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1.
Ecotoxicol Environ Saf ; 276: 116317, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615641

RESUMO

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.


Assuntos
DNA Mitocondrial , Hepatócitos , Estresse Oxidativo , Receptor Toll-Like 9 , Tricloroetileno , Animais , Camundongos , Hepatócitos/efeitos dos fármacos , Tricloroetileno/toxicidade , Receptor Toll-Like 9/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Células RAW 264.7 , Doença Hepática Induzida por Substâncias e Drogas , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL
2.
Journal of Chinese Physician ; (12): 826-830, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-909627

RESUMO

Objective:To investigate the clinicopathological features and factors related to recurrence in patients with cutaneous squamous cell carcinoma (CSCC).Methods:The clinical and pathological data of 279 patients with CSCC diagnosed by histopathology in department of dermatology, plastic surgery, burns and oral and maxillofacial surgery of People′s Hospital of Xinjiang Uygur Autonomous Region from 2008 to 2019 were collected. They were divided into relapse group ( n=114) and non relapse group ( n=165) according to postoperative recurrence. Univariate and multivariate logistic analysis were used to analyze the related factors of CSCC recurrence. Results:Among 279 patients with CSCC surgery, the ratio of male to female was about 1.82∶1; the average age of onset (59.3±14.2)years, age ≥60 years (58.1%) was significantly higher; the average course of disease was 24 months; the incidence of exposed sites (88.2%) was significantly higher than that of non-exposed sites (11.8%); the degree of pathological differentiation was 182(65.2%) cases; postoperative wound healing: good 244 cases (87.5%), poor healing 35 cases (12.5%); first postoperative pathological margin: 239(85.7%) negative and 40(14.3%) positive; 60(21.5%) cases had lymph node metastasis occurred at the CSCC of diagnosis, and 219(78.5%) did not occur. Univariate analysis and multivariate logistic regression showed that the course of disease, the location of the disease, the healing of the postoperative area, the pathological condition of the first incision margin, and whether there was lymph node metastasis at the time of diagnosis were related to the recurrence of CSCC ( OR all >1.6). In addition, the correlation between gender, age, lesion length, preoperative skin ulceration, pathological differentiation, adjuvant radiotherapy and other factors on the recurrence of CSCC was not clear, with no statistically significant difference ( P>0.05). Conclusions:The course of disease (≥ 20 months), the site of the disease (the exposed part of the head), the wound healing (poor), the pathological condition of the first margin (positive) and the lymph node metastasis (with metastasis) were the risk factors for recurrence of CSCC. Early and accurate diagnosis is of great significance for the prognosis of CSCC, especially for patients with independent risk factors, early sentinel lymph node biopsy can detect metastasis and deal with it in time, so as to improve the prognosis of CSCC patients.

3.
Cancer Manag Res ; 12: 921-929, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104074

RESUMO

BACKGROUND: Pancreatic cancer is one of the most common malignant diseases in the world. Gemcitabine chemotherapy remains the most important clinical treatment. However, research found that pancreatic cancer cells have chemoresistance to gemcitabine and the effect is not satisfactory. Therefore, it is urgent to find an effective early diagnosis and treatment strategy. Circular RNA is one of the most popular prognostic biomarkers in GEM-resistant PC. MATERIALS AND METHODS: The present study was designed to evaluate the role of circHIPK3 in PC. The expression of circHIPK3 in PC tissues and cells and its effect on proliferation, migration, invasion, EMT, and apoptosis were investigated in vitro; its effect on tumor xenografts was assessed in vivo. Used bioinformation analysis to predict which miRNAs could potentially interact with circHIPK3, mRNA, and miR-330-5p. RESULTS: RT-PCR showed that the level of circHIPK3 was increased in PC tumor tissues; moreover, circHIPK3 was also increased in GEM-resistant PC tumors tissues and GEM-resistant PC cells. Sh-circHIPK3 could knockdown circHIPK3 in PANC-1-GEM and SW-1990-GEM and could significantly inhibit cell proliferation, invasion, migration, EMT and enhance cell apoptosis, compare with control group, the tumor xenografts of circHIPK3 knockdown group were significantly smaller. CircHIPK3 served as a sponge for miR-330-5p, and miR-330-5p directly bound to the 3' UTR of RASSF1 were revealed by dual luciferase assay and RIP in PC cells. CircHIPK3 knockdown of RASSF1 expression could neutralize the cytological function of PC cells by miR-330-5p inhibitor mediated GEM-resistance. CONCLUSION: CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by targeting RASSF1 via miR-330-5p and regulates proliferation, invasive, migration, EMT, and apoptosis. Our research revealed that circHIPK3 may be a novel biomarker in GEM-resistant PC and could be used as a prognostic target.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-865700

