Laparoscopic continuous seromuscular circumsuture for myomectomy: a real-world, retrospective, East-Asian cohort study.

OBJECTIVE: This study aimed to introduce a novel laparoscopic haemostasis for myomectomy and investigate the independent risk factors for uterine fibroid recurrence. DESIGN: A retrospective cohort study. SETTING: Following strengthening the reporting of observational studies in epidemiology (STROBE) criteria, a retrospective study of prospectively collected available data of the consecutive patients who underwent the myomectomy in the department of obstetrics and gynaecology of the single centre between February 2018 and December 2020. PARTICIPANTS: 177 patients who underwent laparoscopic myomectomy resection were enrolled in the present cohort study. MATERIALS AND METHODS: Patients were classified into two groups according to their different methods of haemostasis in laparoscopic surgery. Recurrence-free survival was compared between the groups during an average follow-up of nearly 2 years. RESULTS: Of the 177 patients from 672 consecutive patients in the retrospective cohort, laparoscopic circular suture and baseball suture were carried out in 102 (57.6%) and 75 (42.4%) patients, respectively. The total amount of blood lost during surgery varied significantly (37.6 vs 99.5 mL) (p<0.001). Univariable analyses identified that age ≥40 years, position at intramural myoma, multiple fibroids and largest fibroid volume ≥50 mm3 (HR 2.222, 95% CI 1.376 to 3.977, p=0.039; HR 3.625, 95% CI 1.526 to 6.985, p=0.003; HR 3.139, 95% CI 1.651 to 5.968, p<0.001; HR 2.328, 95% CI 0.869 to 3.244, p=0.040, respectively) are independent risk factor of the recurrence of uterine fibroids. The formula of the nomogram prediction model was established as the practical clinical tool. CONCLUSION: The laparoscopic continuous seromuscular circumsuture for myomectomy can effectively reduce the amount of surgical bleeding and accelerate the perioperative recovery for surgical safety. The main factors affecting the recurrence of uterine fibroids were age, location, number and volume of uterine fibroids. The nomogram can more straightforwardly assist clinicians to determine the risk of recurrence after laparoscopic myomectomy.

Blocking of FGFR4 signaling by F30 inhibits hepatocellular carcinoma cell proliferation through HMOX1-dependent ferroptosis pathway.

Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.

Major Active Metabolite Characteristics of Dendrobium officinale Rice Wine Fermented by Saccharomyces cerevisiae and Wickerhamomyces anomalus Cofermentation.

Rice, supplemented with Dendrobium officinale, was subjected to cofermentation using Saccharomyces cerevisiae FBKL2.8022 (Sc) and Wickerhamomyces anomalus FBKL2.8023 (Wa). The alcohol content was determined with a biosensor, total sugars with the phenol-sulfuric acid method, reducing sugars with the DNS method, total acids and total phenols with the colorimetric method, and metabolites were analyzed using LC-MS/MS combined with multivariate statistics, while metabolic pathways were constructed using metaboAnalyst 5.0. It was found that the quality of rice wine was higher with the addition of D. officinale. A total of 127 major active substances, mainly phenols, flavonoids, terpenoids, alkaloids, and phenylpropanoids, were identified. Among them, 26 substances might have been mainly metabolized by the mixed-yeasts fermentation itself, and 10 substances might have originated either from D. officinale itself or from microbial metabolism on the newly supplemented substrate. In addition, significant differences in metabolite could be attributed to amino acid metabolic pathways, such as phenylalanine metabolism and alanine, aspartate, and glutamate metabolism. The characteristic microbial metabolism of D. officinale produces metabolites, which are α-dihydroartemisinin, alantolactone, neohesperidin dihydrochalcone, and occidentoside. This study showed that mixed-yeasts cofermentation and fermentation with D. officinale both could increase the content of active substances in rice wine and significantly improve the quality of rice wine. The results of this study provide a reference for the mixed fermentation of brewer's yeast and non-yeast yeasts in rice wine brewing.

MicroRNA let-7d attenuates hypertrophic scar fibrosis through modulation of iron metabolism by reducing DMT1 expression.

