Exosomes as Powerful Engines in Cancer: Isolation, Characterization and Detection Techniques

Exosomes, powerful extracellular nanovesicles released from almost all types of living cells, are considered the communication engines (messengers) that control and reprogram physiological pathways inside target cells within a community or between different communities. The cell-like structure of these extracellular vesicles provides a protective environment for their proteins and DNA/RNA cargos, which serve as biomarkers for many malicious diseases, including infectious diseases and cancers. Cancer-derived exosomes control cancer metastasis, prognosis, and development. In addition to the unique structure of exosomes, their nanometer size and tendency of interacting with cells makes them a viable novel drug delivery solution. In recent years, numerous research efforts have been made to quantify and characterize disease-derived exosomes for diagnosis, monitoring, and therapeutic purposes. This review aims to (1) relate exosome biomarkers to their origins, (2) focus on current isolation and detection methods, (3) discuss and evaluate the proposed technologies deriving from exosome research for cancer treatment, and (4) form a conclusion about the prospects of the current exosome research.

Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.

Toward interventions to reduce internalized ageism

Ageism is an insidious form of injustice that is internalized from an early age with accumulating negative health impacts across the lifespan. Internalized ageism is associated with numerous public health outcomes, including physical and mental health, functional impairment, cognition, cardiovascular stress, hospitalizations, and longevity. Research has begun to document how ageism negatively impacts health through psychological, behavioral, and physiological pathways. Yet, limited research has addressed interventions to reduce internalized ageism. This study integrates stereotype embodiment theory, theories of successful and productive aging, and recent scholarly literature to present a conceptual model with potential downstream, midstream, and upstream interventions at micro, meso, and macro levels. Micro interventions include: social, physical, and cognitive engagement, as well as stress management. Meso interventions include: education, intergenerational contact, and narrative reframing. Macro interventions include anti-ageism policy, such as amendments to the Age Discrimination in Employment Act (ADEA). The conceptual model is described in detail, and implications for practitioners are discussed. The need to examine how policy influences health through the three pathways in stereotype embodiment theory is discussed. This study provides a working model for scholars and practitioners to use when considering paths toward reducing internalized ageism and optimizing well-being for aging adults.

Sequence and structure comparison of ATP synthase F0 subunits 6 and 8 in notothenioid fish

Mitochondrial changes such as tight coupling of the mitochondria have facilitated sustained oxygen and respiratory activity in haemoglobin-less icefish of the Channichthyidae family. We aimed to characterise features in the sequence and structure of the proteins directly involved in proton transport, which have potential physiological implications. ATP synthase subunit a (ATP6) and subunit 8 (ATP8) are proteins that function as part of the F0 component (proton pump) of the F0F1complex. Both proteins are encoded by the mitochondrial genome and involved in oxidative phosphorylation. To explore mitochondrial sequence variation for ATP6 and ATP8 we analysed sequences from C. gunnari and C. rastrospinosus and compared them with their closely related red-blooded species and eight other vertebrate species. Our comparison of the amino acid sequence of these proteins reveals important differences that could underlie aspects of the unique physiology of the icefish. In this study we find that changes in the sequence of subunit a of the icefish C. gunnari at position 35 where there is a hydrophobic alanine which is not seen in the other notothenioids we analysed. An amino acid change of this type is significant since it may have a structural impact. The biology of the haemoglobin-less icefish is necessarily unique and any insights about these animals will help to generate a better overall understanding of important physiological pathways.

Differential expression of Arabidopsis EJC core proteins under short-day and long-day growth conditions

Exon junction complexes (EJCs) associate with mRNAs, mediate the pre-mRNA splicing and eventually gets displaced by ribosomes during the initial phase of translation. EJCs are involved in several critical physiological pathways. The functional nature of EJCs and the underlying molecular mechanism(s) still needs to be elucidated particularly in case of plants. Here, we report that the putative core protein factors of the EJC differentially express under short-day and long-day conditions. Since, plants are constantly exposed to biotic and abiotic factor(s), it would be significant to see how the EJCs respond to different stress inducing conditions. The protein levels of EJC core proteins under short-day conditions were 1.25 times higher relative to the protein levels under long-day conditions. Similar results were observed for the mRNA transcripts of the EJC core protein factors. These results signify that under short-day conditions, the EJC proteins are more activated and might be involved in few events which are yet to be revealed.

