Hindlimb unloading-induced reproductive suppression via Downregulation of hypothalamic Kiss-1 expression in adult male rats.

BACKGROUND: Spaceflights-induced microgravity can alter various physiological processes in human's body including the functional status of the reproductive system. Rodent model of tail-suspension hindlimb unloading is extensively used to stimulate the organs responses to the microgravity condition. This study explores the potential effects of hindlimb unloading on testicular functions and spermatogenesis in adult male rats and the underlying mechanism/s. METHODS: Twenty Sprague-Dawley rats were allotted into two groups: normally loaded group (control; all arms were in touch with the grid floor) and hindlimb unloaded group (HU; only the forearms were in contact with the grid floor). RESULTS: Following 30 days of exposure, the HU group saw a decline in body weight, testicular and epidydimal weights, and all semen parameters. The circulating concentrations of gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone significantly decreased, while levels of kisspeptin, corticosterone, inhibin, prolactin and estradiol (E2) increased in the HU group. Intratesticular levels of 5α-reductase enzyme and dihydrotestosterone (DHT) were suppressed, while the levels of aromatase and kisspeptin were significantly elevated in the HU group. Hypothalamic kisspeptin (Kiss1) mRNA expression levels were downregulated while its receptors (Kiss1R) were upregulated in the HU group. On the contrary, the mRNA expression levels of testicular Kiss1 were upregulated while Kiss1R were downregulated. The pituitary mRNA expression levels of FSHß and LHß decreased in the HU group. The levels of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and nitric oxide (NO) concentrations, and total antioxidant capacity (TAC) were elevated while malondialdehyde (MDA) concentrations declined in the testes of HU group. The testes of the HU rats showed positive immunostaining of caspase-3, heat shock protein 70 (HSP70) and Bcl2. CONCLUSIONS: Altogether, these results revealed an inhibitory effect of hindlimb unloading on kisspeptin signaling in the hypothalamic-pituitary-testicular axis with impaired spermatogenesis and steroidogenesis.

Growth performance, tissue precipitation, metallothionein and cytokine transcript expression and economics in response to different dietary zinc sources in growing rabbits.

The impact of different dietary zinc sources on the growth, serum metabolites, tissue zinc content, economics and relative expression of cytokine and metallothionein genes was evaluated in this study. A total of 120 35-day-old male New Zealand White (NZW) rabbits were randomly distributed into four dietary experimental groups with 10 replicates per group and 3 animals per replicate. The control group was fed basal diet with a Zn-free vitamin-mineral premix; the other three groups received control basal diet supplemented with 50 mg/kg level with zinc oxide (ZnO; as inorganic source), Zn-methionine (Zn-Met; as organic source) and zinc oxide nanoparticles (nano-ZnO). The results indicated that Zn-Met and nano-ZnO groups significantly improved body weight, daily weight gain (DWG), feed conversion ratio (FCR) and nutrient digestibility, as well as decreased mortality, compared to ZnO and control groups. Zn-Met and nano-ZnO significantly reduced serum total cholesterol but did not affect serum proteins and liver function. Nano-ZnO supplemented group also recorded the highest value of serum alkaline phosphatase (ALP), insulin-like growth factor (IGF-1) and lysozymes compared to other groups. Nano-ZnO supplementation had increased hepatic Zn and Cu content and decreased faecal Zn content. Also nano-ZnO group recorded higher expression levels of genes encoding for metallothionein I and metallothionein II, interleukin-2 and interferon-γ in the liver of rabbits. The findings of this study demonstrated zinc nanoparticles, and organic zinc supplementation had improved growth performance and health status of growing rabbits than inorganic zinc oxide.

Cross talk between polysulfide and nitric oxide in rat peritoneal mast cells.