Hypertrophic scar is an unavoidable result of wound healing following burns and trauma, which remains a challenging problem for clinicians. Previously, we demonstrated that exosomal microRNAs (miRs) of human amniotic epithelial cells accelerated wound healing and inhibited scar formation. However, the underlying mechanism is still unclear. In this particular study, we found that miR-let-7d reduced collagen deposition, and this was accompanied by decreased level of iron content in myofibroblasts. Importantly, inhibition of miR-let-7d in myofibroblasts accelerated collagen deposition and promoted cell proliferation. In addition, bioinformatics prediction combined with classical dual-luciferase reporter gene assay demonstrated that the cellular iron importer divalent metal transporter 1 (DMT1) was a target gene of miR-let-7d, and the miR-let-7d mimics inhibited the expression of DMT1 in myofibroblasts. Moreover, silencing of DMT1 with small interfering RNA (siRNA) reduced the deposition of extracellular matrix. Consistent with the results in vitro, the miR-let-7d mimics effectively ameliorated hypertrophic scar fibrosis in a rabbit ear hypertrophic scar model. Taken together, our results indicated for the first time that miR-let-7d attenuated hypertrophic scar fibrosis through modulation of iron metabolism by reducing iron uptake through DMT1, which may provide a novel therapeutic strategy for hypertrophic scar.

Accumulation, metabolites formation and elimination behavior of rac-glufosinate-ammonium and glufosinate-P in zebrafish (Danio rerio).

An efficient trace detection method for the determination of residues of the glufosinate enantiomers and metabolites in zebrafish by HPLC-Q-Exactive Orbitrap Mass Spectrometry was developed. After the purification of dichloromethane and Oasis PRiME HLB SPE column, the recovery ranges from 77% to 104%, with RSD < 10.03%. The limits of quantitation in zebrafish were 0.006-0.02 mg/kg. The results revealed zebrafish absorbed glufosinate slowly, reaching a steady state in 10-14 days, and the bioaccumulation factor (BCF) of D/L-glufosinate-ammonium was less than 0.3. L-glufosinate-ammonium accumulated preferentially in zebrafish. The residue of the metabolite N-acetyl glutamate (NAG) was smaller than that of 3-methyl phosphonic acid (MPP). D/L-glufosinate-ammonium had an elimination half-life of less than 2.3 days during the elimination phase. The bioaccumulation and elimination behavior of glufosinate-ammonium in zebrafish aquatic system was shown in this work, which offered scientific data for assessing the food safety of rac-glufosinate-ammonium and glufosinate-P (pure L-glufosinate-ammonium) in fish.

Ultrasonic Extraction Process of Polysaccharides from Dendrobium nobile Lindl.: Optimization, Physicochemical Properties and Anti-Inflammatory Activity.

To optimize the ultrasonic extraction process of polysaccharides from Dendrobium nobile Lindl. (DNP), the extraction method was conducted through a single-factor test and the response-surface methodology (RSM). With the optimal extraction process (liquid-solid ratio of 40 mL/g, ultrasonic time of 30 min, and ultrasonic power of 400 W), the maximum extraction yield was 5.16 ± 0.41%. DNP1 and DNP2 were then fractionated via DEAE-QFF and Sephacryl S-300 HR chromatography. The molecular weight (Mw) of DNP1 was identified as 67.72 kDa, composed of Man (75.86 ± 0.05%) and Glc (24.14 ± 0.05%), and the Mw of DNP2 was 37.45 kDa, composed of Man (72.32 ± 0.03%) and Glc (27.68 ± 0.03%). Anti-inflammatory assays results showed that as DNPs were 200 µg/mL, and the contents of NO, TNF-α, IL-1ß, IL-6 and IL-10 in LPS-induced RAW 264.7 cells were about 13.39% and 13.39%, 43.88% and 43.51%, 17.80% and 15.37%, 13.84% and 20.66%, and 938.85% and 907.77% of those in control group, respectively. It was indicated that DNP1 and DNP2 inhibited the inflammatory response of RAW 264.7 cells induced by LPS via suppressing the level of NO and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and promoting the secretion of anti-inflammatory cytokine (IL-10). Therefore, DNP1 and DNP2 have potential applications in the treatment of inflammatory injury.

