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1.
World J Gastrointest Surg ; 16(2): 382-395, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38463377

RESUMO

BACKGROUND: The systemic inflammatory response index (SIRI) has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms. However, research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer surgery. AIM: To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients, who received robotic radical gastric cancer surgery. METHODS: Initially, an exhaustive retrieval was performed in the PubMed, the Cochrane Library, EMBASE, Web of Science, and Scopus databases to identify relevant studies. Subsequently, a meta-analysis was executed on 6 cohort studies identifying the value of the SIRI in assessing the survival of gastric cancer patients. Additionally, the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators. The association between preoperative SIRI levels and 5-year overall survival (OS) and disease-free survival (DFS) was assessed. RESULTS: The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer. Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer. SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities, T-stage, carcinoembryonic antigen levels, the development of early serious postoperative complications, and the rate of lymph node metastasis. CONCLUSION: SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

2.
PLoS One ; 18(9): e0291793, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37725618

RESUMO

INTRODUCTION: Ropivacaine oil delivery depot (RODD) can slowly release ropivacaine and block nerves for a long timejavascript:;. The aim of the present work was to investigate the safety, pharmacokinetics, and preliminary pharmacodynamics of RODD in subcutaneous injection among healthy subjects. METHODS: The abdomens of 3 subjects were subcutaneously administered with a single-needle RODD containing 12~30 mg of ropivacaine. The irritation, nerve blocking range and optimum dose were investigated. Forty-one subjects were divided into RODD groups containing 150, 230, 300, 350 and 400 mg of ropivacaine and a ropivacaine hydrochloride injection (RHI) 150 mg group. Multineedle subcutaneous injection of RODD or RHI was performed in the abdomens of the subjects. The primary endpoint was a safe dose or a maximum dose of ropivacaine (400 mg). Subjects' vital signs were observed; their blood was analyzed; their cardiovascular system and nervous systems were monitored, and their dermatological reactions were observed and scored. Second, the ropivacaine concentrations in plasma were determined, pharmacokinetic parameters were calculated, and the anesthetic effects of RODD were studied, including RODD onset time, duration and intensity of nerve block. RESULTS: Single-needle injection of RODD 24 mg was optimal for 3 subjects, and the range of nerve block was 42.5±20.8 mm. Multineedle subcutaneous injection of RODD in the abdomens of subjects was safe, and all adverse events were no more severe than grade II. The incidence rate of grade II adverse events, such as pain, and abnormal ST and ST-T segment changes on electrocardiography, was approximately 1%. The incidence rate of grade I adverse events, including erythema, papules, hypertriglyceridemia, and hypotension was greater than 10%. Erythema and papules were relieved after 24 h and disappeared after 72 h. Other adverse reactions disappeared after 7 days. The curve of ropivacaine concentration-time in plasma presented a bimodal profile. The results showed that ropivacaine was slowly released from the RODD. Compared with the 150 mg RHI group, Tmax was longer in the RODD groups. In particular, Tmax in the 400 mg RODD group was longer than that in the RHI group (11.8±4.6 h vs. 0.77±0.06 h). The Cmax in the 150 mg RODD group was lower than that in the 150 mg RHI group (0.35±0.09 vs. 0.58±0.13 µg·mL-1). In particular, the Cmax increased by 48% when the dose was increased by 2.6 times in the 400 mg group. Cmax, the AUC value and the intensity of the nerve block increased with increasing doses of RODD. Among them, the 400 mg RODD group presented the strongest nerve block (the percentage of level 2 and 3, 42.9%). The corresponding median onset time was 0.42 h, and the duration median was 35.7⁓47.7 h. CONCLUSIONS: RODD has a sustained release effect. Compared with the RHI group, Tmax was delayed in the RODD groups, and the duration of nerve block was long. No abnormal reaction was found in the RODD group containing 400 mg of ropivacaine after subcutaneous injection among healthy subjects, suggesting that RODD was adequately safe. TRIAL REGISTRATION: Chictr.org: CTR2200058122; Chinadrugtrials.org: CTR20192280.