The aim of this study was to define the effects of polysulfide on intracellular Ca(2+) concentration ([Ca(2+)]i) and the underlying machinery, especially from the hydrogen sulfide (H2S) and nitric oxide (NO) perspectives, in rat peritoneal mast cells. We found that a polysulfide donor, Na2S4, increased [Ca(2+)]i, which is both extracellular and intracellular Ca(2+) dependent. Intracellular Ca(2+) release induced by Na2S4 was attenuated by the addition of a ryanodine receptor blocker. A slow-releasing H2S donor, GYY4137, dose dependently increased [Ca(2+)]i that was independent from extracellular Ca(2+) influx. The GYY4137-induced [Ca(2+)]i release was partially attenuated in the presence of the ryanodine receptor blocker. Both polysulfide and H2S donors increased the intracellular NO levels in DAF-2-loaded mast cells, which were abolished by an NO scavenger, cPTIO. Inhibition of NO synthase (NOS) significantly abolished the polysulfide- or H2S-donor-induced [Ca(2+)]i elevation in the absence of extracellular Ca(2+) An NO donor, diethylamine (DEA) NONOate, increased [Ca(2+)]i in a concentration-dependent manner, in which both extracellular and intracellular Ca(2+) are associated. At higher concentrations, the DEA NONOate-induced [Ca(2+)]i increases were attenuated in the absence of extracellular Ca(2+) and by the addition of the ryanodine receptor blocker. H2S and NO dose dependently induced polysulfide production. Curiously, polysulfide, H2S, and NO donors had no effect on mast cell degranulation. Among synthases, cystathionine-γ-lyase, and neuronal NOS seemed to be the major H2S- and NO-producing synthases, respectively. These results indicate that polysulfide acts as a potential signaling molecule that regulates [Ca(2+)]i homeostasis in rat peritoneal mast cells via a cross talk with NO and H2S.

Hydrogen sulfide: a novel gaseous signaling molecule and intracellular Ca2+ regulator in rat parotid acinar cells.

In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a crucial gaseous messenger that exerts many biological actions in various tissues. An attempt was made to assess the roles and underlying mechanisms of both gases in isolated rat parotid acinar cells. Ductal cells and some acinar cells were found to express NO and H2S synthases. Cevimeline, a muscarinic receptor agonist upregulated endothelial NO synthase in parotid tissue. NO and H2S donors increased the intracellular Ca(2+) concentration ([Ca(2+)]i). This was not affected by inhibitors of phospholipase C and inositol 1,4,5-trisphosphate receptors, but was decreased by blockers of ryanodine receptors (RyRs), soluble guanylyl cyclase, and protein kinase G. The H2S donor evoked NO production, which was decreased by blockade of NO synthases or phosphoinositide 3-kinase or by hypotaurine, an H2S scavenger. The H2S donor-induced [Ca(2+)]i increase was diminished by a NO scavenger or the NO synthases blocker. These results suggest that NO and H2S play important roles in regulating [Ca(2+)]i via soluble guanylyl cyclase-cGMP-protein kinase G-RyRs, but not via inositol 1,4,5-trisphosphate receptors. The effect of H2S may be partially through NO produced via phosphoinositide 3-kinase-Akt-endothelial NO synthase. It was concluded that both gases regulate [Ca(2+)]i in a synergistic way, mainly via RyRs in rat parotid acinar cells.

A novel role for carbon monoxide as a potent regulator of intracellular Ca2+ and nitric oxide in rat pancreatic acinar cells.

Carbon monoxide (CO) is known as an essential gaseous messenger that regulates a wide array of physiological and pathological processes, similar to nitric oxide (NO) and hydrogen sulfide. The aim of the present study was to elucidate the potential role of CO in Ca(2+) homeostasis and to explore the underlying mechanisms in pancreatic acinar cells. The exogenous application of a CO-releasing molecule dose-dependently increased intracellular Ca(2+) concentration ([Ca(2+)]i). A heme oxygenase (HO) inducer increased [Ca(2+)]i in a concentration-dependent manner, and the increase was diminished by an HO inhibitor. The CO-induced [Ca(2+)]i increase persisted in the absence of extracellular Ca(2+), indicating that Ca(2+) release is the initial source for the increase. The inhibition of G protein, phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP3) receptor diminished the CO-induced [Ca(2+)]i increase. CO upregulated endothelial nitric oxide synthase (eNOS) expression and stimulated NO production, and NOS inhibitor, calmodulin inhibitor, or the absence of extracellular Ca(2+) eliminated the latter response. Blocking the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway abolished CO-induced NO production. Pretreatment with an NOS inhibitor, NO scavenger, or soluble guanylate cyclase inhibitor, did not affect the CO-induced [Ca(2+)]i increase, indicating that NO, soluble guanylate cyclase, and cyclic guanosine 5'-monophosphate are not involved in the CO-induced [Ca(2+)]i increase. CO inhibited the secretory responses to CCK-octapeptide or carbachol. We conclude that CO acts as a regulator not only for [Ca(2+)]i homeostasis via a PLC-IP3-IP3 receptor cascade but also for NO production via the calmodulin and PI3K-Akt/PKB pathway, and both CO and NO interact. Moreover, CO may provide potential therapy to ameliorate acute pancreatitis by inhibiting amylase secretion.