Assessment of Heavy Metal Uptake in Potatoes Cultivated in a Typical Karst Landform, Weining County, China.

The average content of heavy metals in Weining soil of karst landforms is generally higher than that of other agricultural regions. The aim of this study was to evaluate the heavy metal content in potatoes from Weining county and to analyze the correlation between the content of heavy metals in potatoes planted in the soil of karst landform and the soil's environmental factors (soil heavy metals, soil pH, soil organic matter, altitude). Weining county (Guizhou province, China) is a typical karst landform, and has a potato production yield of 2.7 million tons. In this study, 56 soil and potato samples were collected from Weining county and the heavy metal content in the soils and potatoes was detected by inductively coupled plasma atomic mass spectrometry (ICP-MS). The content of Cr, Ni, and As in the soil was found to be higher, with almost half of the samples exceeding the maximum allowable levels. A total of 9 of the 56 samples tested had pollution load index values greater than 1.0, which indicates serious soil pollution. It was found that the ability of the potato to absorb heavy metals from the soil was very low, with the average bio-concentration factors of the metals Zn, Cu, Pb, Cr, Ni, and As being 0.087, 0.088, 0.0028, 0.0034, 0.0066, and less than 0.001, respectively. The content of the six heavy metals in the potatoes were all lower than the maximum permissible limit. The results show that a high As content in the soil could increase the content of Pb in potatoes, that a lower pH was beneficial to the bioaccumulation of Cr and Ni in potatoes, and that a high altitude is detrimental to the bioaccumulation of zinc and copper in potatoes. The HRI ranged between 1.12 × 10-2 and 5.92 × 10-2.

The novel FGFR inhibitor F1-7 induces DNA damage and cell death in colon cells.

BACKGROUND: Fibroblast growth factor receptor (FGFR) signaling influenced tumour occurrence and development. Overexpression of FGFR had been observed in many types of cancers, including colon cancer. FGFR inhibitor is considered to be effective in treating colon cancer patients. METHODS: First, the kinase inhibition rate was determined. MTT, western blotting, colony formation, EdU and comet assays were performed to evaluate the anti-tumour effects of F1-7 in vitro. RNA-seq and bioinformatics analysis were used for further verification. Additionally, a xenograft model was generated to investigate the anti-tumour effect of F1-7. RESULTS: F1-7 can inhibit the proliferation of colon cancer cells in vitro. It could significantly inhibit FGFR phosphorylation and its downstream signaling pathway. Whole-genome RNA-seq analysis found that the changed genes were not only functionally focused on MAPK signaling pathway but also related to cell apoptosis and ferroptosis. Experimental evidence demonstrated that F1-7 can directly increase the level of cellular DNA damage. The occurrence of DNA damage led to cell cycle arrest and inhibition of cell metastasis and cell apoptosis. Mouse model experiments also confirmed that F1-7 could inhibit tumour growth by inhibiting the FGFR pathway. CONCLUSIONS: F1-7 exhibits anti-tumour activity by inhibiting the FGFR pathway. It could be a novel therapeutic agent for targeting colon cancer cells.

Effect of Yeast Fermentation on the Physicochemical Properties and Bioactivities of Polysaccharides of Dendrobium officinale.

Fermentation is an effective method for enhancing the biological activity of polysaccharides, but research on its effect on Dendrobium officinal polysaccharides is rare. In this study, the effects of mono-fermentation (Saccharomyces cerevisiae FBKL2.8022, Sc; Wickerhamomyces anomalous FBKL2.8023, Wa) and co-fermentation (Sc+Wa) on the physicochemical properties and bioactivity of Dendrobium officinal polysaccharides were investigated. Meanwhile, the polysaccharide (DOP) obtained from Dendrobium officinale was used as a control. Four homogeneous polysaccharides were obtained by isolation and purification and named DOSCP, DOWAP, DOSWP, and DOP. The results showed that DOSCP, DOWAP, DOSWP, and DOP consisted of mannose and glucose with ratios of 3.31:1, 5.56:1, 2.40:1, and 3.29:1, respectively. The molecular weights (Mws) of the four polysaccharides were 25.73 kDa, 15.01 kDa, 17.67 kDa, and 1268.21 kDa. The antioxidant activity of DOSCP, DOWAP, and DOSWP was better than that of DOP. Additionally, all four polysaccharides were able to reduce the inflammatory response of LPS-induced RAW 264.7 macrophages in the mice without a significant difference. Yeast fermentation significantly reduced the molecular weight and improved the antioxidant activity of Dendrobium officinale polysaccharides, indicating a potential way to improve its antioxidant activity.

