This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma.

Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is an effective therapy for the treatment of high‐risk haematological malignant disorders and other life‐threatening haematological and genetic diseases. Acute graft‐versus‐host disease (aGvHD) remains the most frequent cause of non‐relapse mortality following allo‐HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi‐target drug successfully employed for prophylaxis and treatment of veno‐occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo‐HCT. Using a fully MHC‐mismatched murine model of allo‐HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD‐associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo‐HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte‐endothelial interactions by down‐regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo‐HCT, paving the way for new therapeutic approaches.

A single-center, randomized, double-blind, controlled clinical trial with four arms was conducted in healthy subjects with persistent knee discomfort (pain intensity on 1–10 cm visual analog scale (VAS) > 3) aged 40 years and older treated with a dietary supplement for 8 weeks. The study groups were Boswellia serrata extract (n = 29), an omega-3-based product (AvailOm^® 50 High EPA) (n = 31), Boswellia + AvailOm^® (n = 30), and placebo (n = 30). The intake of Boswellia + AvailOm^® improved the quality of life (QoL) (WOMAC index) and some variables of muscle strength. Statistically significant differences between the AvailOm^® and the placebo groups in the decrease of pain intensity were found. Weekly VAS scores showed a significant decrease in pain perception when comparing the AvailOm^® product to the placebo, with the lowest VAS scores at week 8. Consumption of Boswellia improved sleep latency. The time to perform the Up and Go test decreased after the intake of AvailOm^®. There was an increase in the omega-3 fatty acids, with the greatest increase in the Boswellia + AvailOm^® group. AvailOm^® was safe and effective in reducing pain and improving the QoL and functionality of subjects over 40 years with persistent knee pain.

Mesenchymal stem/stromal cells (MSCs) are distributed within all tissues of the body. Though best known for generating connective tissue and bone, these cells also display immunoregulatory properties. A greater understanding of MSC cell biology is urgently needed because culture-expanded MSCs are increasingly being used in treatment of inflammatory conditions, especially life-threatening immune diseases. While studies in vitro provide abundant evidence of their immunomodulatory capacity, it is unknown whether tissue colonization of MSCs is critical to their ability to dampen/counteract evolving immunopathology in vivo. To address this question, we employed a murine model of fulminant immune-mediated inflammation, acute graft-versus-host disease (aGvHD), provoked by donor splenocyte-enriched full MHC-mismatched hematopoietic stem cell transplant. aGvHD induced the expression of E-selectin within lesional endothelial beds, and tissue-specific recruitment of systemically administered host-derived MSCs was achieved by enforced expression of HCELL, a CD44 glycoform that is a potent E-selectin ligand. Compared to mice receiving HCELL⁻MSCs, recipients of HCELL⁺MSCs had increased MSC intercalation within aGvHD-affected site(s), decreased leukocyte infiltrates, lower systemic inflammatory cytokine levels, superior tissue preservation, and markedly improved survival. Mechanistic studies reveal that ligation of HCELL/CD44 on the MSC surface markedly potentiates MSC immunomodulatory activity by inducing MSC secretion of a variety of potent immunoregulatory molecules, including IL-10. These findings indicate that MSCs counteract immunopathology in situ, and highlight a role for CD44 engagement in unleashing MSC immunobiologic properties that maintain/establish tissue immunohomeostasis.

Osteoarthritis (OA) is a prevalent, degenerative joint disease, with knee OA being particularly common and impactful. This systematic review and meta-analysis aimed to assess the efficacy of eggshell membrane (ESM) supplementation in improving joint functionality and reducing pain in individuals with knee OA. A comprehensive search was conducted across PubMed, Scopus, Web of Science, and Cochrane Database up to July 2024, following PRISMA guidelines. Seven randomized controlled trials (RCTs) met the inclusion criteria, with five included in the meta-analysis. The studies compared ESM to a placebo, evaluating outcomes based on assessment tools such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS), and Knee Injury and Osteoarthritis Outcome Score (KOOS). Results indicated that ESM significantly reduced pain and improved functionality, with notable improvements in total WOMAC score (effect size −0.34; 95% CI: −0.56 to −0.13; p < 0.001) and pain subscale (SMD −0.23; 95% CI: −0.42 to −0.04; p < 0.02). The findings support ESM as a promising adjunctive treatment for knee OA, offering a safe, natural supplement to enhance quality of life. Further high-quality RCTs are needed to confirm these results and explore the long-term effects and mechanisms of ESM.

This systematic review and meta-analysis examined the effects of dry needling alone or in combination with exercise therapy for reducing pain and disability in people with subacromial pain syndrome. Systematic searches of randomized clinical trials (RCTs) were performed in five different databases. A meta-analysis was carried out with the data obtained, and the risk of bias and quality of the studies was assessed using the Cochrane ROB 2.0 and GRADE tools. Finally, five RCTs (n = 315) were included in the meta-analysis and qualitative analysis. Our results determine that dry needling alone or combined with exercise therapy showed improvements in pain in the short-term (5RCTs: SMD: −0.27; [−0.49, −0.05]; low-quality) and mid-term (4RCTs: SMD: −0.27; [−0.51, −0.04]; low-quality) compared to a range of interventions. However, no differences were shown for disability at short-term (3 RCTs: SMD: −0.97; [−2.04, 0.11]; very-low quality) and mid-term (3 RCTs: SMD: −0.85; [−1.74, 0.04]; very-low quality). Dry needling alone or in combination with exercise therapy may result in a slight reduction in pain in the short-term and mid-term. However, the evidence about the effect of this therapy on disability in the short- or mid-term is very uncertain compared to the range of interventions analyzed in this systematic review (Registration: INPLASY202260112).