One of the most important complications of diabetes is nephropathy. This study investigates the effects of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of diabetic rats. Male rats were divided into four groups- control rats, diabetic rats, garlic extract-treated diabetic rats, garlic extract-treated normal rats. The glucose, urea, uric acid, and creatinine levels were measured in sera using colorimetric methods. To determine the oxidative stress condition in the kidney tissues, total antioxidant capacity (TAC), malondialdehyde (MDA), and total oxidant status (TOS) were measured using colorimetric methods. Inflammation status was evaluated by the determination of tumor necrosis factor-alpha (TNF-α) gene and protein expression using qRT-PCR and ELISA respectively, while nitric oxide (NO) level in these tissues was measured using the Griess method. Histological examination of Kidneys was carried out by H&E staining. The levels of glucose, urea, and uric acid were found to increase in the serum of diabetic rats and decrease in that of diabetic rats after treatment with garlic. Measurement of MDA, TOS, and TAC revealed oxidative stress in diabetic rats, which improved after receiving the extract. The NO and TNF-α protein levels in diabetic rats were higher than those in control rats. After treatment with garlic, the levels of TNF-α protein and NO became close to the normal levels. Histological results confirmed certain other data as well. Garlic has antioxidant properties; therefore, it can reduce oxidative stress, which plays an important role in the development of diabetic nephropathy. Reduction in oxidative stress has beneficial effects on inflammation because it leads to a decrease in the level of TNF-α.
The Wnt/β-catenin pathway, which interferes with cell proliferation, differentiation, and autophagy, is commonly dysregulated in colorectal cancer (CRC). Mutation of the RAS oncogene is the most prevalent genetic alteration in CRC and has been linked to activation of protein kinase B (AKT) signaling. Phosphorylation of β-catenin at Ser 552 by AKT contributes to β-catenin stability, transcriptional activity, and increase of cell proliferation. Casein kinase 1 alpha (CK1α) is an enzyme that simultaneously regulates Wnt/β-catenin and AKT. The link of the AKT and Wnt pathway to autophagy in RAS-mutated CRC cells has not well identified. Therefore, we investigated how pharmacological CK1α inhibition (D4476) is involved in regulation of autophagy, Wnt/β-catenin, and AKT pathways in RAS-mutated CRC cell lines. qRT-PCR and immunoblotting experiments revealed that phospho-AKT (S473) and phospho-β-catenin (S552) are constitutively increased in RAS-mutated CRC cell lines, in parallel with augmented CK1α expression. The results also showed that D4476 significantly reduced the AKT/phospho-β-catenin (S552) axis concomitantly with autophagy flux inhibition in RAS-mutated CRC cells. Furthermore, D4476 significantly induced apoptosis in RAS-mutated CRC cells. In conclusion, our results indicate that CK1α inhibition reduces autophagy flux and promotes apoptosis by interfering with the AKT/phospho-β-catenin (S552) axis in RAS-mutated CRC cells.
Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.
Traumatic brain injury (TBI) is one of the most concerning health issues in which the normal brain function may be disrupted as a result of a blow, bump, or jolt to the head. Loss of consciousness, amnesia, focal neurological defects, alteration in mental state, and destructive diseases of the nervous system such as cognitive impairment, Parkinson's, and Alzheimer's disease. Parkinson's disease is a chronic progressive neurodegenerative disorder, characterized by the early loss of striatal dopaminergic neurons. TBI is a major risk factor for Parkinson's disease. Existing therapeutic approaches have not been often effective, indicating the necessity of discovering more efficient therapeutic targets. The mammalian target of rapamycin (mTOR) signaling pathway responds to different environmental cues to modulate a large number of cellular processes such as cell proliferation, survival, protein synthesis, autophagy, and cell metabolism. Moreover, mTOR has been reported to affect the regeneration of the injured nerves throughout the central nervous system (CNS). In this context, recent evaluations have revealed that mTOR inhibitors could be potential targets to defeat a group of neurological disorders, and thus, a number of clinical trials are
Infertility impacts a considerable number of women worldwide, and it affects different aspects of family life and society. Although female infertility is known as a multifactorial disorder, there are strong genetic and epigenetic bases. Studies revealed that miRNAs play critical roles in initiation and development of female infertility related disorders. Early diagnosis and control of these diseases is an essential key for improving disease prognosis and reducing the possibility of infertility and other side effects. Investigating the possible use of miRNAs as biomarkers and therapeutic options is valuable, and it merits attention. Thus, in this article, we reviewed research associated with female diseases and highlighted microRNAs that are related to the polycystic ovary syndrome (up to 30 miRNAs), premature ovarian failure (10 miRNAs), endometriosis (up to 15 miRNAs), uterine fibroids (up to 15 miRNAs), endometrial polyp (3 miRNAs), and pelvic inflammatory (6 miRNAs), which are involved in one or more ovarian or uterine disease‐causing processes.
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