Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c more than or equal to 7.0 percent (beta= -0.178, p= 0.034; beta = -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c more than 7.0 percent (beta = -0.205, p= 0.022; beta = -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (beta = -0.282, p= 0.014; beta = -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.

Mammalian spermatogenesis is a complex but well-coordinated process in which spermatogonial stem cells (SSC) of the testis develop to form spermatozoa. During testicular homeostasis, the spermatogonial stem cells self-renew to maintain the stem cell pool or differentiate to form a progeny of germ cells which sequentially transform to spermatozoa. Accumulating evidence from clinical data and diverse model organisms suggest that the fate of spermatogonial stem cells towards self-renewal or differentiation is governed by intrinsic signals within the cells and by extracellular signals from the SSC niche. Here, we review the past and the most recent developments in understanding the nature of spermatogonial stem cells and the regulation of their homeostasis in mice. We also review the potential clinical applications of spermatogonial stem cells in male infertility as well as in germline modification, by virtue of gene correction and conversion of somatic cells to biologically competent male germline cells.

Epithelial-to-mesenchymal transition (EMT) is a fundamental cellular phenomenon that plays an intrinsic role in development, tissue repair, and cancer progression. EMT is tightly regulated by transcription factors that alter gene expression to promote epithelial to mesenchymal phenotype. EMT is also regulated by a diverse array of cytokines and growth factors whose activities are deregulated during malignancy. EMT enables tumor cells to exist in various intermediate states along the epithelial-mesenchymal phenotypic axis that transit from cancer stem cells (CSCs) to circulating tumor cells (CTCs). Recent studies have revealed the importance of CSCs in tumor promotion, invasion and metastasis. The relapsed tumors encompass CSCs which are resistant to radiotherapy and chemotherapy. In this review, we have summarized our current understanding of the molecular mechanisms that regulate EMT induced CSC phenotype. We have highlighted studies implicating the function of TGF-�, Wnt, and Notch regulated non-coding RNAs in driving EMT promoting CSC self-renewal. Finally, we discuss how the EMT and CSCs cause drug resistance with the hope to overcome such resistance as a possible approach for cancer treatment.

Soil constitutes a major component of the agro-ecosystem. Unrestrained uses of chemical pesticides and increased human activities have contributed to unprecedented changes in soil microflora affecting productivity. Modern microbiomics has proven to be an indispensable tool to understand the adaptations underlying complex soil microbial communities and their beneficial applications. In this review, we seek to emphasize the scope of microbiomics in enhancing soil productivity by providing an overview of the various sequencing platforms considering key parameters such as the accuracy, read lengths, reads per run, time involved and weighing out their pros and cons. The advances in modern ultra-high-throughput microbiomics platforms in combination with cloud-based analytics for in-depth exploration of soil-microbe associations can help achieve sustainable soil management contributing to better plant yield and productivity.

Lamiaceae (Labiatae) are an important group of medicinal plants, which have been used for treating heart disease in traditional medicine for centuries. These mainly aromatic plants are used as essential oils, extracts or isolated components (polyphenols, phenolic compounds, terpenes, iridoids etc.). Some Labiatae species (more than 30, such as cornmint, lavender, patchouli, rosemary etc.) are famous for their use in essential oil production worldwide. In this review, cardioprotective effects of Lamiaceae and their active secondary metabolites, as well as mechanism of action against cardiovascular diseases (hypertension, angina pectoris, hyperlipidemia, thromboembolism, coronary heart disease, heart failure, venous insufficiency, arrhythmia) will be discussed. Use of Labiatae as food or food additives (such as spices) may prevent risk of cardiovascular diseases, diabetes and cancer. This approach is also described as a part of the article. Studies on developing new, effective and safe natural products from Lamiaceae (rich source of flavonoids and other active compounds) are promising and may offer prevention and treatment for patients with coronary disease and other related diseases.

Cyclooxygenase-2 (COX-2) is an inducible enzyme which triggers the biosynthesis of prostaglandins. COX-2 is activated in response to inflammatory stimuli and is one of the major molecules that is involved in the development and progression of colorectal cancer (CRC). Consistent with such a conceptual framework, it has been shown that COX-2 inhibitors prevent the carcinogenesis of CRC and aid in the treatment of sporadic or familial cases of CRC as shown by an overall increase in the survival rate. However, prolonged use of these inhibitors is associated with increase risk of development of cardiovascular complications, implying that further research is required to identify COX-2 inhibitors that are associated with lower risks of such complications.