Discovery of a Novel MyD88 Inhibitor M20 and Its Protection Against Sepsis-Mediated Acute Lung Injury.

Myeloid differentiation factor 88 (MyD88) is a hub protein in the Toll-like receptor signaling pathway, which acts as a master switch for numerous inflammatory diseases, including acute lung injury (ALI). Although this protein is considered as a crucial therapeutic target, there are currently no clinically approved MyD88-targeting drugs. Based on previous literature, here we report the discovery via computer-aided drug design (CADD) of a small molecule, M20, which functions as a novel MyD88 inhibitor to efficiently relieve lipopolysaccharide-induced inflammation both in vitro and in vivo. Computational chemistry, surface plasmon resonance detection (SPR) and biological experiments demonstrated that M20 forms an important interaction with the MyD88-Toll/interleukin-1 receptor domain and thereby inhibits the protein dimerization. Taken together, this study found a MyD88 inhibitor, M20, with a novel skeleton, which provides a crucial understanding in the development and modification of MyD88 inhibitors. Meanwhile, the favorable bioactivity of the hit compound is also conducive to the treatment of acute lung injury or other more inflammatory diseases.

Dissipation Dynamics, Terminal Residues and Dietary Risk Assessment of Two Isomers of Dimethacarb in Rice by HPLC-MS/MS.

Dimethacarb is a carbamate insecticide developed in China that contains 3,5-dimethylphenyl methylcarbamate (XMC) and 3,4-dimethylphenyl methylcarbamate (MPMC) isomers. Dimethacarb has been registered for use in rice in China, but no residue or degradation of dimethacarb in rice has been reported and the maximum residue limits (MRLs) for rice have not been established. A versatile high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed with modified QuEChERS sample preparation to determine two isomers of dimethacarb in rice. The average recovery of XMC and MPMC in brown rice, rice husk, and rice straw ranged from 71.69 to 100.60%, with spike levels of 0.01 to 1 mg/kg and relative standard deviations (RSDs) of 0.21 to 8.41%. Field experiments showed that the half-lives of XMC and MPMC in rice straw were 4.08 to 4.23 days and 3.48 to 3.69 days, respectively. Final residues of XMC and MPMC in rice husk after 21 days of spraying at six sites ranged from 0.23-2.65 mg/kg and 0.06-1.10 mg/kg, and <0.01-0.16 mg/kg and <0.01-0.04 mg/kg in brown rice. The ratio of XMC to MPMC content in the rice husk differed from the original 50% dimethacarb EC, indicating the difference in the degradation rate of XMC and MPMC. The estimated risk quotient (RQ) for both XMC and MPMC was less than 30%. These data for residues from six representative locations could provide a reference for establishing the MRL of dimethacarb in rice.

Circular suture of the uterine serosa and myometrium layer around placental attachment site for refractory postpartum hemorrhage.

OBJECTIVE: The aim of the study was to analyze the clinical outcomes of circular suture at placental attachment site for refractory postpartum hemorrhage (PPH), which could block blood supply of the serosa and myometrium layer. METHODS: Eighty cases of refractory PPH were enrolled and retrospective analyzed in this study for further analysis from a consecutive single center database between 2010 and 2018. After undergoing circular suture of the uterine serosa and myometrium layer around placental attachment site, surgical and perioperative outcomes were recorded and analyzed. RESULTS: Among all the patients enrolled, 28 cases (35.0%) of refractory PPH were mainly caused by uterine inertia, 36 cases (45.0%) caused by ectopic placenta, and 2 cases (2.5%) caused by coagulation disorders. After circular suture of the uterine serosa and myometrium layer at placental attachment site, all the uterine active bleeding was controlled below 40 ml without recurrence. The perioperative results were similar between the vaginal and cesarean sections groups. CONCLUSIONS: Circular suture of the uterine serosa and myometrium at the placental attachment site could control refractory PPH with few postoperative complications. Circular suture around placenta site could be applied in time to protect the endometrium even in primary hospital.

