A molecular container providing supramolecular protection against acetylcholine hydrolysis.

Alzheimer's disease (AD) is characterized by cognitive decline, often attributed to the deficiency of acetylcholine, which can undergo hydrolysis by acetylcholinesterase (AChE) within the biological milieu. Here, we report a supramolecular strategy that takes advantage of confinement effects to inhibit such a hydrolysis process, shedding some light on AD therapy. A water-soluble and bowl-shaped molecule, hexacarboxylated tribenzotriquinacene (TBTQ-C6), was employed to shield acetylcholine (G1) from enzymatic degradation through host-guest binding interactions. Our study revealed highly efficient host-guest interactions with a binding ratio of 1 : 3, resulting in a significant reduction in acetylcholine hydrolysis from 91.1% to 7.4% in the presence of AChE under otherwise identical conditions. Furthermore, TBTQ-C6 showed potential for attenuating the degradation of butyrylcholine (G2) by butyrylcholinesterase (BChE). The broader implications of this study extend to the potential use of molecular containers in various biochemical and pharmacological applications, opening new avenues for research in the field of neurodegenerative diseases.

Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis.

BACKGROUND: Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. METHODS: Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. RESULTS: Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a "ceRNA" for miR-4659a/b-3p to increase HBEGF and TGF-ß/Smad expression, then promoted the development of GC. CONCLUSIONS: Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-ß/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Facile production of cellulose nanofibers from raw elephant grass by an aluminum chloride-enhanced acidic deep eutectic solvent.

To develop a greener and more efficient method for producing cellulose nanofibers (CNFs) from raw plants, an AlCl3-enhanced ternary deep eutectic solvent, DES2 (consisting of choline chloride, citric acid, and AlCl3·6H2O in a molar ratio of 1:0.4:0.08), was synthesized. Raw elephant grass (EG) was pretreated with DES2, followed by sodium chlorite (NaClO2) bleaching and ultrasonic disruption to extract high-performance CNFs. The DES2 and NaClO2 treatments effectively removed hemicellulose and lignin, achieving removal rates of 99.23 % and 99.62 %, respectively, while maintaining a cellulose content of 78.3 %. DES2 demonstrated easy recyclability and maintained excellent biomass pretreatment performance even after multiple cycles. Following a brief 30-min intermittent ultrasound treatment, the resulting CNFs demonstrated superior crystallinity, increased carboxyl content, and a narrower width distribution compared to CNFs obtained from AlCl3-free DES1. Optimized conditions at 110 °C yielded CNFs with 85.3 % crystallinity, 0.64 mmol/g carboxyl content, 5.15 nm width distribution, and excellent dispersion in water for at least six months. Additionally, CNFs enhanced the tensile strength of chia seed mucilage (CM) composite films, showing a significant improvement to 26.6 MPa, representing a 231.3 % increase over the control film. This study offers a promising approach for efficiently producing CNFs from raw plants.

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene.

We synthesized a new tetraphenylethylene-modified chitosan bioconjugate, CS-TPE, that shows the aggregation-induced emission effect. It can self-assemble into fluorescent polymeric nanoparticles in an aqueous solution at pH 5.3 either alone or with the water-soluble bowl-shaped six-fold carboxylated tribenzotriquinacene derivative TBTQ-C6 via host-guest binding. The spherical nanoparticles formed by CS-TPE amphiphiles or TBTQ-C6/CS-TPE supra-amphiphiles disintegrated under alkaline stimulation at pH 10.4 and the dispersion of the aggregates after the collapse in the presence of TBTQ-C6 was greatly improved. In addition, the fluorescence of CS-TPE was significantly enhanced by introducing TBTQ-C6, and remained relatively stable with variations in pH for both CS-TPE and TBTQ-C6/CS-TPE. Such pH-responsive supramolecular spherical nanoparticles with stable fluorescence emission based on CS-TPE or TBTQ-C6/CS-TPE may find applications in various fields, including the development of visual oral drug delivery systems.

Facile production of chitin from shrimp shells using a deep eutectic solvent and acetic acid.

