Adamalysins in COVID-19 - Potential mechanisms behind exacerbating the disease.

The coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is a current pandemic that has resulted in nearly 250 million cases and over 5 million deaths. While vaccines have been developed to prevent infection, and most COVID-19 cases end up being fairly light, there are severe cases of COVID-19 that may end up in death, even with adequate healthcare treatment. New options to combat this disease's effects, therefore, could prove to be invaluable in saving lives. Adamalysins are proteins that have several roles in regulating different functions in the human body but are also known to have functions in inflammation. They are also known to have roles in several different diseases, including COVID-19, where ADAM17, in particular, is now well-known to have a prominent role, but also several diseases which include comorbidities that may worsen cases of COVID-19. Therefore, investigating the functions of adamalysins in disease may give us clues to the molecular workings of COVID-19 as well as potentially new therapeutic targets. Understanding these molecular mechanisms may also allow for an understanding of the mechanisms behind the rare severe side effects that occur in response to current COVID-19 vaccines, which may lead to better monitoring measures for people who may be more at risk of developing these side effects. This review investigates the known roles and functions of adamalysins in disease, including what is currently known of their involvement in COVID-19, and how these functions might be involved.

Potential therapeutic compounds from traditional Chinese medicine targeting endoplasmic reticulum stress to alleviate rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which affects about 0.5-1% of people with symptoms that significantly impact a sufferer's lifestyle. The cells involved in propagating RA tend to display pro-inflammatory and cancer-like characteristics. Medical drug treatment is currently the main avenue of RA therapy. However, drug options are limited due to severe side effects, high costs, insufficient disease retardation in a majority of patients, and therapeutic effects possibly subsiding over time. Thus there is a need for new drug therapies. Endoplasmic reticulum (ER) stress, a condition due to accumulation of misfolded proteins in the ER, and subsequent cellular responses have been found to be involved in cancer and inflammatory pathologies, including RA. ER stress protein markers and their modulation have therefore been suggested as therapeutic targets, such as GRP78 and CHOP, among others. Some current RA therapeutic drugs have been found to have ER stress-modulating properties. Traditional Chinese Medicines (TCMs) frequently use natural products that affect multiple body and cellular targets, and several medicines and/or their isolated compounds have been found to also have ER stress-modulating capabilities, including TCMs used in RA treatment by Chinese Medicine practitioners. This review encourages, in light of the available information, the study of these RA-treating, ER stress-modulating TCMs as potential new pharmaceutical drugs for use in clinical RA therapy, along with providing a list of other ER stress-modulating TCMs utilized in treatment of cancers, inflammatory diseases and other diseases, that have potential use in RA treatment given similar ER stress-modulating capacity.

Natural products-based polypharmacological modulation of the peripheral immune system for the treatment of neuropsychiatric disorders.

Chronic inflammation of the central nervous system (CNS) is critical to the pathogenesis of neuropsychiatric disorders (NPDs) that affect the global population. Current therapeutics for NPDs are limited to relieving symptoms and induce many adverse effects. Therefore, the discovery of novel therapeutic agents from natural sources is urgently needed. Intriguingly, the immune responses of peripheral organs are closely linked through the molecular communication between resident and blood-borne cellular components, which shape the neuroinflammatory phenotypes of NPDs. Since the gut and spleen are the two largest immunological organs of the body, the brain-gut-microbiome and brain-spleen axes have been implicated in the connection between the CNS and the peripheral immune system. Accordingly, it has been proposed that the local CNS inflammation observed in NPDs is regulated via the manipulation of the systemic immune system by targeting the gut and spleen. Additionally, the complexity of the signalling network underlying the communication between the CNS and the systemic immune system suggests a strong potential for treating NPDs through a polypharmacological approach. The close association between systemic immunity and the homeostasis of the CNS points to the concept of repurposing interventions for systemic immune disorders to treat NPDs. Notably, natural products represent a promising source of such effective compounds due to both their pharmacological potency and safety. This review discusses the complex implications of dysregulated systemic immunity mediated by the brain-spleen and brain-gut-microbiome axes in NPDs, such as Alzheimer's disease, Parkinson's disease, schizophrenia and major depressive disorder. In addition, the potential of repurposing natural product-based bioactive compounds for treating NPDs via modulating systemic immune disorders is intensively discussed.

A Single-Center Retrospective Analysis of the Efficacy of a New Balloon Catheter in Autogenous Arteriovenous Fistula Dysfunction Resistant to Conventional Balloon Angioplasty.

PURPOSE: The purpose of the study was to present a new alternative balloon catheter option for autogenous arteriovenous fistula (AVF) dysfunction with a stiff constriction resistant to conventional balloon angioplasty. METHODS: Our first series of 51 patients with autogenous AVF dysfunction who were simultaneously treated with VascuTrak™ balloon catheter, following failed conventional balloon therapy (failure was defined as residual stenosis of >30%), were retrospectively observed and analyzed. The indices that were used to evaluate the clinical efficacy of VascuTrak balloon catheter included the immediate technical success rate, residual stenosis, successful dilation times, degree of pain assessed using the Visual Analog Scale, complications, and follow-up patency rate. RESULTS: The stenotic or occlusive lesions of all 51 cases resistant to conventional balloon angioplasty were promptly eliminated or alleviated (residual stenosis rate ≤ 30%), with a 100% immediate technical success rate. VascuTrak balloon catheters were successful in achieving full dilation under working pressure, of which 44 cases required a 1-time dilation (86.3%) and 7 cases required 2 dilations, which differed significantly from the average of 2.4 dilations required by the preceding conventional balloon therapy (P < 0.0001). A statistically significant improvement in the degree of pain experienced by patients who received VascuTrak balloon dilation was observed compared to that of the preceding conventional balloon dilation (P < 0.0001). One case of a brachial artery pseudoaneurysm complication occurred in the perioperative period. The primary patency rate was 88.2% at 6 months and 74.5% at 12 months. CONCLUSION: The use of VascuTrak balloon catheter to treat autogenous AVF dysfunction resistant to conventional balloon angioplasty appears to be safe and effective, although further, large randomized controlled trials are necessary.

Pathogenesis of thromboangiitis obliterans: Gene polymorphism and immunoregulation of human vascular endothelial cells.

Thromboangiitis obliterans (TAO) is a nonatherosclerotic, segmental, inflammatory vasculitis, which commonly affects the small- and medium-sized arteries of the upper and lower extremities. Despite its discovery more than a century ago, little progress has been made in its treatment. Unless the pathogenesis is elucidated, therapeutic approaches will be limited. The purpose of this review article is to collate current knowledge of mechanisms for the pathogenesis of thromboangiitis obliterans and to propose potential mechanisms from a genetic and immunoreactive point of view for its inception. Therefore, we discuss the possibility that the pathogenesis of this disease is due to a type of gene polymorphism, which leads to an immunological inflammatory vasculitis associated with tobacco abuse, highly linked to T cells, human vascular endothelial cells (HVECs), and the TLR-MyD88-NFκB pathway, distinct from arteriosclerosis obliterans and other vasculitides.