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1.
Biomed Chromatogr ; : e4805, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012315

RESUMO

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating nonalcoholic fatty liver disease (NAFLD) in China, composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF are still indistinct to date. Thus, a high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF) method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed into rats, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first time to explore the constituents of QHF and its metabolism in vivo and in vitro, which realize the first step to clarify the chemical basis of QHF qualitatively, and lay the foundation for further research on the anti-NAFLD mechanism of QHF.

2.
Angiology ; : 3319719900734, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013527

RESUMO

We evaluated the relationship between serum bilirubin levels and ankle-brachial index (ABI) to determine whether gender affected the relationship between bilirubin levels and peripheral arterial disease (PAD) in patients with hypertension. A total of 543 patients were included in our studies (78 patients with PAD and 465 without PAD). Peripheral arterial disease was defined as ABI <0.90 for either and/or both sides. Serum bilirubin levels were measured with a vanadate oxidation method by using fasting venous blood samples. Serum total bilirubin (TBiL) and direct bilirubin (DBiL) levels were higher in males compared with females (both P < .05). Total bilirubin and DBiL were significantly lower in the PAD group. After adjustment for cardiovascular risk factors, PAD was independently negatively related to TBiL and DBiL, with odds ratios (OR) 0.914 (95% confidence interval [CI]: 0.845-0.990) and 0.748 (95% CI: 0.572-0.977). In addition, there was a relationship between PAD and bilirubin levels (TBiL-OR = 0.884, 95% CI: 0.792-0.985; DBiL-OR = 0.621; 95% CI: 0.424-0.909) only in males but not in females. Future studies should further evaluate whether interventions that increase serum bilirubin levels will have a particular role in PAD prevention in males.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32028114

RESUMO

For the purpose of obtaining a more comprehensive flavor profile, volatile compounds in traditional Chinese dry-cured hams were studied by dual-fiber solid-phase microextraction (SPME) using two fibers simultaneously. By using the selected pair of fibers and under the optimal extraction time, there were total seventy-two volatile compounds identified, which was higher than the mono-fiber SPME method using a single fiber. Out of the seventy-two compounds, twenty-six compounds were not detected by using mono-fiber SPME and five among them are classified as the major aromatic compounds in the literatures. Due to the higher coverage and less tendency for the occurrence of competition among the volatiles, the total amount of volatiles extracted by dual-fiber SPME (510.02 ng/kg) was higher than mono-fiber SPME. Three grades of dry-cured hams were successfully distinguished based on dual-fiber SPME. The volatile compounds belonged to nine chemical families and differed in different grades of dry-cured hams. These results show that dual-fiber SPME is capable of analyzing flavor profiles more comprehensively and distinguishing traditional Chinese dry-cured hams.

6.
BMC Genomics ; 21(1): 103, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000663

RESUMO

BACKGROUND: Luman is a member of CREB3 (cAMP responsive element-binding) subfamily of the basic leucine-zipper (bZIP) transcription factors. It may play an important regulatory role during the decidualization process since Luman was highly expressed in the decidual cells. However, the exact molecular mechanisms of how Luman regulating decidualization is unknown. RESULTS: Using an in vitro model, we prove that Luman knockdown significantly affects the decidualization process of mice endometrial stromal cells (ESCs) as the expression of two decidual markers PRL8a2 and PRL3c1 were repressed. We employed massively parallel RNA sequencing (RNA-Seq) to understand the changes in the transcriptional landscape associated with knockdown of Luman in ESCs during in vitro decidualization. We found significant dysregulation of genes related to protein processing in the endoplasmic reticulum (ER). Several genes involved in decidualization including bone morphogenetic proteins (e.g. BMP1, BMP4, BMP8A, BMP2, and BMP8B), growth factor-related genes (e.g. VEGFB, FGF10, and FGFR2), and transcription factors (IF4E, IF4A2, WNT4, WNT9A, ETS1, NOTCH1, IRX1, IDB1, IDB2, and IDB3), show altered expression. We also found that the knockdown of Luman is associated with increased expression of cell cycle-related genes including cycA1, cycB1, cycB2, CDK1, CDK2, and PLPK1, which resulted in an increased proportion of ESCs in the G1 phase. Differentially expressed genes (DEGs) were highly enriched on ECM-receptor interaction signaling, endoplasmic reticulum protein processing, focal adhesion, and PI3K-Akt signaling pathways. CONCLUSIONS: Luman knockdown results in widespread gene dysregulation during decidualization of ESCs. Genes involved in protein processing in ER, bone morphogenetic protein, growth factor, and cell cycle progression were identified as particularly important for explaining the decidual deficiency observed in this in vitro model. Therefore, this study provides clues as to the underlying mechanisms that may expand our understanding of gene regulation during decidualization.

