Rn7SK small nuclear RNA is involved in cellular senescence

Rn7SK is a conserved small nuclear noncoding RNA which its function in aging has not been studied. Recently, we have demonstrated that Rn7SK overexpression reduces cell viability and is significantly downregulated in stem cells, human tumor tissues, and cell lines. In this study, we analyzed the role of Rn7SK on senescence in adipose tissue-derived mesenchymal stem cells (AD-MSCs). For this purpose, Rn7SK expression was downregulated and upregulated via transfection and transduction, respectively, in AD-MSCs and subsequently, various distinct characteristics of senescence including cell viability, proliferation, colony formation, senescence-associated β galactosidase activity, and differentiation potency was analyzed. Our results demonstrated the transient knockdown of Rn7SK in MSCs leads to delayed senescence, while its overexpressions shows opposite effects. When osteogenic differentiation was started, however, they exhibited a greater differentiation potential than the original MSCs, suggesting a potential tool for stem cell-based regenerative medicine.     

Effect of curcumin on glioblastoma cells

Curcumin is a polyphenolic compound derived from Curcumin longa L. There are growing bodies of evidence revealing the antitumor effect of curcumin in different tumors; although the molecular mechanism behind this inhibition in glioblastoma multiform (GBM) still remains unclear. Here we investigated the antitumor activity of nano micelles curcumin compared with erlotinib in U-373 cells in monolayer cell cultures and spheroids models. Furthermore, we characterized affecting cell cycle perturbation, as well as apoptosis induction in GBM cells. The antiproliferative activity of nano micelles curcumin and erlotinib were assessed in monolayer and spheroid models. The influence of the cell cycle and expression levels of nuclear factor κB (NF-κB) and Wnt/β-catenin pathway was checked. Nano micelles curcumin suppressed cell growth in U-373 cells via modulation of Wnt and NF-κB pathways. Moreover, cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation posttreatment with nano micelles curcumin and erlotinib. In the core signaling pathways of GBM, nano micelles curcumin either significantly influences the NF-κB pathway by decreasing p-65 expression or significantly inhibits the Wnt/β-catenin pathway by declining cyclin D1 expression. In conclusion, we have shown that nano micelles curcumin effectively prevent proliferation, and invasion of GBM cells through perturbation of Wnt/β-catenin and NF-κB pathways, suggesting further investigations on the therapeutic application of this novel anticancer drug in in vivo models.     

Osteochondral tissue coculture: An in vitro and in silico approach

Osteochondral tissue engineering aims to regenerate functional tissue-mimicking physiological properties of injured cartilage and its subchondral bone. Given the distinct structural and biochemical difference between bone and cartilage, bilayered scaffolds, and bioreactors are commonly employed. We present an osteochondral culture system which cocultured ATDC5 and MC3T3-E1 cells on an additive manufactured bilayered scaffold in a dual-chamber perfusion bioreactor. Also, finite element models (FEM) based on the microcomputed tomography image of the manufactured scaffold as well as on the computer-aided design (CAD) were constructed; the microenvironment inside the two FEM was studied and compared. In vitro results showed that the coculture system supported osteochondral tissue growth in terms of cell viability, proliferation, distribution, and attachment. In silico results showed that the CAD and the actual manufactured scaffold had significant differences in the flow velocity, differentiation media mixing in the bioreactor and fluid-induced shear stress experienced by the cells. This system was shown to have the desired microenvironment for osteochondral tissue engineering and it can potentially be used as an inexpensive tool for testing newly developed pharmaceutical products for osteochondral defects.     

Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis

Cdk9 is a serine-threonine protein kinase that has been recognized as a regulator of cardiac differentiation. Recently, we have reported that transient induction of Cdk9 using noncoding RNA targeting Cdk9 sequences results in efficient cardiac differentiation. Concerning Cdk9 regulatory roles, here, we proposed whether constant overexpression of Cdk9 might influence the differentiation of myoblast C2C12 cells into myotubes. We overexpressed Cdk9 in mouse myoblast C2C12 cells to investigate its regulatory roles on myogenic differentiation. Upon Cdk9 overexpression, the expression level of myogenic regulatory factors was determined. Moreover, the expression profile of three important myomiRs consist of miR 1, 133 and 206 was examined during the differentiation process. Although Cdk9 expression is necessary for inducing differentiation in the early stage of myogenesis, continuous Cdk9 expression inhibits differentiation by modulating myomiRs and myogenic gene expression. Our results indicate that the transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis.     

S100 protein family and embryo implantation

It is well known that embryo implantation is a critical process in which embryo should be able to reach and attach to endometrium. Until now, various types of factors are involved in the regulation of this process. S100 proteins are calcium-binding proteins, which have vital roles in embryo implantation and have been considered as possible candidate markers for endometrial receptivity. However, studies regarding mode of actions of these proteins are scarce and more mechanistic insights are needed to clarify exact roles of each one of the S100 protein family. Understanding of function of these proteins in different compartments, stages, and phases of endometrium, could pave the way for conducting studies regarding the therapeutic significance of these proteins in some disorders such as recurrent implantation failure. In this review, we outlined roles and possible underlying mechanisms of S100 protein family in embryo implantation.     