Case study of chemical and enzymatic degumming processes in soybean oil production at an industrial plant.

The vegetable oil degumming process plays a critical role in refining edible oil. Phospholipids (PL) removal from crude extracted soybean oil (SBO) by the enzymatic degumming process has been investigated in this work. Enzymatic degumming of extracted SBO with microbial phospholipase A1 PLA-1 Quara LowP and Lecitase Ultra enzymes have also been studied comparatively. The main novelty of our work is the use of the enzymatic degumming process on an industrial scale (600 tons a day). Many parameters have been discussed to understand in detail the factors affecting oil losses during the degumming process. The factors such as chemical conditioning (CC) by phosphoric acid 85%, the enzyme dosage mg/kg (feedstock dependent), the enzymatic degumming reaction time, and the characteristics of the plant-processed SBO have been discussed in detail. As a main point, the degummed oil with a phosphorus content of < 10 mg/kg increases yield. Quara LowP and Lecitase Ultra enzymes are not specific for certain phospholipids PL; however, the conversion rate depends on the SBO phospholipid composition. After 4 h, over 99% of Phospholipids were degraded to their lysophospholipid LPL (lysolecithin). The results showed a significant effect of operating parameters and characteristics of different origins of SBO, fatty acids FFA content, Phosphorus content and total divalent metals (Calcium Ca, Magnesium Mg and Iron Fe mg/kg) content on the oil loss. The benefit of using enzymatic degumming of vegetable oils rather than traditional chemical refining is that the enzymatic degumming process reduces total oil loss. This decrease is known as enzymatic yield. The enzymatic degumming also decreases wastewater and used chemicals and running costs; moreover, it enables physical refining by lowering the residue phosphorus to < 10 mg/kg.

An Exploratory Experimental Analysis Backed by Quantum Mechanical Modeling, Spectroscopic, and Surface Study for C-Steel Surface in the Presence of Hydrazone-Based Schiff Bases to Fix Corrosion Defects in Acidic Media.

This work focuses on developing corrosion control and protecting the environment by creating affordable, sustainable, environmentally friendly, and efficient corrosion resistance chemicals. That is, through synthesized three hydrazone Schiff bases E-2-(1-hydrazonoethyl)thiazole (HTZ), 2-((E)-(((Z)-1-(thiazol-2-yl)ethylidene)hydrazono)methyl)phenol (HTZS), and 2-((E)-(((Z)-1-(pyridin-2-yl)ethylidene)hydrazono)methyl)phenol (HPYS) and corrosion inhibitors for C-steel in 8 M H3PO4 solution that were studied. The chemicals were analyzed by using 1H NMR and 13C NMR spectroscopy to learn more about them. Predominantly, the hydrazone-based Schiff bases have been considered powerful inhibitors due to their ability to be adsorbed with very low concentrations through their reactive sites (N, O, and S). Maximum surface (θmax) coverage and inhibition efficiency of 83.33% were sufficiently found at 99.00 × 10-3 mol/L concentration of HTZS at 293 K. Galvanostatic experiments demonstrated that raising the concentration of hydrazones improved mass transfer resistance. To study microstructure, scanning, reflectance, and energy-dispersive X-rays were used. Roughness and qualitative adhesion of the adsorbed layer were estimated by an atomic force microscope. After adding 99.00 × 10-3 mol/L of HTZS, the degree of surface brightness and reflectance increases to 137.20, relative to the corroded electrolyte-free solution 27.70. The roughness (Ra) decreased from 0.468 to 0.088 µm by adding HTZS. A surface morphology study confirmed that adding hydrazones to the C-steel dissolution bath greatly improves the surface's look and texture quality. The atomic absorption spectroscopy technique was used to compare the concentration of the iron ions that remained in the solution after galvanostatic analysis in the absence and presence of the hydrazones under different conditions; it was found that the inhibited solution contained lower concentrations of iron ions as compared to the uninhibited solution. The DFT theoretical analysis verified the observation of hydrazone physical adsorption through bonding electrons that obey kinetic adsorption isotherms. It is based on examining the highest occupied molecular orbital-lowest occupied molecular orbital (HOMO-LUMO), the Fukui functions, and the Mulliken atomic charge. Overall, the results suggest that HTZS is a good corrosion inhibitor with a large surface area due to the presence of S, N, and O atoms, allowing for creating a larger surface due to the large molecular volume of atoms protecting against the corrosion process.

Pure and doped carbon quantum dots as fluorescent probes for the detection of phenol compounds and antibiotics in aquariums.

The resulting antibiotic residue and organic chemicals from continuous climatic change, urbanization and increasing food demand have a detrimental impact on environmental and human health protection. So, we created a unique B, N-CQDs (Boron, Nitrogen doping carbon quantum dots) based fluorescent nanosensor to investigate novel sensing methodologies for the precise and concentrated identification of antibiotics and phenol derivatives substances to ensure that they are included in the permitted percentages. The as-prepared highly fluorescent B, N-CQDs had a limited range of sizes between 1 and 6 nm and average sizes of 2.5 nm in our study. The novel B, N-CQDs showed high sensitivity and selectivity for phenolic derivatives such as hydroquinone, resorcinol, and para aminophenol, as well as organic solvents such as hexane, with low detection limits of 0.05, 0.024, 0.032 and 0.013 µM respectively in an aqueous medium. The high fluorescence B, N-CQDs probes were examined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and UV/VIS spectroscopy. The outcomes were compared to carbon quantum dots (CQDs) previously generated from Urea.

Anticorrosive performance of newly synthesized dipyridine based ionic liquids by experimental and theoretical approaches.

Two newly synthetic nontoxic dipyridine-based ionic liquids (PILs) with the same chain lengths and different polar groups were investigated: bispyridine-1-ium tetrafluoroborate (BPHP, TFPHP) with terminal polar groups Br and CF3, respectively, on Carbon steel (CS) in 8M H3PO4 as corrosion inhibitors. Their chemical structure was verified by performing 1HNMR and 13CNMR. Their corrosion inhibition was investigated by electrochemical tests, especially as mass transfer with several characterizations: Scanning electron microscope/Energy dispersive X-ray spectroscopy (SEM-EDX), UV-visible, Atomic force microscope, Atomic absorbance spectroscopy, X-ray Photoelectron Spectroscopy and Gloss value. Theoretical calculation using density functional theory by calculating several parameters, molecular electrostatic potential, Fukui Indices, and Local Dual Descriptors were performed to demonstrate the reactivity behavior and the reactive sites of two molecules with a concentration range (1.25-37.5 × 10-5 M) and temperature (293-318 K). The maximum inhibition efficiency (76.19%) and uniform coverage were sufficient for BPHP at an optimum concentration of 37.5 × 10-5 M with the lowest temperature of 293 K. TFPHP recorded 71.43% at the same conditions. Two PILs were adsorbed following the El-Awady adsorption isotherm, including physicochemical adsorption. The computational findings agree with Electrochemical measurements and thus confirm CS's corrosion protection in an aggressive environment.

Functionalization Strategies for Electropolishing Process of Carbon Steel Using Novel Quinazoline-4-one Derivatives: Synthesis, Spectroscopic Characterization, and DFT Studies.

A novel class of organic electropolishing (EP) inhibitors, entitled quinazoline-4-one derivatives (benzylidene oxoquinazolineyl acetohydrazide (BOA)), has laid a solid foundation for the creation of a new efficient inhibitor platform for the dissolution of carbon steel (C-steel) in 8 M H3PO4. Fourier-transform infrared (FTIR), 1H NMR, and elemental analyses have all been employed to identify BOA's functional groups, components, and active centers. The inhibition strength of BOA derivatives (m-NBOA, p-HBOA, and p-BBOA) on C-steel was assured by galvanostatic polarization measurements. Within the range of concentrations (0.33-3.43 × 10-3 mol/L) and temperatures (298-313 K) evaluated, the tested derivatives exhibit extraordinarily high gloss and low roughness, and improved the corrosion resistance of the electropolished surface with the lowest negative environmental impact. The dissolution rate (IL) decreases with increasing BOA concentration, supporting a mass transport-controlled technique and demonstrating that BOA is appropriate for anodic inhibitors. Activation energy indicates physical adsorption. Thermodynamic parameters were calculated for further investigation of the heat involved and the mechanism of the EP process. Adsorption isotherm and adsorption thermodynamics parameters were discussed using three models: Langmuir, Flory-Huggins, and kinetic adsorption isotherms, to study the inhibition of EP of the steel surface. The free energy of adsorption was calculated to assert the physisorption process. A scanning electron microscope (SEM) was utilized to inspect the morphology of the metal surface before and after the inclusion of BOA under different conditions. In contrast, the surface roughness was identified using an atomic force microscope (AFM) and reflectance. Eventually, practical results have been proved through computational calculations using the LYP correlation functional by the density functional theory (DFT) method.