Characterization of a carboxylesterase with hyper-thermostability and alkali-stability from Streptomyces lividans TK24.

A gene (estA', 804 bp) from Streptomyces lividans TK24 was artificially synthesized and successfully overexpressed as a 6His-tagged fusion protein in Escherichia coli. It encoded a carboxylesterase (EstA) that composed of 267 amino acids with a predicted molecular weight of 28.56 kDa. Multiple sequence alignment indicated that EstA has typical characteristics of esterases, including a catalytic triad (Ser93-Asp194-His224) and a conserved pentapeptide motif (Gly91-Leu92-Ser93-Met94-Gly95). Simultaneously, phylogenetic analysis indicated that EstA belongs to family VI. Biochemical characterization displayed its optimum enzyme activity was at 55 â„ƒ and pH 8.5. Additionally, EstA exhibited higher activity towards short carbon substrates and showed the outstanding catalytic efficiency for pNPA2 with kcat/Km of 2296.14 ± 10.35 s-1 mM-1. Notably, EstA has hyper-thermostability and good alkali stability. The activity of EstA did not change obviously when incubated at 50 and 100 â„ƒ for 337 and 1 h, independently. Besides, by incubating at 100 â„ƒ for 6 h, EstA remained about half of its initial activity. Moreover, EstA showed stability at pH ranging from 8.0 to 11.0, and about 90% residual enzyme activity was reserved by being treated at pH 8.0 or 9.0 for 80 h, especially. Such multiple features prepare EstA for a potential candidate in the field of biological catalysis of some industrial applications under harsh conditions.

Morphological diversity of the metathoracic spiracle in the Lygaeoidea (Hemiptera: Heteroptera).

Spiracles are the openings in the exoskeleton of insects through which air enters into the respiratory system that is formed by a series of tubes called tracheae. They are primarily located on the abdomen, but can also occur on the thorax, including the metathorax. An insect metathoracic spiracle is usually composed of an external opening and a more internal filter apparatus. We propose new terminology for these structures, and we explore the value in their use in taxonomic and phylogenetic studies within the true bug infraorder Pentatomomorpha, with emphasis on the superfamily Lygaeoidea (Insecta: Hemiptera: Heteroptera). These structures were studied using scanning electron microscopy. Two types of metathoracic spiracle external openings were recognized: a narrow opening (type N), which is slit-like; and a wide opening (type W), with internal fine structures located between the mesothoracic and metathoracic margins of the interpleural suture clearly visible. The filter apparatus in the Pentatomomorpha consists of modified mushroom bodies of the metathoracic scent gland evaporatorium, for which the term mycoid filter processes is proposed. Eight different types of mycoid filter processes, and an unmodified microsculpture type (a type with usual cuticular microsculpture) and filter setae can be found on the anterior or posterior margins of the metathoracic spiracle. We believe the wide opening (type W) to be the plesiomorphic character state in the Pentatomomorpha, with multiple, independent transformations leading to the narrow opening in Lygaeoidea. Considerable variability in the structure of the spiracle opening (in Lygaeoidea), and in the structure of the mycoid filter processes (in Pentatomomorpha) was detected. Overall, we found the morphology of these structures to be of limited value concerning the taxonomy or for determining phylogenetic relationships of the higher taxa (families) of Pentatomomorpha, but they may be useful as additional evidence for taxonomic and phylogenetic studies at the generic and perhaps the tribal levels.

Combining newborn metabolic and genetic screening for neonatal intrahepatic cholestasis caused by citrin deficiency.