7.
Cells ; 9(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023857

RESUMO

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 µM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

8.
Hepatology ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048304

RESUMO

Liver fibrosis is a central pathological process that occurs in most types of chronic liver diseases. Advanced liver fibrosis causes cirrhosis, hepatocellular carcinoma, and liver failure. However, the exact molecular mechanisms underlying the initiation and progression of liver fibrosis remain largely unknown. This study was designed to investigate the role of protein kinase D3 (PKD3, gene name Prkd3) in the regulation of liver homeostasis. We generated global Prkd3 knockout (Prkd3-/- ) mice and myeloid cell-specific Prkd3 knockout (Prkd3∆LysM ) mice, and we found that both Prkd3-/- mice and Prkd3∆LysM mice displayed spontaneous liver fibrosis. PKD3 deficiency also aggravated carbon tetrachloride (CCL4)-induced liver fibrosis. PKD3 is highly expressed in hepatic macrophages, and PKD3 deficiency skewed macrophage polarization toward a profibrotic phenotype. The activated profibrotic macrophages produced TGF-ß that in turn activates hepatic stellate cells (HSCs) to become matrix-producing myofibroblasts. Moreover, PKD3 deficiency decreased the phosphatase activity of SHP1 (a bona fide PKD3 substrate) resulting in sustained STAT6 activation in macrophages. In addition, we observed that PKD3 expression in hepatic macrophages was downregulated in cirrhotic human liver tissues. Conclusion: PKD3 deletion in mice drives liver fibrosis through the profibrotic macrophage activation.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32008991

RESUMO

PURPOSE: First branchial cleft fistula/sinus is a rare congenital developmental deformity that can sometimes be acquired from incision and drainage of a branchial cleft cyst. The aim of the present study was to explore the clinical manifestations, diagnosis, and surgical management of first branchial cleft fistula/sinus in both a large patient series and a review of the pertinent literature. MATERIALS AND METHODS: The data from 31 cases diagnosed from February 2004 to April 2019 as first branchial cleft fistula/sinus were retrospectively reviewed. The patient demographic data and outcomes were explored. In addition, we performed a literature review of studies reported from 1923 to 2018 for first branchial cleft fistula/sinus and summarized those results. RESULTS: The present study included 31 patients (15 males, 16 females) with a median age of 4 years. All the patients reviewed had presented with a unilateral first branchial cleft fistula/sinus. The parotid region was the most frequent site of presentation (41.9%) in these cases. The fistula/sinus had occurred on the left side in 13 patients (41.9%) and on the right side in 18 patients (58.1%). Of the 31 patients, 24 (77.4%) had acquired the disease from infection of an existing brachial cleft cyst or incomplete previous excision. Of the 31 cases, 28 (90%) had an intimate relationship between the tract and the facial nerve. Despite this close association, no patient developed postoperative facial nerve palsy. Of the 31 operations, 30 (97%) successfully accomplished complete resection with no recurrence postoperatively. Only 1 patient with a history of multiple recurrences experienced a subsequent recurrence, which was successfully treated with a second surgery. CONCLUSIONS: First branchial cleft fistula/sinus is a frequently misdiagnosed and, therefore, undertreated entity, which leads to recurrence. It is closely associated with the facial nerve and extra auditory canal. The correct diagnosis and meticulous removal can be effectively achieved with minimal risk to the facial nerve.

10.
Biomed Chromatogr ; : e4810, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043607

RESUMO

Rifampicin is a semi-synthetic broad-spectrum antibiotic obtained from rifamycin B. It is one of the most effective first-line anti-tuberculosis drugs widely used in clinical practice. In the present study, we described a rapid and sensitive method for the determination of rifampin in aquatic products by stable isotope-dilution high liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Samples were extracted with the acetonitrile, degreased by hexane, and then concentrated by nitrogen blowing. After separation by C18 column with mixture of acetonitrile and water as mobile phase, it was determined by HPLC-MS/MS with stable isotope-dilution calibration method. The performance of our method was validated. The limit of detection (LOD) was 0.25 µg kg-1 and the limit of quantification (LOQ) was 0.5 µg kg-1 . At the three spiked levels of 0.5, 1.0 and 5.0 µg kg-1 , the average recoveries of rifampicin in different aquatic products were between 75.28% and 107.6%, and the relative standard deviation ranged from 0.81% to 13.23%. This method was successfully applied for the determination of rifampin in different kinds of aquatic products and rifampicin residue was found in aquatic products obtained from markets in Beijing, China.