RESUMO

One patient with recurrent attacks of pancreatitis and pancreatic head mass had a long history of recurrent abdominal pain, abdominal distension, nausea and vomiting, and no significant alleviations were observed under non-surgical treatment in many hospitals. After the diagnosis and treatment by the multidisciplinary team of gastroenterology, hepatobiliary and pancreatic surgery, oncology, pathology, radiology and other departments of Third Xiangya Hospital of Central South University, the patient underwent pancreaticoduodenectomy to completely remove the painful lesion, without leaving histological basis for canceration caused by chronic inflammation. The safety of the surgery was greatly improved and no obvious complications were observed.

5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-827482

RESUMO

OBJECTIVE@#To help selecting appropriate meridians and acupoints in clinical practice and experimental study for Parkinson's disease (PD), the rules of meridians and acupoints selection of acupuncture and moxibustion were analyzed in domestic and foreign clinical treatment for PD based on data mining techniques.@*METHODS@#Literature about PD treated by acupuncture and moxibustion in China and abroad was searched and selected from China National Knowledge Infrastructure and MEDLINE. Then the data from all eligible articles were extracted to establish the database of acupuncture-moxibustion for PD. The association rules of data mining techniques were used to analyze the rules of meridians and acupoints selection.@*RESULTS@#Totally, 168 eligible articles were included and 184 acupoints were applied. The total frequency of acupoints application was 1,090 times. Those acupoints were mainly distributed in head and neck and extremities. Among all, Taichong (LR 3), Baihui (DU 20), Fengchi (GB 20), Hegu (LI 4) and Chorea-tremor Controlled Zone were the top five acupoints that had been used. Superior-inferior acupoints matching was utilized the most. As to involved meridians, Du Meridian, Dan (Gallbladder) Meridian, Dachang (Large Intestine) Meridian, and Gan (Liver) Meridian were the most popular meridians.@*CONCLUSIONS@#The application of meridians and acupoints for PD treatment lay emphasis on the acupoints on the head, attach importance to extinguishing Gan wind, tonifying qi and blood, and nourishing sinews, and make good use of superior-inferior acupoints matching.

6.
Journal of Experimental Hematology ; (6): 1429-1432, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-827099

RESUMO

Acute myeloid leukemia (AML) is a kind of malignant hematological disease with high mortality. Patients 5-year survival rate is less than 25% and that of elderly patients is lower than 10%. Although the standardized chemotherapy or hematopoetic stem cell transplantation can significantly improve the therapeutic efficacy for AML, but disease recurrence is still a difficult problem in most patients. Chemotherapy combined with immunotherapy has been regarded as the most promising treatment for AML in recent years, but immunotherapy is prone to immune escape, which has become an important factor affecting the therapeutic efficacy. Therefore, understanding the mechanism of immune escape of AML and taking corresponding measures in time to improve the therapeutic effect and reduce the recurrence of AML are of great significance. In this review, the important cells that cause immune escape, such as myeloid-derived suppressor cells (MDSC), natural killer cells (NK), and cell surface inhibitory receptor PD-1 (programmed death 1), which mediate immune escape of AML cells are summarized, so as to provide valuable reference for research to improve the effect of AML immunotherapy.