Potential Role of Cannabidiol on Sports Recovery: A Narrative Review

The use of cannabidiol (CBD) among athletes is becoming extensive and frequent. This could be due to the elimination of CBD from the list of prohibited substances by federations and international institutions of sport. The legalization and resulting production, and commercialization of CBD, could increase its intake in sports professionals. This commercialization of cannabinoids has fueled a race to study their properties, benefits, and risks for health and performance in athletes. Although there is evidence that suggests some beneficial properties such as anxiolytics, antidepressants, anti-inflammatory, and antioxidants among others, the evidence presented so far is neither clear nor conclusive. There are significant gaps in knowledge of the physiological pathways that explain the role of CBD in sports performance. This mini-review examines evidence suggesting that CBD has the potential to be used as a part of the strategies to recover from fatigue and muscle damage related to physical and cognitive exertion in sports.

A PRELIMINARY STUDY OF IN VIVO INJECTION OF AUXIN AND CYTOKININ INTO Rafflesia patma Blume FLOWER BUDS

The controlling mechanisms for the growth and differentiation of Rafflesia from a flower bud into the anthesis stage is currently unknown, particularly if any plant growth regulator (PGR) physiological pathways play some type of roles. In the wild, the number of flower buds available to study are extremely limited. In this study, we grouped six flower buds of Rafflesia patma Blume into three different treatments: two buds injected with auxin (indoleacetic acid, IAA), two buds injected with cytokinin (kinetin), and two buds injected with sterile distilled water as a control. Buds enlarged with both IAA and kinetin treatments compared to the control, but only buds injected with IAA showed a transition stage with the bract revealed (cupule-bract stage from previously cupule stage) within two weeks of five weeks of observation. These results raise further questions whether Rafflesia development is more likely due to auxin exposure when in flower bud as compared to cytokinin. Future studies should include increased sample size for treatments, enhanced PGR administration to allow exposure to the tissue and less tissue damage, injection of other PGRs such as gibberellin (GA) and jasmonic acid (JA), and histological tissue analysis to investigate PGR effects in depth.

Large-scale deregulation of gene expression by artificial light at night in tadpoles of common toads

Artificial light at night (ALAN) affects numerous physiological and behavioural mechanisms in various species by potentially disturbing circadian timekeeping systems. Although gene-specific approaches have already shown the deleterious effect of ALAN on the circadian clock, immunity and reproduction, large-scale transcriptomic approaches with ecologically relevant light levels are still lacking to assess the global impact of ALAN on biological processes. Moreover, studies have focused mainly on variations in gene expression during the night in the presence of ALAN but never during the day. In a controlled laboratory experiment, transcriptome sequencing of Bufo bufo tadpoles revealed that ALAN affected gene expression at both night and daytime with a dose-dependent effect and globally induced a downregulation of genes. ALAN effects were detected at very low levels of illuminance (0.1 lux) and affected mainly genes related to the innate immune system and, to a lesser extend to lipid metabolism. These results indicate that a broad range of physiological pathways is impacted at the molecular level by very low levels of ALAN potentially resulting in reduced survival under environmental immune challenges.

CGRP, adrenomedullin and adrenomedullin 2 display endogenous GPCR agonist bias in primary human cardiovascular cells

Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist bias with physiological consequences for the calcitonin receptor-like receptor, CLR. By switching the receptor-activity modifying protein (RAMP) associated with CLR we can “re-route” the physiological pathways activated by endogenous agonists calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2). AM2 promotes calcium-mediated nitric oxide signalling whereas CGRP and AM show pro-proliferative effects in cardiovascular cells, thus providing a rationale for the expression of the three peptides. CLR-based agonist bias occurs naturally in human cells and has a fundamental purpose for its existence. We anticipate this will be a starting point for more studies into RAMP function in native environments and their importance in endogenous GPCR signalling.