High purity chitin was extracted from shrimp shells by a green, sustainable, and efficient one-pot approach using a deep eutectic solvent consisting of choline chloride and glycerol (ChCl-Gl) combined with a small amount of acetic acid. Under the conditions of an acetic acid concentration of 7.5 wt% and reaction temperature of 120 °C, the purity of isolated chitin was up to 96.1%, which was superior to that of 87.7% obtained by conventional chemical method. In addition, the viscosity-average molecular weight and crystallinity of the extracted chitin were revealed to be larger than for the latter. Moreover, the deep eutectic solvent could be recycled at least three times without losing the quality of the extracted chitin. This facile approach combining recyclable DES with a small amount of acetic acid was expected to be used for the green and sustainable production of chitin from shrimp shells.

Development of active packaging films based on liquefied shrimp shell chitin and polyvinyl alcohol containing ß-cyclodextrin/cinnamaldehyde inclusion.

To maintain the freshness of fruits and to meet environmental and consumer needs, a biobased packaging film with long-lasting antimicrobial activity was developed in this article. Liquefied ball-milled shrimp shell chitin/polyvinyl alcohol (LBSC/PVA) blend films containing varying concentrations (0, 1, 2, 3, 4, 5 wt%) of the ß-cyclodextrin/cinnamaldehyde (ß-CD/CA) inclusion were prepared and characterized. The association between ß-CD and CA and the sustained release behavior of CA were explored. The physicochemical property, antimicrobial activity and food preservation performance of the films were investigated. Results showed that CA was successfully encapsulated into the cavity of CD by host-guest interactions, which greatly improved the sustained release of CA. The 3 wt% ß-CD/CA/LBSC/PVA blend film showed optimized mechanical properties with a tensile strength of 41.5 MPa and an elongation at break of 810 %. In addition, the incorporation of ß-CD/CA inclusion significantly enhanced the antimicrobial activity and food preservation performance of the blend films. Moreover, the 3 wt% ß-CD/CA/LBSC/PVA blend film exhibited evidently longer lasting antimicrobial activity and cherry tomato preservation performance than the 3 wt% CA/LBSC/PVA blend film, further demonstrating the critical role of ß-CD in delaying CA release. These novel ß-CD/CA/LBSC/PVA blend films may have a potential use in active food packaging.

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host-guest interaction for drug delivery.

A new water-soluble hexacarboxylated tribenzotriquinacene derivative (TBTQ-CB6) was synthesized and used as a supramolecular drug carrier to load the model anticancer drugs dimethyl viologen (MV) and doxorubicin (DOX) via host-guest interactions. The drugs could be effectively released by spermine (SM), a molecule overexpressed in cancer cells, through host-guest competitive substitution since TBTQ-CB6 has a stronger binding affinity toward SM than MV and DOX. The host-guest interactions of the complexes of TBTQ-CB6 with MV, DOX and SM were investigated by NMR spectroscopy and fluorescence spectroscopy. The association stoichiometry of the complexes of TBTQ-CB6 with MV, DOX, and SM was found to be 1:1 with association constants of K a = (7.67 ± 0.34) × 104 M-1, K a = (6.81 ± 0.33) × 104 M-1, and K a = (5.09 ± 0.98) × 105 M-1, respectively. The competitive substitution process was visualized by NMR titration. This novel TBTQ-based host-guest drug delivery system may have potential use in supramolecular chemotherapy.

Antioxidant and antibacterial properties of essential oils-loaded ß-cyclodextrin-epichlorohydrin oligomer and chitosan composite films.

Chitosan (CS) is becoming increasingly popular in food packaging due to its natural degradability and great film-forming properties. Nevertheless, its poor antibacterial properties and inadequate antioxidant properties prevent it from being used effectively. In this study, ß-cyclodextrin-epichlorohydrin (ß-CD-EP) oligomers were prepared and encapsulated with natural essential oils cinnamaldehyde and thymol, and then the inclusion complexes (IC) were incorporated into chitosan in various contents to afford a series of CS-IC composite films. The impacts of IC on the morphological, mechanical, thermal, and water resistance properties, antioxidant and antibacterial activities of chitosan films, as well as the loading and sustained release behavior of IC, were thoroughly examined. The results turned out that the essential oils were well-loaded with high encapsulation efficiency and showed a significant slow-release effect. It was also found that the tensile strength and the elongation at break decreased with increasing IC contents, while the thermal stability was enhanced. The incorporation of IC dramatically promoted the antioxidant and antibacterial properties of the chitosan films towards Gram-positive bacteria. Based on our findings, chitosan films containing essential oils-loaded ß-CD-EP oligomers may serve as an effective food packaging material.

hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis.