Assuntos
Hipotensão , Humanos , Ropivacaina/efeitos adversos , Voluntários Saudáveis , Dor , Eletrocardiografia
3.
Mol Cell Endocrinol ; 576: 111996, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37406985

RESUMO

BACKGROUND: Myocardial interstitial fibrosis is an important manifestation of diabetic heart disease, and insulin resistance is one of the mechanisms of myocardial interstitial fibrosis. Some studies have found that miR-543 is associated with insulin resistance, but whether it plays a role in diabetic myocardial interstitial fibrosis remains unclear. This study aimed to investigate the role of miR-543 in diabetic myocardial interstitial fibrosis. METHODS: The combination of high glucose and high insulin was used to establish an insulin-resistant myocardial fibroblast model. The expression levels of miR-543, α-SMA, collagen Ⅰ, collagen Ⅲ and PTEN were detected. Cell proliferation and migration were detected. Luciferase reporter gene assay was used to verify the targeting relationship between miR-543 and PTEN. RESULTS: The expression of miR-543 was up-regulated in myocardial fibroblasts with insulin resistance, which was consistent with the results of bioinformatics analysis. The proliferation and migration levels of myocardial fibroblasts in insulin-resistant states were increased, and the expression levels of α-SMA, collagen Ⅰ and collagen Ⅲ were also increased. Inhibition of miR-543 expression could reverse the above changes. Target gene prediction and dual luciferase reporter assay demonstrated that miR-543 could bind to the 3'UTR region of PTEN. Moreover, the effect of miR-543 on insulin-resistant myocardial fibroblasts is mediated by targeting PTEN. CONCLUSIONS: Inhibition of miR-543 can reduce myocardial fibroblast-myofibroblast transformation and collagen expression in insulin-resistant states by targeting PTEN.


Assuntos
Resistência à Insulina , Insulinas , MicroRNAs , Proliferação de Células/genética , Colágeno/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , Fibrose , Resistência à Insulina/genética , Insulinas/metabolismo , Luciferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miofibroblastos/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Animais , Camundongos
4.
Front Oncol ; 12: 969628, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263224

RESUMO

Early gastric cancer (EGC) has a desirable prognosis compared with advanced gastric cancer (AGC). The surgical concept of EGC has altered from simply emphasizing radical resection to both radical resection and functional preservation. As the mainstream surgical methods for EGC, both endoscopic resection and laparoscopic resection have certain inherent limitations, while the advent of laparoscopic and endoscopic cooperative surgery (LECS) has overcome these limitations to a considerable extent. LECS not only expands the surgical indications for endoscopic resection, but greatly improves the quality of life (QOL) in EGC patients. This minireview elaborates on the research status of LECS for EGC, from the conception and development of LECS, to the tentative application of LECS in animal experiments, then to case reports and retrospective clinical studies. Finally, the challenges and prospects of LECS in the field of EGC are prospected and expounded, hoping to provide some references for relevant researchers. With the in-depth understanding of minimally invasive technology, LECS remains a promising option in the management of EGC. Carrying out more related multicenter prospective clinical researches is the top priority of promoting the development of this field in the future.

5.
Front Oncol ; 12: 947658, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110958

RESUMO

Background: Chemotherapy, radiotherapy, targeted therapy and immunotherapy have demonstrated expected clinical efficacy, while drug resistance remains the predominant limiting factor to therapeutic failure in patients with colorectal cancer (CRC). Although there have been numerous basic and clinical studies on CRC resistance in recent years, few publications utilized the bibliometric method to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and changing trends of drug resistance in CRC over the past 20 years. Methods: The Web of Science Core Collection (WOSCC) was utilized to extracted all studies regarding drug resistance in CRC during 2002-2021. CiteSpace and online platform of bibliometrics were used to evaluate the contributions of various countries/regions, institutions, authors and journals in this field. Moreover, the recent research hotspots and promising future trends were identified through keywords analysis by CiteSpace and VOSviewer. Results: 1451 related publications from 2002 to 2021 in total were identified and collected. The number of global publications in this field has increased annually. China and the USA occupied the top two places with respect to the number of publications, contributing more than 60% of global publications. Sun Yat-sen University and Oncotarget were the institution and journal which published the most papers, respectively. Bardelli A from Italy was the most prolific writer and had the highest H-index. Keywords burst analysis identified that "Growth factor receptor", "induced apoptosis" and "panitumumab" were the ones with higher burst strength in the early stage of this field. Analysis of keyword emergence time showed that "oxaliplatin resistance", "MicroRNA" and "epithelial mesenchymal transition (EMT)" were the keywords with later average appearing year (AAY). Conclusions: The number of publications and research interest on drug resistance in CRC have been increasing annually. The USA and China were the main driver and professor Bardelli A was the most outstanding researcher in this field. Previous studies have mainly concentrated on growth factor receptor and induced apoptosis. Oxaliplatin resistance, microRNA and EMT as recently appeared frontiers of research that should be closely tracked in the future.

