Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease

Dry eye disease (DED) is caused by a reduction in the volume or quality of tears. The prevalence of DED is estimated to be 100 million in the developed world. As aging is a risk factor for DED, the prevalence of DED is expected to grow at a rapid pace in aging populations, thus creating an increased need for new therapies. This review summarizes DED medications currently in clinical use. Most current medications for DED focus on stimulating tear secretion, mucin secretion, or suppressing inflammation, rather than simply replenishing the ocular surface with moisture to improve symptoms. We recently reported that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) induces tear secretion and suppresses corneal injury caused by a reduction in tears. Moreover, it has been reported that a PACAP in water and a 0.9% saline solution at +4 °C showed high stability and achieved 80–90% effectiveness after 2 weeks of treatment. These results reveal PACAP as a candidate DED medication. Further research on the clinical applications of PACAP in DED is necessary.

Metal Complexes and Their Potential Therapeutic Role Against COVID-19: Recent Developments in Drug Designing

COVID-19 is a global pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Being associated with high mortality rates, this pandemic has forced several countries worldwide to impose complete lockdowns to limit the spread of infection. Despite the development of various vaccines, there is still an urgent need to design novel treatments backed with safety data for fighting SARS-CoV-2 and its various mutants. Currently, scientists are putting their strenuous efforts into finding the best treatment option for COVID-19. In this regard, metal complexes being active antiviral agents and immunity enhancers have great potential against SARS-CoV-2. Herein, metal complexes' therapeutic role and significance against treating SARS-CoV-2 or any of its target proteins are discussed.

Effect of Denervation on XBP1 in Skeletal Muscle and the Neuromuscular Junction

Denervation of skeletal muscle is a debilitating consequence of injury of the peripheral nervous system, causing skeletal muscle to experience robust atrophy. However, the molecular mechanisms controlling the wasting of skeletal muscle due to denervation are not well understood. Here, we demonstrate that transection of the sciatic nerve in Sprague–Dawley rats induced robust skeletal muscle atrophy, with little effect on the neuromuscular junction (NMJ). Moreover, the following study indicates that all three arms of the unfolded protein response (UPR) are activated in denervated skeletal muscle. Specifically, ATF4 and ATF6 are elevated in the cytoplasm of skeletal muscle, while XBP1 is elevated in the nuclei of skeletal muscle. Moreover, XBP1 is expressed in the nuclei surrounding the NMJ. Altogether, these results endorse a potential role of the UPR and, specifically, XBP1 in the maintenance of both skeletal muscle and the NMJ following sciatic nerve transection. Further investigations into a potential therapeutic role concerning these mechanisms are needed.

Coenzyme Q10, Ageing and the Nervous System: An Overview

The ageing brain is characterised by changes at the physical, histological, biochemical and physiological levels. This ageing process is associated with an increased risk of developing a number of neurological disorders, notably Alzheimer’s disease and Parkinson’s disease. There is evidence that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of such disorders. In this article, we review the potential therapeutic role in these age-related neurological disorders of supplementary coenzyme Q10, a vitamin-like substance of vital importance for normal mitochondrial function and as an antioxidant. This review is concerned primarily with studies in humans rather than in vitro studies or studies in animal models of neurological disease. In particular, the reasons why the outcomes of clinical trials supplementing coenzyme Q10 in these neurological disorders is discussed.

Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

Despite decades of research, Alzheimer’s Disease (AD) remains a lethal neurodegenerative disorder for which there are no effective treatments. This review examines the latest evidence of a novel and newly introduced perspective, which focuses on the restoration of gamma oscillations and investigates their potential role in the treatment of AD. Gamma brain activity (∼25–100 Hz) has been well-known for its role in cognitive function, including memory, and it is fundamental for healthy brain activity and intra-brain communication. Aberrant gamma oscillations have been observed in both mice AD models and human AD patients. A recent line of work demonstrated that gamma entrainment, through auditory and visual sensory stimulation, can effectively attenuate AD pathology and improve cognitive function in mice models of the disease. The first evidence from AD patients indicate that gamma entrainment therapy can reduce loss of functional connectivity and brain atrophy, improve cognitive function, and ameliorate several pathological markers of the disease. Even though research is still in its infancy, evidence suggests that gamma-based therapy may have a disease-modifying effect and has signified a new and promising era in AD research.