11.
Sci Rep ; 10(1): 2431, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051450

RESUMO

Mandrill (Mandrillus sphinx) is a primate species, which belongs to the Old World monkey (Cercopithecidae) family. It is closely related to human, serving as a model for human health related research. However, the genetic studies on and genomic resources of mandrill are limited, especially in comparison to other primate species. Here we produced 284 Gb data, providing 96-fold coverage (considering the estimated genome size of 2.9 Gb), to construct a reference genome for the mandrill. The assembled draft genome was 2.79 Gb with contig N50 of 20.48 Kb and scaffold N50 of 3.56 Mb. We annotated the mandrill genome to find 43.83% repeat elements, as well as 21,906 protein-coding genes. The draft genome was of good quality with 98% gene annotation coverage by Benchmarking Universal Single-Copy Orthologs (BUSCO). Based on comparative genomic analyses of  the Major Histocompatibility Complex (MHC) of the immune system in mandrill and human, we found that 17 genes in the mandrill that have been associated with disease phenotypes in human such as Lung cancer, cranial volume and asthma, barbored amino acids changing mutations. Gene family analyses revealed expansion of several genes, and several genes associated with stress environmental adaptation and innate immunity responses exhibited signatures of positive selection. In summary, we established the first draft genome of  the mandrill of value for studies on evolution and human health.

12.
Sci Rep ; 10(1): 2432, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051459

RESUMO

The binary blend materials containing the modified recycled rubber powder with maleic a hydride modified polypropylene thermoplastic elastomer were prepared by dynamic vulcanization and blended with a variety of additives such as activated agent, accelerator, solubilizer, and the crosslinking agent. The thermal properties and mechanical properties including tensile strengths and impact strengths of pristine rubber, polypropylene and their corresponding binary blends were investigated. Besides, the effects of the amount of rubber powder, polypropylene, crosslinking agent, accelerator, activator, and solvent were studied and the microstructures of the pristine rubber, pristine polypropylene, and their corresponding binary blends were observed by scanning electron microscopy. It was found that the compatibilizer could effectively disperse the size of 120 mesh of recycled rubber powder into the polypropylene in the same manner and the homogeneous tear section of the rubber/polypropylene thermoplastic elastomer was obtained. The results on the effects of additives on mechanical and morphological properties of recycled rubber/polypropylene binary blends guide the rational design of novel polymeric composites from recycled polymeric materials.

13.
Ecotoxicol Environ Saf ; 191: 110236, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001424

RESUMO

Copper (Cu), a transition metal, is an essential trace element in human and animal nutrition at low concentration, but Cu has toxic effects on tissues and organs at high concentration. Endoplasmic reticulum (ER) is a toxicological target in Cu poison. Thus far, no studies have focused on the relationship among copper, endoplasmic reticulum (ER) stress and apoptosis in animal and human livers. In the present study, mice treated with copper sulfate (CuSO4) were used to assess the impacts of copper on ER stress and hepatic apoptosis. A total of 240 mice were orally administered with 0 (control), 10, 20 and 40 mg/kg of CuSO4 for 42 days. The results indicated that CuSO4 at 10 mg/kg markedly induced hepatocyte apoptosis and ER stress. In addition, ER stress was characterized by the increased mRNA and protein levels of glucose-regulated protein 78 (GRP78) and 94 (GRP94). Furthermore, ER stress-triggered 3 apoptotic pathways were also activated by the increased intracellular calcium and up-regulated expression levels of genes involved in growth arrest- and DNA damage-inducible gene 153 (Gadd153/CHOP), c-Jun N-terminal kinase (JNK) and cysteine aspartate-specific protease 12 (caspase-12) signaling pathways in CuSO4-treated mice. In conclusion, CuSO4-induced ER stress can promote hepatic apoptosis in mice by activating CHOP, JNK and caspase-12 signaling pathways.

