卷 30, 编号 11 (2024)

:Renal disease is a medical condition that poses a potential threat to the life of an individual and is related to substantial morbidity and mortality rates in clinical environments. The aetiology of this condition is influenced by multiple factors, and its incidence tends to increase with progressive aging. Although supportive therapy and kidney transplantation have potential advantages, they also have limitations in terms of mitigating the progression of KD. Despite significant advancements in the domain of supportive therapy, mortality rates in patients continue to increase. Due to their ability to self-renew and multidirectionally differentiate, stem cell therapy has been shown to have tremendous potential in the repair of the diseased kidney. MSCs (Mesenchymal stem cells) are a cell population that is extensively distributed and can be located in various niches throughout an individual's lifespan. The cells in question are characterised by their potential for indefinite replication and their aptitude for undergoing differentiation into fully developed cells of mesodermal origin under laboratory conditions. It is essential to emphasize that MSCs have demonstrated a favorable safety profile and efficacy as a therapeutic intervention for renal diseases in both preclinical as well as clinical investigations. MSCs have been found to slow the advancement of kidney disease, and this impact is thought to be due to their control over a number of physiological processes, including immunological response, tubular epithelial- mesenchymal transition, oxidative stress, renal tubular cell death, and angiogenesis. In addition, MSCs demonstrate recognised effectiveness in managing both acute and chronic kidney diseases via paracrine pathways. The proposal to utilise a therapy that is based on stem-cells as an effective treatment has been put forward in search of discovering novel therapies to promote renal regeneration. Preclinical researchers have demonstrated that various types of stem cells can provide advantages in acute and chronic kidney disease. Moreover, preliminary results from clinical trials have suggested that these interventions are both safe and well-tolerated. This manuscript provides a brief overview of the potential renoprotective effects of stem cell-based treatments in acute as well as chronic renal dysfunction. Furthermore, the mechanisms that govern the process of kidney regeneration induced by stem cells are investigated. This article will examine the therapeutic approaches that make use of stem cells for the treatment of kidney disorders. The analysis will cover various cellular sources that have been utilised, potential mechanisms involved, and the outcomes that have been achieved so far.

Background:Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model.

Methods:Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods.

Results:ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs.

Conclusion:Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.

Background::Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children.

Aims::The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.

Methods::A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.

Results::For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.

Conclusion::It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.