Association Between Trace Element Status and Depression in HTLV-1-Infected Patients: a Retrospective Cohort Study

Depression and Anxiety are two important public health problems that are known to be associated with viral infections. The association between the intake of nutrients such as zinc and copper with symptoms of depression has been studied previously. The aim of the current study was to investigate the association between depression with human T cell lymphotropic virus type 1 (HTLV-1) infection and serum content of zinc and copper in a large Iranian population cohort. The study population consisted of 279 HTLV-1-positive patients who were identified after recruitment as part of a large cohort study: the Mashhad Stroke and Heart Association Disorder (MASHAD) study. They were divided into two groups of diagnosed with or without depression based on their symptoms. Serum zinc and copper levels of all subjects were measured using the flame atomic absorption spectrometry. The population sample comprised of 279 individuals infected with HTLV-1 of whom 192 (68.8%) were women. The mean serum zinc in the group with and without depression was 78.69 ± 13.79 μg/dl and 86.87 ± 19.44 μg/dl, respectively (p < 0.001). Also, the serum copper level was higher in the depressive group (116.75 ± 39.56) than in the non-depressive group (104.76 ± 30.77) (p 0.004). The association between serum zinc and copper with depression in HTLV-1-infected patients which was shown in this study could be considered in the treatment strategies in these patients.

     

Dryland Wheat Domestication Changed the Development of Aboveground Architecture for a Well-Structured Canopy

We examined three different-ploidy wheat species to elucidate the development of aboveground architecture and its domesticated mechanism under environment-controlled field conditions. Architecture parameters including leaf, stem, spike and canopy morphology were measured together with biomass allocation, leaf net photosynthetic rate and instantaneous water use efficiency (WUE_i). Canopy biomass density was decreased from diploid to tetraploid wheat, but increased to maximum in hexaploid wheat. Population yield in hexaploid wheat was higher than in diploid wheat, but the population fitness and individual competition ability was higher in diploid wheats. Plant architecture was modified from a compact type in diploid wheats to an incompact type in tetraploid wheats, and then to a more compact type of hexaploid wheats. Biomass accumulation, population yield, harvest index and the seed to leaf ratio increased from diploid to tetraploid and hexaploid, associated with heavier specific internode weight and greater canopy biomass density in hexaploid and tetraploid than in diploid wheat. Leaf photosynthetic rate and WUE_i were decreased from diploid to tetraploid and increased from tetraploid to hexaploid due to more compact leaf type in hexaploid and diploid than in tetraploid. Grain yield formation and WUE_i were closely associated with spatial stance of leaves and stems. We conclude that the ideotype of dryland wheats could be based on spatial reconstruction of leaf type and further exertion of leaf photosynthetic rate.     

Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases

It is considered a significant challenge to understand the neuronal cell death mechanisms with a suitable cure for neurodegenerative disorders in the coming years. Calpains are one of the best-considered “cysteine proteases activated” in brain disorders. Calpain is an important marker and mediator in the pathophysiology of neurodegeneration. Calpain activation being the essential neurodegenerative factor causing apoptotic machinery activation, it is crucial to develop reliable and effective approaches to prevent calpain-mediated apoptosis in degenerating neurons. It has been recently seen that the “inhibition of calpain activation” has appeared as a possible therapeutic target for managing neurodegenerative diseases. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was conducted. The present article reviews the basic pathobiology and role of selective calpain inhibitors used in various neurodegenerative diseases as a therapeutic target.

Graphical Abstract

     

Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality

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Investigation of the FSHR,CYP11, and INSR Mutations and Polymorphisms in Iranian Infertile Women with Polycystic Ovary Syndrome (PCOS)

Background:Polycystic ovary syndrome (PCOS) is the most common cause of ovarian dysfunction associated with infertility, Oligomenorrhea or amenorrhea, hirsutism, acne, and obesity. A large body of evidence unraveled, three major groups of genes play critical roles in underlying PCOS molecular mechanism. The aim of this study is to investigate critical exonic variant of FSHR, CYP11, and INSR and determine the functionality of these mutations in Iranian patients with PCOS.Methods:In this case-control study, 130 patients with PCOS who referred to the Vali-e-Asr Hospital with infertility were included. DNA extracted from three ml of peripheral blood of the participants for DNA extraction. The PCR was conducted for each gene and the PCR product was genotyped by sequencing. Results:The data showed that there were two polymorphisms in INSR genes which did not change the protein sequences; these alterations can also be considered as a single nucleotide polymorphism (SNP). Moreover, any exonic variant has not been detected in CYP11B1. Whereas, two missense mutation have been detected in FSHR gene including p.Ala307Thr and p.Asn680Ser. It has been shown that the polymorphisms of the FSHR gene affect the hormone response in the ovaries. Our data demonstrated that the FSHR mutations frequencies were higher in the patients with PCOS rather than control people significantly.Conclusion:These data showed that the polymorphisms of FSHR were significantly associated with PCOS in Iranian infertile women. Further studies with larger sample sizes are needed to be performed for explore the strength of the association.Key Words: CYP11, FSHR, Infertile, INSR, PCOS, Polymorphisms     

Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway

ABSTRACT

In solid tumors, cancer stem cells (CSCs) or tumor-initiating cells (TICs) are often found in hypoxic niches. Nevertheless, the influence of hypoxia on TICs is poorly understood. Using previously established, TIC-enrichedpatient-derived colorectal cancer (CRC) cultures, we show that hypoxia increases the self-renewal capacity of TICs while inducing proliferation arrest in their more differentiated counterpart cultures. Gene expression data revealed macroautophagy/autophagy as one of the major pathways induced by hypoxia in TICs. Interestingly, hypoxia-induced autophagy was found to induce phosphorylation of EZR (ezrin) at Thr567 residue, which could be reversed by knocking down ATG5, BNIP3, BNIP3L, or BECN1. Furthermore, we identified PRKCA/PKCα as a potential kinase involved in hypoxia-induced autophagy-mediated TIC self-renewal. Genetic targeting of autophagy or pharmacological inhibition of PRKC/PKC and EZR resulted in decreased tumor-initiating potential of TICs. In addition, we observed significantly reduced in vivo tumor initiation and growth after a stable knockdown of ATG5. Analysis of human CRC samples showed that p-EZR is often present in TICs located in the hypoxic and autophagic regions of the tumor. Altogether, our results establish the hypoxia-autophagy-PKC-EZR signaling axis as a novel regulatory mechanism of TIC self-renewal and CRC progression. Autophagy inhibition might thus represent a promising therapeutic strategy for cancer patients.