Assuntos
Idoso , Humanos , Transplante de Células-Tronco Hematopoéticas , Imunoterapia , Células Matadoras Naturais , Leucemia Mieloide Aguda , Transplante de Células-Tronco
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-828675

RESUMO

OBJECTIVE@#To study the expression and function of long non-coding RNA linc00467 in childhood acute myeloid leukemia (AML).@*METHODS@#Bone marrow samples were collected from 5 children with AML who were diagnosed from May 2016 to June 2018. Normal bone marrow samples based on bone marrow examination were collected from 3 children as controls. Quantitative real-time PCR was used to measure the expression of linc00467 in the two groups. A lentivirus system was used to achieve overexpression of linc00467 in AML cells (HL-60) (linc00467 overexpression group), and empty vector expressing green fluorescent protein (GFP) was transfected into AML cells to establish a GFP control group. A lentivirus system was used to insert an interfering sequence into AML cells (sh-linc00467 interfering group), and a random sequence was inserted to establish an sh-NC control group. Cell proliferation and resistance to doxorubicin were observed for all groups.@*RESULTS@#Compared with the normal control group, the children with AML had a significant increase in linc00467 (P=0.018). Overexpression and interference with linc00467 expression had no significant effect on cell proliferation. Compared with the GFP control group, the linc00467 overexpression group had a significant increase in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 μg/mL (P<0.05). Compared with the sh-NC control group, the sh-linc00467 interfering group had a significant reduction in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 μg/mL (P<0.05). Compared with the untreated group, the adriamycin treatment group had a significant increase in the expression of linc00467 in HL-60 cells (P<0.05).@*CONCLUSIONS@#This study reveals the biological function of linc00467 to promote the resistance to adriamycin in AML, which provides a basis for developing new therapeutic drugs for AML.


Assuntos
Criança , Humanos , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Lentivirus , Leucemia Mieloide Aguda , Genética , RNA Longo não Codificante , Genética
8.
Onco Targets Ther ; 12: 8207-8216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632071

RESUMO

BACKGROUND: Gemcitabine (GEM) is one of the most widely chemotherapy drugs in PC. However, the chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. lncRNA may play an essential role in PC and serve as a prognosis biomarkers in PC with GEM-resistance. In our study, we aim to investigate the role of lncRNA HCP5 in PC. MATERIALS AND METHODS: QRT-PCR detected the expression of lncRNA HCP5. The effects of knockdown lncRNA HCP5 on the proliferation, migration, invasion, cell apoptosis and autophagy were investigated in GEM-resistance PC cells. Bioinformatic analysis, luciferase reporter assay and RNA immunoprecipitation assay were performed to predict for potential miRNAs that can interact with lncRNA HCP5 and mRNAs that can interact with miR-214-3p. RESULTS: Our study revealed that lncRNA HCP5 expression was upregulated in PC tissues, especially increased expression in GEM-resistant PC tissues and GEM-resistant PC cells. Wound healing, Transwell assays, flow cytometry, Western blot, luciferase reporter assay and RNA immunoprecipitation (RIP) results demonstrated lncRNA HCP5 acted as a ceRNA to regulate GEM-resistance PC cells' proliferation, invasion, migration, cell apoptosis and autophagy by targeting HDGF via miR-214-3p. CONCLUSION: Our results revealed that lncRNA HCP5 is highly expressed in HCC, and development of GEM-resistance PC cells involving the processes of proliferation, invasive, migration, cell apoptosis and autophagy through the miR-214-3p/HDGF axis. Targeting lncRNA HCP5 may improve gemcitabine-based therapeutic efficacy.

9.
Ying Yong Sheng Tai Xue Bao ; 30(5): 1743-1753, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31107031

RESUMO

Bamboo forests have an efficient carbon sequestration capacity and play an important role in responding to global climate change. However, the current estimation of bamboo carbon storage has some errors, leading to uncertainty in the spatiotemporal pattern of bamboo forest carbon storage. This study simulated aboveground carbon storage of Zhejiang Province, China, during 1984-2014 based on the combination of an improved BIOME-BGC (biogeochemical cycles) model and remote sensing data, with the accuracy being verified with forest resource inventory data. The spatio-temporal distribution and environmental factors of aboveground carbon storage were analyzed. The results showed that the simulated carbon storage was accurate, with average correlation coefficient (r), root mean square error (RMSE) and relative bias (rBIAS) being 0.75, 7.24 Mg C·hm-2 and -2.57 Mg C·hm-2, respectively. Generally, the aboveground carbon storage of bamboo forests in the whole province tended to increase from 1984 to 2014, the range of aboveground carbon density was 13.10-17.14 Mg C·hm-2, and that of the total aboveground carbon storage was between 9.94-17.19 Tg C. The high aboveground carbon storage of bamboo was mainly distributed in developed bamboo industry areas, such as Anji, Lin'an, and Longyou. The change of aboveground carbon storage in bamboo forest was significantly correlated with temperature, precipitation, radiation, CO2 concentration and nitrogen deposition, with higher partial correlation coefficients between precipitation and temperature and carbon storage.


Assuntos
Sequestro de Carbono , Florestas , Biomassa , Carbono , China , Ecossistema , Monitoramento Ambiental , Sasa , Análise Espaço-Temporal , Árvores
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-791868

RESUMO

Objective To explore the characteristics of patients visiting emergency department by different ways of transportation.Methods The medical information of 23 039 patients visiting emergency department from January 2017 to December 2017 was obtained through the Hospital Information System (HIS).There were 20 856 patients visiting emergency arranged by themselves (self-visiting group),and 2 183 patients sent by ambulance (ambulance group).The characteristics of two groups were compared.Results The proportion of young patients in the self-visit group was the highest (45.97%,9 587/20 856),and the proportion of elderly patients in the ambulance group was the highest (40.04%,874/2 183).Throughout the year,the number of patients who came to the hospital by themselves was the highest in the summer,that by ambulance was the highest in the winter,while that was the lowest in spring for both groups.There was no significant fluctuation in the number of patients who came to the hospital during the week.In the self-visited group,the daily peak hours were 18:00-02:00 at night and the ambulance group were 10:00-18:00.The number of visits for top 5 system diseases were trauma,digestive system,other diseases,respiratory system and urinary system diseases in self-visiting group;and were nervous system,trauma,digestive system,respiratory system and circulatory system diseases in ambulance group.The hospitalization rates of self-visiting group and ambulance group were 14.41% (3 006/20 856) and 76.64% (1 564/2 183),respectively.Conclusion The emergency patients with different visiting modes have different characteristics.The information would be useful for rationally allocate emergency resources,optimize the treatment process,improve the emergency capacity and ensure the safety of patients.

11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-776838

RESUMO

Seven new isoquinoline alkaloids, 9-(2'-formyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy dehydroaporphine (1), 9-(2'-formyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy oxoaporphine (2), 3-methoxy-2'-formyl oxohernandalin (3), (-)-9-(2'-methoxycarbonyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy aporphine (4), (-)-2'-methoxycarbonyl thaliadin (5), (-)-9-(2'-methoxyethyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy aporphine (6), (-)-3-methoxy hydroxyhernandalinol (7), together with six known isoquinoline alkaloids (8-13) were isolated from the roots of Thalictrum foetidum. Their structures were elucidated by extensive spectroscopic measurements. Compounds 1 and 2 showed significant selective cytotoxicity against glioma stem cells (GSC-3 and GSC-18) with IC values ranging from 2.36 to 5.37 μg·mL.

12.
Chinese Journal of Dermatology ; (12): 565-567, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-755801

RESUMO

Objective To evaluate the effect of local flaps on repair of defects after surgical removal of nasal skin tumors.Methods A total of 65 patients with nasal skin tumors were enrolled from Department of Dermatology,People's Hospital of Xinjiang Uygur Autonomous Region between March 2015 and August 2016,and subjected to surgical removal of the nasal skin tumors.According to the location,size,shape and surrounding skin of the nasal defects,nasolabial fold flaps,modified rhomboid flaps,bilobed flaps or frontal nasal flaps were chosen to repair skin and soft tissue defects.Results Of the 65 patients with nasal skin tumors,38 had basal cell carcinoma,20 pigmented nevus,5 keratoacanthoma,and 2 had squamous cell carcinoma.The lengths of the defects after resection were all below 2.5 cm.Nasolabial fold flaps were used in 32 cases,modified rhomboid flaps in 16,bilobed flaps in 12,and frontal nasal flaps in 5.All the flaps survived after the surgery,and no obvious deformation of the nose was observed.No recurrence was observed during 1 year of follow-up.Conclusion For skin defects with the length ≤ 2.5 cm after resection of nasal skin tumors,nasolabial fold flaps,modified rhomboid flaps,bilobed flaps and frontal nasal flaps can be used to repair wounds,with satisfactory efficacy.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-817751

