showed the degradation of the protein content in Albumen silver prints inoculated with A. sydowii, A. flavus, and P. chrysogenum.

Inhibition of boldenone-induced aggression in rats by curcumin: Targeting TLR4/MyD88/TRAF-6/NF-κB pathway.

The illicit abuse of anabolic steroids is associated with brutal aggression, which represents a serious health hazard and social threat. Boldenone is commonly used for doping by athletes and adolescents for esthetic purposes and to enhance performance and endurance during competitions. However, the mechanistic pathways underlying boldenone-induced behavioral deviations and neuronal toxicity have not yet been elucidated. On the other hand, the natural polyphenol curcumin is appreciated for its relative safety, potent antioxidant activity, and anti-inflammatory properties. Therefore, the present study was initiated to explore the signaling pathways underlying boldenone-induced anxiety and aggression in rats, and the protective effects of curcumin. To achieve this aim, male Wistar albino rats were randomly distributed into control, curcumin (100 mg/kg in sesame oil, p.o., once daily), boldenone (5 mg/kg, intramuscular, once weekly), and combination groups. Rats were challenged across the open field, irritability, defensive aggression, and resident-intruder tests. The prefrontal cortex was used to assess serotonin level, oxidative stress markers, and mRNA expression of myeloid differentiation primary response gene (MyD88), TNFR-associated factor 6 (TRAF-6), tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), protein expression of toll-like receptor 4 (TLR4), and phosphorylated nuclear factor-κB transcription factor (NF-κB p65). Unprecedented, the current results showed that boldenone elicited aggression in rats accompanied by depleted serotonin, enhanced oxidative stress, and exaggerated inflammatory response via upregulation of TLR4/MyD88/TRAF-6/NF-κB pathway. Interestingly, curcumin mitigated boldenone-induced neurobehavioral disturbances in rats, normalized the oxidant/antioxidant balance, and suppressed TLR4/MyD88/TRAF-6/NF-κB pathway and its downstream proinflammatory signaling molecules TNF-α and IL-1ß.

Lansoprazole enhances the antidiabetic effect of dapagliflozin in fortified diet-fed streptozotocin-treated diabetic rats.

Dapagliflozin (DAPA) is used for treating type 2 diabetes, whereas lansoprazole (LPZ) is used as a traditional antiulcer drug. The present study investigated the possible antidiabetic effects of LPZ on fortified diet-fed streptozotocin (FDF/STZ)-induced insulin-resistant diabetic rats. On the basis of the current results, it can be concluded that LPZ could be used as an add-on drug along with the conventional treatment for T2D as it showed beneficial effects in the current experimental model of insulin resistance.

Montelukast attenuates rotenone-induced microglial activation/p38 MAPK expression in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic effects.

Montelukast (MK),a cysteinyl leukotriene (CysLT1) receptor antagonist, latterly exhibited a remarkable neuroprotective activity in various neurodegenerative disorders. This study aims to elucidate the neuroprotective effect of MK in rotenone-induced Parkinson's disease(PD) model in rats. Ninety six male rats were split into four groups: vehicle control (0.2 ml/kg/48 h, sc), MK (10 mg/kg/day, ip), rotenone (1.5 mg/kg/48 h, sc.) and rotenone pretreated with MK. Rotenone treatment led to significant reduction in motor functioning and elevation in oxidative stress markers. Additionally, upregulation of p38 mitogen-activated protein kinase (p38 MAPK) and CysLT1 receptor expressions were anchored with enhanced striatal microglial activation generating a severe neuro-inflammatory milieu. Furthermore, an augmentation in p53 expression and cleaved caspases-3 activity increased apoptotic neurodegeneration synchronized with reduction of striatal tyrosine hydroxylase (TH) content. Changes in neuronal morphology was also noted. MK administration significantly mitigated motor impairment and rise in oxidative stress mediators. As well, the anti-inflammatory activity of MK was manifested by hindering the principal controller of inflammatory pathway, nuclear factor-kappa B, followed by its downstream pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta), by attenuating striatal microglial activation and hampering the expression of both p38 MAPK and CysLT1. Moreover, MK revealed a decline in p53 expression with its downstream cleaved caspases-3 which resulted in preservation of striatal TH terminals as verified by increased striatal TH content and improvement in the histopathological changes incited by rotenone. In conclusion, MK endowed neuroprotective effects in rotenone-induced PD animal model via attenuation of microglial cell activation and p38 MAPK expression.