The MEF2A transcription factor interactome in cardiomyocytes.

Transcriptional regulators encoded by the Myocyte Enhancer Factor 2 (MEF2) gene family play a fundamental role in cardiac development, homeostasis and pathology. Previous studies indicate that MEF2A protein-protein interactions serve as a network hub in several cardiomyocyte cellular processes. Based on the idea that interactions with regulatory protein partners underly the diverse roles of MEF2A in cardiomyocyte gene expression, we undertook a systematic unbiased screen of the MEF2A protein interactome in primary cardiomyocytes using an affinity purification-based quantitative mass spectrometry approach. Bioinformatic processing of the MEF2A interactome revealed protein networks involved in the regulation of programmed cell death, inflammatory responses, actin dynamics and stress signaling in primary cardiomyocytes. Further biochemical and functional confirmation of specific protein-protein interactions documented a dynamic interaction between MEF2A and STAT3 proteins. Integration of transcriptome level data from MEF2A and STAT3-depleted cardiomyocytes reveals that the balance between MEF2A and STAT3 activity exerts a level of executive control over the inflammatory response and cardiomyocyte cell survival and experimentally ameliorates Phenylephrine induced cardiomyocyte hypertrophy. Lastly, we identified several MEF2A/STAT3 co-regulated genes, including the MMP9 gene. Herein, we document the cardiomyocyte MEF2A interactome, which furthers our understanding of protein networks involved in the hierarchical control of normal and pathophysiological cardiomyocyte gene expression in the mammalian heart.

Impact of resveratrol-loaded liposomal nanocarriers on heat-stressed broiler chickens: Effects on performance, sirtuin expression, oxidative stress regulators, and muscle building factors.

Climate change is considered to be the primary cause of heat stress (HS) in broiler chickens. Owing to the unique properties of extracted polyphenols, resveratrol-loaded liposomal nanoparticles (Resv-Lipo NPs) were first explored to mitigate the harmful effects of HS. The dietary role of Resv-Lipo NPs in heat-stressed birds was investigated based on their growth performance, antioxidative potential, and the expression of heat shock proteins, sirtuins, antioxidant, immune, and muscle-building related genes. A total of 250 1-day-old Ross 308 broiler chickens were divided into five experimental groups (5 replicates/group, 10 birds/replicate) for 42 days as follows: the control group was fed a basal diet and reared in thermoneutral conditions, and the other four HS groups were fed a basal diet supplemented with Resv-Lipo NPsI, II, and III at the levels of 0, 50, 100, and 150 mg/kg diet, respectively. The results indicated that supplementation with Resv-Lipo NP improved the growth rate of the HS group. The Resv-Lipo NP group showed the most significant improvement in body weight gain (p < 0.05) and FCR. Additionally, post-HS exposure, the groups that received Resv-Lipo NPs showed restored functions of the kidney and the liver as well as improvements in the lipid profile. The restoration occurred especially at higher levels in the Resv-Lipo NP group compared to the HS group. The elevated corticosterone and T3 and T4 hormone levels in the HS group returned to the normal range in the Resv-Lipo NPsIII group. Additionally, the HS groups supplemented with Resv-Lipo NPs showed an improvement in serum and muscle antioxidant biomarkers. The upregulation of the muscle and intestinal antioxidant-related genes (SOD, CAT, GSH-PX, NR-f2, and HO-1) and the muscle-building genes (myostatin, MyoD, and mTOR) was observed with increasing the level of Resv-Lipo NPs. Heat stress upregulated heat shock proteins (HSP) 70 and 90 gene expression, which was restored to normal levels in HS+Resv-Lipo NPsIII. Moreover, the expression of sirtuin 1, 3, and 7 (SIRT1, SIRT3, and SIRT7) genes was increased (p < 0.05) in the liver of the HS groups that received Resv-Lipo NPs in a dose-dependent manner. Notably, the upregulation of proinflammatory cytokines in the HS group was restored in the HS groups that received Resv-Lipo NPs. Supplementation with Resv-Lipo NPs can mitigate the harmful impact of HS and consequently improve the performance of broiler chickens.

A fundamental role for NO-PLC signaling pathway in mediating intracellular Ca2+ oscillation in pancreatic acini.

