Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators.

To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum-MT, MT fusion, autophagosome-lysosome fusion, and autophagosome/endosome-lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome-lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)-MT contact, ER- plasma membrane (PM) junction, autophagosome/endosome-lysosome fusion, sarcoplasmic reticulum-MT, autophagosome-endosome/lysosome fusion, and ER-Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25- T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.

The association of female and male infertility with telomere length (Review).

Telomere length (TL) has long been associated with aging, as telomeres serve as protective caps of chromosomes, and are thus deeply involved in the preservation of genome integrity and are vital to cellular functions. Traditionally, a strong link connects aging and infertility in both sexes, with an earlier onset in females. Over the past decade, telomeres have attracted increasing attention due to the role they play in fertility. In this review, we investigated the potential positive or negative association between relative TL and different factors of female and male infertility. A systematic search of the PubMed database was conducted. Out of the 206 studies identified, 45 were reviewed as they fulfilled the criteria of validity and relevance. Following an analysis and a comparison of the study outcomes, several clear trends were observed. The majority of female infertility factors were associated with a shorter TL, with the exception of endometriosis, premature ovarian failure and clear cell carcinoma that were associated with a longer TL and polycystic ovary syndrome (PCOS), which revealed conflicting results among several studies, leading to ambiguous conclusions. Male infertility factors were associated with a shorter TL. Although this review can provide an outline of general trends in the association of TL with infertility factors, further epidemiological and original research studies are required to focus on investigating the basis of these varying lengths of telomeres.

Association of pesticide exposure with human congenital abnormalities.

Human pesticide exposure can occur both occupationally and environmentally during manufacture and after the application of indoor and outdoor pesticides, as well as through consumption via residues in food and water. There is evidence from experimental studies that numerous pesticides, either in isolation or in combination, act as endocrine disruptors, neurodevelopmental toxicants, immunotoxicants, and carcinogens. We reviewed the international literature on this subject for the years between 1990 and 2017. The studies were considered in this review through MEDLINE and WHO resources. Out of the n = 1817 studies identified, n = 94 were reviewed because they fulfilled criteria of validity and addressed associations of interest. Epidemiological studies have provided limited evidence linking pre- and post-natal exposure to pesticides with cancers in childhood, neurological deficits, fetal death, intrauterine growth restriction, preterm birth, and congenital abnormalities (CAs). In this review, the potential association between pesticide exposure and the appearance of some human CAs (including among others musculoskeletal abnormalities; neural tube defects; urogenital and cardiovascular abnormalities) was investigated. A trend towards a positive association between environmental or occupational exposure to some pesticides and some CAs was detected, but this association remains to be substantiated. Main limitations of the review include inadequate exposure assessment and limited sample size. Adequately powered studies with precise exposure assessments such as biomonitoring, are warranted to clarify with certainty the potential association between pesticide exposure and human CAs.