Frontiers in bioscience (Scholar edition)最新文献

Oocyte quality influences early embryonic survival, establishment and maintenance of pregnancy, fetal development and adult diseases. The developmental competence of oocytes is acquired gradually and increases with follicular development. The ability of an oocyte to develop into an embryo depends on, having enough specific information in the form of mRNA or proteins. If this information is insufficient, defects in nuclear or cytoplasmic maturation, or in both processes, may arise and thus affect the in vitro development of fertilized oocytes. The greater developmental competence of oocytes aspirated from larger follicles is reported as compared with smaller follicles. Oocyte developmental competence is greatly correlated with the morphology of the cumulus oocyte complexes (COCs). Apart from morphological or biochemical markers, molecular markers have also been investigated. Until now, no specific markers of oocyte developmental competence could be described for the oocyte developmental competence. To, utilize female germplasm to its maximum, there is a need to enhance developmental competence of lesser competent oocytes derived from the follicles which are not fully grown. The oocyte pre-maturation and maturation conditions affect gene expression not only in the oocyte but till the blastocyst stages too. Strategies have been discussed in this review would be useful to enhance the developmental competence of oocytes.

Coronary artery disease (CAD) and heart failure (HF) are major worldwide threat to health and well-being. Important progress in the treatment of CAD and HF have contributed to a decline in mortality around the world. A considerable number of epidemiological studies reported a strong independent association between elevated heart rate and major cardiovascular risk factors including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine (IVA) is a pure heart rate-lowering agent with well-documented anti-anginal and anti-ischemic properties comparable to well-established anti-anginal agents, such as beta-blockers and calcium channel blockers. The heart rate reduction with IVA is beneficial in patients with CAD, chronic stable angina pectoris, and chronic HF, with an acceptable tolerance and safety profile. The pharmacodynamic and pharmacokinetic properties of this drug make it an important agent in the management of patients with CAD and HF. The aim of this short review is to explore recent results with IVA, a new medication that lowers heart rate by selectively inhibiting the If current, and to describe others future potential applications.

Atherosclerosis is an inflammatory, progressive, and chronic illness that involves several molecular and epigenetic factors. Despite treatment limitations, clinical and therapeutic approaches have undeniably changed radically in recent decades through better knowledge of the pathophysiological basis of the disease, which has considerably improved patients' survival and quality of life. Some of these advances are attributable to basic biomedical research that provides insights into a better understanding and identification of new molecular and cellular targets for atherosclerosis treatment. Although rodent models have contributed substantially to a better understanding of the development of atherosclerosis, the accuracy of these models remains controversial. Research that utilizes genetic rodent models is well established, but the use of specific diets that are associated with other risk factors (e.g., hypertension, hormone deprivation, and pharmacological tools) is still debatable. The present review provides an update on non-genetic rat models of atherosclerosis and an overview of the main methodologies that are currently available.

In the pharmaceutical industry, the expected surge in production of new therapeutic entities promised by technological advances, such as high-throughput screening, synthetic libraries and advances in molecular biology and genomics, has not materialized. The unique structural diversity of natural products continues to provide opportunities to discover novel compounds. Secondary metabolites, active components of natural products such as marine organisms, microbial organisms and terrestrial plants, are particularly exciting untapped resources for exploration as medicines. Sri Lanka is home to around 3700 plant species, half of which are considered as medicinal plants. Seventy per cent of the Sri Lankan population relies on this plant-based traditional medicine system for treating various illnesses such as tumors. As such these medicinal plant sources should be used to conquer terminal diseases and for prevention of diseases. Sri Lankan researchers have found several plant species that possess cytotoxic activity. This review summarizes the current information regarding the Sri Lankan plant materials that possess anticancer properties.

RNA interference is currently one of the most advanced genomic tools providing promising insight to manage countless pathophysiological conditions that seemed unapproachable few years ago. Researchers across the globe have devised numerous methods in which small RNA molecules can be administered into target cells to manipulate cellular functions at the molecular level and eradicate defects that lead to pronounced phenotypes, which might sometimes be as fatal as malignant tumors. The present review provides an overview of the non-viral delivery approaches for siRNA therapeutics with an emphasis on the PLGA polymeric strategy and its use in different biological applications. Due to its versatile surface, PLGA is not only used in tissue engineering such as remodeling of bone and cartilage, but it indeed plays a crucial role as chemical carrier for a broad range of therapeutic agents. It is greatly implicated in gene therapies and inherited genetic defects.

