Exosomes from bone marrow-derived mesenchymal stem cells facilitate corneal wound healing via regulating the p44/42 MAPK pathway.

PURPOSE: This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. METHODS: The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. RESULTS: BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo, the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. CONCLUSION: BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo. BMSC-Exos may be promising resources for promoting corneal wound healing.

Evaluation on treatment of sustained low-efficiency hemodialysis against patients with multiple organ dysfunction syndrome following wasp stings.

BACKGROUND: To evaluate the treatment of sustained low-efficiency hemodialysis (SLED) against patients with multiple organ dysfunction syndrome (MODS) following wasp stings. METHODS: Clinical data of 35 patients with MODS following wasp stings were retrospectively analysed. These patients were divided into three groups according to the treatment strategy used: 1) hemodialysis (HD) group, 2) continuous veno-venous hemofiltration (CVVH)/HD group, and 3) SLED/HD group. The clinical parameters, treatment outcome, and safety findings were compared among the three groups. RESULTS: The recovery rate (76.92% vs 77.78% vs 91.67%, p = 0.621) and mortality rate (15.38% vs 11.11% vs 8.33%, p = 0.999) were similar among the three groups. When compared to the HD group, patients treated with CVVH/HD or SLED/HD required a shorter period of time to enter into polyuria stage [(24.7 ± 4.3) days vs (20.2 ± 4.7) days vs (18.2 ± 3.0) days, F = 9.11, p = 0.0007], and required a shorter time for serum creatinine to return to normal [(45.7 ± 13.4) days vs (33.1 ± 9.4) days vs (31.9 ± 9.8), F = 5.83, p = 0.0069]; while such parameters had no significant differences between SLED/HD group and CVVH/HD group. The adverse events of hypotension and arrhythmia were found in the HD group, while no adverse events were reported in the SLED/HD and CVVH/HD groups. There was no significant difference in the cost of blood purification treatment between the SLED/HD group and HD group. CONCLUSION: The use of SLED, CVVH and HD provided a comparable recovery and survival rates in patients with MODS secondary to wasp stings. Compared to HD, the use of SLED is recommended as a treatment strategy because of the efficacy on recover of renal function, satisfactory safety outcome, as well as the reasonable treatment cost.

Sustained low-efficiency diafiltration is superior to hemodialysis in promoting renal function recovery in elderly wasp sting victims with stage III acute kidney injury: a retrospective study.

Objective: To study the efficacy and safety of sustained low-efficiency diafiltration (SLEDf) versus hemodialysis (HD) for patients with wasp stings who developed stage III acute kidney injury (AKI). Methods: We retrospectively analyzed the clinical data of consecutive patients who developed AKI following wasp stings. All eligible patients received renal replacement therapy in combination with hemoperfusion. Thereafter, blood purification therapy and HD were performed with a volumetrically controlled machine and 1.7 m2 surface, Fresenius Polysulfone HD filter and SLEDf was undertaken with a volumetrically controlled machine and 1.3 m2 surface, Fresenius Polysulfone HD filter. Results: Forty patients developed stage III AKI following wasp stings, including 14 patients that received SLEDf and 26 patients underwent HD. Thirteen patients were aged less than 60 years and underwent HD (group I), 27 patients were aged at least 60 years, including 13 patients undergoing HD (group II) and 14 patients receiving SLEDf (group III). Groups I and II completed 150 and 162 sessions of HD, respectively, and group III completed 156 sessions of sustained low-efficiency blood purification therapy, including 50 sessions of SLEDf. The time to return to normal serum creatinine levels was 38.8 ± 2.7 days for group I, 47.2 ± 5.3 days for group II, and 39.2 ± 3.3 days for group III. A statistically significant difference was observed in time to normal serum creatinine levels among the three groups. Conclusion: Elderly wasp victims have more severe illness than younger wasp victims and SLEDf is safe and superior to HD in recovery of renal function of elderly wasp victims.

Morphological features of retinal development in premature Chinese infants observed by computer-assisted indirect ophthalmoscope imaging.

OBJECTIVE: To investigate retinal maturation in premature infants (gestation age <37 weeks). using computer-assisted indirect ophthalmoscope imaging. METHODS: Premature infants at postmenstrual age 33-46 weeks, who underwent fundus examinations using computer-aided indirect ophthalmoscopy, were stratified into seven postmenstrual-age groups. Images of macular morphology, peripheral retinal vascularization and fundus pigmentation were compared. RESULTS: The study included 268 infants in the following postmenstrual-age groups: 33-34 weeks (n = 19), 35-36 weeks (n = 37), 37-38 weeks (n = 49), 39-40 weeks (n = 55), 41-42 weeks (n = 49), 43-44 weeks (n = 34), and 45-46 weeks (n = 25). The macula matured with increasing postmenstrual age. A mature macula was observed in 92% of infants at 45-46 weeks. Complete vascularization was achieved at 41-42 weeks in the nasal retina and at 43-44 weeks in the temporal retina. The number of retinas with normal pigmentation increased with postmenstrual age (rising to 84% of infants at postmenstrual age 45-46 weeks). CONCLUSIONS: Following premature birth, macular morphology, retinal vascularization and retinal pigmentation continue to develop. This study provides reference images of normal retinal development in premature infants.

Differential expression of claudins in retinas during normal development and the angiogenesis of oxygen-induced retinopathy.

PURPOSE: Angiogenesis accompanies several retinal pathologies that impair the inner blood-retinal barrier. Claudins are key structural and functional proteins of the barrier. This study compared the expression of claudins during the normal angiogenesis of development with that of oxygen-induced retinopathy. METHODS: Real-time PCR was used to monitor mRNA from postnatal day 8 (P8) to P21 in normal mice and oxygen-induced retinopathy (OIR) mice. Protein expression was monitored by immunoblotting and immunofluorescence. Isolectin B4 was used to identify blood vessels and occludin was used to identify tight junctions. Neovascularization and permeability were monitored using FITC-dextran and Evans blue. RESULTS: The mRNA of claudin-1, -2, -3, -4, -5, -12, -22, and -23 was developmentally regulated, but only claudin-1, -2, and -5 were found in the tight junctions of retinal vessels. OIR induced the formation of leaky neovascular vessels. The mRNA and protein of claudin-2 and -5 were overexpressed, whereas claudin-1 and occludin were unaffected. Despite their overexpression, each claudin was distributed throughout the cell, especially in the neovascular tufts. Occludin was retained at the lateral membranes but exhibited a punctate distribution. CONCLUSIONS: Claudin-1, -2, and -5 are the most prominent claudins of the inner blood-retinal barrier. The pathologic angiogenesis induced by oxygen formed a leaky barrier due to the mislocalization of these claudins. Studies of the mechanisms that regulate the intracellular distribution of claudins may lead to new therapeutic approaches for retinal vascular disease.