RESUMO

@#【Objective】 To examine a potential correlation between corneal biomechanical properties with lamina cribrosa thickness.【Methods】Thirty-two patients with POAG,20 with NTG,15 with OHT and 26 healthy controls were included in the cross- sectional study. The parameters of corneal biomechanical properties and lamina cribrosa thickness were compared among POAG,NTG,OHT and healthy subjects by mixed-model analysis of variance(ANOVA). Spearman′ s coefficient of rank correlation analysis was used to assess the association between parameters of deformation response and clinical factors. 【Results】 The Cronbach′ s α of lamina cribrosa thickness was 0.911,and ICC was more than 0.8. Laminar thickness was thinner in the POAG and NTG groups than in the OHT group and Normal group(P < 0.05). There were no significant differences between OHT and normal groups(P = 0.653). Correlation analysis showed that LCT and some important corneal biomechanical properties had significant correlation (P = 0.000). 【Conclusions】 LCT showed different characteristic in glaucoma,and it may be an important factor for glaucoma progression. LCT and corneal biomechanical properties showed significant correlation ,and corneal biomechanical properties may be used to evaluate the biomechanical properties of optic nerve.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-773524

RESUMO

OBJECTIVE@#To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on hematopoietic function in rats after combined chemotherapy with doxorubicin and cyclophosphamide.@*METHODS@#Eighty rats were randomized into control group and LIPUS group (=40) for treatment with intraperitoneal injection of doxorubicin (2 mg/kg)+cyclophosphamide (20 mg/kg) for 4 consecutive days and continuous irradiation with LIPUS for 7 days following the injections, respectively. The white blood cells, red blood cells and platelets counts in each group were measured at 0, 4, 7, 9, 11, 14 and 18 days after the start of drug administration. The pathological sections of the bone marrow were examined at 0, 4 and 11 days, and the flow cytometry was performed for detecting the cell apoptosis; qPCR was performed for detecting the expressions of SCF, ICAM-1, and VCAM-1 mRNAs, and ELISA was used to detect the expressions of IL-3 and GM-CSF.@*RESULTS@#The white blood cell count was significantly higher in LIPUS group than in the control group ( < 0.05). Histopathological examination of the bone marrow revealed significantly increased hematopoietic tissue in LIPUS group ( < 0.05). Flow cytometry demonstrated an obviously lower cell apoptosis rate in the bone marrow in LIPUS group than in the control group ( < 0.05). Compared with those in the control group, the mRNA expression levels of ICAM-1 and VCAM-1 as well as the protein levels of IL-3 and GM-CSF were significantly increased in LIPUS group ( < 0.05).@*CONCLUSIONS@#LIPUS can alleviate the hematopoietic damage after combined chemotherapy with doxorubicin with cyclophosphamide probably by increasing the expressions of ICAM- 1, VCAM-1, IL- 3, and GM-CSF.


Assuntos
Animais , Ratos , Medula Óssea , Ciclofosfamida , Doxorrubicina , Transplante de Células-Tronco Hematopoéticas , Ondas Ultrassônicas
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-797366

RESUMO

Objective@#To explore the characteristics of patients visiting emergency department by different ways of transportation.@*Methods@#The medical information of 23 039 patients visiting emergency department from January 2017 to December 2017 was obtained through the Hospital Information System (HIS). There were 20 856 patients visiting emergency arranged by themselves (self-visiting group), and 2 183 patients sent by ambulance (ambulance group). The characteristics of two groups were compared.@*Results@#The proportion of young patients in the self-visit group was the highest (45.97%, 9 587/20 856), and the proportion of elderly patients in the ambulance group was the highest (40.04%, 874/2 183). Throughout the year, the number of patients who came to the hospital by themselves was the highest in the summer, that by ambulance was the highest in the winter, while that was the lowest in spring for both groups. There was no significant fluctuation in the number of patients who came to the hospital during the week. In the self-visited group, the daily peak hours were 18:00-02:00 at night and the ambulance group were 10:00-18:00. The number of visits for top 5 system diseases were trauma, digestive system, other diseases, respiratory system and urinary system diseases in self-visiting group; and were nervous system, trauma, digestive system, respiratory system and circulatory system diseases in ambulance group. The hospitalization rates of self-visiting group and ambulance group were 14.41% (3 006/20 856) and 76.64% (1 564/2 183), respectively.@*Conclusion@#The emergency patients with different visiting modes have different characteristics. The information would be useful for rationally allocate emergency resources, optimize the treatment process, improve the emergency capacity and ensure the safety of patients.

