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The anti-fibrosis efficacy of Ganoderma lucidum (GL) was investigated on thioacetamide (TAA)-induced liver fibrosis. Experimental fibrosis was induced by (200 mg/kg TAA, i.p.) twice weekly for 6 weeks in male Sprague-Dawley rats. GL was administered to TAA rats, either as (250/500 mg/kg, i.p) daily for further 3 weeks. Repeated administration of TAA caused liver fibrosis evidenced by significant elevation of hepatic TGF-β1 accompanied by an increase in the hydroxyproline content, oxidative stress levels and liver biomarkers. Contrarily, GL treatment significantly reduced ALT, AST, total bilirubin, MDA, NO concentrations and restored SOD activity. H & E and Masson trichrome staining confirmed that GL suppressed liver fibrosis, inflammation and attenuated the histopathological alterations. GL also elicited a statistical decrease in TGF-β1 level and hydroxyproline content with a concomitant decline in NFk-B and α-SMA immunoexpression in the TAA treated rats. Furthermore, GL downregulated TNF-α and IL-1β levels in TAA-treated rats compared to the control group. Conclusion: GL possesses a pronounced protective activity against TAA-induced fibrosis in rats; It significantly inhibits oxidative stress, inflammation and diminishes fibrosis by: inhibiting NFk-B activation, reducing TGF-β mediated by PI3K-AKT pathway thus restoring the liver function, the effect was in a dose dependent manner.

Diabetic cardiomyopathy is diagnosed by the development of abnormality in the structure and performance of myocardium in diabetic mellitus (DM) patients. Recent studies reported the association between altered gut microbiota and metabolic disorders like diabetes and cardiovascular diseases. Here, we aimed to investigate the gut-heart axis in an experimental animal model where we developed a novel therapeutic combination of dapagliflozin, crocin prebiotic and Lactobacilli probiotic to correct induced diabetic cardiomyopathy.Diabetes mellitus was induced by Intraperitoneal (i.p) streptozotocin in male rats. The experimental design includes the administration of the tested drugs (Crocin, Dapagliflozin) solely and with Lactobacillus, or in combination therapy with and without Lactobacillus to the diabetic rats for six weeks. Clinical and microscopic evaluation scoring for cardiac tissues were determined. Biochemical markers including blood glucose level, adiponectin, resistin, cardiac injury markers, lipid profile, antioxidant enzymes, pro and anti-inflammatory markers were assessed. In addition, quantitative relative expression of PPARγ and TXINP genes and capsase-3 levels were measured. The change in the microbiota abundance was investigated using real-time PCR.This study demonstrated the synergistic effect of the triple combination; dapagliflozin, crocin prebiotic, and Lactobacillus fermentum and Lactobacillus delbrueckii probiotic in treating diabetic cardiomyopathy in rats. The triple combination significantly reduced the oxidative, inflammatory, apoptotic activities induced by streptozotocin STZ and helped in restoring the symbiotic gut microbiota.It is worthy to perform this study in clinical trials as a primary step to include crocin and Lactobacilli in the therapeutic protocols of diabetic cardiomyopathy.

Background. Cisplatin (cis-diaminedichloroplatinum, CDDP) is a broad-spectrum antineoplastic agent. However, CDDP has been blamed for its nephrotoxicity, which is the main dose-limiting adverse effect. Ganoderma lucidum (GL), a medicinal mushroom, has antioxidant and inflammatory activities. Therefore, this study is aimed at finding out the potential nephroprotection of GL against CDDP-induced nephrotoxicity in rats and the possible molecular mechanisms including the EGFR downstream signaling, apoptosis, and autophagy. Methods. Rats were given GL (500 mg/kg) for 10 days and a single injection of CDDP (12 mg/kg, i.p). Results. Nephrotoxicity was evidenced by a significant increase in renal indices and oxidative stress markers. Additionally, CDDP showed a plethora of inflammatory and apoptotic responses as evidenced by a profound increase of HMGB-1, NF-κB, and caspase-3 expressions, whereas administration of GL significantly improved all these indices as well as the histopathological insults. Renal expression of EGFR showed a similar trend after GL administration. Furthermore, activation of autophagy protein, LC3 II, was found to be involved in GL-mediated nephroprotection correlated with the downregulation of apoptotic signaling, caspase-3 and terminal deoxynucleotidyl transferase (TDT) renal expressions. Conclusion. These results suggest that GL might have improved CDDP-induced nephrotoxicity through antioxidant, anti-inflammatory, and autophagy-mediated apoptosis mechanisms and that inhibition of EGFR signaling might be involved in nephroprotection.

