Unveiling the Role of Exosomes in the Pathophysiology of Sepsis: Insights into Organ Dysfunction and Potential Biomarkers.

Extracellular vesicles (EVs) are tools for intercellular communication, mediating molecular transport processes. Emerging studies have revealed that EVs are significantly involved in immune processes, including sepsis. Sepsis, a dysregulated immune response to infection, triggers systemic inflammation and multi-organ dysfunction, posing a life-threatening condition. Although extensive research has been conducted on animals, the complex inflammatory mechanisms that cause sepsis-induced organ failure in humans are still not fully understood. Recent studies have focused on secreted exosomes, which are small extracellular vesicles from various body cells, and have shed light on their involvement in the pathophysiology of sepsis. During sepsis, exosomes undergo changes in content, concentration, and function, which significantly affect the metabolism of endothelia, cardiovascular functions, and coagulation. Investigating the role of exosome content in the pathogenesis of sepsis shows promise for understanding the molecular basis of human sepsis. This review explores the contributions of activated immune cells and diverse body cells' secreted exosomes to vital organ dysfunction in sepsis, providing insights into potential molecular biomarkers for predicting organ failure in septic shock.

Integrative Epigenetic and Molecular Analysis Reveals a Novel Promoter for a New Isoform of the Transcription Factor TEAD4.

TEAD4 is a transcription factor that plays a crucial role in the Hippo pathway by regulating the expression of genes related to proliferation and apoptosis. It is also involved in the maintenance and differentiation of the trophectoderm during pre- and post-implantation embryonic development. An alternative promoter for the TEAD4 gene was identified through epigenetic profile analysis, and a new transcript from the intronic region of TEAD4 was discovered using the 5'RACE method. The transcript of the novel promoter encodes a TEAD4 isoform (TEAD4-ΔN) that lacks the DNA-binding domain but retains the C-terminal protein-protein interaction domain. Gene expression studies, including end-point PCR and Western blotting, showed that full-length TEAD4 was present in all investigated tissues. However, TEAD4-ΔN was only detectable in certain cell types. The TEAD4-ΔN promoter is conserved throughout evolution and demonstrates transcriptional activity in transient-expression experiments. Our study reveals that TEAD4 interacts with the alternative promoter and increases the expression of the truncated isoform. DNA methylation plays a crucial function in the restricted expression of the TEAD4-ΔN isoform in specific tissues, including the umbilical cord and the placenta. The data presented indicate that the DNA-methylation status of the TEAD4-ΔN promoter plays a critical role in regulating organ size, cancer development, and placenta differentiation.

Long-Term Effects of ART on the Health of the Offspring.

Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences.

Composition and effects of seminal plasma in the female reproductive tracts on implantation of human embryos.

The function of seminal plasma involves acting as a transport medium for sperm and as a means of communication between the reproductive tissues of the male and female. It is also a vital factor to prime the reproductive tracts of the female for optimal pregnancy. When the reproductive tract of the female is exposed to seminal plasma, serious alterations take place, enhancing pathogen and debris clearance observed in the uterus throughout mating. It is also capable of supporting embryo growth, promoting the receptivity of the uterus, and establishing tolerance to the semi-allogenic embryo. Moreover, seminal plasma is capable of regulating the functions of several female reproductive organs and providing an ideal condition for effective embryo implantation and pregnancy. It is believed that the health state of the offspring is affected by exposure to seminal plasma. For the treatment of infertility, assisted reproductive technologies have been extensively employed. The application of seminal plasma as a therapeutic approach to enhance the development of embryo competency and rate of implantation, receptivity of endometrium, and establishment of maternal immune tolerance in cycles of ART appears possible. Herein, current knowledge on the composition of seminal plasma and the physiological roles it possesses on various parts of the female reproductive tract are summarized. Moreover, the role of seminal plasma in the development of embryos, implantation, and the following fetal growth and survival have been reviewed in this article.

DNA Methylation-Governed Gene Expression in Autoimmune Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease hallmarked by progressive and irreversible joint destruction. RA pathogenesis is a T cell-regulated and B cell-mediated process in which activated lymphocyte-produced chemokines and cytokines promote leukocyte infiltration that ultimately leads to destruction of the joints. There is an obvious need to discover new drugs for RA treatment that have different biological targets or modes of action than the currently employed therapeutics. Environmental factors such as cigarette smoke, certain diet components, and oral pathogens can significantly affect gene regulation via epigenetic factors. Epigenetics opened a new field for pharmacology, and DNA methylation and histone modification-implicated factors are feasible targets for RA therapy. Exploring RA pathogenesis involved epigenetic factors and mechanisms is crucial for developing more efficient RA therapies. Here we review epigenetic alterations associated with RA pathogenesis including DNA methylation and interacting factors. Additionally, we will summarize the literature revealing the involved molecular structures and interactions. Finally, potential epigenetic factor-based therapies will be discussed that may help in better management of RA in the future.

The chemokine CCL28 is elevated in the serum of patients with celiac disease and decreased after treatment.

Accumulating evidence show that many inflammatory cytokines are involved in pathophysiology of celiac disease (CD). CCL28 known as mucosa associate epithelial chemokine (MEC) is produced by mucosa and chemoattracts IgA-producing B cells into the mucosa. However, its levels in patients with CD have not yet been elucidated. CCL28 levels and anti-tTTG (IgA) were detected in the serum of 28 new cases of CD, 32 cases of treated patents and 32 normal individuals by Elisa. Moreover, the effect of gluten on intestinal cells, Caco-2, was examined by RT-PCR. Our data show that (i) the levels of CCL28 is significantly higher in patients with CD than normal individuals, (ii) CCL28 levels is reduced in patients with CD who had gluten-free diets. Accordingly, we observed that CCL28 expression is upregulated in a dose-dependent manner when the Caco-2 cells were cultured in the presence of gluten. In conclusion, gluten enhances CCL28 expression and that CCL28 could be a novel biomarker for diagnosis and following up the patients with CD. However, further investigation in a larger number of patients is required.