Knoxroth7090
Prostate cancer-associated transcript 6 (PCAT6) is a long non-coding RNA (lncRNA) firstly identified in 2013 through an integrative genomic analysis of different cancer tissues. This oncogenic lncRNA has been found to regulate carcinogenesis process in different tissues, including breast, ovary, stomach, bladder, colon, pancreas and liver. The role of PCAT6 in sequestering certain microRNAs has been well established. For instance, miR-4723-5p, miR-185-5p, miR-143-3p, miR-30, miR-15a, miR-513a and miR-204, and miR-326 are among those being sequestered by PCAT6. Over-expression of PCAT6 has been associated with poor clinical outcomes in diverse types of cancers including ovarian, bladder, colorectal and pancreatic cancers. In the present review, we summarize the impact of PCAT6 in the development of diverse types of cancers, based on the results of functional studies in cell lines, experiments in xenograft models of cancers and expression studies in samples obtained from human subjects.Betulinic acid (BA) is a pentacyclic triterpene compound that can be obtained by separation, chemical synthesis and biotransformation from birch. BA has antitumour activity, and its mechanisms of action mainly include the induction of mitochondrial oxidative stress; the regulation of specificity protein transcription factors, and the inhibition of signal transducer and activator of transcription 3 and nuclear factor-κB signalling pathways. In addition, BA can increase the sensitivity of cancer cells to other chemotherapy drugs. Recent studies have shown that BA plays an anticancer role in several kinds of tumour diseases. In this article, the anticancer mechanism of BA and its application in the treatment of tumour diseases are reviewed.The pharmacological characteristics of phytochemicals have prompted a lot of interest in their application in disease management. Due to the high incidence of cancer related mortality and morbidity throughout the world; experiments have concentrated on identifying the anticancer potential of natural substances. Many phytochemicals such as flavonoids and their derivatives produced from food offer a variety of new anti-cancer agents which prevent the cancer progression. Taxifolin, a unique bioactive flavonoid, is a dietary component that has grabbed the interest of dietitians and medicinal chemists due to its wide range of health benefits. It is a powerful antioxidant with a well-documented effect in the prevention of several malignancies in humans. Taxifolin has shown promising inhibitory activity against inflammation, malignancies, microbial infection, oxidative stress, cardiovascular disease, and liver disease. Anti-cancer activity has been shown to be relatively significant than other activities investigated in vitro and in vivo with a little or no side effects to the normal healthy cells. In summary this review offers the synopsis of recent breakthroughs in the use of taxifolin as a cancer treatment, as well as mechanisms of action. However, to develop a medicine for human usage, more study on pharmacokinetic profile, profound molecular mechanisms, and drug safety criteria should be conducted utilizing well-designed randomized clinical trials.Uterine lipoleiomyomas are variants of uterine leiomyomas and are characterized by progressive enlargement that can occur even after menopause. These tumors can produce serious clinical symptoms and are difficult to diagnosis preoperatively. The growth rate of uterine lipoleiomyomas after menopause is comparatively higher than that of conventional uterine leiomyomas, and lipoleiomyosarcomas as well as tumor-to-tumor metastasis associated with lipoleiomyomas have been reported. However, detailed histogenic mechanisms of the tumor remain unclear. Surgical treatments are the current choice for the management of lipoleiomyomas. The purpose of this review is to promote greater awareness of lipoleiomyoma characteristics with a focus on histogenesis, diagnosis, and treatment. We performed an exhaustive literature review and have summarized the available data. We assessed the interpretation of auxiliary examinations to help physicians in making an early accurate diagnosis of the disease and to help with treatment decision-making, particularly regarding whether surgery should be performed or avoided.Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Nutraceuticals, mainly based on natural products, have been proven to control the risk factors of CVDs effectively. Rhodomyrtus tomentosa is an underutilized fruit that is rich in phenolic compounds and has antioxidant activities. Scientific investigation was needed to verify the pharmacological properties of R. tomentosa fruit juice in Sprague-Dawley rats fed with high fat high cholesterol (HFHC) as antihypercholesterolemic and antiatherosclerotic agents. The experiments were carried out using male albino rats fed with HFHC diet for 75 days and at the same time orally supplemented with R. tomentosa fruit juice (RTFJ) in doses of 0.5, 1, and 2 g/kg body weight (BW) daily for 75 days. Simvastatin was used as a positive control. At the end of the experiment, the blood was collected, and the serum was assayed for total triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). The histopathology of coronary and aorta arteries was observed under the light microscope. The results demonstrated that the supplementation of RTFJ significantly prevented the increase of total triglycerides, total cholesterol, low-density lipoprotein, and the decrease of high-density lipoprotein in serum. Supplementation of RTFJ also prevents atherosclerosis development by preventing the thickening of the blood vessel wall, deposition of lipid formation, and foam cells in the tunica intima of the aorta and coronary arteries. These findings suggested that supplementation of R. tomentosa fruit juice prevents hypercholesterolemia and atherosclerosis.