6.
World J Gastrointest Surg ; 14(6): 594-610, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35979420

RESUMO

BACKGROUND: Conventional Billroth II (BII) anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer (GC) is associated with bile reflux gastritis, and Roux-en-Y anastomosis is associated with Roux-Y stasis syndrome (RSS). The uncut Roux-en-Y (URY) gastrojejunostomy reduces these complications by blocking the entry of bile and pancreatic juice into the residual stomach and preserving the impulse originating from the duodenum, while BII with Braun (BB) anastomosis reduces the postoperative biliary reflux without RSS. Therefore, the purpose of this study was to compare the efficacy and safety of laparoscopic URY with BB anastomosis in patients with GC who underwent radical distal gastrectomy. AIM: To evaluate the value of URY in patients with GC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database, and VIP Database for Chinese Technical Periodicals (VIP) were used to search relevant studies published from January 1994 to August 18, 2021. The following databases were also used in our search: Clinicaltrials.gov, Data Archiving and Networked Services, the World Health Organization International Clinical Trials Registry Platform Search Portal (https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal), the reference lists of articles and relevant conference proceedings in August 2021. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). We cited high-quality references using its results analysis functionality. The methodological quality of the eligible randomized clinical trials (RCTs) was evaluated using the Cochrane Risk of Bias Tool, and the non-RCTs were evaluated using the Newcastle-Ottawa scale. Statistical analyses were performed using Review Manager (Version 5.4). RESULTS: Eight studies involving 704 patients were included in this meta-analysis. The incidence of reflux gastritis [odds ratio = 0.07, 95% confidence interval (CI): 0.03-0.19, P < 0.00001] was significantly lower in the URY group than in the BB group. The pH of the postoperative gastric fluid was lower in the URY group than in the BB group at 1 d [mean difference (MD) = -2.03, 95%CI: (-2.73)-(-1.32), P < 0.00001] and 3 d [MD = -2.03, 95%CI: (-2.57)-(-2.03), P < 0.00001] after the operation. However, no significant difference in all the intraoperative outcomes was found between the two groups. CONCLUSION: This work suggests that URY is superior to BB in gastrointestinal reconstruction after LDG when considering postoperative outcomes.