Purpose Drug-induced liver injury (DILI) is the most common cause of acute liver failure. The aim of this study was to investigate the molecular mechanisms by which Ganoderma lucidum mushroom (GLM) may ameliorate cisplatin (CP)-induced hepatotoxicity theoretically and experimentally. Materials and Methods Thirty-six male Sprague-Dawley (SD) rats were divided into six groups, two of them are normal and Ganoderma lucidum control groups. Liver injury was induced by a single dose of CP (12 mg/kg i.p) in four groups, one of them is CP control group. Besides cisplatin injection in day 1, rats in groups (4-6) were subjected to GLM (500 mg/kg/day) either every other day or daily oral dose or via i.p injection for 10 consecutive days. Results In this study, GLM supplementation caused significant reduction of elevated high-mobility group box-1 (HMGB-1) with a concurrent decline in TNF-α and upregulation of IL-10 compared to the CP group (P

The spectroscopic, solvent effects, reactivity and MD simulations of N'-[(1E)-(2,6-dichlorophenyl-methylidene]adamantane-1-carbohydrazide (DMC) are reported. Solvation free energies of DMC in chloroform, ethanol and acetonitrile are −21.96, −24.39 and −12.31 kcal/mol and ethanol may be better for the solubilization. Electron donating and electron accepting powers are somewhat lower in solution, revealing a certain increase in the tendency to receiving electrons and a decrease in donate electrons in solution, except in acetonitrile, in which showed slightly higher values then in vacuum. ALIE surface show that regions where low energy is required to remove electrons are on benzene ring, chlorine atoms and N5. DMC is forming good contacts with protein's binding site residues and is important in the complex's stability showing antiviral activity.

A detailed exploration of crystal packing of two adamantane-isothiourea hybrid derivatives along with a known closely related structure has been performed to delineate the effect of halogen substituents and the role of weak intermolecular interactions in their supramolecular architectures. The adamantane-isothiourea hybrid derivatives used in the present study are (

Objectives Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus and it is considered as a principal cause for end-stage renal failure. Ganoderma lucidum (GL) has been studied for its reno-protective effect against different kidney injury models. The aim of our study is to investigate the mechanisms by which GL can improve kidney injury and consequent renal inflammation and fibrosis. Methods GL either in a low dose (250 mg/kg, i.p.) or high dose (500 mg/kg, i.p.) was administered to DN rat model, and nephropathy indices were investigated. Key findings GL treatment significantly down-regulated kidney injury molecule-1 (KIM-1) gene expression and inhibited TLR-4 (Toll-like receptor-4)/NFκB (nuclear factor kappa B) signalling pathway. As well, GL treatment significantly decreased the pro-inflammatory mediator; IL-1β (interleukin-1 beta) level and fibrosis-associated growth factors; FGF-23 (fibroblast growth factor-23) and TGFβ-1 (transforming growth factor beta-1) levels. In addition, GL remarkably inhibited (Bax) the pro-apoptotic protein and induced (Bcl-2) the anti-apoptotic protein expression in kidneys. Moreover, GL treatment significantly alleviates kidney injury indicated by correcting the deteriorated kidney function and improving oxidative stress status in DN rats. Conclusions GL significantly improved renal function indices through dose-dependent kidney function restoration, oxidative stress reduction, down-regulation of gene expression of KIM-1 and TLR4/NFκB signalling pathway blockage with subsequent alleviation of renal inflammation and fibrosis.

A detailed exploration of crystal packing of two adamantane-isothiourea hybrid derivatives along with a known closely related structure has been performed to delineate the effect of halogen substituents and the role of weak intermolecular interactions in their supramolecular architectures. The adamantane-isothiourea hybrid derivatives used in the present study are (Z)-3-(Adamantan-1-yl)-S-(4-bromobenzyl)-1-phenylisothiourea (1), C24H27BrN2S and (Z)-3-(Adamantan-1-yl)-S-(4-bromobenzyl)-1-(3-chlorophenyl)isothiourea (2), C24H26BrClN2S, characterized by X-ray crystallography. The X-ray structures revealed that the molecular conformation of 1 and 2 are different and stabilized by intramolecular C–H···N interactions. In addition, a short intramolecular H···H contact is formed in 2. The Hirshfeld surface analysis was used to delineate the nature of different intermolecular interactions and their contributions toward crystal packing. The quantitative analysis of strengths of molecular dimers existed in 1 and 2 has been performed using the PIXEL method. The electrostatic potential map clearly revealed nature and strength of σ-holes at Br and Cl atoms. The topological analysis was used to characterize the nature and the strength of various intermolecular interactions including the type I Br···Br contact. Interestingly, all the H–H bonding observed in 1 and 2 show closed-shell in nature. Further, an in-vitro antimicrobial activity studies suggest that the title compounds exhibited potent antibacterial activity against all the tested Gram-positive bacterial strains and Gram-negative Escherichia coli. Compound 2 showed marked anti-proliferative activity against MCF-7 and HeLa cell lines. Communicated by Ramaswamy H. Sarma

The density functional calculations were performed at the B3LYP/6-311++G (5D, 7F) level to find the geometrical parameters, vibrational wavenumbers and various molecular properties of three fluorophenyl derivatives, methyl 4,4″-difluoro-5′-methoxy-1,1':3′,1″-terphenyl-4′-carboxylate (MDFMTPC), 2,2'-(disulfanediyl)bis[4,6-(4-fluorophenyl)pyrimidine] (DFFPPY) and (6Z)-3,5′-bis(4-fluorophenyl)-6-(1-hydroxyethylidene)cyclohex-2-en-1-one (FPHYCY). The phenyl ring C C, C O and C H stretching modes produces VCD spectrum and these modes are efficient configuration markers. Using natural bond orbital analysis the stability of the molecules due to hyper-conjugative interactions were discussed. From the HOMO and LUMO energies, the chemical descriptors are compared for the title compounds. The first hyperpolarizabilities of MDFMTPC, DFFPPY and FPHYCY are respectively, 41.08, 69.27 and 38.38 times that of urea. Molar refractivity values are increasing in the order, FPHYCY > MDFMTPC > DFFPPY and this is responsible for the binding nature of the molecular assembly and can be used for the cure of different diseases. PASS analysis of the title compounds predicts chlordecone reductase inhibitor activity for MDFMTPC, thioredoxin inhibitor activity for DFFPPY and testosterone 17beta-dehydrogenase (NADP+) inhibitor activity for FPHYCY. Docking studies reveal that MDFMTPC, DFFPPY and FPHYCY can be lead compounds for developing new anti-cancerous, anti-tumor, prostate cancer drugs. Using Hirshfeld surface and 2D-finger print plots, the type and nature of intermolecular interactions were reported.

The promising anti-Candida agent, 4-chlorophenyl ({[1E-3(1H-imidazole-1-yl)-1-phenylpropylidene}oxy)methanone (4-CPIPM) was comprehensively characterized by FT-IR, FT-Raman, UV, as well as 1H and 13C spectroscopic techniques. The theoretical calculations in the current study utilized Gaussian 09 W software with DFT approach of the B3LYP/6-311++G(d,p) method. The experimental X-ray diffraction data of the 4-CPIPM molecule were compared with the optimized structure and showed well agreement. Intermolecular electronic interactions and their stabilization energies have been analyzed by natural bond orbital method. Potential energy distribution confirmed the normal fundamental mode of vibration with the aid of MOLVIB software. The chemical shift values of the 1H and 13C spectra of the title compound were computed using gauge independent atomic orbital and the results were compared with the experimental values. The time-dependent density function theory method was used to predict the electronic, absorption wavelength and frontier molecular orbital energies. The HOMO-LUMO plots proved the charge transfer in the molecular system of the title compound through conjugated paths. The molecular electrostatic potential analysis provided the electrophilic and nucleophilic reactive sites in the title molecule which have been analyzed using Hirshfeld surface and two dimensions fingerprint plots. Non covalent interactions were also studied using reduced density gradient analysis and color filled electron density diagram. Molecular docking studies of the ligand-protein interactions along with their binding energies were carried out aiming to explain the potent anti-Candida activity of the title molecule.

Investigation of the local reactive properties, ALIE and Fukui functions of 3-(adamantan-1-yl)-4-phenyl-1-[(4-phenylpiperazin-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione (APMT) are reported using DFT method. The BDE for hydrogen abstraction served us to determine the mechanism of autoxidation is possible for the title molecule. The MD simulations explore the site of interactions with water molecules. The strongest noncovalent interactions occurred between the hydrogen atoms of piperazine and benzene rings. The weakest noncovalent interactions occurred between hydrogen atoms of piperazine and atoms N3 and S1. A significant decrease of density occurs at temperatures higher than 335 K, which is much higher than the temperature critical for the human body. This is an important indicator of stability for eventual practical applications of APMT for pharmaceutical purposes. Different spectroscopic and chemical properties are also investigated.

Male reproductive dysfunction is one of the overlooked findings of diabetes mellitus (DM) that deserves greater scientific attention. This study is designed to explore the therapeutic potential of metformin and montelukast, in combination with Lactobacillus, for modulation of intestinal flora and suppression of oxidative stress in testicular and liver damage in diabetic male rats. A DM model was induced by streptozotocin (STZ)which caused functional, biochemical, and inflammatory injuries to the testicular and liver tissues. The experimental panel included nine rat groups: normal control, normal control plus metformin, normal control plus montelukast, DM control, DM plus montelukast, DM plus a combination of metformin and Lactobacillus, DM plus a combination of montelukast and Lactobacillus, and DM plus a combination of metformin and montelukast. In parallel, clinical evaluation of microscopic examination scoring, and hepatic and testicular injuries, were evaluated. Biochemical markers including glucose level, lipid profile, inflammatory markers (tumor necrosis factor- (TNF-α) and interleukin-17 (IL-17), Caspase-3, and Bax proteins expressions were measured. The change in the microbiota abundance was investigated using conventional and real-time PCR. The current study revealed a significant difference in the relative abundance of microbiota, where DM is associated with an enormous increase of Bacteroides spp., Clostridium spp., E. coli, and Fusobacterium spp., and a significant decrease in Bifidobacteria spp., and Lactobacillus spp., in contrast with normal control. Metformin and montelukast, in combination with Lactobacillus, significantly reversed the testicular and liver damage caused by STZ. Moreover, the drugs significantly reduced the oxidative, inflammatory, and apoptotic activities induced by STZ.

The reaction of 4-(adamantan-1-yl)-3-thiosemicarbazide 3 with various aromatic aldehydes yielded the corresponding thiosemicarbazones 4a&ndash, g. 1-Adamantyl isothiocyanate 2 was reacted with 1-methylpiperazine or piperidine to yield the corresponding N-(adamantan-1-yl)carbothioamides 5 and 6, respectively. The latter was reacted with benzyl or substituted benzyl bromides to yield the S-arylmethyl derivatives 7a&ndash, c. Attempted cyclization of 1,3-bis(adamantan-1-yl)thiourea 8 with chloroacetic acid via prolonged heating to the corresponding thiazolidin-4-one 9 resulted in desulfurization of 8 to yield its urea analogue 10. The thiazolidin-4-one 9 and its 5-arylidene derivatives 11a,b were obtained via microwave-assisted synthesis. The in vitro antimicrobial activity of the synthesized compounds was evaluated against a panel of Gram-positive and Gram-negative bacteria and yeast-like pathogenic fungus Candida albicans. Compounds 7a&ndash, c displayed marked broad spectrum antibacterial activities (minimal inhibitory concentration (MIC), 0.5&ndash, 32 &mu, g/mL) and compounds 4a and 4g showed good activity against Candida albicans. Nine representative compounds were evaluated for anti-proliferative activity towards three human tumor cell lines. Compounds 7a&ndash, c displayed significant generalized anti-proliferative activity against all the tested cell lines with IC50 &lt, 10 &mu, M.

The reaction of 4-(adamantan-1-yl)-3-thiosemicarbazide 3 with various aromatic aldehydes yielded the corresponding thiosemicarbazones 4a–g. 1-Adamantyl isothiocyanate 2 was reacted with 1-methylpiperazine or piperidine to yield the corresponding N-(adamantan-1-yl)carbothioamides 5 and 6, respectively. The latter was reacted with benzyl or substituted benzyl bromides to yield the S-arylmethyl derivatives 7a–c. Attempted cyclization of 1,3-bis(adamantan-1-yl)thiourea 8 with chloroacetic acid via prolonged heating to the corresponding thiazolidin-4-one 9 resulted in desulfurization of 8 to yield its urea analogue 10. The thiazolidin-4-one 9 and its 5-arylidene derivatives 11a,b were obtained via microwave-assisted synthesis. The in vitro antimicrobial activity of the synthesized compounds was evaluated against a panel of Gram-positive and Gram-negative bacteria and yeast-like pathogenic fungus Candida albicans. Compounds 7a–c displayed marked broad spectrum antibacterial activities (minimal inhibitory concentration (MIC), 0.5–32 μg/mL) and compounds 4a and 4g showed good activity against Candida albicans. Nine representative compounds were evaluated for anti-proliferative activity towards three human tumor cell lines. Compounds 7a–c displayed significant generalized anti-proliferative activity against all the tested cell lines with IC50 < 10 μM.

The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thione 3 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding N-Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 4a–l or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 5a–d, respectively. The in vitro inhibitory activity of compounds 4a–l and 5a–d was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus Candida albicans. The piperazinomethyl derivatives 5c and 5d displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5–8 μg/mL) and compounds 4j, 4l, 5a, and 5b showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithelioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds 4l, 5a, 5c, and 5d.

C28H34BrN3S, monoclinic, P21/c (no. 14), a = 10.4529(8) Å, b = 11.8724(10) Å, c = 21.3800(19) Å, β = 101.864(3)°, V = 2596.6(4) Å3, Z = 4, R gt(F) = 0.060, wR ref(F 2) = 0.148, T = 296(2).

Gleevec (imatinib) is an antineoplastic chemotherapeutic agent used in the treatment of many types of cancer. The current study was conducted to examine the possible modifying effects of grape seeds proanthocyandins extract (GSPE) against apoptosis, liver injury and Ki67 alterations induced by Gleevec in male rats. 40 male albino rats were equally divided into four groups (First and second groups were control and GSPE groups; third group was Gleevec group and fourth group was treated with Gleevec and GSPE). Gleevec induced elevations in P53 and depletion of Bcl2 levels in liver tissues were compared with the control group. Liver sections in rats treated with Gleevec exhibited marked cellular infiltrations, vacuolar degeneration hepatocytes, numerous apoptotic cells, and congestion in central and portal veins, as well as a significant increase in the proliferating of Ki67 after Gleevec injection as compared with control group. In contrast, treatment with Gleevec and GSPE showed a moderate to good degree of improvement in hepatocytes with a significant increase in Ki67, a decrease in P53 and an increase in Bcl2 levels in liver tissues compared to treatment with Gleevec. Therefore, Gleevec induces apoptosis, injury and Ki67 changes in rat liver, whereas GSPE modulates these alternations.

The two implementation choices for the baseband part of wireless radios are the application-specific platforms (e.g. application-specific integrated circuits (ASICs)) and the programmable processors (e.g. digital signal processors (DSPs)). An application-specific instruction-set processor (ASIP) is a customised processor that bridges the gap between the two platforms. In this work, a novel implementation of the signal processing part of an orthogonal frequency division multiplexing (OFDM) baseband processor using three ASIPs is presented. The ASIPs provide novel architectures for the symbol chain, including fast Fourier transform, channel estimation subsystem and synchronisation subsystem. This design provides a close to DSPs level of flexibility, making it suitable for supporting all the modes of a large number of OFDM standards. In the meantime, the system maintains a performance level comparable to ASICs. This is demonstrated by providing post-layout results for 0.13 μm Taiwan semiconductor manufacturing company complementary metal-oxide semiconductor technology.

