Intravenous infusions of glucose stimulate key lipogenic enzymes in adipose tissue of dairy cows in a dose-dependent manner

The present study was investigated whether increasing amounts of glucose supply have a stimulatory effect on the mRNA abundance and activity of key lipogenic enzymes in adipose tissue of midlactation dairy cows. Twelve Holstein-Friesian dairy cows in midlactation were cannulated in the jugular vein and infused with either a 40% glucose solution (n=6) or saline (n=6). For glucose infusion cows, the infusion dose increased by 1.25%/d relative to the initial net energy for lactation (NEL) requirement until a maximum dose equating to a surplus of 30% NEL was reached on d 24. This maximum dose was maintained until d 28 and stopped thereafter (between d 29-32). Cows in the saline infusion group received an equivalent volume of 0.9% saline solution. Samples of subcutaneous adipose tissue were taken on d 0, 8, 16, 24, and 32 when surplus glucose reached 0, 10, 20, and 30% of the NEL requirement, respectively. The mRNA abundance of fatty acid synthase, cytoplasmic acetyl- coenzyme A synthetase, cytoplasmic glycerol 3-phosphate dehydrogenase-1, and glucose 6-phosphate dehydrogenase showed linear treatment × dose interactions with increasing mRNA abundance with increasing glucose dose. The increased mRNA abundance was paralleled by a linear treatment × dose interaction for fatty acid synthase and acetyl-coenzyme A synthetase enzymatic activities. The mRNA abundance of ATP-citrate lyase showed a tendency for linear treatment × dose interaction with increasing mRNA abundance with increasing glucose dose. The mRNA abundance of all tested enzymes, as well as the activities of fatty acid synthase and acetyl-coenzyme A synthetase, correlated with plasma glucose and serum insulin levels. In a multiple regression model, the predictive value of insulin was dominant over that of glucose. In conclusion, gradual increases in glucose supply upregulate key lipogenic enzymes in adipose tissue of midlactating dairy cows with linear dose dependency. Insulin appears to be critically involved in this regulation. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved

Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats

BACKGROUND: Previous studies reported that 17β-estradiol may influence the progression of diabetic renal disease in females. The present study was intended to provide an insight into the specific effects of progesterone, the other female sex hormone, in the diabetic renal complications. METHODS: Adult female wistar rats were divided into four groups (n = 6/group): intact control (non-diabetic, ND), intact diabetic (D), ovariectomized diabetic (D-OVX) and ovariectomized diabetic which were treated with progesterone (D-OVX + P; 10 mg/kg, s.c, every second day) for 10 weeks. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin. Expressions of transforming growth factor-β (TGF-β), fibronectin, vascular endothelial growth factor-A (VEGF-A), angiotensin II type 1 receptor (ATR1) and podocyte markers (nephrin and podocin) were assessed by immunohistochemistry and real-time PCR. RESULTS: The treatment of D-OVX rats with progesterone attenuated diabetic-associated increases in the urinary albumin to creatinine ratio, glomerulosclerosi and the expression of profibrotic and angiogenic factors (TGF-β, Fibronectin and VEGF-A). Furthermore, progesterone supplementation prevented diabetes-induced downregulation of nephrin and podocin while the overexpression of ATR1 in the diabetic rats was inhibited by the progesterone supplementation. CONCLUSION: These results provided evidence, for the first time, that the replacement of progesterone can ameliorate the renal damage in the experimental models of diabetic nephropathy through improving the renal function; the inhibition of renal fibrosis and abnormal angiogenesis; along with the amelioration of podocyte injury. Additionally, the blocking of renin-angiotensin system through the down-regulation of ATR1 expression may also account for the reno-protective effect of progesterone. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13098-015-0097-1) contains supplementary material, which is available to authorized users

Molecular and cellular effects of gold nanoparticles treatment in experimental diabetic myopathy.