14.
Elife ; 92020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031521

RESUMO

Genome wide association studies for non-syndromic orofacial cleft (OFC) have identified single nucleotide polymorphisms (SNPs) at loci where the presumed risk-relevant gene is expressed in oral periderm. The functional subsets of such SNPs are difficult to predict because the sequence underpinnings of periderm enhancers are unknown. We applied ATAC-seq to models of human palate periderm, including zebrafish periderm, mouse embryonic palate epithelia, and a human oral epithelium cell line, and to complementary mesenchymal cell types. We identified sets of enhancers specific to the epithelial cells and trained gapped-kmer support-vector-machine classifiers on these sets. We used the classifiers to predict the effect of 14 OFC-associated SNPs at 12q13 near KRT18. All the classifiers picked the same SNP as having the strongest effect, but the significance was highest with the classifier trained on zebrafish periderm. Reporter and deletion analyses support this SNP as lying within a periderm enhancer regulating KRT18/KRT8 expression.

15.
Mol Nutr Food Res ; : e1900535, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914235

RESUMO

SCOPE: Recent findings indicate that ketogenic diet is neuroprotective and electrical stimulation can improve functional recovery from peripheral nerve injury. However, it is not clear whether ketogenic diet and electrical stimulation play synergistical role in the peripheral nerve recovery following injury. METHODS AND RESULTS: We used ketogenic diet consisting of 3:1 ratio of fat to carbohydrate+protein and coupled it with electrical stimulation treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery was evaluated by electromyography, and axonal regeneration and myelination by histological methods. We also investigated the effects on IGF-1 and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury. Combination of ketogenic diet and electrical stimulation synergistically increased muscle force in biceps femoris and gluteus maximus and prevented development of hypersensitivity in biceps femoris. It promoted peripheral nerve regeneration by increasing total axons, axons density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects were due to modulation of IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue. CONCLUSION: Our results establish that ketogenic diet and electrical stimulation promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach. This article is protected by copyright. All rights reserved.

16.
BMC Neurosci ; 21(1): 1, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941442

RESUMO

BACKGROUND: Depression is characterized by significant and low mood. Classical antidepressants are still not adequate in treating depression because of undesirable side effects. Folic acid, a member of the vitamin B complex, in considered to be strongly associated with the function and development of the central nervous system. Thus, in this study, we established a model of depression through chronic unpredictable mild stress (CUMS) in rats and assessed the antidepressant effects and mechanisms of folic acid. METHODS: Sprague-Dawley rats were randomly divided into four groups: control, chronic unpredictable mild stress (CUMS), CUMS treated with folic acid, and CUMS treated with citalopram. Rats were assessed in terms of weight change, open-field test and sucrose preference. Homocysteine, monoamine neurotransmitters, interleukin-6, brain-derived neurotrophic factor (BDNF), ß-endorphin levels in the serum and brains of rats were analysed. RESULTS: Folic acid exhibited antidepressant-like effects in open-field and sucrose preference tests. Folic acid treatment effectively increased the levels of monoamine neurotransmitters, BDNF and ß-endorphin, interleukin-6 and homocysteine levels were also significantly suppressed by folic acid administration. CONCLUSIONS: These findings serve as preclinical evidence that folic acid plays an antidepressant-like role in several pathways involving monoamine neurotransmitters. Thus, folic acid may be used as a potential antidepressant.

17.
J Biochem Mol Toxicol ; : e22444, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954379

RESUMO

Smoking is associated with an increased risk of respiratory diseases, including lung cancer and asthma. However, the mechanisms or diagnostic markers for smoking-related diseases remain largely unknown. Here we investigated the role of cigarette smoke condensate (CSC) in the regulation of human bronchial epithelial cell (BEAS-2B) behavior. We found that exposure to CSC significantly inhibited BEAS-2B cell viability, impaired cell morphology, induced cell apoptosis, triggered oxidative damage, and promoted inflammatory response, which suggests a deleterious effect of CSC on bronchial epithelial cells. In addition, CSC markedly altered the expression of apoptosis-associated protein factors, including p21, soluble tumor necrosis factor receptor 1, and Fas ligand. In sum, our study identified a panel of novel protein factors that may mediate the actions of CSC on bronchial epithelial cells and have a predictive value for the development and progression of smoking-related diseases, thus providing insights into the development of potential diagnostic and therapeutic strategies against these diseases.