Very-Low-Calorie Ketogenic Diet: A Potential Treatment for Binge Eating and Food Addiction Symptoms in Women. A Pilot Study

Background: many patients who struggle to lose weight are unable to cut down certain ultra-processed, refined types of food with a high glycemic index. This condition is linked to responses similar to addiction that lead to overeating. A very-low-calorie ketogenic diet (VLCKD) with adequate protein intake could be considered a valid dietary approach. The aim of the present study was to evaluate the feasibility of a VLCKD in women with binge eating and/or food addiction symptoms. Methods: subjects diagnosed with binge eating and/or food addiction symptoms (measured with the Binge Eating Scale and the Yale Food Addiction Scale 2.0) were asked to follow a VLCKD with protein replacement for 5–7 weeks (T1) and a low-calorie diet for 11–21 weeks (T2). Self-reported food addiction and binge eating symptoms and body composition were tested at T0 (baseline) and at the end of each diet (T1 and T2 respectively); Results: five women were included in the study. Mean age was 36.4 years (SEM = 4.95) and mean BMI was 31.16 (SEM = 0.91). At T0, two cases of severe food addiction, one case of mild food addiction, one case of binge eating with severe food addiction, and one case of binge eating were recorded. Weight loss was recorded at both T1 and T2 (ranging from 4.8% to 11.6% of the initial body weight at T1 and from 7.3% to 12.8% at T2). No case of food addiction and/or binge eating symptoms was recorded at T2. Muscle mass was preserved. Conclusions: recent findings have highlighted the potential therapeutic role of ketogenic diets for the treatment of addiction to high-calorie, ultra-processed and high-glycemic food. Our pilot study demonstrates the feasibility of a ketogenic diet in women with addictive-like eating disorders seeking to lose weight.

The Potential Therapeutic Role of Mesenchymal Stem Cells-Derived Exosomes in Osteoradionecrosis

As one of the most serious complications of radiotherapy, osteoradionecrosis (ORN) seriously affects the quality of life of patients and even leads to death. Vascular injury and immune disorders are the main causes of bone lesions. The traditional conservative treatment of ORN has a low cure rate and high recurrent. Exosomes are a type of extracellular bilayer lipid vesicles secreted by almost all cell types. It contains cytokines, proteins, mRNA, miRNA, and other bioactive cargos, which contribute to several distinct processes. The favorable biological functions of mesenchymal stem cells-derived exosomes (MSC exosomes) include angiogenesis, immunomodulation, bone regeneration, and ferroptosis regulation. Exploring the characteristic of ORN and MSC exosomes can promote bone regeneration therapies. In this review, we summarized the current knowledge of ORN and MSC exosomes and highlighted the potential application of MSC exosomes in ORN treatment.

Roseburia intestinalis: A Beneficial Gut Organism From the Discoveries in Genus and Species

Roseburia intestinalis is an anaerobic, Gram-positive, slightly curved rod-shaped flagellated bacterium that produces butyrate in the colon. R. intestinalis has been shown to prevent intestinal inflammation and maintain energy homeostasis by producing metabolites. Evidence shows that this bacterium contributes to various diseases, such as inflammatory bowel disease, type 2 diabetes mellitus, antiphospholipid syndrome, and atherosclerosis. This review reveals the potential therapeutic role of R. intestinalis in human diseases. Patients with inflammatory bowel disease exhibit significant changes in R. intestinalis abundance, and they may benefit a lot from modulations targeting R. intestinalis. The data reviewed here demonstrate that R. intestinalis plays its role in regulating barrier homeostasis, immune cells, and cytokine release through its metabolite butyrate, flagellin and other. Recent advancements in the application of primary culture technology, culture omics, single-cell sequencing, and metabonomics technology have improved research on Roseburia and revealed the benefits of this bacterium in human health and disease treatment.

MicroRNA-15a-5p acts as a tumor suppressor in histiocytosis by mediating CXCL10-ERK-LIN28a-let-7 axis

Erdheim–Chester disease (ECD) is characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD patients harbor recurrent mutations of genes associated with the RAS/RAF/MEK/ERK signaling pathway, particularly, the BRAFV600E mutation. Following our previous finding that miR-15a-5p is the most prominently downregulated microRNA in ECD patients compared to healthy individuals, we elucidated its role in ECD pathogenesis. Bioinformatics analysis followed by a luciferase assay showed that chemokine ligand 10 (CXCL10) is a target gene regulated by miRNA-15a-5p. This was confirmed in 24/34 ECD patients that had low expression of miR-15a-5p concurrent with upregulated CXCL10. Overexpression of miR-15a-5p in cell lines harboring BRAF or RAS mutations (Ba/F3, KG-1a and OCI-AML3) resulted in CXCL10 downregulation, followed by LIN28a and p-ERK signaling downregulation and let-7 family upregulation. Overexpression of miR-15a-5p inhibited cell growth and induced apoptosis by decreasing Bcl-2 and Bcl-xl levels. Analysis of sequential samples from 7 ECD patients treated with MAPK inhibitors (vemurafenib/cobimetinib) for 4 months showed miR-15a-5p upregulation and CXCL10 downregulation. Our findings suggest that miR-15a-5p is a tumor suppressor in ECD through the CXCL10-ERK-LIN28a-let7 axis, highlighting another layer of post-transcriptional regulation in this disease. Upregulation of miR-15a-5p in ECD patients may have a potential therapeutic role.