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Sodium bismuth titanate samples with different morphology were synthesized via varying the sintering temperature from 1000 to 1150 °C. The conductivity was significantly affected with the morphology of the system. The dynamics of ions was understood from the conductivity spectra. The dc conductivity, hopping frequency and exponent values were extracted from the conductivity spectra analysis. The impedance and modulus spectroscopy along with exponent behaviour suggested short range hopping for the sample sintered at 1000 °C and followed Ghosh scaling instead of Summerfield scaling. While long-range hopping was observed for the samples sintered at 1150 °C and it followed both the Summerfield scaling and Ghosh scaling. Moreover, the stability of the sample is checked in reducing atmosphere. Image 1 • Dynamics of ions is studied with the sintering temperature in Na 0.5 Bi 0.5 TiO 3-δ. • The conduction mechanism has altered with the sintering temperature. • A correlation between hopping and lattice parameters is also established for NBT. • Stability of the sample is checked in reducing atmosphere. [ABSTRACT FROM AUTHOR]

Due to continuous rapid miniaturization of the MOSFET based Integrated Circuits; it is becoming difficult to suppress the gate leakage at the oxide-silicon interface using traditional silicon dioxide. Thus, it is necessary to switch from the present state of the art to the next by replacing the traditional SiO 2 with the materials with higher dielectric constants. In this paper, a study has been carried out on materials like Al 2 O 3 , ZrO 2 , and HfO 2 to extract their properties and compare the problems associated to use them. Also, a new doping profile termed as steep retrograde doping has been included to further suppress the second order effects associated with lower technology node. The mathematical calculations have been performed using MATLAB and the device has been simulated using the Sentaurus TCAD. [ABSTRACT FROM AUTHOR]

Pancreastatin (PST) is a crucial bioactive peptide derived from chromogranin A (CHGA) proprotein that exhibits an anti-insulin effect on adipocytes. Herein, we investigated the effects of PST on brown adipose tissues (BAT) and white adipose tissue (WAT) in connection with uncoupling protein-1 (UCP-1) regulated energy expenditure in high fructose diet (HFrD) fed and vinylcyclohexenediepoxide (VCD) induced perimenopausal rats. We administered VCD in rats for 17 consecutive days and fed HFrd for 12 weeks. After 12 weeks estradiol and progesterone levels were detected. Furthermore, detection of glucose tolerance, insulin sensitivity, and body composition revealed impaired glucose homeostasis and enhanced PST levels. Effects of enhanced PST on UCP-1 level in BAT and WAT of perimenopausal rats were further investigated. Reduced serum estradiol, progesterone, and attenuated insulin response confirmed perimenopausal model development. Furthermore, enhanced PST serum level and its increased expression in BAT and WAT downregulated the UCP-1 expression. Subsequently, impaired ATP level, NADP/NADPH ratio, citrate synthase activity, enhanced mitochondrial reactive oxygen species (ROS) generation and perturbed mitochondrial membrane potential, further exacerbated mitochondrial dysfunction, cellular ROS production, and promoted apoptosis. Interestingly, PST inhibition by PST inhibitor peptide-8 (PSTi8) displayed a favorable impact on UCP-1 and energy expenditure. The aforementioned outcomes indicated the substantial role of PST in altering the UCP-1 expression and associated energy homeostasis. Hence our results corroborate novel avenues to unravel the quest deciphering PST's role in energy homeostasis and its association with perimenopause. [Display omitted] • PST downregulated UCP-1 in brown and white adipose tissues of perimenopausal rats. • PST promotes mitochondrial ROS production in adipose tissues of perimenopausal rats. • PST diminished mitochondrial membrane potential in perimenopausal rats. • Mitochondrial dysfunction promoted cellular ROS generation in perimenopausal rats. • PST promotes reduced energy expenditure in adipose tissue of perimenopausal rats. [ABSTRACT FROM AUTHOR]