The reaction of 5-(1-adamantyl)-4-ethyl or allyl-1,2,4-triazoline-3-thione with formaldehyde solution and various 1-substituted piperazines yielded the corresponding N-Mannich bases. The newly synthesized N-Mannich bases were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Six compounds showed potent antibacterial activity against one or more of the tested microorganisms, while two compounds exhibited moderate activity against the tested Gram-positive bacteria. None of the newly synthesized compounds were proved to possess marked activity against Candida albicans. The oral hypoglycemic activity of six compounds was determined in streptozotocin (STZ)-induced diabetic rats. Four compounds produced significant strong dose-dependent reduction of serum glucose levels, compared to gliclazide at 10 mg/kg dose level (potency ratio &gt, 75%).

A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidates 7a–e and 4-arylmethyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidates 8a–e were prepared via the reaction of N-(adamantan-1-yl)morpholine-4-carbothioamide 5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide 6 with benzyl or substituted benzyl bromides, in acetone, in the presence of anhydrous potassium carbonate. The structures of the synthesized compounds were confirmed by 1H-NMR, 13C-NMR, electrospray ionization mass spectral (ESI-MS) data, and X-ray crystallographic data. The in vitro antimicrobial activity of the new compounds was determined against certain standard strains of pathogenic bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 7b, 7d and 7e displayed potent broad-spectrum antibacterial activity, while compounds 7a, 7c, 8b, 8d and 8e were active against the tested Gram-positive bacteria. The in vivo oral hypoglycemic activity of the new compounds was carried on streptozotocin (STZ)-induced diabetic rats. Compounds 7a, 8ab, and 8b produced potent dose-independent reduction of serum glucose levels, compared to the potent hypoglycemic drug gliclazide.

Simvastatin has important immune-modulatory and anti-inflammatory effects independent of lipid lowering effects. Therefore, our study was conducted to investigate the anti-inflammatory effects of simvastatin either alone or in combination with aspirin. Air pouch granuloma model was used for induction of inflammation in 72 male Wistar albino rats, which were treated with simvastatin (20 mg/kg/day), aspirin (25 mg/kg/day) or both for 3 or 6 executive days. Inflammatory exudates were collected and measured. Oxidative stress was assessed by measuring exudates' malondialdehyde (MDA) and nitric oxide (NO). Inflammatory mediator C-reactive protein (CRP) was investigated using slide agglutination test. Exudates' levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-4 were measured by ELISA. We found that simvastatin alone or in combination with aspirin exerts anti-inflammatory effects by reducing volume of exudates. Simvastatin significantly reduced serum level of CRP and exudates levels of TNF-α, IL-6 and MDA as well as significantly elevated exudates level of NO and IL-4. The results of simvastain were comparable to those of aspirin. In conclusion, air pouch granuloma interrupted the balance between inflammatory and anti-inflammatory markers, which is restored by simvastatin. The anti-inflammatory effects of simvastatin are comparable to aspirin and their combination may produce better effects especially in the attenuation of the oxidative stress and IL-6.

SERT, YUSUF/0000-0001-8836-8667 WOS: 000489698800014 In this study, the optimized molecular structure, Hirshfeld surface analysis, vibrational frequencies and corresponding vibrational modes of a potential bioactive agent namely; 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea were studied experimentally and theoretically. The theoretical calculations of the title compound were carried out using the density functional theory (DFT/B3LYP and DFT/M06-2X) quantum mechanical method with 6-311 + + G(d,p) basis set and Gaussian 09W program. The vibrational assignments of the title compound were obtained using VEDA 4 program by %10 precision with the help of potential energy distributions (PED). The experimental (FT-IR and Laser-Raman) spectra were recorded in solid phase at 4000-400 cm(-1) (FT-IR) and 4000-100 cm(-1) (Laser-Raman). Additionally, the experimental and theoretical H-1 and C-13 NMR chemical shifts in DMSO-d(6) and UV-Vis. Spectral analysis in DMF were studied theoretically and experimentally. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) analyses were performed. The molecular docking studies of the title compound revealed that it may exhibit antibacterial activity via inhibition of bacterial DNA gyrase PDB: 3U2D enzyme. Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Research Group Program [RGP-1438-0010] This work was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Research Group Program (Grant No. RGP-1438-0010).

Objectives: Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). Methods: Seventy adult male Sprague–Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid–Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. Results: NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. Discussion: NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.