The aim of the present study was to investigate the possible interaction between intracellular Ca(2+) and nitric oxide (NO) in rat pancreatic acinar cells, especially intracellular signaling events. (1) Nitric oxide donors SNP (0.1-100 µM) and NOR-3 (50-400 µM) induced Ca(2+) oscillations in fluo-4-loaded acini, that appeared to be analogous to what we usually observe in acini stimulated with physiological secretagogues such as CCK-8 and this oscillations were abolished in the presence of carboxy-PTIO. (2) The NO donors-evoked Ca(2+) oscillations were not abolished even in the absence of extracellular Ca(2+) but totally disappeared when cells were pretreated with thapsigargin, a sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitor. (3) Inhibition of guanylate cyclase with 1 H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) attenuated Ca(2+) oscillations evoked by SNP in the absence of extracellular Ca(2+). (4) Inhibitors of phospholipase C activity, U73122 and the IP(3)R blocker xestospongin C, both abolished the SNP-induced Ca(2+) response. (5) Furthermore, we found that both CCK-8 and carbachol (CCh) induced NO production in DAF-2-loaded acinar cells and that an inhibitor of NO synthase, N(G)-monomethyl-l-arginine (L-NMMA), significantly reduced CCK-8-induced Ca(2+) oscillation. These results indicate that NO mobilizes Ca(2+) from internal stores through activation of guanylate cyclase and resultant cGMP production. In addition, PLC activation of IP(3) production is also suggested to be involved in Ca(2+) mobilization via IP(3) receptors. This suggests the presence of cross-talk between Ca(2+) and NO in pancreatic acini and this cascade may, at least partially, participate in physiological secretagogue-evoked Ca(2+) dynamics in pancreatic acinar cells.

Nitric oxide stimulates IP3 production via a cGMP/ PKG-dependent pathway in rat pancreatic acinar cells.

In an attempt to explore the functioning of nitric oxide (NO) in pancreatic exocrine cells, we have recently obtained several lines of circumstantial evidence indicating that one of molecular targets of NO is phospholipase C (PLC), the activation of which leads to an increase in the cytosolic Ca2+ concentration ([Ca2+]i) via inositol 1, 4, 5-trisphosphate, IP3. However, whether IP3 is actually produced by NO has not yet been substantiated. The present study was therefore designed to directly measure the intracellular IP3, concentration ([IP3]i) for better understanding of the underlying mechanisms with the help of pharmacological tools. [IP3]i was measured using a fluorescence polarization technique (HitHunter). We obtained the following results: 1) varying concentrations of an NO donor, sodium nitroprusside (SNP), elevated [IP3]i, 2) this elevation was completely inhibited in the presence of the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ), 3) varying concentrations of the cGMP analogue, 8-Br-cGMP, also increased [IP3]i, 4) the cGMP analogue-induced IP3 production was abolished by pretreatment with either a PLC inhibitor, U73122, or a G-protein inhibitor, GP2A, and 5) KT5823, a potent and highly selective inhibitor of cGMP-dependent protein kinase G (PKG), also abolished the IP3 production induced by 8-Br-cGMP. These results suggest that the NO-induced [Ca2+]i increase is triggered by an increase in [IP3]i located downstream from intracellular cGMP elevation. In this intracellular pathway, each sGC, cGMP-dependent PKG, G-protein and PLC were suggested to be involved. The present work provides new insights into the intracellular signaling accelerated by NO. NO triggers a [Ca2+]I increase via cGMP and IP3 in pancreatic acinar cells.

Chronic Exposure to Continuous Brightness or Darkness Modulates Immune Responses and Ameliorates the Antioxidant Enzyme System in Male Rats.

Circadian rhythms are considered vital regulators of immune functions. This study aims to elucidate the effects of chronic circadian disruption on immune functions, clock genes expression, and antioxidant enzymes levels in lymphoid tissues. Adult male Sprague-Dawley rats were subjected to a normal light/dark cycle or either continuous light (LL) or continuous dark (DD) for 8 weeks. The results demonstrated (1) significant decreases in the circulating levels of interleukin 1ß, interleukin 6 and tumor necrosis factor alpha (TNF-α) and significant increases in the levels of interleukin 10, interleukin 12, C-reactive protein (CRP) and corticosterone in both LL and DD groups; (2) upregulation in mRNA expression of core clock genes Cry1, Cry2, Per1, Per2, and Per3 in the spleen of the DD group and downregulation in Cry1 and Cry2 genes in the LL group; (3) elevation of total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide (NO) and the lipid peroxidation marker malondialdehyde (MDA) in the spleen, lymph node and bone marrow of both the LL and DD groups and decreases in the levels of the same markers in the thymus of the LL group; (4) decreased numbers of CD4+ and CD8+ cells in lymphoid tissues of both the LL and the DD groups; (5) reduced platelets count and suppressed immunoglobulin (IgM, IgE) in the LL and DD groups with marked erythropenia and leukocytosis in the DD group. Taken together, circadian misalignment leads to hematological disruptions, dysregulation of clock genes, and inflammatory mediators, which further enhances the antioxidant enzyme system that is crucial for an organism's adaptation to stresses.