Liver inflammation leads to the activation of hepatic stellate cells (HSCs), resulting in the development of liver fibrosis. The present study aimed to investigate the effects of prostaglandin E
(PGE
), which is biosynthesized by Kupffer cells, hepatocytes, and HSCs during inflammation, on HSC activation, including its combinatory effect with caffeine.
HSCs isolated from mice were activated by culturing in a medium supplemented with 10% fetal bovine serum for 7 days on plastic plates. The activation of HSCs was evaluated by immunofluorescence of α-smooth muscle actin in HSCs. selleck Comprehensive gene expression analysis was performed using mRNA-sequencing to compare HSCs cultured for 1 or 7 days, with or without PGE
, caffeine, or both.
PGE
(1μM) facilitated the activation of HSCs but inhibited the HSC activation in the presence of caffeine (3mM). Comprehensive gene expression analysis revealed that HSCs treated with PGE
in the presence of caffeine were classified in the same class as HSCs cultured for 1day, i.e., quiescent HSCs. In contrast, PGE
did not exhibit an inhibitory effect on HSC activation when co-treated with any isoform-specific phosphodiesterase inhibitors. Although the adenylate cyclase inhibitor 2',5'-dideoxyadenosine suppressed the elevation of intracellular cAMP level induced by PGE
in the presence of caffeine, it had no effect on the inhibition of HSC activation by PGE
plus caffeine.
The effect of PGE
on HSC activation is changed from facilitatory to inhibitory when combined with caffeine, suggesting that caffeine may effectively suppress liver fibrosis during inflammation.
The effect of PGE2 on HSC activation is changed from facilitatory to inhibitory when combined with caffeine, suggesting that caffeine may effectively suppress liver fibrosis during inflammation.Genetic factors that affect variability in metformin response have been poorly studied in the Latin American population, despite its being the initial drug therapy for type 2 diabetes, one of the most prevalent diseases in that region. Metformin pharmacokinetics is carried out by members of the membrane transporters superfamily (SLCs), being the multidrug and toxin extrusion protein 1 (MATE1), one of the most studied. Some genetic variants in MATE1 have been associated with reduced in vitro metformin transport. They include rs77474263 p.[L125F], a variant present at a frequency of 13.8% in Latin Americans, but rare worldwide (less than 1%). Using exome sequence data and TaqMan genotyping, we revealed that the Mexican population has the highest frequency of this variant 16% in Mestizos and 27% in Amerindians, suggesting a possible Amerindian origin. To elucidate the metformin pharmacogenetics, a children cohort was genotyped, allowing us to describe, for the first time, a MATE1 rs77474263 TT homozygous individual. An additive effect of the L125F variant was observed on blood metformin accumulation, revealing the highest metformin and lactate serum levels in the TT homozygote, and intermediate metformin values in the heterozygotes. Moreover, a molecular dynamics analysis suggested that the genetic variant effect on metformin efflux could be due to a decreased protein permeability. We conclude that pharmacogenetics could be useful in enhancing metformin pharmacovigilance in populations having a high frequency of the risk genotype, especially considering that these populations also have a higher susceptibility to the diseases for which metformin is the first-choice drug.The remediation of co-located contaminants in the vadose zone can be challenging due to accessibility and responses of different contaminants to remedial actions. At the Hanford Site (WA, USA), multiple radionuclides and other hazardous contaminants are present in the vadose zone and groundwater, including iodine-129 (I), technetium-99 (Tc), uranium-238 (U), chromium (Cr), and nitrate (NO3-). We evaluated a layered Bi oxyhydroxide material for its potential to remove individual and co-located contaminants with a series of batch experiments that investigated a range of plume conditions, followed by solid phase characterization of the reacted bismuth material. The results demonstrated successful removal of four contaminants (>98% removal of I, Tc, U, and Cr from the aqueous phase after 30 days) when tested individually. When contaminants were combined, a slight decrease in Tc removal occurred (-6%p). The addition of sediment decreased the removal for Tc and I, but U and Cr removal was unaffected. The results of these batch tests demonstrated that the bismuth based oxy-hydroxide material is a promising material for sequestering multiple contaminants in situ.The present article introduces data on natural radioactivity (40K, 230,232Th, 234,238U) in the Antarctic marine and terrestrial environment. Various biota samples were analysed due to internal exposure to 40K, 230,232Th, 234,238U. Activity concentration of 40K was the highest in both marine and terrestrial samples. Mean values of 40K activity concentration are 1340 Bq/kg and 370 Bq/kg for the marine and terrestrial samples respectively. 234U/238U ratios analysis revealed that sea waters and sea spray are the main source of the uranium in the terrestrial samples. Average 230,232Th, 234,238U activity concentrations in the Antarctic biota do not exceed 6 Bq/kg. Weighted internal dose rates are relatively low; they range from approximately 0.1 to 0.6 μGy/h. Statistically significant differences in radionuclide accumulation were discovered between the mosses and lichens. It may point to various mechanisms of the nutrient absorption from the environment by these organisms.
