Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.

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)-ß 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-ß 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.

Alzheimer's Disease Treatment: The Search for a Breakthrough.

As the search for modalities to cure Alzheimer's disease (AD) has made slow progress, research has now turned to innovative pathways involving neural and peripheral inflammation and neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing the disease course. The recently FDA-approved anti-amyloid drugs, aducanumab and lecanemab, have demonstrated unclear real-world efficacy with a substantial side effect profile. Interest is growing in targeting the early stages of AD before irreversible pathologic changes so that cognitive function and neuronal viability can be preserved. Neuroinflammation is a fundamental feature of AD that involves complex relationships among cerebral immune cells and pro-inflammatory cytokines, which could be altered pharmacologically by AD therapy. Here, we provide an overview of the manipulations attempted in pre-clinical experiments. These include inhibition of microglial receptors, attenuation of inflammation and enhancement of toxin-clearing autophagy. In addition, modulation of the microbiome-brain-gut axis, dietary changes, and increased mental and physical exercise are under evaluation as ways to optimize brain health. As the scientific and medical communities work together, new solutions may be on the horizon to slow or halt AD progression.

Potential therapeutic effects of adjunct osteopathic manipulative treatments in SARS-CoV-2 patients.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects various human organ systems, including the lymphatic, pulmonary, gastrointestinal, and neurologic systems. The utilization of osteopathic manipulative treatment (OMT) techniques has been clinically effective in the alleviation of various upper respiratory infection symptoms. Consequently, the use of osteopathic manipulative medicine (OMM) in SARS-CoV-2 patients as adjunct treatment can be beneficial in promoting overall recovery. This paper attempts to address the pathophysiology of SARS-CoV-2 infection at the cellular level and its downstream effects. Subsequently, osteopathic principles were investigated to evaluate potential therapeutic effects, providing a holistic approach in the SARS-CoV-2 treatment. Although the association between the benefits of OMT on clinical improvement during the 1918 Spanish influenza pandemic can be seen, further investigation is required to establish a direct correlation between OMT and symptom management in SARS-CoV-2.