7.
Medicine (Baltimore) ; 101(25): e29250, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35758354

RESUMO

RATIONALE: Femtosecond laser-assisted cataract surgery (FLACS) has grown in popularity among ophthalmologists as a novel surgical technique. However, malignant glaucoma (MG) is a complication of FLACS. Herein, we report a case of MG following FLACS. PATIENT CONCERNS: A 66-year-old woman presented with complaints of blurred vision in the right eye and a foreign body sensation in both eyes. Ophthalmological examinations showed that the corrected distance visual acuity was 20/50 and 20/25 in the right and left eyes, respectively. Without any topical anti-glaucoma medication, the intraocular pressure (IOP) was 20 mmHg in the right eye and 17 mmHg in the left eye. Slit-lamp examination of the right eye revealed a transparent cornea with a defect in the punctate overlying epithelium; the central anterior chamber depth was shallow the peripheral iris laser shot was visible, the pupil was normal, and the lens was mainly cortical opacified. DIAGNOSES: Based on the patient's symptoms, examination results, and preliminary diagnoses, age-related cataract in the right eye, binocular post-antiglaucoma surgery, pseudophakicin in the left eye, and Sjogren syndrome were included. INTERVENTIONS: FLACS was performed to facilitate anterior capsulotomy and segmentation of the nucleus in the right eye. MG occurred after the femtosecond procedure, and with the treatment of medicines combined with phacoemulsification, IOP was eventually normal without further antiglaucoma therapy. OUTCOMES: IOP was 16 mmHg on postoperative day 1. Ocular ultrasonography revealed no choroid detachment or hemorrhage in the right eye. Two weeks postoperatively, uncorrected visual acuity was 20/25, and IOP remained normal with no further antiglaucoma treatment on 1 month postoperatively. CONCLUSIONS: We describe the occurrence of MG after FLACS and illustrate that miosis and bubble formation after FLACS may be risk factors for MG during FLACS.


Assuntos
Extração de Catarata , Catarata , Glaucoma , Terapia a Laser , Facoemulsificação , Idoso , Catarata/complicações , Extração de Catarata/efeitos adversos , Extração de Catarata/métodos , Feminino , Glaucoma/complicações , Glaucoma/cirurgia , Humanos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers , Facoemulsificação/métodos
8.
J Burn Care Res ; 43(3): 735-741, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34665252

RESUMO

Burns often cause loss of skin barrier protection, fluid exudation, and local tissue edema, which hinder functional recovery. Effectively improving the quality of deep burn wound healing, shortening the wound healing time, and reducing tissue fluid leakage are urgent problems in the medical field. Human mesenchymal stem cells (MSCs) can effectively stabilize vascular endothelial injury. Fetal dermal MSCs (FDMSCs) are a newly discovered source of MSCs derived from the skin of accidentally aborted fetuses. However, the effect of FDMSCs on vascular permeability remains poorly understood. In this study, conditioned media from FDMSCs (F-CM) extracted from fetal skin tissue was prepared. The effect of F-CM on vascular permeability was evaluated using the internal circulation method FITC-dextran in vivo, and several in vitro assays, including cell viability assay, transwell permeability test, immunofluorescence, and western blotting. Altogether, our results demonstrate that F-CM could inhibit burn-induced microvascular hyperpermeability by increasing the protein expression levels of occludin and VE-cadherin, while restoring the expression of endothelial F-actin, and providing the foundation of a novel therapy for the treatment of burns with F-CM.


Assuntos
Queimaduras , Células-Tronco Mesenquimais , Queimaduras/metabolismo , Queimaduras/terapia , Permeabilidade Capilar , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Humanos , Cicatrização
9.
Saudi J Biol Sci ; 28(8): 4155-4163, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34354395

RESUMO

Mismanagement of crop straw and coal gas residue threatens the atmosphere and the economy. Nevertheless, thermal-pyrolysis is an option for management that turns bio-waste into biochar; its viability and adoption by the public as soil amendments is dependent on the agronomic and environmental values compared between biochar and the raw materials. We undertook a 60-day short-term analysis to assess the impact of various wastes and biochars, as well as inorganic nutrients (N), on carbon dioxide (CO2) fluxes, soil enzyme activities, soil fertility status, and microbial activities. There were eight treatments of soil amendments: without an amendment (CK), Nutrients (N), straw + nutrients (S+N), straw biochar + nutrients (SB+N), coal gas residue + nutrients (C+N), coal gas residue biochar + nutrients (CB+N), straw + straw biochar + nutrients (S+SB+N) and coal gas residue waste + coal gas residue biochar + nutrients (C+ CB +N). The results indicated that soil EC, pH, nitrate N (NO3 -- N), SOC, TN and available K were significantly (p < 0.05) increased coal gas residue biochar and combined with coal fly ash as compared to maize straw biochar and combined with maize straw and N treatments. The higher concentrations of soil MBC and MBN activities were increased in the maize straw application, while higher soil enzyme activity such as, invertase, urease and catalase were enhanced in the coal fly ash derived biochar treatments. The higher cumulative CO2 emissions were recorded in the combined applications of maize straw and its biochar as well as coal gas residue and its biochar treatment. Our study concludes, that maize straw and coal fly ash wastes were converted into biochar product could be a feasible substitute way of discarding, since land amendment and decreased CO2 fluxes and positive changes in soil microbial, and chemical properties, and can be confirmed under long-term conditions for reduction of economical and environment issues.

10.
Talanta ; 224: 121810, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379035

RESUMO

Microfluidic system with multi-functional integration of high-throughput protein/peptide separation ability has great potential for improving the identification capacity of biological samples in proteomics. In this paper, a sample treatment platform was constructed by integrating reversed phase chromatography, immobilized enzyme reactor (IMER) and imprinted monolith through a microfluidic chip to achieve the online proteins fractionation, denaturation, digestion and peptides enrichment. We firstly synthesized a poly-allyl phenoxyacetate (AP) monolith and a lysine-glycine-glycine (KGG) imprinted monolith separately, and investigated in detail their performance in fractionating proteins and extracting KGG from the protein digests of MCF-7 cell. The removal percentage of 94.6% for MCF-7 cell protein and the recovery of 90.8% for KGG were obtained. The number of proteins and peptides identified on this microfluidic platform was 2,004 and 8,797, respectively, which was 2.8-fold and 3.0-fold higher than that of untreatment sample. The time consumed by this platform for a sample treatment was about 9.6 h, less than that of conventional method (approximate 13.3 h). In addition, this platform can enrich some peptide fragments containing KGG based on imprinted monolith, which can be served for the identification of ubiquitin-modified proteomics. The successful construction of this integrated microfluidic platform provides a considerable and efficient technical tool for simultaneous identification of proteomics and post-translational modification proteomics information.


Assuntos
Microfluídica , Proteínas , Digestão , Peptídeos , Tripsina
11.
Hum Gene Ther ; 31(5-6): 286-296, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013585

RESUMO

Osteonecrosis of the femoral head (ONFH) is a common and disabling joint disease. Although there is no clear consensus on the complex pathogenic mechanism of ONFH, trauma, abuse of glucocorticoids, and alcoholism are implicated in its etiology. The therapeutic strategies are still limited, and the clinical outcomes are not satisfactory. Mesenchymal stem cells (MSCs) have been shown to exert a positive impact on ONFH in preclinical experiments and clinical trials. The beneficial properties of MSCs are due, at least in part, to their ability to home to the injured tissue, secretion of paracrine signaling molecules, and multipotentiality. Nevertheless, the regenerative capacity of transplanted cells is impaired by the hostile environment of necrotic tissue in vivo, limiting their clinical efficacy. Recently, genetic engineering has been introduced as an attractive strategy to improve the regenerative properties of MSCs in the treatment of early-stage ONFH. This review summarizes the function of several genes used in the engineering of MSCs for the treatment of ONFH. Further, current challenges and future perspectives of genetic manipulation of MSCs are discussed. The notion of genetically engineered MSCs functioning as a "factory" that can produce a significant amount of multipotent and patient-specific therapeutic product is emphasized.


Assuntos
Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/terapia , Terapia Genética/métodos , Células-Tronco Mesenquimais/fisiologia , Animais , Quimiocinas/fisiologia , Fator 2 de Crescimento de Fibroblastos/fisiologia , Engenharia Genética , Fator de Crescimento de Hepatócito/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Osteogênese , Fator A de Crescimento do Endotélio Vascular/fisiologia
12.
Drug Deliv Transl Res ; 10(1): 136-145, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31625025

RESUMO

Previous evidence has shown that the increased expression of aurora kinase is closely related to melanoma progression and is an important therapeutic target in melanoma. Danusertib is an inhibitor of aurora kinase, and recent studies have shown that danusertib treatment induces autophagy in several types of cancer. Interestingly, autophagy plays a dual function in cancer as a pro-survival and anti-survival factor. In this study, we investigated the role of danusertib on the induction of autophagy in melanoma and determined the impact of autophagy induction on its anticancer activity against melanoma. Our results showed that danusertib can significantly inhibit melanoma growth by inducing cell cycle arrest and apoptosis. In addition, we demonstrated that danusertib treatment significantly inhibits the oncogenic Akt/mTOR signaling pathway and induces autophagy in melanoma cells. Furthermore, we identified that the inhibition of autophagy can enhance the inhibitory effects of danusertib on melanoma growth. Thus, the induction of autophagy by danusertib appears to be a survival mechanism in melanoma cells that may counteract its anticancer effects. These findings suggest a novel strategy to enhance the anticancer efficacy of danusertib in melanoma by blocking autophagy.