• PSTi8 exhibits antidiabetic activity by suppressing hepatic glucose release. • PSTi8 interacts with GRP78 receptor and activates its catalytic ATPase activity. • Indirect calorimeter findings showed enhanced energy expenditure. • PSTi8 improves lipid homeostasis and ameliorates oxidative stress. • Activation of AMPK enhances insulin signalling pathway through PKC inhibition. To investigate the role of pancreastatin inhibitor (PSTi8) in lipid homeostasis and insulin sensitivity in dexamethasone induced fatty liver disease associated type 2 diabetes. Glucose releases assay, lipid O staining and ATP/AMP ratio were performed in HepG2 cells. Twenty four mice were randomly divided into 4 groups: Control group (saline), DEX (1 mg/kg, im) for 17 days, DEX+PSTi8 (acute 5 mg/kg and chronic 2 mg/kg, ip) for 10 days. The glucose, insulin and pyruvate tolerance tests (GTT, ITT and PTT), biochemical parameters and Oxymax-CLAMS were performed. Further to elucidate the action mechanisms of PSTi8, we performed genes expression and western blotting of biological samples. We found that PSTi8 suppresses hepatic glucose release, lipid deposition, oxidative stress induced by DEX, stimulates the cellular energy level in hepatocytes and enhances GRP78 activity. It reduces lipogensis and enhances fatty acid oxidation to improve insulin sensitivity and glucose tolerance in DEX induced diabetic mice. The above cellular effects are the result of activated AMPK signalling pathway in liver, which increases Srebp1c and ACC phosphorylation. The increased ACC phosphorylation suppresses protein kinase C activity and enhances insulin sensitivity. The increased expression of UCP3 in liver elicits fatty acid oxidation and energy expenditure, which suppress oxidative stress. Thus the activation of AMPK signalling through GRP78, improves lipid homeostasis, enhances insulin sensitivity via inhibition of PKC activity. PSTi8 suppresses inflammation associated with incomplete fatty acid oxidation. Hence, PSTi8 may be a potential therapeutic agent to treat glucocorticoid-induced fatty liver associated type 2 diabetes. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is a significant complication in menopausal women, which predisposes them to cardiovascular disorder, obesity, and diabetes. Cissus quadrangularis is a polyphenolic plant rich in nutrients and is used as an edible vegetable in Nigeria. Previously, we investigated that C. quadrangularis extract (EECQ) treatment ameliorates IR, hyperlipidemia, and overweight in diabetic rats. Accordingly, in the current study, we further evaluated the adiponectin mimetic activity of EECQ in peri -/post-menopausal rats. Perimenopause was induced by High-fat diet/4-vinylcyclohexenediepoxide/(HFD-VCD), while postmenopause was by HFD/bilateral ovariectomy (HFD-OVX). Both the menopausal rats demonstrated an abnormal level of sex hormones, IR, hyperlipidemia, increased fat mass, and abnormal weight gain. Nevertheless, EECQ treated group revealed protection from these untoward complications. Furthermore, the docking score of major constituents of EECQ on adiponectin receptor 1 (AdipoR1) depicted a strong binding affinity, which was comparable to the ligand adipoRon. Besides, AdipoR1 expression determined by RT-PCR, Western blotting, and immunohistochemistry was downregulated in peri -/post-menopausal rats. Similarly, the expression of AdipoR1 downstream marker APPL1 and insulin sensitivity markers, including IRS1, Akt1, and GLUT4, were also dysregulated in menopausal rats. However, EECQ treated rats manifested restoration of normal expression of APPL1, IRS1, Akt1, and GLUT4 by upregulating AdipoR1. Altogether, the current study promulgated the adiponectin mimetic activity of EECQ, which is substantial to mitigate IR in menopausal conditions. [Display omitted] • EECQ decreases lipid profile and maintains cellular integrity of liver tissue. • Active constituents of EECQ depict binding affinity towards AdipoR1. • EECQ improves adiponectin level and AdipoR1 expression in peri/postmenopausal rats. • EECQ potentiates insulin sensitivity by restoring the altered expression of APPL1. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is among the key factors for the advancement of hepatic steatosis to NAFLD and NASH. Pancreastatin (PST: human ChgA250-301) is a dysglycemic hormone, previously reported to promote steatosis and inflammation in various animal models of metabolic disorders. Recently, we observed PST deregulates energy expenditure and mitochondrial functioning in perimenopausal rats. In the current study, we aimed to decipher the role of PST instigated altered mitochondrial functioning in hepatic steatosis. The HepG2 cells were PST exposed and the Chga gene was knocked down using siRNA and lipofectamine. Parallelly, type 2 diabetes (T2D) was developed in C57BL/6 mice by HFD feeding and administered PST inhibitor (PSTi8). The PST exposed cells and HFD fed mice depicted: enhanced CHGA expression detected by IF/IHC, WB, and ELISA; dysregulated cellular ROS, mitochondrial ROS, oxygen consumption rate, mitochondrial membrane potential, ATP level, and NADP/NADP ratio; enhanced apoptosis determined by MTT, TUNEL, Annexin-V FITC, and WB of Bax/bcl2 and caspase 3; hepatic lipid accumulation upon Nile Red, Oil Red O, H&E staining, and the expression of SREBP-1c, FAS, ACC, and SCD; inflammation based on expression and circulatory level of IL6, IL-1β, and TNF-α. However, Chga knocked down HepG2 cells and PSTi8 treated mice unveiled protection from all the above abnormalities. Collectively, the aforementioned data suggested the alteration in mitochondrial function induced by PST is responsible for hepatic steatosis in T2D. [Display omitted] • Pancreastatin impedes mitochondrial functioning in HepG2 cells. • Pancreastatin increases lipid accumulation and inflammation in HepG2 cells. • Pancreastatin impedes mitochondrial functioning in HFD-induced T2D mice. • Pancreastatin instigates steatosis and inflammation in HFD-induced T2D mice. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • LC-MS/MS method has been developed and validated for the first time for S012-1332. • Absolute oral bioavailability of S012-1332 was 7.04% in rats. • In vitro findings show low solubility, high metabolism, moderate protein binding. • Stable in plasma and biorelevant media and highly permeable. Abstract S012-1332 is the first DNA ligase I inhibitor that demonstrated in vivo anti-breast cancer activity. The present study aimed to assess the in vivo pharmacokinetics of S012-1332 in rats and interpret them with in vitro findings. A sensitive and selective liquid chromatography-tandem mass spectrometry bioanalytical method was developed and validated to determine S012-1332. Following oral administration, the absolute bioavailability was 7.04%. The absorption was prolonged which can be explained by low solubility in simulated gastric fluid and several folds higher solubility in simulated intestinal fluid. The effective permeability across the intestinal membrane in in situ single pass perfusion study for S012-1332 was 5.58 ± 1.83 * 10−5 cm/sec compared to 5.99 ± 0.65 * 10−5 cm/sec for carbamazepine, with no significant difference, indicating S012-1332 has high permeability. It was rapidly partitioning into plasma in blood, where it was stable. Plasma protein binding was moderate which may have attributed to the rapid distribution out of the vascular compartment. The pharmacokinetics of S012-1332 was characterized by extensive clearance as seen with rat liver and intestinal microsomes. In vitro results elucidate the in vivo pharmacokinetic data. These findings provide crucial information for further development of S012-1332 as anti-breast cancer agent. [ABSTRACT FROM AUTHOR]

Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species (ROS) mediated mitochondrial dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. Naringin, a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties. Consequently, we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced steatohepatitis. Hepatic HepG2 cells were cultured in palmitic acid medium with and without naringin. Lipid content was examined by Oil Red O and Nile Red staining. Cellular apoptosis was determined by Annexin V-FITC/PI staining. An experimental T2DM-induced steatohepatitis was developed in Sprague Dawley rats by high-fat diet (HFD) for 12 weeks. The naringin was administrated orally at a dose of 100 mg/kg, daily for eight weeks. Glucose and insulin tolerance test was performed. Liver sections were stained by hematoxylin-eosin and picrosirius red. The mRNA and protein expression of RAGE and NF-κB were determined by qPCR, Immunofluorescence, and Immunoblotting. Mitochondrial membrane potential (MMP), cellular and mitochondrial ROS were measured by FACS. Palmitic acid encountered HepG2 cells and HFD fed rats exhibited hyperlipidemia, insulin resistance, abnormal aminotransferases, steatosis, and fibrosis. Besides, the level of AGEs, RAGE, NF-κB, and oxidative stress were exacerbated. Moreover, MMP, cellular and mitochondrial ROS were altered in diabetic rats. Nevertheless, the naringin treatment ameliorated the steatohepatitis by improving the levels of aforementioned parameters. Collectively, these findings suggested anti-steatohepatitis potential of naringin in diabetics. Unlabelled Image • Naringin alleviates glucose intolerance in T2DM-induced steatohepatitis. • Naringin safeguards from steatosis and hepatic inflammation. • Naringin inhibits AGEs formation, thereby inhibits RAGE activation. • Naringin mitigates oxidative stress by down regulating NF-κB. • Naringin protects from NF-κB mediated mitochondrial apoptosis. [ABSTRACT FROM AUTHOR]

• scFOS treatment does not affect body weight and composition, energy metabolism and mineral metabolism. • scFOS restores trabecular bone in OVX rats and promotes bone formation. • scFOS selectively increases serum osteogenic markers in OVX rats. • scFOS stimulated surface referent bone formation. • scFOS increased the osteogenic short-chain fatty acid, butyrate in serum. In preclinical studies, fructooligosaccharide (FOS) showed beneficial skeletal effects but its effect on peak bone mass (PBM) and bone loss caused by estrogen (E2) deficiency has not been studied, and we set out to study these effects in rats. Short-chain (sc)-FOS had no effect on body weight, body composition, and energy metabolism of ovary intact (sham) and ovariectomized (OVX) rats. scFOS did not affect serum and urinary calcium and phosphorus levels, and on calcium absorption, although an increasing trend was noted in the sham group. Sham and OVX rats given scFOS had better skeletal parameters than their respective controls. scFOS treatment resulted in a higher bone anabolic response but had no effect on the catabolic parameters. scFOS increased serum levels of a short-chain fatty acid, butyrate which is known to have osteogenic effect. Our study for the first time demonstrates that in rats scFOS at the human equivalent dose enhances PBM and protects against E2 deficiency-induced bone loss by selective enhancement of new bone formation, and implicates butyrate in this process. [ABSTRACT FROM AUTHOR]