Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-β is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury. While current therapies are limited, the search for more effective diagnostic and treatment modalities is intensive. Although biopsy with histology is the most accurate method of diagnosis and staging, imaging techniques such as diffusion-weighted magnetic resonance imaging and shear wave elastography ultrasound are less invasive ways to stage fibrosis. Current therapies such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors aim to delay progression. Newer antifibrotic agents that suppress the downstream inflammatory mediators involved in the fibrotic process are in clinical trials, and potential therapeutic targets that interfere with TGF-β signaling are being explored. Small interfering RNAs and stem cell-based therapeutics are also being evaluated. Further research and clinical studies are necessary in order to avoid dialysis and kidney transplantation.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent decades, clinical research has made significant advances, resulting in improved survival and recovery rates for patients with CVD. Despite this progress, there is substantial residual CVD risk and an unmet need for better treatment. The complex and multifaceted pathophysiological mechanisms underlying the development of CVD pose a challenge for researchers seeking effective therapeutic interventions. Consequently, exosomes have emerged as a new focus for CVD research because their role as intercellular communicators gives them the potential to act as noninvasive diagnostic biomarkers and therapeutic nanocarriers. In the heart and vasculature, cell types such as cardiomyocytes, endothelial cells, vascular smooth muscle, cardiac fibroblasts, inflammatory cells, and resident stem cells are involved in cardiac homeostasis via the release of exosomes. Exosomes encapsulate cell-type specific miRNAs, and this miRNA content fluctuates in response to the pathophysiological setting of the heart, indicating that the pathways affected by these differentially expressed miRNAs may be targets for new treatments. This review discusses a number of miRNAs and the evidence that supports their clinical relevance in CVD. The latest technologies in applying exosomal vesicles as cargo delivery vehicles for gene therapy, tissue regeneration, and cell repair are described.

Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer’s disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of P110 as a neuroprotective agent in AD remains unclear. Therefore, we performed cell culture studies to evaluate the neuroprotective effect of P110 on amyloid-β accumulation and mitochondrial functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM and 10 µM of P110, and Real-Time PCR and Western blot analysis were done to quantify the expression of genes pertaining to AD and neuronal health. Exposure of SH-SY5Y cells to P110 significantly increased APP mRNA levels at 1 µM, while BACE1 mRNA levels were increased at both 1 µM and 10 µM. However, protein levels of both APP and BACE1 were significantly reduced at 10 µM of P110. Further, P110 treatment significantly increased ADAM10 and Klotho protein levels at 10 µM. In addition, P110 exposure significantly increased active mitochondria and reduced ROS in live SH-SY5Y cells at both 1 µM and 10 µM concentrations. Taken together, our results indicate that P110 might be useful in attenuating amyloid-β generation and improving neuronal health by maintaining mitochondrial function in neurons.

Despite progress in treating rheumatoid arthritis, this autoimmune disorder confers an increased risk of developing cardiovascular disease (CVD). Widely used screening protocols and current clinical guidelines are inadequate for the early detection of CVD in persons with rheumatoid arthritis. Traditional CVD risk factors alone cannot be applied because they underestimate CVD risk in rheumatoid arthritis, missing the window of opportunity for prompt intervention to decrease morbidity and mortality. The lipid profile is insufficient to assess CVD risk. This review delves into the connection between systemic inflammation in rheumatoid arthritis and the premature onset of CVD. The shared inflammatory and immunologic pathways between the two diseases that result in subclinical atherosclerosis and disrupted cholesterol homeostasis are examined. The treatment armamentarium for rheumatoid arthritis is summarized, with a particular focus on each medication’s cardiovascular effect, as well as the mechanism of action, risk–benefit profile, safety, and cost. A clinical approach to CVD screening and treatment for rheumatoid arthritis patients is proposed based on the available evidence. The mortality gap between rheumatoid arthritis and non-rheumatoid arthritis populations due to premature CVD represents an urgent research need in the fields of cardiology and rheumatology. Future research areas, including risk assessment tools and novel immunotherapeutic targets, are highlighted.

Nilotinib, a tyrosine kinase inhibitor that targets the Abelson tyrosine kinase (c-Abl) signaling pathway, is FDA-approved to treat chronic myeloid leukemia. Nilotinib has properties indicative of a possible utility in neuroprotection that have prompted exploration of repurposing the drug for the treatment of Alzheimer’s disease (AD) and Parkinson’s disease (PD). AD is a progressive age-related neurodegenerative disorder characterized by the deposition of extracellular amyloid-β plaques and intracellular neurofibrillary tangles. It is incurable and affects approximately 50 million patients worldwide. Nilotinib reduces c-Abl phosphorylation, amyloid-β levels, and dopaminergic neuron degeneration in preclinical AD models. This study explores the effects of nilotinib on amyloid processing and mitochondrial functioning in the SH-SY5Y human neuroblastoma cell line. SH-SY5Y cells were exposed to nilotinib (1, 5, and 10 µM). Real-time PCR and immunoblot analysis were performed to quantify the expression of genes pertaining to amyloid-β processing and neuronal health. Nilotinib did not significantly change APP, BACE1, or ADAM10 mRNA levels. However, BACE1 protein was significantly increased at 1 µM, and ADAM10 was increased at 10 µM nilotinib without affecting APP protein expression. Further, nilotinib treatment did not affect the expression of genes associated with neuronal health and mitochondrial functioning. Taken together, our findings do not support the efficacy of nilotinib treatment for neuroprotection.

Background/Objectives: Localized prostate cancer may be treated with total cryotherapy, focal cryotherapy, stereotactic body radiotherapy (SBRT), or radical prostatectomy (RP). However, the immune response to these therapies is not fully understood despite its potential importance in determining extent and timing of recovery, disease control and cancer recurrence rate. This exploratory study measured cytokine expression changes in the urine and blood of prostate cancer patients as a means of monitoring immune response to these four alternative treatments. Methods: Urine and blood multiplex ELISA cytokine assays were performed in 37 men with histologically confirmed prostate adenocarcinoma before, 2 weeks after, and 3 months after therapy. Results: Treatment method alone significantly affected levels of plasma but not urine cytokines. Both plasma and urine showed significant changes across visit number and significant interactions between treatment and visit number for some cytokines. In plasma, SBRT was associated with the highest cytokine levels when compared to RP and cryotherapy. Urinary IL-8 levels increased over time following cryoablation, whereas they remained relatively stable across visits after SBRT and RP (β = 1.51, 95% CI [0.89–2.13], p < 0.001). Urinary IL-6 levels reached their highest point at visit three following both SBRT and cryoablation, whereas after RP, the peak occurred earlier at visit two (β = 0.07, 95%CI [0.04–0.11], p < 0.001). The pattern of plasma levels of IL-10 differed by time elapsed after treatment depending upon treatment group (β = −0.05, 95%CI [−0.08–−0.01], p = 0.005). Conclusions: These findings show that the prostate cancer treatment method employed may affect post-operative inflammatory mechanisms. This small study encourages expansion to determine the prognostic utility of urine and plasma cytokine expression patterns based on prostate cancer treatment and time elapsed following treatment. Understanding these changes may inform a personalized medicine approach to prostate cancer immunotherapies.