18.
Anal Chim Acta ; 1099: 39-45, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-31986275

RESUMO

Malachite Green (MG), a cationic triphenylmethane dye, has adverse effects on the immune and reproductive system. Thus, it is essential to develop a rapid, sensitive and high-selective method for determination of MG. Black phosphorus (BP) has high charge-carrier mobility (∼1000 cm2 V-1 s-1) and high adsorption capacity for cationic dyes (i.e. MG) through both electrostatic and hydrophobic interactions. Thus, it potentially plays as a high-sensitive sensing platform for detecting MG. However, BP degrades within 12 h under humid condition, which limits its applications. To overcome this issue, cysteine (CYS) is used for protecting BP from oxidation and ceasing its degradation. To the best of our knowledge, it is the first time that CYS is used to functionalize BP, and a silicon interdigital electrode is fabricated with the functionalized BP and aptamer. The BP-based interdigital electrode shows a lowest detection limit of 0.3 ng L-1 toward MG. This work provides a new route to prepare a large scale and selective biosensor for MG monitoring on site in future.

19.
Comp Biochem Physiol C Toxicol Pharmacol ; 230: 108701, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911191

RESUMO

Environmental endocrine disruptors 4-nonylphenol (NP) and 4-tert-octylphenol (OP) may cast huge harm to human health. We used a rat model to observe the influence of NP or/and OP exposure on anxiety-related behaviors and the underlying mechanisms. Eighty male Sprague-Dawley (SD) rats were randomly divided into 10 groups: control group (corn oil), NP groups [30, 90, 270 mg/kg], OP groups [40, 120, 360 mg/kg] and NO groups [(mixed with the corresponding NP, OP alone exposed low, medium and high dose according to the natural environment exists NP:OP = 4:1]. The rats were orally administered every other day for 30 days. The neurobehaviors of rats were evaluated by open-field test (OFT) and elevated plus-maze test (EPM), and the concentrations of 5-HT, monoamine oxidase (MAOA), serotonin transporter (SERT), vesicular monoamine transporter 2 (VAMT2), 5-hydroxytryptamine 1A (5-HT1A), 5-hydroxytryptamine 2A (5-HT2A),and 5-hydroxytryptamine 2C (5-HT2C) in the rat prefrontal cortex were analyzed by ELISA. OFT and EPM tests showed that NP or/and OP exposure induced anxiety-related behaviors in rats. 5-HT levels were significantly increased compared with the control group. The levels of MAOA, SERT, VAMT2, 5-HT1A, 5-HT2A, and 5-HT2C in the prefrontal cortex reduced in different degrees by high-doses NP or/and OP exposure. In summary, NP or/and OP exposure might cause anxiety-related behaviors in rats through regulating neurotransmitter 5-HT levels by altering the expression of 5-HT decomposition enzyme MAOA, transporters SERT and VMAT2, and 5-HT receptors 5-HT1A, 5-HT2A, and 5-HT2C.

20.
Autophagy ; : 1-16, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31959090

RESUMO

Mesenchymal stem cell (MSC) transplantation has been widely applied as a potential therapeutic for multiple diseases. However, the underlying therapeutic mechanisms are not fully understood, especially the paradox between the low survival rate of transplanted cells and the beneficial therapeutic effects generated by these cells. Herein, in a myocardial infarction (MI) model, we found that transplanted MSCs released apoptotic bodies (ABs) to enhance angiogenesis and improve cardiac functional recovery via regulating macroautophagy/autophagy in the recipient endothelial cells (ECs). Mechanistically, after local transplantation, MSCs underwent extensive apoptosis in the short term and released ABs, which were engulfed by the recipient ECs. Then, in the ECs, ABs activated lysosome functions and promoted the expression of TFEB (transcription factor EB), which is a master gene in lysosomal biogenesis and autophagy. Finally, the increase in TFEB enhanced autophagy-related gene expression in ECs and promoted angiogenesis and cardiac functional recovery after MI. Collectively, we found that apoptotic donor MSCs promote angiogenesis via regulating autophagy in the recipient ECs, unveiling the role of donor cell apoptosis in the therapeutic effects generated by cell transplantation.Abbreviations: 3-MA: 3-methyladenine; ABs: apoptotic bodies; BECN1: beclin 1; CASP3: caspase 3; CQ: chloroquine; ECs: endothelial cells; EVs: extracellular vesicles; LAMP1: lysosomal-associated membrane protein 1; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MI: myocardial infarction; MSC: mesenchymal stem cell; NO: nitric oxide; TFEB: transcription factor EB; TUNEL: TdT-mediated dUTP Nick-End Labeling.

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