Non-Photochemical Quenching: From Light Perception to Photoprotective Gene Expression

Light is essential for photosynthesis but light levels that exceed an organism’s assimilation capacity can cause serious damage or even cell death. Plants and microalgae have developed photoprotective mechanisms collectively referred to as non-photochemical quenching to minimize such potential damage. One such mechanism is energy-dependent quenching (qE), which dissipates excess light energy as heat. Over the last 30 years, much has been learned about the molecular mechanism of qE in green algae and plants. However, the steps between light perception and qE represented a gap in our knowledge until the recent identification of light-signaling pathways that function in these processes in the green alga Chlamydomonas reinhardtii. In this review, we summarize the high light and UV-mediated signaling pathways for qE in Chlamydomonas. We discuss key questions remaining about the pathway from light perception to photoprotective gene expression in Chlamydomonas. We detail possible differences between green algae and plants in light-signaling mechanisms for qE and emphasize the importance of research on light-signaling mechanisms for qE in plants.

The Roles of Human Endogenous Retroviruses (HERVs) in Inflammation

Human endogenous retroviruses (HERVs) are ancient, currently inactive, and non-infectious due to recombination, deletions, and mutations in the host genome. However, HERV-derived elements are involved in physiological phenomena including inflammatory response. In recent studies, HERV-derived elements were involved directly in various inflammatory diseases including autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Sjogren’s syndrome. Regarding the involvement of HERV-derived elements in inflammation, two possible mechanisms have been proposed. First, HERV-derived elements cause nonspecific innate immune processes. Second, HERV-derived RNA or proteins might stimulate selective signaling mechanisms. However, it is unknown how silent HERV elements are activated in the inflammatory response and what factors and signaling mechanisms are involved with HERV-derived elements. In this review, we introduce HERV-related autoimmune diseases and propose the possible action mechanisms of HERV-derived elements in the inflammatory response at the molecular level.

Two-Component Systems of S. aureus: Signaling and Sensing Mechanisms

Staphylococcus aureus encodes 16 two-component systems (TCSs) that enable the bacteria to sense and respond to changing environmental conditions. Considering the function of these TCSs in bacterial survival and their potential role as drug targets, it is important to understand the exact mechanisms underlying signal perception. The differences between the sensing of appropriate signals and the transcriptional activation of the TCS system are often not well described, and the signaling mechanisms are only partially understood. Here, we review present insights into which signals are sensed by histidine kinases in S. aureus to promote appropriate gene expression in response to diverse environmental challenges.

Molecular and cellular mechanisms that regulate human erythropoiesis

To enable effective oxygen transport, approximately 200 billion red blood cells (RBCs) need to be produced every day in the bone marrow through the fine-tuned process of erythropoiesis. Erythropoiesis is regulated at multiple levels to ensure that defective RBC maturation or overproduction can be avoided. Here, we provide an overview of different layers of this control, ranging from cytokine signaling mechanisms that enable extrinsic regulation of RBC production to intrinsic transcriptional pathways necessary for effective erythropoiesis. Recent studies have also elucidated the importance of post-transcriptional regulation and highlighted additional gatekeeping mechanisms necessary for effective erythropoiesis. We additionally discuss the insights gained by studying human genetic variation impacting erythropoiesis and highlight the discovery of BCL11A as a regulator of hemoglobin switching through genetic studies. Finally, we provide an outlook of how our ability to measure multiple facets of this process at single-cell resolution, while accounting for the impact of human variation, will continue to refine our knowledge of erythropoiesis and how this process is perturbed in disease. As we learn more about this intricate and important process, additional opportunities to modulate erythropoiesis for therapeutic purposes will undoubtedly emerge.