Non-alcoholic fatty liver disease resolution following sleeve gastrectomy.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a disease highly prevalent among the morbidly obese population, is one of the most common causes of chronic liver disease today. The purpose of this study was to observe the effect of laparoscopic sleeve gastrectomy (LSG) on the resolution of NAFLD. METHODS: A retrospective study was conducted of 84 patients diagnosed with NAFLD prior to undergoing LSG. The diagnosis of NAFLD was achieved based on transabdominal ultrasonographic imaging as per the 2012 joint guidelines for the diagnosis of NAFLD (American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology). The patients had follow-up anthropometric measurements and were re-evaluated with postoperative ultrasounds at different time frames to assess the resolution of the disease. RESULTS: The median age of the patients was 44 (17-62), and 66.7 % were female. Average time since surgery was 3.3 years (range 1-5 years). The mean pre- and postoperative BMIs were 46.6 ± 7.8 and 33.0 ± 7.1, respectively, with a mean percent excess weight loss (%EWL) of 55.7 % ± 23.0. A total of 47 (56 %) patients showed complete resolution of NAFLD postoperatively. Multivariate analysis showed a significant resolution of NAFLD in patients achieving >50 % EWL (OR 10.1; p < 0.001) after controlling for age and sex. CONCLUSIONS: Weight loss after LSG effectively resolved NAFLD in more than half of the obese patients in this study and can prove to be a useful tool in tackling the disease in the future.

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway.

The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free ß-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10mg/kg/week, I.M.), taurine (100mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3ß-HSD, and 17ß-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats.

Lipoic acid and pentoxifylline mitigate nandrolone decanoate-induced neurobehavioral perturbations in rats via re-balance of brain neurotransmitters, up-regulation of Nrf2/HO-1 pathway, and down-regulation of TNFR1 expression.

Behavioral perturbations associated with nandrolone decanoate abuse by athletes and adolescents may be attributed to oxidative stress and inflammation. However, the underlying mechanisms are not yet fully explored. On the other hand, the natural antioxidant lipoic acid can pass the blood brain barrier and enhance Nrf2/HO-1 (nuclear factor erythroid-2 related factor 2/heme oxygenase-1) pathway. In addition, the phosphodiesterase-IV inhibitor xanthine derivative pentoxifylline has a remarkable inhibitory effect on tumor necrosis factor-alpha (TNF-α). Therefore, this study aimed at investigation of the possible protective effects of lipoic acid and/or pentoxifylline against nandrolone-induced neurobehavioral alterations in rats. Accordingly, male albino rats were randomly distributed into seven groups and treated with either vehicle, nandrolone (15mg/kg, every third day, s.c.), lipoic acid (100mg/kg/day, p.o.), pentoxifylline (200mg/kg/day, i.p.), or nandrolone with lipoic acid and/or pentoxifylline. Rats were challenged in the open field, rewarded T-maze, Morris water maze, and resident-intruder aggression behavioral tests. The present findings showed that nandrolone induced hyperlocomotion, anxiety, memory impairment, and aggression in rats. These behavioral abnormalities were accompanied by several biochemical changes, including altered levels of brain monoamines, GABA, and acetylcholine, enhanced levels of malondialdehyde and TNF-α, elevated activity of acetylcholinesterase, and up-regulated expression of TNF-α receptor-1 (TNFR1). In addition, inhibited catalase activity, down-regulated Nrf2/HO-1 pathway, and suppressed acetylcholine receptor expression were observed. Lipoic acid and pentoxifylline combination significantly mitigated all the previously mentioned deleterious effects mainly via up-regulation of Nrf2/HO-1 pathway, inhibition of TNF-α and down-regulation of TNFR1 expression. In conclusion, the biochemical and histopathological findings of this study revealed the protective mechanisms of lipoic acid and pentoxifylline against nandrolone-induced behavioral changes and neurotoxicity in rats.

Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats.