The Effects of Magnesium and Vitamin E Co-Supplementation on Hormonal Status and Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome

Synergistic approach of magnesium and vitamin E may benefit clinical symptoms of patients with polycystic ovary syndrome (PCOS) through improving their metabolic profiles and reducing oxidative stress and inflammation. This study was designed to determine the effects of magnesium and vitamin E co-supplementation on hormonal status and biomarkers of inflammation and oxidative stress in women with PCOS. This randomized, double-blind, placebo-controlled trial was conducted among 60 women with PCOS, aged 18–40 years old. Participants were randomly divided into two groups to take 250 mg/day magnesium plus 400 mg/day vitamin E supplements or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to quantify related variables. Magnesium and vitamin E co-supplementation resulted in a significant reduction in hirsutism (β − 0.37; 95% CI, − 0.70, − 0.05; P = 0.02) and serum high-sensitivity C-reactive protein (hs-CRP) (β − 0.67 mg/L; 95% CI, − 1.20, − 0.14; P = 0.01), and a significant increase in plasma nitric oxide (NO) (β 3.40 μmol/L; 95% CI, 1.46, 5.35; P = 0.001) and total antioxidant capacity (TAC) levels (β 66.32 mmol/L; 95% CI, 43.80, 88.84; P < 0.001). Overall, magnesium and vitamin E co-supplementation for 12 weeks may benefit women with PCOS on hirsutism, serum hs-CRP, plasma NO, and TAC levels. Clinical trial registration number http://www.irct.ir: IRCT2017082733941N8

     

R-92L and R-92W mutations in cardiac troponin T lead to distinct energetic phenotypes in intact mouse hearts

It is now known that the flexibility of the troponin T (TnT) tail determines thin filament conformation and hence cross-bridge cycling properties, expanding the classic structural role of TnT to a dynamic role regulating sarcomere function. Here, using transgenic mice bearing R-92W and R-92L missense mutations in cardiac TnT known to alter the flexibility of the TnT tropomyosin-binding domain, we found mutation-specific differences in the cost of contraction at the whole heart level. Compared to age- and gender-matched sibling hearts, mutant hearts demonstrate greater ATP utilization measured using (31)P NMR spectroscopy as decreases in [ATP] and [PCr] and |DeltaG(~ATP)| at all workloads and profound systolic and diastolic dysfunction at all energetic states. R-92W hearts showed more severe energetic abnormalities and greater contractile dysfunction than R-92L hearts. The cost of increasing contraction was abnormally high when [Ca(2+)] was used to increase work in mutant hearts but was normalized with supply of the beta-adrenergic agonist dobutamine. These results show that R-92L and R-92W mutations in the TM-binding domain of cardiac TnT alter thin filament structure and flexibility sufficiently to cause severe defects in both whole heart energetics and contractile performance, and that the magnitude of these changes is mutation specific.     

Effect of host plants on developmental time and life table parameters of <Emphasis Type="Italic">Amphitetranychus viennensis</Emphasis> (Acari: Tetranychidae)

The effect of host plant species including black cherry (Prunus serotina cv. Irani), cherry (Prunus avium cv. siahe Mashhad) and apple (Malus domestica cv. shafi Abadi) was studied on biological parameters of Amphitetranychus viennensis (Zacher) in the laboratory at 25 ± 1°C, 70 ± 10% RH and 16L: 8D photoperiod. Duration of each life stage, longevity, reproduction rate, the intrinsic rate of natural increase (r _m ), net reproductive rate (R ₀ ), mean generation time (T), doubling time (DT), and finite rate of increase (λ) of the hawthorn spider mite on the three host plants were calculated. Differences in fertility life table parameters of the spider mite among host plants were analyzed using pseudo-values, which were produced by jackknife re-sampling. The results indicated that black cherry might be the most suitable plant for hawthorn spider mite due to the shorter developmental period (10.6 days), longer adult longevity (25.5 days), higher reproduction (65.6 eggs), and intrinsic rate of natural increase (0.194 females/female/day). Cherry was the least suitable host plant. To determine the effect of host shifts, the mite was transferred from black cherry onto cherry and apple. In the first generation after shifting to apple, the developmental period, reproduction and life table parameters were negatively influenced. However, population growth parameters in the first generation on cherry were actually better than after three generations on this new host. This underscores the relevance of the mites’ recent breeding history for life table studies.     

Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue

Triacylglycerol (TAG) stored in adipose tissue can be rapidly mobilized by the hydrolytic action of lipases, with the release of fatty acids (FA) that are used by other tissues during times of energy deprivation. Unlike synthesis of TAG, which occurs not only in adipose tissue but also in other tissues such as liver for very-low-density lipoprotein formation, hydrolysis of TAG, lipolysis, predominantly occurs in adipose tissue. Until recently, hormone-sensitive lipase was considered to be the key rate-limiting enzyme responsible for regulating TAG mobilization. However, recent studies on hormone-sensitive lipase-null mice have challenged such a concept. A novel lipase named desnutrin/ATGL has been recently discovered to play a key role in lipolysis in adipocytes. Lipolysis is under tight hormonal regulation. Although opposing regulation of lipolysis in adipose tissue by insulin and catecholamines is well understood, autocrine/paracrine factors may also participate in its regulation. Intricate cooperation of these endocrine and autocrine/paracrine factors leads to a fine regulation of lipolysis in adipocytes, needed for energy homeostasis. In this review, we summarize and discuss the recent progress made in the regulation of adipocyte lipolysis.