BACKGROUND: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. METHODS: In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. RESULTS: hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1ß, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. CONCLUSION: hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

Production of cellulose nanofibrils and films from elephant grass using deep eutectic solvents and a solid acid catalyst.

A new strategy was developed to produce cellulose nanofibrils (CNFs) and films from raw elephant grass using deep eutectic solvents and a recyclable spent coffee-derived solid acid (SC-SO3H) catalyst with assistance of ultrasonic disintegration and a suction filtration film forming method. The effects of a solid acid and reused solid acid were comprehensively studied by comparing with catalyst-free conditions and using sulfuric acid as the catalyst. The CNF fibers obtained from this novel SC-SO3H catalyst method showed the longest fiber length. The corresponding films achieved the strongest tensile strength of 79.8 MPa and the elongation at break of 13.6%, and best thermostability. In addition, the performance of CNFs and films prepared by the fourth recovered SC-SO3H-4 catalyst was close to that obtained with the first use. The SC-SO3H could be reused by a simple decantation method, meaning this novel method has the potential for green and sustainable preparation of CNFs and films.

Water-soluble host-guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres.

A sugar-functionalized water-soluble tribenzotriquinacene derivative bearing six glucose residues, TBTQ-(OG) 6 , was synthesized and its interaction with C60 and C70-fullerene in co-organic solvents and aqueous solution was investigated by fluorescence spectroscopy and ultraviolet-visible spectroscopy. The association stoichiometry of the complexes TBTQ-(OG) 6 with C60 and TBTQ-(OG) 6 with C70 was found to be 1:1 with binding constants of K a = (1.50 ± 0.10) × 105 M-1 and K a = (2.20 ± 0.16) × 105 M-1, respectively. The binding affinity between TBTQ-(OG) 6 and C60 was further verified by Raman spectroscopy. The geometry of the complex of TBTQ-(OG) 6 with C60 deduced from DFT calculations indicates that the driving force of the complexation is mainly due to the hydrophobic effect and to host-guest π-π interactions. Hydrophobic surface simulations showed that TBTQ-(OG) 6 and C60 forms an amphiphilic supramolecular host-guest complex, which further assembles to microspheres with diameters of 0.3-3.5 µm, as determined by scanning electron microscopy.

In situ generated silica reinforced polyvinyl alcohol/liquefied chitin biodegradable films for food packaging.

In previous report, polyvinyl alcohol/liquefied ball-milled chitin (PVA/LBMC) blend films with good antibacterial activity were successfully prepared. To further develop a biodegradable food packaging material, various amounts of nano-silica were introduced in situ by the hydrolysis of Na2SiO3 to give a series of silica-reinforced PVA/LBMC blend films. Their structure, morphology, mechanical and thermal properties, food preservation and degradation behavior in soil were comprehensively characterized. The results showed that when the content of Na2SiO3 was 0.2 wt %, the blend film 4PVA-LBMC-0.2Si displayed the optimized performance. Its tensile strength, and the maximum weight loss rate temperature reached 51 MPa and 307 ℃, respectively, which were significantly improved than those of silica-free film. The preservation tests of cherries showed its good fresh keeping performance. Although the degradation rate of silica-reinforced blend films in the soil was slightly decreased, it remained at a good level of 43 % after 30 days of burial.

Efficacy of low-dose D2/D3 partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study.

