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The Planctomycetes bacteria have unique cell architectures with heavily invaginated membranes as confirmed by three-dimensional models reconstructed from FIB-SEM images of Tuwongella immobilis and Gemmata obscuriglobus. The subcellular proteome of T. immobilis was examined by differential solubilization followed by LC-MS/MS analysis, which identified 1569 proteins in total. The Tris-soluble fraction contained mostly cytoplasmic proteins, while inner and outer membrane proteins were found in the Triton X-100 and SDS-soluble fractions, respectively. For comparisons, the subcellular proteome of Escherichia coli was also examined using the same methodology. A notable difference in the overall fractionation pattern of the two species was a fivefold higher number of predicted cytoplasmic proteins in the SDS-soluble fraction in T. immobilis. One category of such proteins is represented by innovations in the Planctomycetes lineage, including unique sets of serine/threonine kinases and extracytoplasmic sigma factors with WD40 repeat domains for which no homologs are present in E. coli. Other such proteins are members of recently expanded protein families in which the newly evolved paralog with a new domain structure is recovered from the SDS-soluble fraction, while other paralogs may have similar domain structures and fractionation patterns as the single homolog in E. coli. The expanded protein families in T. immobilis include enzymes involved in replication-repair processes as well as in rRNA and tRNA modification and degradation. These results show that paralogization and domain shuffling have yielded new proteins with distinct fractionation characteristics. this website Understanding the molecular intricacies of these adaptive changes might aid in the development of a model for the evolution of cellular complexity.Non-alcoholic fatty liver disease (NAFLD) is a multimorbidity disorder ranging from excess accumulation of fat in the liver (steatosis) to steatohepatitis (NASH) and end-stage cirrhosis, and the development of hepatocellular carcinoma (HCC) in a subset of patients. The defining features of NASH are inflammation and progressive fibrosis. Currently, no pharmaceutical therapies are available for NAFLD, NASH and HCC; therefore, developing novel treatment strategies is desperately needed. Reversion Inducing Cysteine Rich Protein with Kazal motifs (RECK) is a well-known modifier of the extracellular matrix in hepatic remodeling and transition to HCC. More recently, its role in regulating inflammatory and fibrogenic processes has emerged. Here, we summarize the most relevant findings that extend our current understanding of RECK as a regulator of inflammation and fibrosis, and its induction as a potential strategy to blunt the development and progression of NASH and HCC.Infertility is becoming much more common and affects more couples. The past years witnessed the rapid development of the diagnosis and treatment upon infertility, which give numerous coupled more opportunities become parents. Extracellular vesicles are known as nano-sized membrane vesicles to play a major role in intracellular communication. In recent years, several basic and clinical studies have tried to investigate the correlation between the reproductive health/disorder and extracellular vesicles. However, the mechanism is still unclear. In this review, we reviewed the relationship between reproductive physiology and extracellular vesicles, and then collectively focused on the recent findings on the relationship between extracellular and infertility, and its consequent influence on the novel insight regarding the therapeutic strategies for infertility in the future clinical practice.

Cancer stem cells (CSCs) refer to cells with self-renewal capability in tumors. CSCs play important roles in proliferation, metastasis, recurrence, and tumor heterogeneity. This study aimed to identify immune-related gene-prognostic models based on stemness index (mRNAsi) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively.

X-tile software was used to determine the best cutoff value of survival data in LUAD and LUSC based on mRNAsi. Tumor purity and the scores of infiltrating stromal and immune cells in lung cancer tissues were predicted with ESTIMATE R package. Differentially expressed immune-related genes (DEIRGs) between higher- and lower-mRNAsi subtypes were used to construct prognostic models.

mRNAsi was negatively associated with StromalScore, ImmuneScore, and ESTIMATEScore, and was positively associated with tumor purity. LUAD and LUSC samples were divided into higher- and lower-mRNAsi groups with X-title software. The distribution of immune cells was significantlymodels of LUAD and LUSC.

Cancer stemness was not only an important biological process in cancer progression but also might affect TME immune cell infiltration in LUAD and LUSC. The mRNAsi-related immune genes could be potential biomarkers of LUAD and LUSC. Evaluation of integrative characterization of multiple immune-related genes and pathways could help to understand the association between cancer stemness and tumor microenvironment in lung cancer.