16.
J Control Release ; 276: 84-92, 2018 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-29501723

RESUMO

Controlled drug delivery and gene expression is required for a large variety of applications including cancer therapy, wound healing, cell migration, cell modification, cell-analysis, reproductive and regenerative medicine. Controlled delivery of precise amounts of drugs to a single cell is especially interesting for cell and tissue engineering as well as therapeutics and has until now required the application of micro-pipettes, precisely placed dispersed drug delivery vehicles, or injections close to or into the cell. Here we present surface bound micro-chamber arrays able to store small hydrophilic molecules for prolonged times in subaqueous conditions supporting spatiotemporal near infrared laser mediated release. The micro-chambers (MCs) are composed of biocompatible and biodegradable polylactic acid (PLA). Biocompatible gold nanoparticles are employed as light harvesting agents to facilitate photothermal MC opening. The degree of photothermal heating is determined by numerical simulations utilizing optical properties of the MC, and confirmed by Brownian motion measurements of laser-irradiated micro-particles exhibiting similar optical properties like the MCs. The amount of bioactive small molecular cargo (doxycycline) from local release is determined by fluorescence spectroscopy and gene expression in isolated C2C12 cells via enhanced green fluorescent protein (EGFP) biosynthesis.


Assuntos
Sistemas de Liberação de Medicamentos , Antibacterianos/administração & dosagem , Linhagem Celular , Doxiciclina/administração & dosagem , Ouro/administração & dosagem , Proteínas de Fluorescência Verde/genética , Humanos , Lasers , Luz , Nanopartículas Metálicas/administração & dosagem , Poliésteres/administração & dosagem
17.
Drug Deliv ; 25(1): 435-447, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29383961

RESUMO

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10-20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.


Assuntos
Dor Crônica/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanocápsulas/administração & dosagem , Anestésicos Locais/administração & dosagem , Anestésicos Locais/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Dor Crônica/metabolismo , Dor Crônica/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Lidocaína/administração & dosagem , Lidocaína/análogos & derivados , Lidocaína/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Resultado do Tratamento
18.
Chinese Pharmacological Bulletin ; (12): 1235-1242, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-705182

RESUMO

Aim To investigate the protective roles of sonic hedgehog( Shh) signaling pathway in hypoxia-in-duced DNA damage with the neonatal rat cardiomyo-cytes. Methods The hypoxia model on neonatal car-diomyocytes was established with one to two days old Sprague Dawley rats by deprivation of oxygen and glu-cose ( OGD) . After pretreated with Shh pathway ago-nist SAG1.3 or antagonist GANT61, the survival rates of cardiomyocytes were assayed by MTT after OGD 6 hours or 12 hours. The protein levels of Shh pathway, phosphorylated histone H2AX at serine 139 (γH2AX), phosphorylated ATM (p-ATM), phospho-rylated p53 ( p-p53 ) , cleaved-caspase-3, Bcl-2 and Bax were detected by Western blot. The γH2AX foci was detected by immunofluorescence. Results Com-pared to control group, the protein expression of γH2AX, p-ATM, cleaved-caspase-3, p-p53 in OGD cardiomyocytes significantly increased, and Bcl-2/Bax ratio proportionally decreased. Particularly, the ex-pression of γH2AX, p-ATM was highest at OGD 6 h, and then gradually declined after OGD 12 h. After SAG1.3 pretreatment, the expression of γH2AX, p-ATM, cleaved-caspase-3 and p-p53 dramatically de-creased and the Bcl2/Bax ratio increased in OGD 6 h or OGD 12 h cardiomyocytes. On the contrary, in GANT61 pretreatment group, the expression of γH2AX, p-ATM, cleaved-caspase-3 and p-p53 signifi-cantly increased and the Bcl-2/Bax ratio decreased compared to the OGD 6 h or OGD 12 h cardiomyo-cytes. Conclusion The activation of Shh pathway protects cardiomyocytes against hypoxia-induced apop-tosis through inhibition of DNA damage.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-702423

RESUMO

Objective To investigate the impact of low intensity pulsed ultrasound (LIPUS) with different intensities on the migration of bone marrow mesenchymal stem cells (BMSCs) in vitro.Methods BMSCs were divided into control group,30 mW/cm2 group,60 mW/cm2 group and 90 mW/cm2 group.Control group was treated by sham LIPUS exposure,and the other three groups were treated by LIPUS with corresponding intensities.The impact of LIPUS on scratch healing was tested with scratch assay,and the interference of proliferation was eliminated with MTT assay.The migration of BMSCs were evaluated with transwell migration assay.The expression of F-actin was analyzed with fluorescein isothiocyanate (FITC) fluorescent coloration.Results 24 h and 48 h after LIPUS exposure,there were statistical differences of scratch area among groups (F=26.559,106.110,both P<0.001),and the scratch area of control group was the largest ([0.93 ± 0.26)mm2 of 24 h after LIPUS exposure and [0.70 ± 0.11]mm2 of 48 h after LIPUS exposure),while that of 30 mW/cm2 group was the smallest ([0.47 ±0.21]mm2 of 24 h after LIPUS exposure and [0.19±0.10]mm2 of 48 h after LIPUS exposure).There was no statistical difference of scratch area among the four groups immediately after LIPUS exposure (F=2.921,P=0.063).MTT assay results showed there was no statistical difference of absorbance among the four groups immediately,nor 24 h,48 h after LIPUS exposure (F=1.616,0.720,1.408;P=0.196,0.544,0.378).Significant difference was found in the number of cells migrated through the transwell chamber among the four groups (F=43.145,P<0.001),and the cell number of 30 mW/cm2 group was the largest (212.53±35.32),while that of the control group was the least (89.53±19.27).F-actin fluorescence staining results showed the morphology of F-actin was changed after LIPUS exposure.The cytoskeleton became narrow and elongated.Statistical difference of relative fluorescence intensity was found among the four groups (F 64.350,P<0.001).The relative fluorescence intensity of 30 mW/cm2 group was the largest (125.43 ± 17.43),while that of control group was the least (51.94± 12.76).Conclusion LIPUS can promote the migration ability of BMSCs in vitro with the best intensity was 30 mW/cm2.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-808108

RESUMO

Objective@#To investigate the incidence of occupational diseases in Chongqing, China, from 2006 to 2014, and to analyze the harm, features, and trend of occupational diseases in Chongqing.@*Methods@#The data of new cases of occupational diseases from 2006 to 2014 were collected, and the patients with a confirmed diagnosis of occupational diseases were selected as study subjects to analyze the incidence of occupational diseases in Chongqing.@*Results@#There were 17499 cases of occupational diseases in total in Chongqing from 2006 to 2014. Among these patients, 17124 (97.86%) were male, most of whom (95.40%) had occupational pneumoconiosis, and 375 (2.14%) were female, most of whom (72.80%) had occupational chemical poisoning. There were 16400 cases (93.72%) of occupational pneumoconiosis in total, mainly coal workers' pneumoconiosis (55.87%) and silicosis (43.02%) , and the main industries involved were coal mining and washing, railway transport equipment manufacturing, and mining and washing of bituminous coal and anthracite. There were 724 cases of occupational poisoning in total; there were 281 cases of acute occupational poisoning, mainly gas poisoning (39.86%) and carbon monoxide poisoning (33.10%) ; there were 443 cases of chronic occupational poisoning, mainly poisoning caused by benzene (47.63%) , mercury and its inorganic compounds (32.74%) , and lead and its inorganic compounds (9.03%) .@*Conclusion@#Occupational diseases in Chongqing are mainly occupational pneumoconiosis, and occupational health supervision should be enhanced in the industries of coal mining and washing and railway transport equipment manufacturing to protect workers’ health.

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