Human adult stem cells hold promise for regenerative medicine. They are usually expanded for multiple passages in vitro to increase cell yield prior to transplantation. Unfortunately, prolonged culture leads to cell senescence, a major drawback from successful outcomes in cell therapy approaches. Here, we show that an extract from early Zebrafish embryo (ZF1) counteracted senescence progression in human adipose-derived stem cells (hASCs) along multiple culture passages (from the 5th to the 20th). Exposure to ZF1 strongly reduced the expression of senescence marker beta-galactosidase. Both stemness (NANOG, OCT4, and MYC) and anti-senescence (BMI1, and telomerase reverse transcriptase - TERT) related genes were overexpressed at specific experimental points, without recruitment of the cyclin-dependent kinase Inhibitor 2A (CDKN2A, ali-as p16). Increased telomerase activity was associatt-ed with TERT overexpression. Both osteogenic and adipogenic abilities were enhanced. In conclusion, hASCs exposure to ZF1 is a feasible tool to counteract and reverse human stem cell senescence in long-term culturing conditions.

African-American (AA) women are more likely to die from breast cancer (BC), at any age, compared to European-American women. Although breakthroughs in pre-clinical studies have resulted in potentially actionable targets in AA BC, drugs that were rationally designed for these targets have performed poorly in clinical trials. Challenges with interpatient and intratumoral heterogeneity, lack of drug sensitivity and specificity, suboptimal biomarker cut-offs, lack of drug response predictive biomarkers, drug side effects, high costs of drug development, and under-representation of AAs in clinical trials complicate the development of targeted therapies for AA BC patients. Accumulating evidence suggests that racial disparities exist in non-genetic risk factors that can alter genetic and epigenetic programs to promote breast tumorigenesis. Herein, we present a "roadmap" that addresses non-genetic risk factors that are suspected to contribute to the racial disparity in BC mortality. Increased targeting of these non-genetic risk factors may proffer a safer and more economical route to alleviating the racially disparate burden in BC.

The etio-pathogenesis of necrotizing enterocolitis (NEC) is complex and multifactorial. Decades of research have not identified a definite etiology. Prematurity, enteral feeding, intestinal hypoxia/ischemia, inflammation and an abnormal microbiome are potential risk factors for developing this multisystem illness. Lack of specific diagnostic and prognostic markers adds to the challenges faced in managing NEC. Vascular mediators such as Nitric oxide (NO), catecholamines and endothelin (ET) regulate neonatal intestinal vascular resistance and may influence the pathophysiology of NEC. Neonatal morbidities, medications, transfusions, an altered microbiome and breast milk feeds may influence the vasculature in various ways. Better understanding of these mediators and their role in regulation of intestinal microcirculation and pathogenesis of NEC will assist in identifying strategies in prevention and management of this devastating illness.

Growing evidence now links circadian disruption (CD) to increased risk of developing multiple types of cancer, including breast cancer (BC). In the US, African-American (AA) BC patients have a higher mortality rate than European-Americans (EAs) with BC, and a prime suspect in this racially disparate burden has been the greater incidence of an aggressive and highly heterogeneous BC subtype called triple-negative BC (TNBC), among AAs. AAs are also more prone to CD as larger proportions of AAs engage in night shift work than EAs, and the chronotype of AAs makes it harder for them to adapt to CD than EAs. Although clock gene dysregulation has been shown to perturb transactivation of key cell cycle and apoptosis regulators, little is known about how clock gene mis-expression affects TNBC outcomes. This review examines the prognostic value of clock genes in TNBC, and evaluates patterns of clock gene dysregulation in the individual TNBC molecular subtypes. Better understanding of how CD contributes to TNBC biology may illuminate new paths to improving disease outcomes and reducing BC-related racial disparities.