Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disorder ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). This study aimed at assessing the regulatory and protective role of miR-26a on lipid metabolism and progression of NAFLD in human HepG2 cells loaded with free fatty acids (FFA). Lentivirus expressing miR-26a or negative control miR was used to transduce HepG2 cells and to establish stable cell lines. Gain or loss of function using an miR-26a inhibitor was used to compare triglyceride content (TG), total cholesterol level (CL), total antioxidant capacity (TAC), malondialdehyde (MDA) and the level of apoptosis. In addition, quantitative reverse transcription polymerase chain reaction (qPCR) was used to assess the mRNA levels of lipogenesis, TG synthesis, storage genes, inflammatory and fibrogenic markers, and autophagic besides endoplasmic reticulum (ER) stress markers after gaining or losing the function of miR-26a. miR-26a levels decreased in response to FFA in human HepG2 cells. After the establishment of a stable cell line, the upregulation of miR-26a resulted in the downregulation of TG, CL, and MDA levels, through regulating mRNA levels of genes involved in lipid homeostasis, ER stress marker, inflammatory and fibrogenic markers. Nevertheless, there was a marked increment in the mRNA expression of autophagic marker genes. Moreover, miR-26a overexpression protects the cells from apoptosis, whereas inhibition of miR-26a, using an anti-miR-26a oligonucleotide, decreased the expression of miR-26a which potentially contributes to altered lipid metabolism in HepG2 cells loaded with FFA. In conclusion, these findings suggested that miR-26a has a crucial role in regulating fatty acid and cholesterol homeostasis in HepG2 cells, along with the offered protection against the progression of NAFLD in vitro. Hence, miRNAs could receive growing attention as useful noninvasive diagnostic markers to follow the progression of NAFLD and to identify novel therapeutic targets.
VD was highly prevalent in Egyptian T1D patients. VD supplementation improved glycemic control at 3 months after therapy with no reduction in insulin requirements.
Twelve cases of galactorrhea in women with normal menstrual cycles who were radiologically free of any pituitary adenomas were investigated. Determinations were made for serum thyroid-stimulating hormone (TSH), T3 resin uptake (T3RU), total thyroxine by radioimmunoassay (T4), free thyroxine index (FT4I), norepinephrine, epinephrine, prolactin and urinary luteinizing hormone, total estrogens, pregnanediol and total catecholamines. Psychologic evaluation and assessment were also done using the Middlesex Hospital Questionnaire and the Eysenk, manual dexterity, Bender Gestalt and trial-making scales. Hypothyroidism associated with moderate hyperprolactinemia and anovulation were the main features in eight cases. Associated psychologic disturbances were reported. The other four cases showed significant elevations in serum epinephrine, norepinephrine and urinary total catecholamines with concomitant pathologic scales of anxiety and neuroticism. Thyroxine replacement and psychotherapy are recommended in the treatment of such cases.
Imatinib mesylate (IM) is the gold standard for treatment of Chronic Myeloid
Leukemia (CML). This study aimed to gain more knowledge of the altered PK,
pharmacogenetic factors, and gene expression leading to variable IM levels.
Fifty patients with chronic phase-CML were enrolled in this study and divided as
25 responders and 25 non-responders (patients are directly recruited after
response assessment). HPLC/MS/MS was used to determine trough
and peak concentration of imatinib and N-desmethyl imatinib in the blood.
PCR-RFLP technique was used to detect IDH1 gene mutation (R132). The median
value of IM trough level was significantly higher, the P/T ratio was
significantly lower and the α-1-acid glycoprotein (AGP) was
significantly higher among responders compared to non-responders
(P=0.007, 0.009 and 0.048, respectively). Higher N-desmethyl imatinib
peak plasma concentration was observed with low mRNA expression of ABCG2 and
OCT1 (P=0.01 and 0.037, respectively). IDH1 R132 gene mutation was
associated with a significant increase in toxicities (P=0.028). In
conclusion, IM trough level, P/T ratio and AGP was significantly higher
in responders. In addition, ABCG2 and OCT1 gene expression may affect the
interindividual PK variation. Although a prospective study with a larger patient
population is necessary to validate these findings. IDH1 mutation is a predictor
of increased toxicity with IM treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.