Heavy metals in street dust represent a risk to the human health due to their toxicity, persistence and bioaccumulation. Using the US Environmental Protection Agency (USEPA) assessment, here, we review the human health risks of such dust world-wide. The street dust in such cities is contaminated by As, Cd, Cr, Cu, Hg, Mn Ni, Pb and Zn beyond the median levels of the world soil background values. Among these elements, the median values of the hazard risk indices (non-carcinogenic risk) are highest for As, Cr and Pb and the median values of the risk indices (carcinogenic risk) for As are in the tolerable risk range for children and adults and in the case of Pb, the median value of the carcinogenic risk indices are also in the tolerable range for children. We emphasize that the level of heavy metals in street dust pose a considerable risk to the human health and require monitoring and approaches to reduce such toxic levels.

Aging leads to and is associated with aberrant function of multiple signaling pathways and a host of factors that maintain cellular health. Under normal conditions, the prolongevity, 5' AMP-activated protein kinase (AMPK), is dedicated to the homeostasis of metabolism and autophagy for removal of damaged cellular compartments and molecules. A host of sirtuin family of molecules, that extend life-span, regulate metabolism and repair DNA damage, and possess either mono-ADP-ribosyltransferase, or deacylase activity. Another group of pro-longevity factors, include FOX (forkhead box) proteins, a family of transcription factors that regulate the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide (NMN), a requisite step for production of NAD+, which is known to increase longevity. Loss of Klotho, a transmembrane enzyme that controls the sensitivity of the organism to insulin and suppresses oxidative stress and inflammation, leads to premature aging in mice. Hydrogen sulfide and transsulfuration pathways are crucial to the long life and are required in protection of cells against damage. Aging also leads to the imbalanced activation of other pathways and factors including p53, insulin and IGF signaling, P13K/AKT, mTOR, PKA, RAS, RTK, MEK, ERK, MAPK, CRTC-1/CREB and NFkB. Such aberrant cellular functions, disturb cell metabolism, derail autophagy and other housekeeping actions, inhibit cell division, induce inflammaging and immunosenecence, cause stem cell exhaustion and induce either senescence, apoptosis or cancer.

Vitamin D deficiency has been estimated to affect roughly 30% to 50% of the global population and thus labeled as a silent pandemic. In addition to its role in skeletal and calcium homeostasis, vitamin D has been implicated in brain functioning across both preclinical research and human populations studies. These findings have also been extended to various neurodevelopmental and neuropsychiatric conditions. Furthermore, these individuals tend to display diminishing cognition symptoms. In this regard, this review is dedicated to address the relationship between vitamin D and dementia, mood disorders, and the various neuropsychological disorders of psychosis. The review takes both preclinical and clinical studies into consideration. While there are many literature suggesting the critical role of vitamins in cognition on the above said diseases, it is still premature to unequivocally postulate the role of vitamin D on cognitive symptoms. Further research is necessary to establish this association, including the need to increase the ecological validity of animal models, delineating the core cognitive symptoms associated with the disorders, and establishing the optimal source of vitamin D consumption.

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by presence of the BCR-ABL fusion gene which encodes the constitutively active BCR-ABL chimeric protein. Imatinib is first FDA approved first-line BCR-ABL targeting drug for the treatment of newly diagnosed CML cases. Nowadays there are recently developed and more efficient TKIs in the market. Despite the improvements in the CML therapy by using tyrosine kinase inhibitors (TKIs) primary/secondary resistance or progression from chronic to accelerated and blastic phase may be developed in some cases. Underlying mechanisms of TKI resistance and disease progression may results from BCR/ABL dependent or independent alterations. Recently it was revealed that tumor microenvironment is very important for cancer cell growth, survival, proliferation, hemostasis, invasion and metastasis. Exosomes derived from tumor cells contain many important signaling molecules and transfer these molecules in the neighbouring cells. In the bone marrow matrix CML cells, CML leukemic stem cells,cells, bone marrow mesenchymal stromal cells can communicate with each other through exosomes. In this review we focused on biological and clinical importance of CML derived exosomes and we will summarize the recent studies in this field.