Development of Wound Dressing for Regenerative Medicine

The understanding of the pathophysiological mechanisms of the wound process deepened with the development of science. The technological base that was creating has enabled to serve the clinical needs of tissue repair. These factors, combined with the growing need for healing of infected and chronic wounds, have led to the expansion of the market for wound dressings materials supplies. In this connection, there is a need to generalize and update information about new types of dressings. This review provides an up-to-date understanding of the wound process: cellular and signaling mechanisms of repair, characteristics of the optimal microclimate of the wound bed, morphofunctional re-arrangements of tissues during the healing process. Based on these data, the requirements for the modern wound dressings are formulated. Existing wound dressings have been classified as interacting with body tissue. The bio-functional characteristics of the synthetic and natural polymers used in the dressing are described, including their effect on regenerative processes. A classification of the active medicinal ingredients used in the manufacture of dressings is given, the characteristics of their use on the background of the pathological wound process are considered.

The Bidirectional Signal Communication of Microbiota-Gut-Brain Axis in Hypertension

Hypertension is a critical risk factor of cardiovascular diseases. A new concept of microbiota-gut-brain axis has been established recently, mediating the bidirectional communication between the gut and its microbiome and the brain. Alterations in bidirectional interactions are believed to be involved in the blood pressure regulation. Neuroinflammation and increased sympathetic outflow act as the descending innervation signals from the brain. Increased sympathetic activation plays a recognized role in the genesis of hypertension. The present evidence demonstrates that gut dysbiosis is associated with central nervous system neuroinflammation. However, how the gut influences the brain remains unclear. We reviewed the roles of neuroinflammation and gut microbiota and their interactions in the pathogenesis of hypertension and described the ascending signaling mechanisms behind the microbiota-gut-brain axis in detail. Additionally, the innovative prohypertensive mechanisms of dietary salt through the microbiota-gut-brain axis are summarized. The bidirectional communication mechanisms were proposed for the first time that the descending signals from the brain and the ascending connections from the gut form a vicious circle of hypertension progression, acting as a premise for hypertension therapy.

Clomiphene Citrate and Enclomiphene Hydrochloride Exposure Is Associated With Interfrontal Suture Fusion in Zebrafish

Background: The last several decades have witnessed an increase in metopic craniosynostosis incidence. Population-based studies suggest that pharmacological exposure in utero may be responsible. This study examined effects of the fertility drug clomiphene citrate (CC) on calvarial development in an established model for craniofacial development, the zebrafish Danio rerio. Results: Zebrafish larvae were exposed to clomiphene citrate or its isomer enclomiphene for five days at key points during calvarial development. Larvae were then raised to adulthood in normal rearing water. Zebrafish were analyzed using whole-mount skeletal staining. We observed differential effects on survivability, growth and suture formation depending on the treatment. Treatments with CC or enclomiphene at 5.5 mm SL led to increased fusion of the interfrontal suture (p < .01) compared to controls. Conclusions: Exposure to fertility drugs appears to affect development of the cranial vault, specifically the interfrontal suture, in zebrafish. Further research is required to identify the signaling mechanisms at play. This work suggests that fertility drug treatment may contribute to the increased incidence of metopic craniosynostosis observed globally.

A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy

: PCSK9 is a strongly expressed protein in the liver and brain that binds to the LDLR and regulates cholesterol in the liver effectively. Other receptors with which it interacts include VLDLR, LRP1, ApoER2, and OLR1. PCSK9 gain-of-function results in lysosomal degradation of these receptors, which may result in hyperlipidemia. PCSK9 deficiency results in a lower amount of cholesterol, which reduces cholesterol's accessibility to cancer cells. PCSK9 regulates several proteins and signaling pathways in cancer, including JNK, NF-κВ, and the mitochondrial-mediated apoptotic pathway. In the liver, breast, lungs, and colon tissue, PCSK9 initiates and facilitates cancer development, while in prostate cancer cells, it induces apoptosis. PCSK9 has a significant impact on brain cancer, promoting cancer cell survival by manipulating the mitochondrial apoptotic pathway and exhibiting apoptotic activity in neurons by influencing the NF-κВ, JNK, and caspase-dependent pathways. The PCSK9 impact in cancer at different organs is explored in this study, as well as the targeted signaling mechanisms involved in cancer growth. As a result, these signaling mechanisms may be aimed for the development and exploration of anti-cancer drugs in the immediate future.