Advances in mesenchymal stem cell-derived extracellular vesicles therapy for Sjogren's syndrome-related dry eye disease.

Sjogren's syndrome (SS) is a chronic autoimmune disorder that affects exocrine glands, particularly lacrimal glands, leading to dry eye disease (DED). DED is a common ocular surface disease that affects millions of people worldwide, causing discomfort, visual impairment, and even blindness in severe cases. However, there is no definitive cure for DED, and existing treatments primarily relieve symptoms. Consequently, there is an urgent need for innovative therapeutic strategies based on the pathophysiology of DED. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool for various autoimmune disorders, including SS-related DED (SS-DED). A particularly intriguing facet of MSCs is their ability to produce extracellular vesicles (EVs), which contain various bioactive components such as proteins, lipids, and nucleic acids. These molecules play a key role in facilitating communication between cells and modulating a wide range of biological processes. Importantly, MSC-derived EVs (MSC-EVs) have therapeutic properties similar to those of their parent cells, including immunomodulatory, anti-inflammatory, and regenerative properties. In addition, MSC-EVs offer several notable advantages over intact MSCs, including lower immunogenicity, reduced risk of tumorigenicity, and greater convenience in terms of storage and transport. In this review, we elucidate the underlying mechanisms of SS-DED and discuss the relevant mechanisms and targets of MSC-EVs in treating SS-DED. In addition, we comprehensively review the broader landscape of EV application in autoimmune and corneal diseases. This review focuses on the efficacy of MSC-EVs in treating SS-DED, a field of study that holds considerable appeal due to its multifaceted regulation of immune responses and regenerative functions.

Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies.

OBJECTIVES: Gout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia. DESIGN: Systematic review and meta-analysis of cohort studies. DATA SOURCES: Studies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases. ELIGIBILITY CRITERIA: Cohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled. DATA EXTRACTION AND ANALYSIS: Two reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger's and Begg's tests. Quality assessment was performed according to the Newcastle-Ottawa Scale. RESULTS: Four cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer's disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6-8 points). CONCLUSIONS: Our study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

Disease Severity Determines Timing of Initiating Continuous Renal Replacement Therapies: A Systematic Review and Meta-Analysis.

Background: Timing of initiating continuous renal replacement therapies (CRRTs) among the patients with acute kidney injury (AKI) in intensive care units (ICU) has been discussed over decades, but the definition of early and late CRRT initiation is still unclear. Methods: The English language randomized controlled trials (RCTs) and cohort studies were searched through MEDLINE, EMBASE, and Cochrane Library on July 19, 2019, by the two researchers independently. The study characteristics; early and late definitions; outcomes, such as all-cause, in-hospital, 28- or 30-, 60-, 90-day mortality; and renal recovery were extracted from the 18 eligible studies. Pooled relative risk ratios (RRs) and 95% CIs were estimated with the fixed effects model and random effects model as appropriate. This study is registered with PROSPERO (CRD 42020158653). Results: Eighteen studies including 3,914 patients showed benefit in earlier CRRT (n = 1,882) over later CRRT (n = 2,032) in all-cause mortality (RR 0.78, 95% CI 0.66-0.92), in-hospital mortality (RR 0.81, 95% CI 0.67-0.99), and 28- or 30-day mortality (RR 0.81, 95% CI 0.74-0.88), but in 60- and 90-day mortalities, no significant benefit was observed. The subgroup analysis showed significant benefit in the disease-severity-based subgroups on early CRRT initiation in terms of in-hospital mortality and 28- or 30-day mortality rather than the time-based subgroups. Moreover, early CRRT was found to have beneficial effects on renal recovery after CRRT (RR 1.21, 95% CI 1.01-1.45). Conclusions: Overall, compared with late CRRT, early CRRT is beneficial for short-term survival and renal recovery, especially when the timing was defined based on the disease severity. CRRT initiation on Acute Kidney Injury Network (AKIN) stage 1 or Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE)-Risk or less may lead to a better prognosis.

Regulating p-block metals in perovskite nanodots for efficient electrocatalytic water oxidation.

Water oxidation represents the core process of many sustainable energy systems, such as fuel cells, rechargeable metal-air batteries, and water splitting. Material surface defects with high-energy hanging bonds possess superb intrinsic reactivity, whose actual performance is limited by the dimension and conductivity of the electrocatalyst. Herein we propose a surface defect-rich perovskite electrocatalyst through a p-block metal regulation concept to achieve high performance for oxygen evolution. As a typical p-metal, Sn4+ dissolves from the solid phase from model SnNiFe perovskite nanodots, resulting in abundant surface defects with superior water oxidation performance. An oxygen pool model and a fusion-evolution mechanism are therefore proposed for the in-depth understanding of p-block metal regulation and the oxygen evolution reaction. The energy chemistry unveiled herein provides insights into water oxidation and helps to tackle critical issues in multi-electron oxygen electrocatalysis.Electrocatalysts that possess high densities of surface defects show great promise for efficient water oxidation. Here the authors demonstrate that regulating the p-block metal content in perovskite nanodots imparts these materials with abundant surface defects and excellent electrocatalytic activity.