To evaluate the feasibility of incorporating genetic screening for neonatal intrahepatic cholestasis, caused by citrin deficiency (NICCD), into the current newborn screening (NBS) program. We designed a high-throughput iPLEX genotyping assay to detect 28 SLC25A13 mutations in the Chinese population. From March 2018 to June 2018, 237 630 newborns were screened by tandem mass spectrometry at six hospitals. Newborns with citrulline levels between 1/2 cutoff and cutoff values of the upper limit were recruited for genetic screening using the newly developed assay. The sensitivity and specificity of the iPLEX genotyping assay both reached 100% in clinical practice. Overall, 29 364 (12.4%) newborns received further genetic screening. Five patients with conclusive genotypes were successfully identified. The most common SLC25A13 mutation was c.851_854del, with an allele frequency of 60%. In total, 658 individuals with one mutant allele were identified as carriers. Eighteen different mutations were observed, yielding a carrier rate of 1/45. Notably, Quanzhou in southern China had a carrier rate of up to 1/28, whereas Jining in northern China had a carrier rate higher than that of other southern and border cities. The high throughput iPLEX genotyping assay is an effective and reliable approach for NICCD genotyping. The combined genetic screening could identify an additional subgroup of patients with NICCD, undetectable by conventional NBS. Therefore, this study demonstrates the viability of incorporating genetic screening for NICCD into the current NBS program.

Newborn Screening for Spinal Muscular Atrophy in China Using DNA Mass Spectrometry.

Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disorder and the leading genetic cause of infant mortality. Early detection of SMA through newborn screening (NBS) is essential to selecting pre-symptomatic treatment and ensuring optimal outcome, as well as, prompting the urgent need for effective screening methods. This study aimed to determine the feasibility of applying an Agena iPLEX SMA assay in NBS for SMA in China. Methods: We developed an Agena iPLEX SMA assay based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and evaluated the performance of this assay through assessment of 167 previously-genotyped samples. Then we conducted a pilot study to apply this assay for SMA NBS. The SMN1 and SMN2 copy number of screen-positive patients were determined by multiplex ligation-dependent probe amplification analysis. Results: The sensitivity and specificity of the Agena iPLEX SMA assay were both 100%. Three patients with homozygous SMN1 deletion were successfully identified and conformed by multiplex ligation-dependent probe amplification analysis. Two patients had two SMN2 copies, which was correlated with severe SMA type I phenotype; both of them exhibited neurogenic lesion and with decreased muscle power. Another patient with four SMN2 copies, whose genotype correlated with milder SMA type III or IV phenotype, had normal growth and development without clinical symptoms. Conclusions: The Agena iPLEX SMA assay is an effective and reliable approach for population-based SMA NBS. The first large-scale pilot study using this assay in the Mainland of China showed that large-scale implementation of population-based NBS for SMA is feasible.

Exosomal MicroRNAs Derived from Human Amniotic Epithelial Cells Accelerate Wound Healing by Promoting the Proliferation and Migration of Fibroblasts.

Previous work in our laboratory demonstrated that exosomes derived from human amniotic epithelial cells (hAECs) accelerated wound healing by promoting the proliferation and migration of fibroblasts. It is reported that exosomes, which are carriers of the microRNAs (miRNAs) and proteins, play an important role in the regulation of cell-to-cell communication. However, it is still unclear precisely which molecule or which group of molecules carried within hAEC-derived exosomes (hAEC-Exos) mediated wound healing. Here, we explored purified hAEC-Exos together with either proteinase K (PROse) or RNase A on the effect of fibroblasts and cutaneous wound healing. Our experiments demonstrated that hAEC-Exos were positive for exosomal markers CD9, CD63, and CD81. Also, we found that hAEC-Exos could be internalized by fibroblasts and then stimulated cell migration and proliferation. However, the promotive effect of hAEC-Exos was abolished by pretreating hAEC-Exos with RNase A, not PROse. Importantly, in vivo wound healing assay showed that local injection of hAEC-Exos or PROse pretreated hAEC-Exos at skin wounds significantly accelerated wound healing. Our findings revealed an important role of exosomal miRNAs in wound healing.