Objective: Some lines of evidence show that D2/D3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375-0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability. Methods: Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit. Results: SAS total scores decreased significantly during the study in patients with DIP (P<0.001), and mild AEs were detected. Treatments with pramipexole did not show an anti-akathisia effect during the study, while 2 subjects experienced deterioration of akathisia and mood symptoms. The psychiatric symptoms of schizophrenia showed a trend of improvement during the study, but there was no improvement in depressive mood. Conclusion: A low dose of pramipexole can significantly relieve antipsychotic-induced parkinsonism, but not akathisia. Improvements in psychiatric symptoms of schizophrenia were found, but the results of this study need to be validated in a larger sample. No improvement of mood disorder was detected.

Chitin and waste shrimp shells liquefaction and liquefied products/polyvinyl alcohol blend membranes.

Ball-milled chitin was liquefied with an optimal yield of 92% under sulfuric acid in diethylene glycol (DEG) at 160 °C for 120 min. The resulting liquid mixture was roughly separated into two portions: the real products of the reaction (liquefied ball-milled chitin, LBMC) and the remaining unreacted DEG. LBMC was further mingled with polyvinyl alcohol (PVA) to prepare LBMC/PVA blend membranes. To promote the direct utilization of shellfishery waste, raw shrimp shells were used to replace chitin for the liquefaction and membrane preparation operations. Liquefied ball-milled shrimp shells (LBMS) and the corresponding LBMS/PVA blend membranes were obtained. After adding LBMC or LBMS, the mechanical, thermal, water content and antibacterial performance of blend membranes were significantly improved compared to pure PVA membrane. Surprisingly, all the measured properties of LBMC/PVA and LBMS/PVA blend membranes were comparable, and even some properties of the latter were slightly superior than those of the former.

Enhanced oral bioavailability of fluvastatin by using nanosuspensions containing cyclodextrin.

BACKGROUND: In this study, fluvastatin (FVT) nanosuspensions containing cyclodextrin were developed to improve oral bioavailability. METHODS: FVT nanosuspensions containing cyclodextrin were prepared by a high pressure homogenization technique. The nanosuspensions system was then characterized by transmission electron microscopy (TEM), particle size, differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD). In addition, in vitro drug release properties, pharmacokinetics and pharmacodynamics were also investigated in detail. RESULTS: After lyophilization, the nanosuspensions could be redispersed gently and with a narrow particle size distribution, but the particle size has no obvious change. The powder X-ray diffraction and differential scanning calorimetry of FVT nanosuspensions showed that FVT existed in amorphous form in nanosuspensions. In vitro release, FVT nanosuspensions have sustained-release properties. Meanwhile, FVT nanosuspensions could significantly modify the pharmacokinetic profile and increase the bioavailability of FVT by more than 2.4-fold in comparison with the FVT capsules group. In vivo irritation test showed that there was almost no evidence of hemorrhagic mucosal erosion and intestinal villus destruction in rat gastric mucosa. CONCLUSION: The combination of nanocrystallization and cyclodextrin complexation techniques is a new attempt to formulate poorly water-soluble FVT.

Trachoma in Yunnan province of southwestern China: findings from trachoma rapid assessment.

BACKGROUND: To understand the situation of active trachoma among children aged 6 to 8 years old and scarring trachoma among those aged 15 and over in Yunnan Province, South-western China. METHODS: A rapid assessment of trachoma was conducted to determine the presence or absence of trachoma in Yunnan. Through risk assessment, 9 sites in 8 suspected trachoma epidemic counties were selected. Trachoma Rapid Assessment was conducted in these areas afterwards. Within each sites, 50 students from grade one in local primary school and adults aged 15 and above with suspected scarring trachoma were examined by survey teams. RESULTS: A total of 450 children aged 6-8 years and 160 adults aged 15 and above were screened in 9 sites of 8 counties. Only 1 case of active trachoma was found. Detection rate of active trachoma in children was 0.2%(1/450) in all sites and 2% (1/50)in Pingbian County. Out of 150 adults only 1 case of TT and 1 case of CO were found in all the highest at risk communities. People with scarring trachoma were aged over 60 years. CONCLUSIONS: The active trachoma was rarely seen and trachoma is unlikely to be a significant public health problem in Yunnan Province, South-western China.

Exosomes derived from human umbilical cord mesenchymal stem cells improve myocardial repair via upregulation of Smad7.

