Cell based and In vivo systematic evaluation of some Egyptian plant extracts targeting breast cancer.

The prevalence of breast cancer as a significant public health concern necessitates continued exploration of natural resources for novel anti-cancer agents is crucial. MATERIAL AND METHODS: Anticancer activity of plant extracts on monolayer breast cancer cell line (MCF7) with lower levels of toxicity towards normal (RPE1) underwent further assessment using a three-dimensional model (3D). The extract's effects were investigated through multiple assays including apoptosis induction using quantifying cleaved cytokeratin-18 (CK18) and DNA fragmentation. Additionally, the expression of Bcl-2 and Bax was quantitative using real-time PCR. The median lethal dose (LD50) was determined by the acute oral toxicity, while biomarkers associated with tumorigenesis, metastasis, and cell death were quantified by ELISA. RESULTS: Limoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts. They demonstrated potent cytotoxicity against MCF7 with no significant effect on hTERT RPE-1, with an IC50 of 100 µM. The extract demonstrated effectiveness in killing cancer cells within 3D tumor-like structures, induced apoptosis through caspase-3 activation and cleavage of cytokeratin-18, up-regulated the tumor suppressor p53, down-regulated the anti-apoptotic Bcl-2 gene, and caused DNA fragmentation. Acute oral toxicity studies in mice indicated low toxicity, and in a syngeneic mouse tumor model, the extract significantly inhibited tumor growth, suggesting its potential for further development. CONCLUSION: Limoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts.

Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.

Expression profiling and analysis of some miRNAs in subcutaneous white adipose tissue during development of obesity.

BACKGROUND: MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity management METHOD: A hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at intervals 2 weeks, serum lipid, hormone levels, total body fat mass, and inguinal subcutaneous white adipose tissue mass (WAT) measurements were recorded using dual-energy X-ray absorptiometry (DEXA). The expression levels of microRNAs were evaluated using real-time PCR. RESULTS: Significant alterations were observed in serum glucose, lipid profile, and adipokine hormones during the early stages of obesity development. Alteration in rno-mir 30a-5p, rno-mir 133a-5p, and rno-mir 107-5p expression levels were observed at more than one time point. While rno-let-7a-5p, rno-mir 193a-5p, and rno-mir125a-5p were downregulated and rno-mir130a-5p was upregulated at all time points within 2 to 4 weeks in response to H.F.D feeding for 10 weeks. The impact of switching to normal diet has a reversed effect on lipid profile, adipokine hormone levels, and some miRNAs. The bioinformatics results have identified a novel and important pathway related to inflammatory signalling. CONCLUSION: Our research demonstrated significant alterations in some adipocyte-expressed miRNAs after a short time of high caloric diet consumption. This provides further evidence of the significant role of nutrition as an epigenetic factor in regulation of lipid and glucose metabolism genes by modulating of related key miRNAs. Therefore, we suggest that miRNAs could be used as biomarkers for adiposity during diet-induced obesity. Perhaps limitation in calories intake is a way to manipulate obesity and associated metabolic disorders. Further studies are needed to fully elucidate the role of microRNAs in the development of obesity.