Assuntos
Benzamidas/administração & dosagem , Cloroquina/administração & dosagem , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirazóis/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Benzamidas/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/farmacologia , Sinergismo Farmacológico , Feminino , Humanos , Melanoma/metabolismo , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nat Prod Res ; 34(21): 3108-3116, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31264446

RESUMO

Two new cembrane diterpenoids, named populeuphrines A and B (1 and 2), together with three known analogues (3-5) were isolated from the resins of Populus euphratica. The planar structures and relative configurations of 1 and 2 were elucidated by detailed 1 D and 2 D NMR spectroscopic analyses. The absolute configurations of 1 and 2 were determined by X-ray diffraction analysis and quantum chemical computation. Biological activities of all the isolates against proliferation of human cancer cells and umbilical cord mesenchymal stem cells were evaluated.


Assuntos
Diterpenos/química , Diterpenos/farmacologia , Populus/química , Resinas Vegetais/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/isolamento & purificação , Sangue Fetal/citologia , Humanos , Espectroscopia de Ressonância Magnética , Células-Tronco Mesenquimais/efeitos dos fármacos , Estrutura Molecular
14.
Onco Targets Ther ; 12: 4033-4046, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239698

RESUMO

Background: Malignant melanoma is the most lethal form of cutaneous tumor and has a high metastatic rate and motility capacity. Owing to the poor prognosis, it is urgent to seek an effective therapeutic regimen. Human mesenchymal stem cells (MSCs) can home to tumor cells and have been shown to play important roles in both promoting and inhibiting tumor development. Fetal dermal MSCs (FDMSCs), derived from fetal skin are a novel source of MSCs. Nevertheless, the antitumor capacity of FDMSCs on malignant melanoma is not clearly understood. Materials and methods: FDMSCs were extracted from the dorsal skin of fetal tissues. A375 melanoma cells lines were obtained from American Type Culture Collection. The effects of conditioned media from FDMSCs (CM-FDMSC) on A375 melanoma cells were tested in vivo using tumor formation assay and in vitro using cell viability, 5-ethynyl-2'-deoxyuridine incorporation, flow cytometry, TdT-mediated dUTP Nick-End Labeling (TUNEL), wound healing, transwell invasion, and Western blotting. Results: CM-FDMSC inhibited A375 tumor formation in vivo. In vitro, CM-FDMSC inhibited the tumor-related activities of A375 melanoma cells, as evidenced reductions in viability, migration, and invasion. CM-FDMSC-treated A375 cells showed decreased phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation, and up-regulation of Bcl-2-Associated X (BAX) and down-regulation of B-cell lymphoma-2 (BCL-2) expression. Conclusion: CM-FDMSC can inhibit the tumor-forming behaviors of A375 melanoma cells and inhibit PI3K/AKT and mitogen-activated protein kinase signaling to shift their BCL-2/BAX ratio toward a proapoptotic state. Identification of the bioactive components in CM-FDMSC will be important for translating these findings into novel therapies for malignant melanoma.

15.
Burns ; 45(7): 1685-1694, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31072713

RESUMO

It is the basic task of burn therapy to cover the wound with self-healthy skin timely and effectively. However, for patients with extensive burns, autologous skin is usually insufficient, and allogenic or heterogeneous skin leads to strong immune response. It is vital to choose an appropriate treatment for deep extensive burns. Nowadays, the dermal substitute combined with bone marrow mesenchymal stem cells (BM-MSCs) is a prospective strategy for burn wound healing. Denatured acellular dermal matrix (DADM), as one of dermal substitutes, which prepared by burn skin discarded in escharotomy, not only maintains a certain degree of 3D structure of collagen, but also has good biocompatibility. In this study, the preparation method of DADM was improved and DADM was seeded with BM-MSCs. Then BM-MSCs-seeded DADM (DADM/MSCs) was implanted into mice cutaneous wound, and the effect of DADM/MSCs dermal substitute was assessed on skin regeneration. As a result, BM-MSCs survived well and DADM/MSCs scaffolds significantly promoted wound healing in terms of angiogenesis, re-epithelialization and skin appendage regeneration. DADM/MSCs scaffold may represent an alternative promising therapy for wound healing in deep extensive burns.


Assuntos
Derme Acelular , Queimaduras/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Neovascularização Fisiológica , Reepitelização , Transplante de Pele/métodos , Animais , Células da Medula Óssea , Proliferação de Células , Sobrevivência Celular , Células-Tronco Mesenquimais , Camundongos , Microscopia Eletrônica de Varredura , Cicatrização
16.
Org Lett ; 21(6): 1837-1840, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30810324

RESUMO

Populusone (1), a cembrane-type macrocyclic trinorditerpenoid, was isolated from the exudates of Populus euphratica and shown to have an unprecedented carbon skeleton, The structure was identified using spectroscopic methods and X-ray crystallography. A possible pathway for the biosynthesis of 1 was proposed. Populusone (10 µM) was found to promote proliferation and differentiation of umbilical cord derived mesenchymal stem cells into keratinocyte like cells.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Populus/fisiologia , Cordão Umbilical/fisiologia , Diferenciação Celular , Células-Tronco Mesenquimais/química , Estrutura Molecular , Populus/química , Cordão Umbilical/química
17.
Am J Emerg Med ; 37(5): 828-831, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30060965

RESUMO

BACKGROUND: Skin flap-like wounds are common. These wound flaps are prone to avascular necrosis with simple debrided and sutured, and postoperative hyperplastic scarring and contracture of wound surfaces can adversely affect the patient's appearance. Here, we evaluate the data of cases with flap-like wounds to identify the causes of flap necrosis. METHODS: Six hundred patients with skin flap-like wounds between January 1, 2013 and December 31, 2016 were retrospectively reviewed. Their age, sex, injury reason, size of flap, length-width ratio of wound, thickness of pedicle, operation time, injury site, direction of blood perfusion in the flap and operating methods were recorded. The risks for flap necrosis were analyzed with one-factor analysis. RESULTS: A total success rate of 92.5% (555/600) for flap-like wound reconstruction was obtained. Among 67 flaps with vascular crisis, 22 were salvaged by subcutaneous injection of anisodamine, selective suture removal, and pressure dressing with elastic bandages. For the 45 patients with flap necrosis, there was no significant difference from patients without necrosis in terms of sex, age, and size of flap (P > 0.05). The incidence of flap necrosis was significantly different in terms of injury reason, length-width ratio of wound, thickness of pedicle, operation time, injury site, direction of blood perfusion in the flap and operating methods (P < 0.05). CONCLUSION: Injury reason, length-width ratio of wound, thickness of pedicle, operation time, injury site, direction of blood perfusion in the flap and operating methods, rather than age, sex and size of flap, were significant risk factors for necrosis of flap-like wounds.


Assuntos
Necrose/prevenção & controle , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Técnicas de Sutura , Adulto , Desbridamento/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/cirurgia
18.
Ann Transplant ; 23: 615-621, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30166501

RESUMO

BACKGROUND Mesenchymal stem cells (MSCs) have the potential of self-renewal and multi-differentiation and have a wide application prospect in organ transplantation for the effect of inducing immune tolerance. It has found that interleukin 17 (IL-17) could enhance the inhibition effect of MSCs on T cell proliferation and increase the immunosuppressive effect of MSCs. In this study, we aimed to investigate the effect of IL-17-induced MSCs on allograft survival time after transplantation. MATERIAL AND METHODS BMSCs were characterized by differential staining. The allogenic skin transplantations were performed and the BMSCs pre-treated by IL-17 were injected. To assess the immunosuppressive function of IL-17-induced BMSCs, the morphology of the grafts, the homing ability of the BMSCs, and the survival time of the grafts were analyzed. RESULTS BMSCs from BALB/c have multidirectional differentiation potential to differentiate into osteogenic, chondrogenic, and adipogenic lineage cells. IL-17-induced BMSCs prolonged the survival time of allogeneic skin grafts dramatically. We found that there were more labeled MSCs in the skin grafts, and the Treg subpopulations percentage, IL-10, and TGF-ß were significantly increased, while the IFN-γ level was decreased compared to the control group and MSCs group. In conclusion, IL-17 can enhance the homing ability of MSCs and regulate the immunosuppressive function of MSC. CONCLUSIONS Our data demonstrate that IL-17 plays the crucial role in MSC homing behaviors and promotes immunosuppression of MSCs during transplantation procedures, suggesting that IL-17-pre-treated MSCs have potential to prolong graft survival and reduce transplant rejection.


Assuntos
Proliferação de Células/efeitos dos fármacos , Sobrevivência de Enxerto/efeitos dos fármacos , Interleucina-17/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Transplante de Pele/métodos , Linfócitos T/efeitos dos fármacos , Animais , Sobrevivência de Enxerto/imunologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Linfócitos T/imunologia
19.
Stem Cell Res Ther ; 8(1): 170, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720118

RESUMO

BACKGROUND: Keloid is one kind of benign skin disease caused by hyperplasia of fibroblasts and collagen fibrils. It is refractory due to the lack of an effective treatment at present, which puts pressure on seeking a new therapeutic regimen. Mesenchymal stem cells (MSCs) from fetal skin are considered to play a crucial role in scarless healing. Nevertheless, the efficacy of them in keloid disorders remains poorly understood. METHODS: Keloid fibroblasts (KFs), human adult dermal fibroblasts (ADFs), and human fetal dermal mesenchymal stem cells (FDMSCs) were isolated to single cells and cultured in Dulbecco's modified Eagle's medium (DMEM). ADFs and FDMSCs were used to generate ADF-conditioned medium (A-CM) and FDMSC-conditioned medium (F-CM). The effects of A-CM and F-CM on KFs were tested using MTT assay, BrdU assay, TUNEL assay, quantitative polymerase chain reaction, Western blot, and annexin V-FITC/PI binding assay,. RESULTS: FDMSCs inhibited the bioactivity of KFs, downregulated the expression of the antiapoptotic protein BCL-2, and upregulated the expression of the proapoptotic protein BAX of KFs by secreting some soluble substances, thus accelerating the apoptosis of KFs. CONCLUSION: F-CM induces apoptosis of KFs, providing a novel treatment strategy for keloid disorders.


Assuntos
Derme/metabolismo , Regulação para Baixo , Feto/metabolismo , Fibroblastos/metabolismo , Queloide/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Técnicas de Cocultura , Derme/citologia , Feminino , Feto/citologia , Humanos , Masculino , Células-Tronco Mesenquimais/citologia
20.
Int J Biol Sci ; 13(3): 319-326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28367096

RESUMO

Keloid is a common and refractory disease characterized by abnormal fibroblast proliferation and excessive deposition of extracellular matrix components. Hypocrellin B (HB) is a natural perylene quinone photosensitizer. In this experiment, we studied the effects of photodynamic therapy (PDT) using yellow light from light-emitting diode (LED) combined with HB on keloid fibroblasts (KFB) in vitro. Our results showed that HB-LED PDT treatment induced significant KFB apoptosis and decreased KFB cell viability. HB-LED PDT treatment lead to significant BAX upregulation and BCL-2 downregulation in KFB cells, which led to elevation of intracellular free Ca2+ and activation of caspase-3. Our data provides preliminary evidence for the potential of HB-LED PDT as a therapeutic strategy for keloid.


Assuntos
Apoptose/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Queloide , Luz , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Quinonas/farmacologia , Perileno/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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