Cancer stemness was not only an important biological process in cancer progression but also might affect TME immune cell infiltration in LUAD and LUSC. The mRNAsi-related immune genes could be potential biomarkers of LUAD and LUSC. Evaluation of integrative characterization of multiple immune-related genes and pathways could help to understand the association between cancer stemness and tumor microenvironment in lung cancer.Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the consequences of foetal exposure to metformin on the fertility of exposed offspring remain poorly documented. In this study, we investigated the effect of in utero metformin exposure on the fertility of female and male offspring. We observed that metformin is detectable in the blood of the mother and in amniotic fluid and blood of the umbilical cord. Metformin was not measurable in any tissues of the embryo, including the gonads. The effect of metformin exposure on offspring was sex specific. The adult females that had been exposed to metformin in utero presented no clear reduction in fertility. However, the adult males that had been exposed to metformin during foetal life exhibited a 30% reduction in litter size compared with controls. The lower fertility was not due to a change in sperm production or the motility of sperm. Rather, the phenotype was due to lower sperm head quality - significantly increased spermatozoa head abnormality with greater DNA damage - and hypermethylation of the genomic DNA in the spermatozoa associated with lower expression of the ten-eleven translocation methylcytosine dioxygenase 1 (TET1) protein. In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility.Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy, cell growth, and differentiation. However, PRL is nowadays known to have a strong implication in oncogenic processes, making it essential to delve into the mechanisms governing these actions. PRL and its receptor (PRLR) activate a series of effects such as survival, cellular proliferation, migration, invasion, metastasis, and resistance to treatment, being highly relevant in developing certain types of cancer. Because women produce high levels of PRL, its influence in gynecological cancers is herein reviewed. It is interesting that, other than the 23 kDa PRL, whose mechanism of action is endocrine, other variants of PRL have been observed to be produced by tumoral tissue, acting in a paracrine/autocrine manner. Because many components, including PRL, surround the microenvironment, it is interesting to understand the hormone's modulation in cancer cells. This work aims to review the most important findings regarding the PRL/PRLR axis in cervical, ovarian, and endometrial cancers and its molecular mechanisms to support carcinogenesis.Obesity, especially central obesity, is a strong risk factor for developing type 2 diabetes (T2D). However, the mechanism underlying the progression from central obesity to T2D remains unknown. Therefore, we analyzed the gut microbial profiles of central obese individuals with or without T2D from a Chinese population. Here we reported both the microbial compositional and gene functional alterations during the progression from central obesity to T2D. Several opportunistic pathogens were enriched in obese T2D patients. We also characterized thousands of genes involved in sugar and amino acid metabolism whose abundance were significantly depleted in obese T2D group. Moreover, the abundance of those genes was negatively associated with plasma glycemia level and percentage of individuals with impaired plasma glucose status. Therefore, our study indicates that the abundance of those depleted genes can be used as a potential biomarker to identify central obese individuals with high risks of developing T2D.The hypothalamus-pituitary-thyroid-axis (HPT) is one of the main neuroendocrine axes that control energy expenditure. The activity of hypophysiotropic thyrotropin releasing hormone (TRH) neurons is modulated by nutritional status, energy demands and stress, all of which are sex dependent. Sex dimorphism has been associated with sex steroids whose concentration vary along the life-span, but also to sex chromosomes that define not only sexual characteristics but the expression of relevant genes. In this review we describe sex differences in basal HPT axis activity and in its response to stress and to metabolic challenges in experimental animals at different stages of development, as well as some of the limited information available on humans. Literature review was accomplished by searching in Pubmed under the following words "sex dimorphic" or "sex differences" or "female" or "women" and "thyrotropin" or "thyroid hormones" or "deiodinases" and "energy homeostasis" or "stress". The most representative articles were discussed, and to reduce the number of references, selected reviews were cited.Growth hormone (GH) deficiency is a common pituitary hormone deficiency in childhood cancer survivors (CCS). The identification, diagnosis, and treatment of those individuals at risk are important in order to minimize associated morbidities that can be ameliorated by treatment with recombinant human GH therapy. However, GH and insulin-like growth factor-I have been implicated in tumorigenesis, so there has been concern over the use of GH therapy in patients with a history of malignancy. Reassuringly, GH therapy has not been shown to increase risk of tumor recurrence. These patients have an increased risk for development of meningiomas, but this may be related to their history of cranial irradiation rather than to GH therapy. In this review, we detail the CCS who are at risk for GHD and the existing evidence on the safety profile of GH therapy in this patient population.

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