Effect of Omega-3 or Omega-6 Dietary Supplementation on Testicular Steroidogenesis, Adipokine Network, Cytokines, and Oxidative Stress in Adult Male Rats.

This study was undertaken to elucidate the effect of omega-3 and omega-6 supplementation on the levels of different adipokines and cytokines, as well as the antioxidant system, in relation to male reproductive hormones and testicular functions. Adult male Sprague-Dawley rats were daily gavaged with either physiological saline (control group), sunflower oil (omega 6 group; 1 mL/kg body weight), or fish oil (omega-3 group; 1000 mg/kg body weight) for 12 weeks. The administration of omega-3 or omega-6 resulted in decreased serum concentrations of kisspeptin 1, gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, it downregulated the mRNA expression levels of steroidogenic genes. The intratesticular levels of apelin, adiponectin, and irisin were elevated while chemerin, leptin, resistin, vaspin, and visfatin were declined following the administration of either omega-3 or omega-6. The testicular concentration of interleukin 10 was increased while interleukin 1 beta, interleukin 6, tumor necrosis factor α, and nuclear factor kappa B were decreased after consumption of omega-3 or omega-6. In the testes, the levels of superoxide dismutase, catalase, glutathione peroxidase 1, and the total antioxidant capacity were improved. In conclusion, the administration of omega-3 or omega-6 adversely affects the process of steroidogenesis but improves the antioxidant and anti-inflammatory status of the reproductive system via modulating the levels of testicular adipokines.

Changes in nitric oxide, carbon monoxide, hydrogen sulfide and male reproductive hormones in response to chronic restraint stress in rats.

Gasotrasmitters are endogenously synthesized gaseous molecules that are engaged in cellular physiological and pathological processes. Stress influences various physiological aspects of an organism and amends a normal system's functions, including those of the reproductive system. This study aims to investigate the effect of long-term exposure to restraint stress on the male reproductive system as well as the possible impact of stress on the levels of nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), and the expression of their producing-enzymes. In this study, rats were subjected to the restraint condition for 2 h per day and 7 days per week for 8 consecutive weeks. The results revealed decreases in the serum levels of kisspeptin-1(Kiss-1), gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and dehydroepiandrosterone sulfate (DHEA-s); however, corticosterone, gonadotropin-inhibitory hormone (GnIH), estradiol (E2) and prolactin levels increased following restraint stress. The mRNA expression levels of NO synthases (NOSs); neuronal NOS (nNOS), inducible NOS (iNOS) and H2S synthases; cystathionine-γ-lyase- (CSE), 3-mercaptopyruvate-sulfurtransferase- (3MST) and CO-producing enzyme; heme oxygenase-2 (HO-2) were upregulated in the hypothalamus of restraint rats. Testicular mRNA expression levels of endothelial NOS (eNOS), nNOS, HO-1 and HO-2 were upregulated whereas cystathionine ß-synthase (CBS), CSE and 3MST expression levels were downregulated following restraint stress. Concentrations of NO increased in the testes but decreased in the semen of restraint rats. On the contrary, CO levels were reduced in the testes while they were elevated in the semen, whereas H2S concentrations decreased in both testes and semen of restraint rats. Concentrations of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), as well as total antioxidant capacity (TAC) rose in the testes, while they declined in the semen of the restraint group. Restraint stress decreases the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the testes while increasing them in the semen. Collectively, restraint stress negatively impacts male reproductive functions and modulates gasotransmitters producing-enzymes expression in the hypothalamus and testes.

Irisin/FNDC5: A participant in camel metabolism.