CONTEXT: Ulcerative colitis is a chronic inflammatory bowel disease. Recent studies reported a pivotal role of elevated intracellular calcium in this disorder. Coenzyme Q10 (CoQ10) and amlodipine are known to maintain cellular energy, decrease intracellular calcium concentration in addition to their antioxidant and anti-inflammatory properties. OBJECTIVE: The aim of this study was to evaluate the possible protective effects of CoQ10, amlodipine and their combination on ulcerative colitis. MATERIALS AND METHODS: Colitis was induced in rats by intracolonic injection of 3% acetic acid. CoQ10 (10 mg/kg), amlodipine (3 mg/kg) and their combination were administered for 8 consecutive days before induction of colitis. RESULTS: Our results showed that administration of CoQ10, amlodipine and their combination decreased colon tissue malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), prostaglandin E2 (PGE2), myeloperoxidase (MPO) and heat shock protein (HSP70) levels induced by intracolonic injection of acetic acid and restored many of the colon structure in histological examination. On the other hand, they increased superoxide dismutase (SOD) activity, adenosine-5'-triphosphate (ATP) and interleukin-10 (IL-10) colonic contents. DISCUSSION AND CONCLUSION: Administration of either CoQ10 or amlodipine was found to protect against acetic acid-induced colitis. Moreover, their combination was more effective than individual administration of either of them. The protective effect of CoQ10 and amlodipine may be in part via their antioxidant, anti-inflammatory and energy restoration properties.

Neuroprotective effects of idebenone against pilocarpine-induced seizures: modulation of antioxidant status, DNA damage and Na(+), K (+)-ATPase activity in rat hippocampus.

The current study investigated the neuroprotective activity of idebenone against pilocarpine-induced seizures and hippocampal injury in rats. Idebenone is a ubiquinone analog with antioxidant, and ATP replenishment effects. It is well tolerated and has low toxicity. Previous studies reported the protective effects of idebenone against neurodegenerative diseases such as Friedreich's ataxia and Alzheimer's disease. So far, the efficacy of idebenone in experimental models of seizures has not been tested. To achieve this aim, rats were randomly distributed into six groups. Two groups were treated with either normal saline (0.9 %, i.p., control group) or idebenone (200 mg/kg, i.p., Ideb200 group) for three successive days. Rats of the other four groups (P400, Ideb50 + P400, Ideb100 + P400, and Ideb200 + P400) received either saline or idebenone (50, 100, 200 mg/kg, i.p.) for 3 days, respectively followed by a single dose of pilocarpine (400 mg/kg, i.p.). All rats were observed for 6 h post pilocarpine injection. Latency to the first seizure, and percentages of seizures and survival were recorded. Surviving animals were sacrificed, and the hippocampal tissues were separated and used for the measurement of lipid peroxides, total nitrate/nitrite, glutathione and DNA fragmentation levels, in addition to catalase and Na(+), K(+)-ATPase activities. Results revealed that in a dose-dependent manner, idebenone (100, 200 mg/kg) prolonged the latency to the first seizure, elevated the percentage of survival and diminished the percentage of pilocapine-induced seizures in rats. Significant increases in lipid peroxides, total nitrate/nitrite, DNA fragmentation levels and catalase activity, in addition to a significant reduction in glutathione level and Na(+), K(+)-ATPase activity were observed in pilocarpine group. Pre-administration of idebenone (100, 200 mg/kg, i.p.) to pilocarpine-treated rats, significantly reduced lipid peroxides, total nitrate/nitrite, DNA fragmentation levels, and normalized catalase activity. Moreover, idebenone prevented pilocarpine-induced detrimental effects on brain hippocampal glutathione level, and Na(+), K(+)-ATPase enzyme activity in rats. Data obtained from the current investigation emphasized the critical role of oxidative stress in induction of seizures by pilocarpine and elucidated the prominent neuroprotective and antioxidant activities of idebenone in this model.

Neuroprotective effects of vitamin D in an Alzheimer's disease rat model: Improvement of mitochondrial dysfunction via calcium/calmodulin-dependent protein kinase kinase 2 activation of Sirtuin1 phosphorylation.

Mitochondrial dysfunction is an early event in Alzheimer's disease (AD) pathogenesis. To assess the impact of vitamin D3 (Vit.D) on neurogenesis, we investigated its role in mitigating cognitive impairment and mitochondrial dysfunction through calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)-mediated phosphorylation of Sirtuin1 (SIRT1) in an aluminum-chloride-D-galactose (AlCl3-D-gal)-induced AD rat model. Rats were distributed into four groups: control, AlCl3 + D-gal (10 + 60 mg/kg, ip), Vit.D (500 IU/kg, po), and AlCl3 + D-gal+Vit.D. Novel object recognition (NOR), Morris Water Maze, and passive avoidance (PA) tests were used to measure memory abilities. The hippocampal tissue was used to assess vitamin D3 receptor (VDR) and peroxisome-proliferator-activated-receptor-γ-coactivator-1α (PGC-1α) expression by quantitative real-time polymerase chain reaction (qRT-PCR), CAMKK2, p-SIRT1, phosphorylated-AMP-activated protein kinase (p-AMPK), dynamin-related-protein-1 (Drp1), and mitofusin-1 (Mnf1) proteins by western blot and Ca2+ levels, endothelial nitic oxide synthase (eNOS), superoxide dismutase (SOD), amyloid beta (Aß), and phospho tau (p-Tau) via enzyme-linked immunosorbent assay(ELISA) in addition to histological and ultrastructural examination of rat's brain tissue. Vit.D-attenuated hippocampal injury reversed the cognitive decline and Aß aggregation, and elevated p-Tau levels in the AlCl3 + D-gal-induced AD rat model. In AlCl3 + D-gal-exposed rats, Vit.D induced VDR expression, normalized Ca2+ levels, elevated CAMKK2, p-AMPK, p-SIRT1, and PGC-1α expression. Vit.D reduced Drp1, induced Mnf1, increased mitochondrial membrane potential, preserved mitochondrial structure, restored normal mitochondrial function, and retained normal eNOS level and SOD activity in AlCl3 + D-gal rats. In conclusion, our findings proved that Vit.D may ameliorate cognitive deficits in AlCl3 + D-gal-induced AD by restoring normal mitochondrial function and reducing inflammatory and oxidative stress via CAMKK2-AMPK/SIRT1 pathway upregulation.

The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Melatonin protects against diazinon-induced neurobehavioral changes in rats.

Diazinon is an organophosphorous pesticide with a prominent toxicity on many body organs. Multiple mechanisms contribute to diazinon-induced deleterious effects. Inhibition of acetyl-cholinesterase, cholinergic hyperstimulation, and formation of reactive oxygen species may play a role. On the other hand, melatonin is a pineal hormone with a well-known potent antioxidant activity and a remarkable modulatory effect on many behavioral processes. The present study revealed that oral diazinon administration (25 mg/kg) increased anxiety behavior in rats subjected to elevated plus maze and open-field tests possibly via the induction of changes in brain monoamines levels (dopamine, norepinephrine, and serotonin). Additionally, brain lipid peroxides measured as malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) levels were elevated, while the activity of brain glutathione peroxidase enzyme was reduced by diazinon. Co-administration of oral melatonin (10 mg/kg) significantly attenuated the anxiogenic activity of diazinon, rebalanced brain monoamines levels, decreased brain MDA and TNF-α levels, and increased the activity of brain glutathione peroxidase enzyme.

Pathogenicity Spectra and Screening for Resistance in Barley Against Tunisian Pyrenophora teres f. teres.

This work aimed to determine patterns of pathogenicity in Pyrenophora teres f. teres and to identify potentially effective resistance sources that could be used as breeding material to control net blotch in Tunisia. Extensive pathogenic variability was detected in 85 isolates of P. teres causing net blotch of barley in Tunisia. Based on unweighted pair-group method with arithmetic averaging clustering and mean disease rating scores, three distinct virulence groups were identified. The isolates were classified into 23 pathotypes. Pathogenic variability within the groups was higher than that between the groups, a finding that can guide a rational choice of isolates for screening lines as part of a breeding program. Conversely, studying the relationship between geographic and pathotypic structure allowed us to detect a significant isolation by distance pattern, suggesting a regular and gradual dispersal of the pathogen over this spatial scale. Using specific resistance properties of individual barley genotypes as virulence markers, all the differential barley genotypes were shown to be distinct, and no single source of resistance was totally effective against all isolates.

Addressing Peroxisome Proliferator-Activated Receptor-gamma in 3-Nitropropionic Acid-Induced Striatal Neurotoxicity in Rats.

Telmisartan (TEL) is an angiotensin II type 1 receptor blocker and a partial activator of peroxisome proliferator-activated receptor-gamma (PPARγ), which regulates inflammatory and apoptotic pathways. Increasing evidence has demonstrated the PPARγ agonistic property of TEL in several brain disorders. This study aims to explore the neuroprotective impact of TEL in 3-nitropropionic acid (3-NP)-induced neurotoxicity in rats. The PPARγ effect of TEL was affirmed by using the PPARγ agonist pioglitazone (PIO), and the antagonist GW9662. 3-NP led to a significant reduction in body weight alongside motor and cognitive functioning. The striata of the 3-NP-treated rats showed energy-deficit, microglia-mediated inflammatory reactions, apoptotic damage as well as histopathological lesions. PIO and TEL improved motor and cognitive perturbations induced by 3-NP, as confirmed by striatal histopathological examination, energy restoration, and neuronal preservation. Both drugs improved mitochondrial biogenesis evidenced by elevated mRNA expression of PPARγ, PGC-1α, and TFAM, alongside increased striatal ATP and SDH. The mitochondrial effect of TEL was beyond PPARγ activation. As well, their anti-inflammatory effect was attributed to suppression of microglial activation, and protein expression of pS536 p65 NF-κB with marked attenuation of striatal inflammatory mediator's release. Anti-inflammatory cytokine IL-10 expression was concurrently increased. TEL effectively participated in neuronal survival as it promoted phosphorylation of Akt/GSK-3ß, further increased Bcl-2 expression, and inhibited cleavage of caspase-3. Interestingly, co-treatment with GW9662 partially revoked the beneficial effects of TEL. These findings recommend that TEL improves motor and cognitive performance, while reducing neuronal inflammation and apoptosis in 3-NP-induced neurotoxicity via a PPARγ-dependent mechanism.

Protective effects of Folic acid against reproductive, hematological, hepatic, and renal toxicity induced by Acetamiprid in male Albino rats.

Acetamiprid (ACP) is a widespread used insecticide belonging to neonicotinoids (NNs) that are introduced for controlling pests, and for domestic use to control fleas on cats and dogs. The current experiment pertains to a comprehensive overview of the toxic effects of acetamiprid and the protective role of folic acid against reproductive, hematological, histopathological and biochemical toxicity induced by ACP during 5 weeks. Male Albino rats were divided into four groups of seven each: First group served as control rats (CL group); Second group received acetamiprid (ACP group) (10 mg/Kg body weight) by oral gavage. Third group received both acetamiprid and folic acid (ACP + FA group) (2 mg/Kg body weight); Fourth group received folic acid (FA group) (2 mg/Kg body weight). Exposure of rats to acetamiprid caused significant changes in the reproductive indices as it cause a significant decrease in the sperm count, viability and motility. Furthermore, reproductive hormones such as testosterone and gonadotropin-releasing hormones (GnRH) were found significantly decreased in acetamiprid treated group. In addition, acetamiprid administration causes significant changes of some hematological and immunological parameters (red blood cells (RBC), hemoglobin (Hb), platelet (Plt), white blood cells (WBCs), lymphocyte, monocyte, neutrophil, eosinophil, IgG, IgM and IgA) in treated rats compared to controls. Significant increases in the levels of hepatic markers enzymes (aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) in acetamiprid treated group, as well as severe toxic effect was found on the liver and kidney after acetamiprid delivery according to the histopathological examinations which were confirmed after applying histological, histochemical, and Immunohistochemistry tests. The most conspicuous histopathological changes occurred on the liver and kidney of the acetamiprid treated group represented in the liver by fatty liver cells, leukocytic infiltration, and hemorrhage while in kidney tissues revealed tubular atrophy, dense eosinophilic cytoplasm and dilated congested blood vessels. Both liver and kidney tissues showed an increase in the amount of collagenous fibers and immune reactivity of fatty acid synthase. Moreover, other markers such as uric acid and total antioxidant capacity (TAC) were significantly decreased in acetamiprid treated rats. Co-administration of folic acid to the third group restored all the parameters cited above to near-normal values. Therefore, our investigation revealed that acetamiprid induce severe toxicity on different body systems and parameters and folic acid appeared to be a promising agent for protection against acetamiprid-induced toxicity.

Recent developments in alginate-based adsorbents for removing phosphate ions from wastewater: a review.

The huge development of the industrial sector has resulted in the release of large quantities of phosphate anions which adversely affect the environment, human health, and aquatic ecosystems. Naturally occurring biopolymers have attracted considerable attention as efficient adsorbents for phosphate anions due to their biocompatibility, biodegradability, environmentally-friendly nature, low-cost production, availability in nature, and ease of modification. Amongst them, alginate-based adsorbents are considered one of the most effective adsorbents for removing various types of pollutants from industrial wastewater. The presence of active COOH and OH- groups along the alginate backbone facilitate its physical and chemical modifications and participate in various possible adsorption mechanisms of phosphate anions. Herein, we focus our attention on presenting a comprehensive overview of recent advances in phosphate removal by alginate-based adsorbents. Modification of alginate by various materials, including clays, magnetic materials, layered double hydroxides, carbon materials, and multivalent metals, is addressed. The adsorption potentials of these modified forms for removing phosphate anions, in addition to their adsorption mechanisms are clearly discussed. It is concluded that ion exchange, complexation, precipitation, Lewis acid-base interaction and electrostatic interaction are the most common adsorption mechanisms of phosphate removal by alginate-based adsorbents. Pseudo-2nd order and Freundlich isotherms were figured out to be the major kinetic and isotherm models for the removal process of phosphate. The research findings revealed that some issues, including the high cost of production, leaching, and low efficiency of recyclability of alginate-based adsorbents still need to be resolved. Future trends that could inspire further studies to find the best solutions for removing phosphate anions from aquatic systems are also elaborated, such as the synthesis of magnetic-based alginate and various-shaped alginate nanocomposites that are capable of preventing the leaching of the active materials.

Nano-ivabradine averts behavioral anomalies in Huntington's disease rat model via modulating Rhes/m-tor pathway.

Huntington's disease (HD) is characterized by abnormal involuntary movements together with cognitive impairment and disrupted mood changes. 3-nitropropionic acid (3-NP) is one of the chemo-toxic models used to address the striatal neurotoxicity pattern encountered in HD. This study aims to explain the neuroprotective effect of nano-formulated ivabradine (nano IVA) in enhancing behavioral changes related to 3-NP model and to identify the involvement of ras homolog enriched striatum (Rhes)/mammalian target of rapamycin (m-Tor) mediated autophagy pathway. Rats were divided into 6 groups, the first 3 groups received saline (control), ivabradine (IVA), nano IVA respectively, the fourth received a daily dose of 3-NP (20 mg/kg, s.c) for 2 weeks, the fifth received 3-NP + IVA (1 mg/kg, into the tail vein, every other day for 1 week) and the last group received 3-NP + nano IVA (1 mg/kg, i.v, every other day for 1 week). Interestingly, nano IVA reversed motor disabilities, improved memory function and overcame the psychiatric changes. It boosted expression of autophagy markers combined with down regulation of Rhes, m-Tor and b-cell lymphoma 2 protein levels. Also, it restored the normal level of neurotransmitters and myocardial function related-proteins. Histopathological examination revealed a preserved striatal structure with decreased number of darkly-degenerated neurons. In conclusion, the outcomes of this study provide a well-recognized clue for the promising neuroprotective effect of IVA and the implication of autophagy and Rhes/m-Tor pathways in the 3-NP induced HD and highlight the fact that nano formulations of IVA would be an auspicious approach in HD therapy.

Liraglutide mends cognitive impairment by averting Notch signaling pathway overexpression in a rat model of polycystic ovary syndrome.

AIMS: Polycystic ovary syndrome (PCOS), the rifest endocrine disorder in women, is involved in disrupting many metabolic processes. However, the impact of PCOS on cognitive deficits is still uncertain. Recently, Notch signaling pathway was identified as a key modifier in regulating the pathological process in the ovary and various neurodegenerative disorders. Liraglutide has favourable neuroprotective effects that may protect against the possible cognitive dysfunction in PCOS. MAIN METHODS: PCOS was induced in rats by administrating Letrozole orally for 21 successive days. Then, Liraglutide (LIR) was administered intraperitoneally for 30 days. Memory was examined using Y-maze, novel object recognition (NOR), and Morris water maze (MWM) tests. Western blotting, enzyme immunoassay, and quantitative real-time PCR were used to examine Notch signaling downstream targets, as well as assessing the expression of the components of various pathways cross talked with Notch signaling in memory impairment. Furthermore, histopathological examination was performed to examine neuronal changes. KEY FINDINGS: Notch signaling was overexpressed in PCOS rats, which increased Aß aggregation, apoptosis, and neuroinflammation. Additionally, histopathological examination showed neuronal degeneration, which was marked by diminished acetylcholine levels in the PCOS rats' hippocampi. Finally, serum levels of insulin and testosterone were elevated while estradiol was reduced. Treatment with LIR repaired Notch signaling-attributed changes and improved the PCOS-induced memory impairment in rats. SIGNIFICANCE: The obtained findings confirm that Notch signaling activation in the hippocampus of rats impairs cognitive functions in PCOS, which is mitigated by LIR. Therefore, LIR may offer a novel therapeutic intervention to impede PCOS-induced dementia.

CRISPR/Cas9 mediated knock-out of VPREB1 gene induces a cytotoxic effect in myeloma cells.

BACKGROUND: Multiple Myeloma (MM) is a heterogeneous, hematological neoplasm that accounts 2% of all cancers. Although, autologous stem cell transplantation and chemotherapy are currently the most effective therapy, it carries a notable hazards, in addition for being non curative. Recently, the Clustered Regular Interspaced Short Palindromic Repeats (CRISPR-cas9) has been successfully tried at the experimental level, for the treatment of several hematological malignancies. OBJECTIVES: We aimed to investigate the in-vitro effect of CRISPR-cas9-mediated knock-out of V-set pre B-cell surrogate light chain 1"VPREB1" gene on the malignant proliferation of primary cultured myeloma cells. METHODS: Bioinformatics' analysis was performed to explore the gene expression profile of MM, and the VPREB1 gene was selected as a target gene for this study. We knocked-out the VPREB1 gene in primary cultured myeloma cells using CRISPR-cas9, the VPREB1 gene editing efficacy was verified by determining VPREB1 gene expression at both the mRNA and protein levels by qPCR and immunofluorescence, respectively. Furthermore, the cytotoxic effect on primary myeloma cells proliferation was evaluated using cytotoxicity assay. RESULTS: There was a statistically significant reduction of both VPREB1 mRNA and protein expression levels (p<0.01). knock-out of VPREB1 gene in myeloma cell line resulted in a statistically significant reduction of myeloma cell proliferation. CONCLUSION: CRISPR-cas9-mediated knock-out of VPREB1 gene is effective for inhibiting the proliferation of primary myeloma cells. This would provide a basis for a promising therapeutic strategy for patients with multiple myeloma.

pH-Sensitive Alginate/Carboxymethyl Chitosan/Aminated Chitosan Microcapsules for Efficient Encapsulation and Delivery of Diclofenac Sodium.

To develop an effective pH-sensitive drug carrier, alginate (Alg), carboxymethyl chitosan (CMCs), and aminated chitosan (AmCs) derivatives were employed in this study. A simple ionic gelation technique was employed to formulate Alg-CMCs@AmCs dual polyelectrolyte complexes (PECs) microcapsules as a pH-sensitive carrier for efficient encapsulation and release of diclofenac sodium (DS) drug. The developed microcapsules were characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analyzer (TGA), and scanning electron microscope (SEM). The results clarified that formation of dual PECs significantly protected Alg microcapsules from rapid disintegration at colon conditions (pH 7.4), and greatly reduced their porosity. In addition, the dual PECs microcapsules can effectively encapsulate 95.4% of DS-drug compared to 86.3 and 68.6% for Alg and Alg-CMCs microcapsules, respectively. Higher DS-release values were achieved in simulated colonic fluid [SCF; pH 7.4] compared to those obtained in simulated gastric fluid [SGF; pH 1.2]. Moreover, the drug burst release was prevented and a sustained DS-release was achieved as the AmCs concentration increased. The results confirmed also that the developed microcapsules were biodegradable in the presence of the lysozyme enzyme. These findings emphasize that the formulated pH-sensitive microcapsules could be applied for the delivery of diclofenac sodium.