Background This study aims to address the effects of gold nanoparticles (AuNPs) on diabetic myopathy in streptozotocin (STZ)-induced diabetic rats. Materials and methods Adult male rats were separated into three groups (n = 15): non-diabetic control (ND), diabetic (D), and diabetic treated with AuNPs (2.5 mg/kg, D + AuNPs) intraperitoneally for 4 weeks. A single injection of 50 mg/kg STZ was used to induce diabetes. Results Treatment with AuNPs lowered blood glucose levels. Skeletal muscle mRNA expression of two muscle-specific E3 ubiquitin-ligases enzymes, F-box-only protein 32 (FBXO32) and muscle RING-finger protein-1 (MuRF1) were upregulated in the D group. Diabetic rats showed significant increases in the skeletal muscle expression levels of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and a decrease in glucose transporter 4 (GLUT4) expression. Superoxide dismutase (SOD) activity decreased and malondialdehyde (MDA) level increased in skeletal muscles of D group. Compared to the D group, expression levels of FBXO32, MuRF1, PAI-1 TNF-α, and TGF-β1 were decreased in the D + AuNPs group, and mRNA of GLUT4 increased. Furthermore, in D + AuNPs group, skeletal muscle MDA levels decreased while SOD activity increased. Conclusion In experimental models, AuNPs can ameliorate muscle atrophy by reducing hyperglycemia, inflammation, and oxidative stress, and by suppressing the ubiquitin-proteasome proteolytic process

Exploring the Impact of Cigarette Smoke Extracts on Vitamin B12: Insights into the Transformation of Methylcobalamin and Hydroxycobalamin to Cyanocobalamin through in Vitro Evaluation

Vitamin B12 (cobalamin) is a water-soluble molecule required for the proper functioning of metabolism, blood and DNA synthesis, and neurological development. Vitamin B12 exists in several forms: methylcobalamin (MeCbl), adenosylcobalamin (AdoCbl), hydroxycobalamin (OHCbl), and cyanocobalamin (CNCbl). This study aimed to evaluate the effect of cigarette smoke on the chemical structure of methylcobalamin and hydroxycobalamin forms of vitamin B12. MeCbl and OHCbl were markedly affected by exposure to cigarette smoke. The resemblance of the Rt between MeCbl and OHCbl and CNCbl indicates that exposure to cigarette smoke extracts chemically alters MeCbl and OHCbl to CNCbl, warranting in vivo research investigations

Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin‐induced type 1 diabetes in rats

Abstract This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end‐stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24‐h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor‐β1, fibronectin, collagen‐IV, tumour necrosis factor‐α and vascular endothelial growth factor‐A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase‐9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy

In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA

Background: The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the pathogenesis of SCs-induced AKI is not well-understood. Methods: We investigated the nephrotoxic effect of acute administration of N-[(1S)- 1-(aminocarbonyl)-2-methylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide (AB-FUBINKA) (3 mg/kg for 5 days) in mice. Various parameters of oxidative stress, inflammation, and apoptosis have been quantified. The expressions of mitochondrial complexes (I-V) in renal tissues were also assessed. Results: Our findings showed that AB-FUBINACA induced substantial impairment in the renal function that is accompanied by elevated expression of renal tubular damage markers; KIM-1 and NGAL. Administration of AB-FUBINACA was found to be associated with a significant increase in the expression of oxidative stress markers (iNOS, NOX4, NOX2, NOS3) and the level of lipid peroxidation in the kidney. The expression of pro-inflammatory markers (IL-6, TNF-alpha, NF-kB) was also enhanced following exposure to AB-FUBINACA. These findings were also correlated with increased expression of major apoptosis regulatory markers (Bax, caspase-9, caspase-3) and reduced expression of mitochondrial complexes I, III, and IV. Conclusion: These results indicate that AB-FUBINACA can trigger oxidative stress and inflammation, and activate caspase-dependent apoptosis in the kidney, with these processes being possibly linked to disruption of mitochondrial complexes and could be an underlying mechanism of SCs-induced nephrotoxicity.Open Access funding provided by the Qatar National Library. This study is funded by a grant from the Deanship of Scientific Research, Yarmouk University, Jordan (Grant # 29/2021).Scopu

Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1 alpha

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients