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1.
Stem Cell Res Ther ; 15(1): 2, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38169422

ABSTRACT

BACKGROUND: Although both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity. METHODS: Cell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo. RESULTS: Our data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317+ MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317+ MSCs. CONCLUSIONS: Thus, CD317+ MSCs might be a promising candidate for treating immunological disorder-related diseases.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Cell Differentiation , Cell Proliferation , Extracellular Matrix , Anti-Inflammatory Agents/pharmacology
2.
Heliyon ; 9(12): e22650, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38058447

ABSTRACT

Background: and Purpose: Fuzitang decoction (FZT), a classic prescription of traditional Chinese medicine (TCM), has excellent efficacy in treating gouty arthritis (GA). However, the underlying molecular mechanism remains obscure. In the present study, we aimed to explore the underlying mechanisms of FZT in treating GA by virtual screening combined with experimental verification. Methods: In this study, the active components of FZT and their corresponding targets were screened from the TCMSP database and TargetNet database. Then, the potential targets of FZT against GA were retrieved from multiple databases to generate a network. Protein-protein interaction, herbal-component-target, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were applied to identify potential targets and related signaling pathways. Furthermore, molecular docking simulation was applied to identify the interactions between the drug and targets. Finally, in vitro experiments were conducted to validate the potential targets and signaling pathways. Results: In the present study, several crucial components, including kaempferol, luteolin, catechin, deoxyandrographolide, and perlolyrine in FZT, were obtained through network pharmacology, and several potential targets to treat GA were developed, such as PPARG, CYP3A4, PTGS2 (known as COX2), VEGFA, and CYP1A1. Experimental validation suggested that deoxyandrographolide significantly suppressed the expression of IL-1ß, COX2, NLRP3 and IL-6 in inflammatory monocyte cells. Conclusions: Our results identified a novel anti-inflammatory compound, deoxyandrographolide, which helps to explain the potential mechanism of FZT in treating GA and provides evidence to support FZT's clinical use.

3.
BMC Genomics ; 24(1): 692, 2023 Nov 18.
Article in English | MEDLINE | ID: mdl-37980503

ABSTRACT

BACKGROUND: Artemisia annua is the major source for artemisinin production. The artemisinin content in A. annua is affected by different types of light especially the UV light. UVR8, a member of RCC1 gene family was found to be the UV-B receptor in plants. The gene structures, evolutionary history and expression profile of UVR8 or RCC1 genes remain undiscovered in A. annua. RESULTS: Twenty-two RCC1 genes (AaRCC1) were identified in each haplotype genome of two diploid strains of A. annua, LQ-9 and HAN1. Varied gene structures and sequences among paralogs were observed. The divergence of most RCC1 genes occurred at 46.7 - 51 MYA which overlapped with species divergence of core Asteraceae during the Eocene, while no recent novel RCC1 members were found in A. annua genome. The number of RCC1 genes remained stable among eudicots and RCC1 genes underwent purifying selection. The expression profile of AaRCC1 is analogous to that of Arabidopsis thaliana (AtRCC1) when responding to environmental stress. CONCLUSIONS: This study provided a comprehensive characterization of the AaRCC1 gene family and suggested that RCC1 genes were conserved in gene number, structures, constitution of amino acids and expression profiles among eudicots.


Subject(s)
Arabidopsis , Artemisia annua , Artemisinins , Artemisia annua/genetics , Artemisia annua/metabolism , Artemisinins/metabolism , Genes, Plant , Arabidopsis/genetics , Arabidopsis/metabolism , Chromosomes/metabolism
4.
Environ Int ; 181: 108296, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37924603

ABSTRACT

Irregularly shaped microplastics (MPs) released from infant feeding bottles (PP-IFBs) may exhibit increased cytotoxicity, in contrast to the commonly studied spherical MPs. This study presents an initial analysis of the thermal-oxidative aging process of plastic shedding from feeding bottles, and investigates the inflammatory response induced by these atypical MPs in human intestinal cells (Caco-2). The PP-IFBs' surface displayed non-uniform white patches and increased roughness, revealing substantial structural alteration and shedding, especially during actions such as shaking, boiling water disinfection, and microwave heating. FT-IR and 2D-COS analyses revealed that oxygen targeted the C-H and C-C bonds of polypropylene molecular chain, producing RO· and ·OH, thereby hastening polypropylene degradation. When human intestinal cells were exposed to MPs from PP-IFBs, oxidative stress was triggered, resulting in lowered glutathione levels, augmented reactive oxygen species (ROS), and heightened lipid peroxidation. Elevated levels of pro-inflammatory cytokines (IL-6 and TNFα) signified an active inflammatory process. The inflammatory response was notably more intense when exposed to MPs released through boiling water disinfection and microwave heating treatments, primarily due to the larger quantity of MPs released and their higher proportion of smaller particles. Furthermore, the NLRP3 inflammasome was identified as critical in initiating this inflammatory chain reaction due to the mitochondrial ROS surge caused by MPs exposure. This was further validated by inhibitor studies, emphasizing the role of the ROS/NLRP3/Caspase-1/IL-1ß signaling pathway in in promoting intestinal inflammation. Therefore, swift actions are recommended to protect infants against the potential health effects of MPs exposure.


Subject(s)
NLR Family, Pyrin Domain-Containing 3 Protein , Plastics , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Reactive Oxygen Species/metabolism , Caspase 1/metabolism , Microplastics , Caco-2 Cells , Polypropylenes , Spectroscopy, Fourier Transform Infrared , Inflammation/metabolism , Signal Transduction , Water
5.
Nat Commun ; 14(1): 4872, 2023 Aug 12.
Article in English | MEDLINE | ID: mdl-37573442

ABSTRACT

Inferring optical response from other correlated optical response is highly demanded for vast applications such as biological imaging, material analysis, and optical characterization. This is distinguished from widely-studied forward and inverse designs, as it is boiled down to another different category, namely, spectra-to-spectra design. Whereas forward and inverse designs have been substantially explored across various physical scenarios, the spectra-to-spectra design remains elusive and challenging as it involves intractable many-to-many correspondences. Here, we first dabble in this uncharted area and propose a generation-elimination framework that can self-orient to the best output candidate. Such a framework has a strong built-in stochastically sampling capability that automatically generate diverse nominations and eliminate inferior nominations. As an example, we study terahertz metasurfaces to correlate the reflection spectra from low to high frequencies, where the inaccessible spectra are precisely forecasted without consulting structural information, reaching an accuracy of 98.77%. Moreover, an innovative dimensionality reduction approach is executed to visualize the distribution of the abstract correlated spectra data encoded in latent spaces. These results provide explicable perspectives for deep learning to parse complex physical processes, rather than "brute-force" black box, and facilitate versatile applications involving cross-wavelength information correlation.

6.
Phytomedicine ; 116: 154882, 2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37210961

ABSTRACT

BACKGROUND: Artemisia annua, a well-known traditional Chinese medicine, is the main source for production of artemisinin, an anti-malaria drug. A. annua is distributed globally, with great diversity of morphological characteristics and artemisinin contents. Diverse traits among A. annua populations impeded the stable production of artemisinin, which needs an efficient tool to identify strains and assess population genetic homogeneity. PURPOSE: In this study, ribosomal DNA (rDNA), were characterized for A. annua for strains identification and population genetic homogeneity assessment. METHODS: The ribosomal RNA (rRNA) genes were identified using cmscan and assembled using rDNA unit of LQ-9 as a reference. rDNA among Asteraceae species were compared performing with 45S rDNA. The rDNA copy number was calculated based on sequencing depth. The polymorphisms of rDNA sequences were identified with bam-readcount, and confirmed by Sanger sequencing and restriction enzyme experiment. The ITS2 amplicon sequencing was used to verify the stability of ITS2 haplotype analysis. RESULTS: Different from other Asteraceae species, 45S and 5S linked-type rDNA was only found in Artemisia genus. Rich polymorphisms of copy number and sequence of rDNA were identified in A. annua population. The haplotype composition of internal transcribed spacer 2 (ITS2) region which had moderate sequence polymorphism and relative short size was significantly different among A. annua strains. A population discrimination method was developed based on ITS2 haplotype analysis with high-throughput sequencing. CONCLUSION: This study provides comprehensive characteristics of rDNA and suggests that ITS2 haplotype analysis is ideal tool for A. annua strain identification and population genetic homogeneity assessment.


Subject(s)
Artemisia annua , Artemisinins , Asteraceae , Artemisia annua/genetics , DNA, Ribosomal/genetics , Medicine, Chinese Traditional
7.
Front Neurol ; 13: 894951, 2022.
Article in English | MEDLINE | ID: mdl-35756940

ABSTRACT

Objective: Tic disorders (TDs) are common mental disorders in children and adolescents, and the clinical application of acupuncture for treating TDs is becoming increasingly widespread. However, the criteria for selecting acupoint prescriptions and combinations have not been summarized. Therefore, data mining was used herein to determine the treatment principles and the most effective acupoint selection and compatibility criteria for the treatment of TDs. Methods: Clinical studies and observations of the efficacy of acupuncture treatment for TDs were obtained from the PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Chinese Biomedical (CBM) databases. The data on the acupoint prescriptions applied in these studies were collected, and network and association analyses were used to reveal the relationships between acupoints and to identify acupoint combinations. Additionally, the principles of acupuncture for TDs were determined through cluster analysis. Subgroup analysis of acupuncture prescriptions based on specific categorical diagnoses was performed to further assess the selection of acupoints. Results: Eighty-six trials were identified, and 257 groups of effective prescriptions involving 121 acupoints were extracted. Bai-hui (DU20), Feng-chi (GB20), Tai-chong (LR3), He-gu (LI4), and San-yin-jiao (SP6) were the most regularly used acupoints for treating TDs. The Governor Vessel, gallbladder, and large intestine meridians were more commonly used than other meridians. Moreover, most acupoint sites focused on the head and neck. Network analysis revealed potentially effective acupoint prescriptions for their commonly used acupoints, namely, Bai-hui (DU20), Si-shen-cong (EX-HN1), Feng-chi (GB20), Nei-guan (PC6), Shen-men (HT7), He-gu (LI4), Zu-san-li (ST36), San-yin-jiao (SP6) and Tai-chong (LR3). Association rule mining indicated that potential point combinations that should be prioritized in TD treatment are Bai-hui (DU20), Neiguan (PC6) and Sanyinjiao (SP6). Cluster analysis revealed the treatment principle of "coordinating yin and yang, tonifying qi and blood, dispelling pathogenic wind and eliminating phlegm". The core acupoint prescription of TS treatment comprised He-gu (LI4), Feng-chi (GB20), Tai-chong (LR3), Bai-hui (DU20), Yin-tang (EX-HN3), Si-shen-cong (EX-HN1), San-yin-jiao (SP6), and Nei-guan (PC6). The core group included He-gu (LI4) and Feng-chi (GB20). Proximal points were usually used in TS as an additional method of point selection. Conclusion: Using data mining analysis of published studies, this study provides valuable information regarding the selection of the most effective acupoints and point combinations for clinical acupuncture practice for treating TDs.

8.
J Oncol ; 2022: 9321763, 2022.
Article in English | MEDLINE | ID: mdl-35528237

ABSTRACT

Background: Response surveillance of neoadjuvant chemotherapy is needed to facilitate treatment decisions. We aimed to assess the imaging features of cone-beam breast computed tomography (CBBCT) for predicting the pathologic response of breast cancer after neoadjuvant chemotherapy. Methods: This prospective study included 81 women with locally advanced breast cancer who underwent neoadjuvant chemotherapy from August 2017 to January 2021. All patients underwent CBBCT before treatment, and 55 and 65 patients underwent CT examinations during the midtreatment (3 cycles) and late-treatment phases (7 cycles), respectively. Clinical information and quantitative parameters such as the diameter, volume, surface area, and CT density were compared between pathologic responders and nonresponders using the T-test and the Mann-Whitney U test. The performance of meaningful parameters was evaluated with the receiver operating characteristic curve, sensitivity, and specificity. Results: The quantitative results for the segmented volume, segmented surface area, segmented volume reduction, maximum enhancement ratio, wash-in rate and two-minute enhancement value in the mid- and late-treatment periods had predictive value for pathologic complete response. The area under the curve for the prediction model after multivariate regression analysis was 0.874. Conclusion: After comparing the outcomes of each timepoint, mid- and late-treatment parameters can be used to predict pathologic outcome. The late-treatment parameters showed significant value with a predictive model.

9.
Sci Total Environ ; 833: 155097, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35421496

ABSTRACT

Differentially charged microplastics (MPs) engendered by plastic aging (e.g., plastic film) widely existed in the agricultural ecosystem, yet minimal was known about the toxic effects of MPs on plants and their absorption and accumulation characteristics. Root absorption largely determined the migration and accumulation risks of MPs in the soil-crop food chain. Here, five types of MPs exposure experiments of leaf lettuce were implemented to simulate root absorption by hydroponics. MPs exposure caused different degrees of growth inhibition, root lignification, root cell apoptosis, and oxidative stress responses; accelerated chlorophyll decomposition and hampered normal electron transfer within the PSII photosystem. Moreover, the uptake of essential elements by roots was inhibited to varying degrees due to the pore blockage in the cell wall and the hetero-aggregation of opposite charges after MPs exposure. MPs exposure observably up-regulated the organic metabolic pathways in roots, thus affecting MPs mobility and absorption through the electrostatic and hydrophobic interactions between the root exudations and MPs. Importantly, MPs penetrated the root extracellular cortex into the stele and were transported to the shoots by transpiration through xylem vessels based on confocal laser scanning microscopy and scanning electron microscopy images. Quantitative analysis of MPs indicated that their toxic effects on plants were determined to a greater extent by the types of surface functional groups than just their accumulation contents, that is, MPs were confirmed edible risks through crop food chain transfer, but bioaccumulation varied by surface functional groups.


Subject(s)
Microplastics , Soil Pollutants , Ecosystem , Microplastics/toxicity , Plastics/toxicity , Soil , Soil Pollutants/analysis , Soil Pollutants/toxicity
10.
Br J Radiol ; 95(1132): 20210466, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34930038

ABSTRACT

OBJECTIVE: To evaluate whether contrast-enhanced cone-beam breast CT (CE-CBBCT) features can risk-stratify prognostic stage in breast cancer. METHODS: Overall, 168 biopsy-proven breast cancer patients were analysed: 115 patients in the training set underwent scanning using v. 1.5 CE-CBBCT between August 2019 and December 2019, whereas 53 patients in the test set underwent scanning using v. 1.0 CE-CBBCT between May 2012 and August 2014. All patients were restaged according to the American Joint Committee on Cancer eighth edition prognostic staging system. Following the combination of CE-CBBCT imaging parameters and clinicopathological factors, predictors that were correlated with stratification of prognostic stage via logistic regression were analysed. Predictive performance was assessed according to the area under the receiver operating characteristic curve (AUC). Goodness-of-fit of the models was assessed using the Hosmer-Lemeshow test. RESULTS: As regards differentiation between prognostic stage (PS) I and II/III, increased tumour-to-breast volume ratio (TBR), rim enhancement pattern, and the presence of penetrating vessels were significant predictors for PS II/III disease (p < 0.05). The AUCs in the training and test sets were 0.967 [95% confidence interval (CI) 0.938-0.996; p < 0.001] and 0.896 (95% CI, 0.809-0.983; p = 0.001), respectively. Two features were selected in the training set of PS II vs III, including tumour volume [odds ratio (OR)=1.817, p = 0.019] and calcification (OR = 4.600, p = 0.040), achieving an AUC of 0.790 (95% CI, 0.636-0.944, p = 0.001). However, there was no significant difference in the test set of PS II vs III (P>0.05). CONCLUSION: CE-CBBCT imaging biomarkers may provide a large amount of anatomical and radiobiological information for the pre-operative distinction of prognostic stage. ADVANCES IN KNOWLEDGE: CE-CBBCT features have distinctive promise for stratification of prognostic stage in breast cancer.


Subject(s)
Breast Neoplasms , Breast/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Cone-Beam Computed Tomography/methods , Female , Humans , Mammography/methods , Neoplasm Staging , Prognosis , Reproducibility of Results , Retrospective Studies
11.
Front Oncol ; 10: 585486, 2020.
Article in English | MEDLINE | ID: mdl-33194733

ABSTRACT

Objectives: The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of breast tumors remains debatable among published studies. Therefore, this meta-analysis aimed to pool relevant evidence regarding the diagnostic performance of IVIM-DWI in the differential diagnosis of breast tumors. Methods: Studies on the differential diagnosis of breast lesions using IVIM-DWI were systemically searched in the PubMed, Embase and Web of Science databases in recent 10 years. The standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated using Review Manager 5.3, and Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as assess publication bias and heterogeneity. Fagan's nomogram was used to predict the posttest probabilities. Results: Sixteen studies comprising 1,355 malignant and 362 benign breast lesions were included. Most of these studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer had significant lower ADC (SMD = -1.38, P < 0.001) and D values (SMD = -1.50, P < 0.001), and higher f value (SMD = 0.89, P = 0.001) than benign lesions, except D* value (SMD = -0.30, P = 0.20). Invasive ductal carcinoma showed lower ADC (SMD = 1.34, P = 0.01) and D values (SMD = 1.04, P = 0.001) than ductal carcinoma in situ. D value demonstrated the best diagnostic performance (sensitivity = 86%, specificity = 86%, AUC = 0.91) and highest post-test probability (61, 48, 46, and 34% for D, ADC, f, and D* values) in the differential diagnosis of breast tumors, followed by ADC (sensitivity = 76%, specificity = 79%, AUC = 0.85), f (sensitivity = 80%, specificity = 76%, AUC = 0.85) and D* values (sensitivity = 84%, specificity = 59%, AUC = 0.71). Conclusion: IVIM-DWI parameters are adequate and superior to the ADC in the differentiation of breast tumors. ADC and D values can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. IVIM-DWI is also superior in identifying lymph node metastasis, histologic grade, and hormone receptors, and HER2 and Ki-67 status.

12.
BMC Cancer ; 20(1): 799, 2020 Aug 24.
Article in English | MEDLINE | ID: mdl-32831052

ABSTRACT

BACKGROUND AND OBJECTIVES: The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of pulmonary tumors remained debatable among published studies. This study aimed to pool and summary the relevant results to provide more robust evidence in this issue using a meta-analysis method. MATERIALS AND METHODS: The researches regarding the differential diagnosis of lung lesions using IVIM-DWI were systemically searched in Pubmed, Embase, Web of science and Wangfang database without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan's nomogram was used to predict the post-test probabilities. RESULTS: Eleven studies with 481 malignant and 258 benign lung lesions were included. Most include studies showed a low to unclear risk of bias and low concerns regarding applicability. Lung cancer demonstrated a significant lower ADC (SMD = -1.17, P < 0.001), D (SMD = -1.02, P < 0.001) and f values (SMD = -0.43, P = 0.005) than benign lesions, except D* value (SMD = 0.01, P = 0.96). D value demonstrated the best diagnostic performance (sensitivity = 89%, specificity = 71%, AUC = 0.90) and highest post-test probability (57, 57, 43 and 43% for D, ADC, f and D* values) in the differential diagnosis of lung tumors, followed by ADC (sensitivity = 85%, specificity = 72%, AUC = 0.86), f (sensitivity = 71%, specificity = 61%, AUC = 0.71) and D* values (sensitivity = 70%, specificity = 60%, AUC = 0.66). CONCLUSION: IVIM-DWI parameters show potentially strong diagnostic capabilities in the differential diagnosis of lung tumors based on the tumor cellularity and perfusion characteristics, and D value demonstrated better diagnostic performance compared to mono-exponential ADC.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Image Interpretation, Computer-Assisted , Lung Neoplasms/diagnosis , Lung/diagnostic imaging , Diagnosis, Differential , Feasibility Studies , Humans , Motion , Sensitivity and Specificity
13.
Biotechniques ; 69(1): 410-413, 2020 07.
Article in English | MEDLINE | ID: mdl-32285683

ABSTRACT

Mesenchymal stem cells (MSCs) represent a promising therapeutic candidate for treating many diseases. However, their proliferation and therapeutic abilities decline during the aging process and disease development. Therefore, fetal MSCs derived from the umbilical cord (UC) attract more attention. Storing and delivering the UC is one critical step for efficient MSC isolation. Although the culture medium-based solution is suitable for UC storage, it is not feasible for large-scale preparation because of its high price. Thus, we demonstrate here that a simple solution containing a pH buffering reagent, calcium, magnesium and glucose could be used as a cost-effective storage solution for UC delivery and efficient MSC isolation.


Subject(s)
Mesenchymal Stem Cells/cytology , Umbilical Cord/cytology , Aging/physiology , Cell Proliferation/physiology , Cells, Cultured , Cost-Benefit Analysis/methods , Culture Media/metabolism , Humans
14.
Stem Cell Res Ther ; 11(1): 125, 2020 03 19.
Article in English | MEDLINE | ID: mdl-32192530

ABSTRACT

OBJECTIVES: Mesenchymal stem cells (MSCs) have been intensively investigated as to their therapeutic potentials. However, the full chemical-defined medium supporting the isolation and expansion of human MSCs has not been developed yet. MATERIALS AND METHODS: Here, we developed the full chemical-defined medium, NBVbe medium, via RNA sequencing, bioinformatic analysis, and growth factor screening. RESULTS: The NBVbe medium contains N2B27 medium with the BSA (bovine serum albumin) replaced by the recombinant human albumin, bFGF (basic fibroblast growth factor), vitamin C, and EGF (epidermal growth factor). The NBVbe medium could support the isolation and expansion of human MSCs from the umbilical cords. CONCLUSIONS: The full chemical-defined medium supporting the isolation and expansion of human MSCs has been developed. This would be helpful for further optimization of the MSC medium, their clinical applications, and molecular characterization.


Subject(s)
Mesenchymal Stem Cells , Cell Differentiation , Cell Proliferation , Cells, Cultured , Culture Media , Humans , Umbilical Cord
15.
J Am Soc Nephrol ; 31(1): 54-65, 2020 01.
Article in English | MEDLINE | ID: mdl-31604808

ABSTRACT

BACKGROUND: Although mesenchymal stem cells (MSCs) might offer a promising strategy for treating SLE, their immunoregulatory plasticity makes their therapeutic effects unpredictable. Whether overexpressing IL-37, an IL-1 family member with immunosuppressive activity, might enhance the therapeutic effects of these cells for SLE is unknown. METHODS: We genetically modified MSCs to overexpress IL-37 and assessed their effects on immune suppression in vitro. We also evaluated the effects of such cells versus effects of various controls after transplanting them into MRL/lpr mice (model of SLE). RESULTS: Stem cell characteristics did not appear altered in MSCs overexpressing IL-37. These cells had enhanced immunosuppression in vitro in terms of inhibiting splenocyte proliferation, reducing proinflammatory factors (IL-1ß, TNF-α, IL-17, and IL-6), and suppressing autoantibodies (anti-dsDNA and anti-ANA). Compared with animals receiving control MSCs or IL-37 treatment alone, MRL/lpr mice transplanted with IL-37-overexpressing cells displayed improved survival and reduced signs of SLE (indicated by urine protein levels, spleen weight, and renal pathologic scores); they also had significantly lower expression of proinflammatory factors, lower total antibody levels in serum and urine, lower autoantibody production, and showed reduced T cell numbers in the serum and kidney. Expression of IL-37 by MSCs can maintain higher serum levels of IL-37, and MSCs had prolonged survival after transplantation, perhaps through IL-37 suppressing the inflammatory microenvironment. CONCLUSIONS: Mutually reinforcing interaction between MSCs and IL-37 appears to underlie their additive therapeutic effects. Genetic modification to overexpress IL-37 might offer a way to enhance the stability and effectiveness of MSCs in treating SLE.


Subject(s)
Interleukin-1/biosynthesis , Interleukin-1/therapeutic use , Lupus Erythematosus, Systemic/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Animals , Cells, Cultured , Combined Modality Therapy , Female , Mice , Mice, Inbred MRL lpr
16.
Biotechniques ; 66(5): 231-234, 2019 05.
Article in English | MEDLINE | ID: mdl-30924368

ABSTRACT

Mesenchymal stem cells (MSCs) have been intensively investigated and widely applied in regenerative medicine and immune modulation. However, their efficacy declines during the aging or disease process. Thus, genome-edited MSCs with over-expression or inhibition of specific genes hold a great deal of promise in terms of their therapeutic application. Here we optimized the direct PCR approach for rapid identification of genome-edited MSCs with only ten cells required, which reduces the time and labor to expand the MSC colonies. Combined with our previously optimized guide RNA structure and plasmid construction strategy for Cas9, we successfully identified MSC colonies over-expressing IL-10 in the AAVS1 locus.


Subject(s)
CRISPR-Associated Protein 9/genetics , Gene Editing , Mesenchymal Stem Cells/microbiology , CRISPR-Cas Systems/genetics , Humans , Interleukin-10/genetics , Plasmids/genetics , RNA, Guide, Kinetoplastida/genetics
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(4): 546-550, 2018 Jul.
Article in Chinese | MEDLINE | ID: mdl-30378307

ABSTRACT

OBJECTIVE: To determine the expression of microRNA-221 (miR-221) in endometrial tissues and its impact on the proliferation of ectopic endometrial stromal cells. METHODS: Endometrial stromal cells were isolated, cultured and identified from normal endometrial tissues (taken from patients without endometriosis) and ectopic endometrial tissues (taken from patients with ovarian endometriosis). The expression of microRNA-221 was detected by stem-loop qRT-PCR. Changes in the expression of miR-221-3p in endometrial stromal cells exposed to estraldiol (10-8 mol/L) for 48 h were detected. The effects of miR-221-3p inhibitor on the expressions of miR-221-3p, phosphatase and tensin homology deleted on chromosome ten (PTEN) and cell proliferations were compared with those of the negative control (NC, 10 nmol/L). RESULTS: The expression of miR-221-3p in ectopic endometrial tissues was 4.2 times higher than that in normal endometrial tissues (P=0.039): 2.66 times higher in ectopic endometrial stromal cells compared with normal endometrial stromal cells (P=0.029). But no differences in the expression of miR-221-5p were found (P>0.05). No differences in the change of miR-221-3p expression after exposure to estrogen for 48h were found between normal and ectopic stromal cells. Inhibition of miR-221-3p function was associated with decreased cell proliferation (P=0.018) and increased expression of PTEN gene (P=0.021). CONCLUSION: The expression of microRNA-221 is upregulated in ectopic endometrial tissues and ectopic endometrial stroma cells. Inhibiting the function of miR-221-3p may result in increased PTEN expression and decreased cell proliferation in endometrial stromal cells.


Subject(s)
Endometriosis/metabolism , MicroRNAs/metabolism , Stromal Cells/cytology , Cell Proliferation , Endometrium/cytology , Female , Humans , PTEN Phosphohydrolase/metabolism , Stromal Cells/metabolism
18.
Dis Esophagus ; 30(1): 1-7, 2017 01 01.
Article in English | MEDLINE | ID: mdl-26918692

ABSTRACT

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.


Subject(s)
Adenocarcinoma/epidemiology , Alcohol Drinking/epidemiology , Carcinoma, Squamous Cell/epidemiology , Diet/statistics & numerical data , Esophageal Neoplasms/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Case-Control Studies , China/epidemiology , Drinking Water , Female , Food Preservation , Fruit , Humans , Incidence , Male , Middle Aged , Odds Ratio , Protective Factors , Risk Factors , Sex Distribution , Vegetables
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