The quantification, localization, production, function, and regulation of irisin/FNDC5 in camel species have not been previously studied. The objective of this study was to detect the irisin content in Arabian camel blood and tissues and study the gene expression of FNDC5 and PGC-1α in camel skeletal muscles and white adipose tissue depots under basal conditions. To monitor if exercise influences blood and tissue irisin protein levels as well as FNDC5 and PGC-1α gene expression levels, we analyzed irisin concentrations in the serum, skeletal muscles (soleus and gastrocnemius), and white adipose tissues (hump, subcutaneous, visceral, epididymal, and perirenal) in both control (n = 6) and exercised group (n = 6) using ELISA and determined the cellular localization of irisin/FNDC5 and the mRNA levels of FNDC5 and PGC-1α in skeletal muscles and adipose tissues via immunohistochemistry and real-time PCR, respectively. The possible regulatory roles of exercise on some hormones and metabolites as well as the detection of links between serum irisin and other circulating hormones (insulin, leptin, and cortisol) and metabolites (glucose, free fatty acids, triglycerides, and ATP) were explored for the first time in camels. Our results indicated that exercise induces tissue-specific regulation of the camel irisin, FNDC5, and PGC-1α levels, which subsequently regulates the circulating irisin level. Significant associations were detected between the levels of irisin/FNDC5/PGC-1α in camels and the metabolic and hormonal responses to exercise. Our study suggested that irisin regulates, or is regulated by, glucose, FFA, insulin, leptin, and cortisol in camels. The novel results of the present study will serve as baseline data for camels.

Immunological Responses and the Antioxidant Status in African Catfish (Clarias gariepinus) Following Replacement of Dietary Fish Meal with Plant Protein.

African catfish (Clarias gariepinus) were subjected to a 30-day feeding trial to determine the appropriateness of using plant protein (PP) (soybean and sunflower meal) as a fishmeal (FM) replacement in the diet and its effects on immune status, antioxidant activity, pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression, and disease resistance. A total of 150 C. gariepinus (51.01 ± 0.34 g) were randomly distributed among five groups in triplicate. Five experimental diets were formulated to replace 0 (control), 33.5, 50, 66.5, and 100% FM with soybean and sunflower meal to form the experimental diets (R0, R33.5, R50, R66.5, and R100, respectively). After 30 days, the diet containing PP for FM had no significant impact on total, and differential leukocyte counts determined at the end of the feeding period. The total globulin concentration showed significantly greater differences in the following order R0 > R33.5 > R50 > R66.5 > R100. The R0 group had the highest concentration of serum γ-globulin, while R100 had the lowest concentration. The antioxidant status complements 3 (C3), lysozyme activity (LYZ), and antiprotease activity were not significantly different between R0, R33.5, and R50 groups, while they were significantly lower in R100. The serum nitric oxide activity (NO) exhibited significantly greater differences in the following order R0 > R33.5 > R50 > R66.5 > R100. PACAP was significantly higher in the R33.5 group. The highest cumulative mortality caused by Aeromonas sobria was recorded in the R100 group (60%) and the lowest in the R0 group (30%). In conclusion, the results indicate that the immunological responses and antioxidant status of C. gariepinus were not affected when they consumed a diet with FM replaced by up to 50% with PP (SBM and SFM) with methionine and lysine supplementation, but total globulin, NO, and cumulative mortality were impaired with a diet containing a 100% FM replacement.

Growth, Hemato-Biochemical Parameters, Body Composition, and Myostatin Gene Expression of Clarias gariepinus Fed by Replacing Fishmeal with Plant Protein.

In this study, we evaluated the consequences of replacement of fishmeal with plant protein sources (soybean and sunflower meal) on fish growth parameters, haemato-biochemical factors, body composition, and myostatin gene expression of Clarias gariepinus. A total of 150 C. gariepinus were organized in glass aquaria into five investigational groups, with each group in triplicate (30 fish/group; 10 fish/replicate). Group 1 was fed a control diet (15% fishmeal). The other groups were fed diets where fishmeal was replaced gradually with plant protein, with 10% fishmeal in the second group (D1), 7.5% fishmeal in the third group (D2), 5% fishmeal in the fourth group (D3), and 0% fishmeal in the fifth group (D4). There were no significant differences regarding growth performances and body composition among the groups, except that the feed conversion ratio was improved in D4. The different diet types did not affect hematologic parameters and blood indices. Serum growth hormone and amylase levels also revealed no significant (p = 0.09 and 0.55, respectively) differences among the groups, while serum lipase levels decreased significantly (p = 0.000) due to partial (D2) or complete (D4) substitution of fishmeal with plant protein. The replacement of fishmeal had no effects on liver (p = 0.51) and kidney functions (p = 0.34). However, D4 showed the best profit and economic efficiency compared to the other groups. Altogether, we concluded that substitution of fishmeal with plant protein sources is economically beneficial and may be without any adverse effects on growth parameters, body composition, or hematologic and biochemical parameters, but with the addition of synthetic amino acids.