SERT, YUSUF/0000-0001-8836-8667; , Nuri/0000-0001-8742-0160 WOS: 000444541400006 In this paper, the experimental and theoretical vibrational frequencies of a potential bioactive pyrimidine derivative molecule named 2-benzylsulfanyl-4-pentyl-6-(phenylsulfanyl)pyrimidine-5-carbonitrile has been investigated. The experimental FT-IR and Laser-Raman spectra of the studied molecule are in the region (4000-400 cm(-1)) and (4000-100 cm(-1)), respectively, in gas phase. The vibrational modes and optimized ideal structure parameters(bond lengths, bond angles and selected dihedral angles) were calculated by using DFT/B3LYP, DFT/BHandHLYP and DFT/PBE1PBE methods with 6-311++G(d,p) basis set. The theoretical mode assignments have been obtained by using potential energy distribution (PED) with the VEDA4 software program. Additionally, infrared and Raman intensities, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) energies and their clouds, and other related molecular properties were calculated and evaluated. The proton (H-1) and carbon-13 (C-13) nuclear magnetic resonance (NMR) chemical shifts have been investigated for the title molecule, both experimentally (in DMSO-d(6)) and theoretically (in vacuum and DMSO). The thermodynamic properties of the tile compound have been investigated using the mentioned theoretical computational methods. The results revealed that there isgood agreement between experimental and theoretical results and these results have supported the related literature. Deanship of Scientic Research at Princess Nourah Bint Abdulrahman University through the Research Group Program [RGP-1438-0010] This work was funded by the Deanship of Scientic Research at Princess Nourah Bint Abdulrahman University through the Research Group Program (Grant No. RGP-1438-0010).

Background: Resistin is a hormone that is linked to the development of insulin resistance (IR), but information on the direct relationship of resistinlevels in humans with nonalcoholic fatty liver disease (NAFLD), and their effect on the histological severity of NAFLD, is lacking.Objective: The aim of the current study is to determine the circulating resistin levels obtained from patients with NAFLD and to correlate them withinsulin resistance and hepatic histological features.Methods: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 subjects as controls. Serum resistin levels were measured. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also measured.Results: Mean serum resistin level and BMI in the NAFLD group were significantly higher than in the controls (both P < 0.001). Both men and women in the NAFLD group had higher mean serum resistin levels than did the men and women in the control group (all P < 0.001). Multivariate analysis showed that the percentage of hepatic steatosis, sex, BMI, and homeostasis model assessment of insulin resistance [HOMA(IR)] were related to serum resistin levels.Conclusion: These data suggest increased resistin levels in NAFLD patients which are related to histological severity of the disease. These findings support the link between resistin, insulin resistance and BMI in these patients.Keywords: resistin; nonalcoholic fatty liver disease; insulin resistance

The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a–e, 6, 7, 8a–c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantyl)piperazine-1,4-dicarbothioamides 10a and 10b, respectively. The reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4-(1-adamantyl)thiosemicarbazide 12 as a minor product. The reaction of the carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives 15a–g. The compounds 5a–e, 6, 7, 8a–c, 9, 10a, 10b, 14a, 14b and 15a–g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6, 7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds 5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ)-induced diabetic rats. Compound 5c produced significant reduction of serum glucose levels, compared to gliclazide.

In this paper, A novel architecture of an Application Specific Instruction Processor (ASIP) for scalable DFT/IDFT DCT/IDCT 1D (N-point) and 2D (N × M point) engine is proposed. An in place configurable radix 2/3/4 butterfly, makes possible the implementation of two radix N/M is varied in the form of 2x × 3y. Therefore the engine can support different communication and signal processing applications. A new address generator scheme is proposed which achieves conflict-free memory access. This scheme is based on partitioning the memory to 4 dual-port memory banks with a continuous address generator to accommodate high-speed requirements. Using same reduction techniques, the twiddle factors memory size is reduced to 28%. By taking advantage of programmability, the engine provides more configurability and flexibility in switching between modes in run-time. Moreover it can be easily adapt to new applications. The DFT/DCT engine requires only 1280 clock cycles for a 1024-point DFT-1D and runs at 120 MHz with SQNR 75.2 dB.