It has been previously reported that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC)­exosomes exhibit cardioprotective effects on the rat acute myocardial infarction (AMI) models and cardiomyocyte hypoxia injury models in vitro, however the exact mechanisms involved require further investigation. The present study aimed to investigate the repair effects of hucMSC­exosomes on myocardial injury via the regulation of mothers against decapentaplegic homolog 7 (Smad7) expression. Compared with sham or normoxia groups (in vivo and in vitro, respectively), western blotting demonstrated that Smad7 expression was significantly decreased in the borderline area of infraction myocardium and in H9C2(2­1) cells following hypoxia­induced injury. Additionally, microRNA (miR)­125b­5p expression was markedly increased using reverse transcription­quantitative polymerase chain reaction, but was reversed by hucMSC­exosomes. Trypan blue staining and lactate dehydrogenase release detection demonstrated that cell injury was significantly increased in the AMI + PBS and hypoxia group compared with in the sham and normoxia groups and was inhibited by hucMSC­exosomes. A dual luciferase reporter gene assay confirmed that Smad7 is a target gene of miR­125b­5p. In addition, miR­125b­5p mimics promoted H9C2(2­1) cell injury following 48 h exposure to hypoxia. Downregulation of Smad7 expression under hypoxia was increased by miR­125b­5p mimics compared with the mimic negative control, and hucMSC­exosomes partially alleviated this phenomenon. In conclusion, hucMSC­exosomes may promote Smad7 expression by inhibiting miR­125b­5p to increase myocardial repair. The present study may provide a potential therapeutic approach to improve myocardial repair following AMI.

Liquefied chitin/polyvinyl alcohol based blend membranes: Preparation and characterization and antibacterial activity.

To expand the applications of fishing industrial wastes, the liquefaction technique was employed to convert chitin into liquids, which were first further used for the modification of polymer materials. Ball-mill treated chitin was effectively liquefied into polyols in polyethylene glycol 400/glycerin mixed solvent. FTIR, 1H NMR and size exclusion chromatography analyses of liquefied chitin turned out that depolymerization and deacetylation reactions occurred during liquefaction process. The liquefied chitin/polyvinyl alcohol blend membranes with various mixing ratios were prepared and characterized by FTIR and SEM. In addition, transparency, tensile strength, elongation at break, water absorption, water retention and antibacterial properties were thoroughly discussed. The mechanical property and thermal stability were greatly enhanced under the optimized conditions of 25wt% liquefied chitin incorporation to polyvinyl alcohol. Moreover, the blend membranes showed improvements in water absorption and water retention capacity. In particular, the antibacterial activity was significantly improved after incorporation of liquefied chitin.

Intragenic hypomethylation of DNMT3A in patients with myelodysplastic syndrome.

BACKGROUND: DNMT3A is a DNA methyltransferase that acts in de novo methylation. Aberrant expression of DNMT3A has been reported in several human diseases, including myelodysplastic syndrome (MDS). However, the pattern of DNMT3A methylation remains unknown in MDS. METHODS: The present study was aimed to investigate the methylation status of DNMT3A intragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR and analyze its clinical significance in MDS. RESULTS: Aberrant hypomethylation of DNMT3A was found in 57% (51/90) MDS cases. There were no significant differences in age, sex, white blood cell counts, platelet counts, hemoglobin counts and World Health Organization, International Prognostic Scoring System and karyotype classifications between DNMT3A hypomethylated and DNMT3A hypermethylated groups. However, the patients with DNMT3A hypomethylation had shorter overall survival time than those without DNMT3A hypomethylation (11 months vs. 36 months, p=0.033). Multivariate analysis confirmed the independent adverse impact of DNMT3A hypomethylation in MDS. CONCLUSIONS: Our data suggest that DNMT3A DMR2 hypomethylation may be a negative prognostic hallmark in MDS.

Gastric cancer tissue-derived mesenchymal stem cells impact peripheral blood mononuclear cells via disruption of Treg/Th17 balance to promote gastric cancer progression.

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro. PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo. Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naïve CD4+ T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME.