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1.
Acta Pharmacol Sin ; 45(7): 1492-1505, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538718

RESUMO

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.


Assuntos
Linfócitos T CD8-Positivos , Células Matadoras Naturais , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Microambiente Tumoral , Animais , Células Matadoras Naturais/imunologia , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Linfócitos T CD8-Positivos/imunologia , Camundongos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Linfócitos do Interstício Tumoral/imunologia , Fenótipo , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia
2.
Zhongguo Zhen Jiu ; 43(9): 993-5, 2023 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-37697872

RESUMO

Benign prostatic hyperplasia is caused by kidney deficiency and impaired qi transformation of the urinary bladder and is manifested by the stagnation of essence chamber. Based on jingjin (muscle region of meridian, sinew/fascia) theory and taking the visceral membrane as the principal, acupuncture is delivered at sinew/fascia to promote qi circulation, resolve stasis and open the orifice. Guided by CT, the needle is inserted at Zhongji (CV 3), the front-mu point of the urinary bladder, and then goes to the prostatic capsule, meaning "the disease of zang organ is treated by needling the front-mu point". In treatment of benign prostatic hyperplasia, this acupuncture therapy stimulates the different layers of fascia, by which, the defensive qi on the exterior is regulated and "essence orifice" in the interior is adjusted so that the urination can be promoted.


Assuntos
Terapia por Acupuntura , Meridianos , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/terapia , Próstata , Bexiga Urinária
3.
Zhen Ci Yan Jiu ; 48(1): 44-52, 2023 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-36734497

RESUMO

OBJECTIVE: To explore the rules of acupoints selection of acupuncture and moxibustion in the treatment of allergic rhinitis (AR) by using data mining technology, as well as to compare the efficacy of different acupoints selection methods. METHODS: Papers about acupuncture and moxibustion for treating AR published from January 2002 to August 2022 was retrieved from Chinese and English databases including CNKI, Wanfang, VIP, SinoMed and PubMed by using keywords of "acupuncture", "moxibustion" and "allergic rhinitis". According to the inclusion and exclusion criteria, the collected literature was screened to establish the AR database. Frequency statistic analysis was conducted for detecting high-frequency acupoints and specific acupoints frequency, and the curative effects of different acupoints selection methods were compared. SPSS26.0 software was used for factor analysis, cluster analysis and QUEST decision tree model identification. RESULTS: A total of 289 papers were included, with 384 acupuncture prescriptions extracted. A total of 99 acupoints were involved with the application frequency of 2 430 times. Among them, the application frequency of Yingxiang (LI20) is the highest (296 times, 12.18%), followed by Yintang (GV24+) and Hegu (LI4), etc. The main invloved meridians are the Bladder Meridian of Foot-Taiyang, the Large Intestine Meridian of Hand-Yangming and the Governor Vessel. The involved specific acupoints with the highest frequency of application is the crossing acupoints. Nine common factors of acupoints combinations units were extracted by factor analysis, and two cluster prescriptions of acupoints combinations correlation were obtained by cluster analysis. Three decision paths of simplified acupoints selection were simulated by the decision tree, with LI20 as the dependent variable. CONCLUSION: In the treatment of AR with acupuncture and moxibustion, the regularities and characteristics of acupoints selection are as follows: 1) often selecting local acupoints and acupoint combinations along meridians, 2) focusing on combination of dispelling pathogenic factors with strengthening vital energy, 3) advocating diversification of acupoint matching methods. The combination of factor analysis, cluster analysis and QUEST decision tree application provides three directions for clinical acupoints selection of AR.


Assuntos
Terapia por Acupuntura , Meridianos , Moxibustão , Rinite Alérgica , Rinite , Humanos , Pontos de Acupuntura , Rinite Alérgica/terapia
4.
Zhongguo Zhen Jiu ; 43(1): 101-6, 2023 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-36633248

RESUMO

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The Chinese Medical Code (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc., were systematically sorted out. As a result, a total of 140 articles of ancient literature were included. The common indications of Qugu (CV 2) used alone were urinary retention, profuse vaginal discharge and hernia. The common indications of Qugu (CV 2) used with compatible acupoints were profuse vaginal discharge, stranguria and hernia. Sixty-four acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, bladder meridian and liver meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Sanyinjiao (SP 6); five-shu points were the most used special acupoints, and moxibustion therapy was often used. A total of 73 modern articles were included. The common indications of Qugu (CV 2) used alone were urinary retention, erectile dysfunction and chronic prostatitis; the common indications of Qugu (CV 2) used with compatible scupoints were urinary retention, erectile dysfunction and prostatic hyperplasia. Thirty-six acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, kidney meridian and spleen meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Zusanli (ST 36); front-mu points were the most used special acupoints, and acupuncture therapy was often used. Qugu (CV 2) treats a wide range of diseases in ancient times, the distant treatment effectiveness of acupoints is emphasized; and it mainly treats local diseases in modern times, the nearby treatment effectiveness of acupoints is emphasized.


Assuntos
Terapia por Acupuntura , Disfunção Erétil , Literatura Moderna , Meridianos , Moxibustão , Retenção Urinária , Descarga Vaginal , Feminino , Masculino , Humanos , Pontos de Acupuntura
5.
Front Neurosci ; 16: 992577, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090267

RESUMO

Objective: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). Patients and methods: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1-3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1-3 and 4-6. Results: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17-0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82-1.07) in the acupuncture group and 0.61 (95% CI, 0.50-0.71) in the medication group over cycles 1-3. Conclusion: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. Clinical trial registration: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606].

6.
Chin J Integr Med ; 27(5): 394-400, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32524396

RESUMO

Cupping therapy has been accepted worldwide, and many studies have been conducted to reveal its curative effects and mechanisms. To comprehensively evaluate the effect of cupping therapy, database including China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database VIP, Wan Fang Database, Chinese Biomedicine (CBM), PubMed and Web of Science were searched from 2009-2019. We summarized all the meta-analyses, randomized controlled trials, clinical trials and the mechanisms studies of cupping therapy in the previous 10 years, hoping to provide a reference for the clinical applications and studies.


Assuntos
Ventosaterapia , China
7.
J Cell Physiol ; 234(11): 19640-19654, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30950039

RESUMO

Angiotensin II (AngII) facilitates angiogenesis that is associated with the continuous progression of atherosclerotic plaques, but the underlying mechanisms are still not fully understood. Several microRNAs (miRNAs) have been shown to promote angiogenesis; however, whether miRNAs play a crucial role in AngII-induced angiogenesis remains unclear. This study evaluated the functional involvement of miRNA-21 (miR-21) in the AngII-mediated proangiogenic response in human microvascular endothelial cells (HMECs). We found that AngII exerted a proangiogenic role, indicated by the promotion of proliferation, migration, and tube formation in HMECs. Next, miR-21 was found to be upregulated in AngII-treated HMECs, and its specific inhibitor potently blocked the proangiogenic effects of AngII. Subsequently, we focused on the constitutive activation of STAT3 in the AngII-mediated proangiogenic process. Bioinformatic analysis indicated that STAT3 acted as a transcription factor initiating miR-21 expression, which was verified by ChIP-PCR. A reporter assay further identified three functional binding sites of STAT3 in the miR-21 promoter region. Moreover, phosphatase and tensin homolog (PTEN) was recognized as a target of miR-21, and STAT3 inhibition restored AngII-induced reduction in PTEN. Similarly, the STAT3/miR-21 axis was shown to mediate AngII-provoked angiogenesis in vivo, which was demonstrated by using the appropriate inhibitors. Our data suggest that AngII was involved in proangiogenic responses through miR-21 upregulation and reduced PTEN expression, which was, at least in part, linked to STAT3 signaling. The present study provides novel insights into AngII-induced angiogenesis and suggests potential treatment strategies for attenuating the progression of atherosclerotic lesions and preventing atherosclerosis complications.


Assuntos
MicroRNAs/genética , Neovascularização Patológica/genética , PTEN Fosfo-Hidrolase/genética , Placa Aterosclerótica/genética , Fator de Transcrição STAT3/genética , Indutores da Angiogênese/farmacologia , Angiotensina II/genética , Angiotensina II/farmacologia , Animais , Movimento Celular/genética , Proliferação de Células/genética , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Neovascularização Patológica/patologia , Placa Aterosclerótica/patologia , Transdução de Sinais/genética
8.
Cell Physiol Biochem ; 41(5): 2016-2026, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28420001

RESUMO

BACKGROUND: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 µM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9) mono-, di-, and trimethylation and NNMT protein levels were measured by western blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen-activated protein kinase 3 (MAP2K3) and dickkopf1 (DKK1), were determined by qPCR analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+) to reduced NAD (NADH) and SAM/SAH ratio were determined. RESULTS: Exposure of BEAS-2B cells to nickel increased H3K9 dimethylation (H3K9me2), suppressed the expressions of H3K9me2-associated genes (MAP2K3 and DKK1), and induced NNMT repression at both the protein and mRNA levels. Furthermore, over-expression of NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio. Additionally, the NADH oxidant phenazine methosulfate (PMS) not only reversed the nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2. CONCLUSIONS: These findings indicate that the repression of NNMT may underlie nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.


Assuntos
Histonas/metabolismo , Níquel/farmacologia , Nicotinamida N-Metiltransferase/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Linhagem Celular , Histonas/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MAP Quinase Quinase 3/genética , MAP Quinase Quinase 3/metabolismo , Metilação/efeitos dos fármacos , Nicotinamida N-Metiltransferase/genética
9.
Cell Physiol Biochem ; 40(3-4): 633-643, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27898410

RESUMO

BACKGROUND: Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. METHODS: A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. RESULTS: The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p <0.01). The prevalence of dyslipidemia increased dose-dependently with elevations in blood cadmium concentrations (p for trend <0.001). Elevated levels of blood cadmium were associated with BMI, education attainment, income, smoking status and duration of exposure (all p <0.01). Furthermore, the profile of blood lipid was obviously changed in this occupational population. The prevalence of high TC, high TG, Low HDL-C and high LDL-C rose with increases in blood cadmium levels dose-dependently (p for trend <0.001). The odds ratios (95% confidence interval) for dyslipidemia across the increasing blood cadmium quartiles were 1.21(1.16-1.55), 1.56(1.11-1.87), 1.79(1.26-2.25) respectively (referencing to 1.00; p for trend <0.001), after multivariate adjustment for BMI, education attainment, income, lifestyle factors and duration of exposure, the association between blood cadmium concentrations and the prevalence of dyslipidemia remained unchanged (all p for trend <0.001). CONCLUSION: Elevated blood cadmium concentration is associated with prevalence of dyslipidemia. Cadmium exposure could alter lipid metabolism in humans. It is imperative to control cadmium exposure of occupational population in cadmium related industries and reduce adverse health effects.


Assuntos
Cádmio/sangue , Dislipidemias/sangue , Dislipidemias/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Adulto , Feminino , Humanos , Lipídeos/sangue , Masculino , Análise Multivariada , Razão de Chances , Prevalência
10.
Cell Physiol Biochem ; 39(3): 961-74, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27513750

RESUMO

BACKGROUND: Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear. METHODS: In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (γH2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP). RESULTS: The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 µM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity. CONCLUSION: These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.


Assuntos
Poluentes Ocupacionais do Ar/farmacologia , Compostos Benzidrílicos/farmacologia , Cloreto de Cádmio/farmacologia , Dano ao DNA , DNA Glicosilases/antagonistas & inibidores , Estrogênios não Esteroides/farmacologia , Fenóis/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Combinação de Medicamentos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Histonas/genética , Histonas/metabolismo , L-Lactato Desidrogenase/metabolismo , Camundongos , Células NIH 3T3 , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo
11.
Chin J Integr Med ; 22(6): 467-72, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26129899

RESUMO

OBJECTIVE: To provide an evidence-based overview regarding the efficacy of Ashi points stimulation for the treatment of shoulder pain. METHODS: A comprehensive search [PubMed, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Chongqing Weipu Database for Chinese Technical Periodicals (VIP) and Wanfang Database] was conducted to identify randomized or quasi-randomized controlled trials that evaluated the effectiveness of Ashi points stimulation for shoulder pain compared with conventional treatment. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. RevMan 5.0 was used for data synthesis. RESULTS: Nine trials were included. Seven studies assessed the effectiveness of Ashi points stimulation on response rate compared with conventional acupuncture. Their results suggested significant effect in favour of Ashi points stimulation [odds ratio (OR): 5.89, 95% confidence interval (CI): 2.97 to 11.67, P<0.01, heterogeneity: χ(2) =3.81, P=0.70, I (2) =0% ]. One trial compared Ashi points stimulation with drug therapy. The result showed there was a significantly greater recovery rate in group of Ashi points stimulation (OR: 9.58, 95% CI: 2.69 to 34.12). One trial compared comprehensive treatment on the myofascial trigger points (MTrPs) with no treatment and the result was in favor of MTrPs. CONCLUSIONS: Ashi points stimulation might be superior to conventional acupuncture, drug therapy and no treatment for shoulder pain. However, due to the low methodological quality of included studies, a firm conclusion could not be reached until further studies of high quality are available.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor de Ombro/terapia , Humanos , Viés de Publicação , Fatores de Risco , Dor de Ombro/tratamento farmacológico , Pontos-Gatilho
12.
Toxicol Appl Pharmacol ; 286(2): 80-91, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25840356

RESUMO

With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni(2+) inside the cells. NiONPs at doses of 5, 10, and 20µg/cm(2) inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity.


Assuntos
Apoptose/efeitos dos fármacos , Brônquios/metabolismo , Células Epiteliais/metabolismo , Nanopartículas/toxicidade , Níquel/toxicidade , Sirtuína 1/antagonistas & inibidores , Brônquios/citologia , Brônquios/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos , Nanopartículas/metabolismo , Níquel/metabolismo , Sirtuína 1/genética
13.
Neurotoxicology ; 38: 9-16, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23727075

RESUMO

The oral ingestion of soluble nickel compounds leads to neurological symptoms in humans. Deficiencies in aerobic metabolism induced by neurotoxic stimulus can cause an energy crisis in the brain that results in a variety of neurotoxic effects. In the present study, we focused on the aerobic metabolic states to investigate whether disturbance of aerobic metabolism was involved in nickel-induced neurological effects in mice. Mice were orally administered nickel chloride, and neurobehavioral performance was evaluated using the Morris water maze and open field tests at different time points. Aerobic metabolic states in the cerebral cortex were analyzed at the same time points at which neurobehavioral changes were evident. We found that nickel exposure caused deficits in both spatial memory and exploring activity in mice and that nickel was deposited in their cerebral cortex. Deficient aerobic metabolism manifested as decreased O2 consumption and ATP concentrations, lactate and NADH accumulation, and oxidative stress. Meanwhile, the activity of prototypical iron-sulfur clusters (ISCs) containing enzymes that are known to control aerobic metabolism, including complex I and aconitase, and the expression of ISC assembly scaffold protein (ISCU) were inhibited following nickel deposition. Overall, these data suggest that aerobic metabolic disturbances, which accompanied the neurobehavioral changes, may participate in nickel-induced neurologic effects. The inactivation of ISC containing metabolic enzymes may result in the disturbance of aerobic metabolism. A better understanding of how nickel impacts the energy metabolic processes may provide insight into the prevention of nickel neurotoxicity.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Níquel/toxicidade , Aconitato Hidratase/metabolismo , Trifosfato de Adenosina/metabolismo , Aerobiose/efeitos dos fármacos , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Regulação para Baixo , Proteínas Ferro-Enxofre/metabolismo , Ácido Láctico/metabolismo , Masculino , Camundongos , NAD/metabolismo , Estresse Oxidativo , Consumo de Oxigênio/efeitos dos fármacos
14.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(4): 450-4, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22803420

RESUMO

OBJECTIVE: To study on the Chinese medicine (CM) syndrome distribution of ulcerative colitis (UC) and the distribution of CM syndrome types at different staging periods. METHODS: From March 2007 to April 2010, 110 UC out- or inpatients at the Department of Digestive Diseases of Guangzhou Municipal Hospital of Traditional Chinese Medicine were recruited. The patients' symptoms were calculated. The systematic clustering was used. The symptom was taken as the variable in the clustering. The syndrome types were confirmed according to the clustering results. The syndrome typing was performed and its results were analyzed. RESULTS: There were 64 main symptoms in UC patients, including diarrhea, mushy stool, watery stool, abdominal pain, and bloody stool. Seventy cases belonged to the active period and 40 to the remission period. The UC syndrome types were sequenced from high to low as the dampness-heat of Dachang syndrome, Pi-Wei qi deficiency syndrome, Gan depression and Pi deficiency syndrome, Pi-Shen yang deficiency syndrome, blood stasis in the intestinal collaterals syndrome, yin and blood deficiency syndrome. There was statistical difference in the case number among different syndrome types (P < 0.05). In the active period, dominated were the dampness-heat of Dachang syndrome (28 cases, 25.5%), Gan depression and Pi deficiency syndrome (14 cases, 12.7%), and blood stasis in the intestinal collaterals syndrome (10 cases, 9.0%). In the remission period, dominated were Pi-Wei qi deficiency syndrome (18 cases, 16.4%) and Pi-Shen yang deficiency syndrome (10 cases, 9.0%), showing statistical difference (P<0.05). The typical symptoms of patients of the dampness-heat of Dachang syndrome were sequenced from high to low as yellow tongue fur (31 cases, 28.1%), tenesmus (26 cases, 23.6%), mucopurulent bloody stool (25 cases, 227%), diarrhea (24 cases, 21.8%), anal burning (24 cases, 21.8%), watery stool (21 cases, 19.0%), abdominal pain (19 cases, 17.2%), red tongue (19 cases, 17.2%), and greasy tongue fur (19 cases, 17.2%). The typical symptoms of patients of Pi-Wei qi deficiency syndrome were sequenced from high to low as tastelessness (25 cases, 22.7%), fine pulse (25 cases, 22.7%), pink tongue (22 cases, 20.0%), eructation (21 cases, 19.1%), hypodynamia (21 cases, 19.1%), loss of appetite (20 cases, 18.2%), and white tongue fur (20 cases, 18.2%). The typical symptoms of patients of Pi-Shen yang deficiency syndrome were sequenced from high to low as abdominal pain (17 cases, 15. 5%), preference for warmth (17 cases, 15. 5%), diarrhea (16 cases, 14.5%), aggravation while encountering cold (15 cases, 13.6%), white tongue fur (15 cases, 13.6%), pale white tongue (14 cases, 12.7%). The typical symptoms of patients of Gan depression and Pi deficiency syndrome were sequenced from high to low as emotions inducing (18 cases, 16.4%), eructation (16 cases, 14.5%), white tongue coating (16 cases, 14.5%), dry stool before loose stool (15 cases, 13.6%), frequent break wind (15 cases, 13.6%), and frequent sigh (15 cases, 13.6%). The typical symptoms of patients of blood stasis in the intestinal collaterals syndrome were sequenced from high to low as abdominal pain (12 cases, 10.9%), sting (12 cases, 10.9%), soreness of the waist (12 cases, 10.9%), dark red tongue with petechiae (12 cases, 10.9%), thick fur (12 cases, 10.9%). There was statistical difference in the symptom ratio among each syndrome types (P<0.05). There was no statistical difference in other symptoms except yin and blood deficiency syndrome (P>0.05). CONCLUSIONS: The dampness-heat of Dachang syndrome, Gan depression and Pi deficiency syndrome, and blood stasis in the intestinal collaterals syndrome were dominated in the UC active period. Pi-Wei qi deficiency syndrome and Pi-Shen yang deficiency syndrome were dominated in the remission period.


Assuntos
Colite Ulcerativa/classificação , Colite Ulcerativa/diagnóstico , Medicina Tradicional Chinesa/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência da Energia Yang , Deficiência da Energia Yin , Adulto Jovem
15.
Zhongguo Zhen Jiu ; 31(11): 975-7, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22136017

RESUMO

OBJECTIVE: To observe the clinical efficacy of the needling depth recorded in Lingshu (Miraculous Pivot) for irritable bowel syndrome of diarrhea (IBS-D) in Germany. METHODS: With the needling technique recorded in Lingshu: Jingshui (Miraculous Pivot: Meridian Water), 21 cases of IBSD were treated with acupuncture at Zhangmen(lR 13), Zhongwan(CV 12), Tianshu (ST 25), Guanyuan(CV 4), Qimen (LR 14), Quchi (LI 11), Hegu (LI 4), Yinlingquan(SP 9), Zusanli (ST 36) and Taichong (LR 3), 0. 1-0. 6 cun (2-12 mm) in depth. Even needling technique was applied. The treatment was given 2-3 times each week, and 8 treatments made one session. The efficacy and the scale for the severity degree of symptom (IBS-SSS) were observed in 1-2 sessions of treatment. RESULTS: The total effective rate was 52.4% (11/21) in the 1st session and was 90.5% (19/21) in the 2nd session. The efficacy in the 2nd session was superior to that in the 1st session (P < 0.05). IBS-SSS was 143.58 +/- 70.15 in the 1st session and was 115.98 +/- 72.68 in the 2nd session, all reduced obviously as compared with those before treatment (all P < 0.01). The reducing degree in the 2nd session was much remarkable than that in the 1st session (P < 0.05). CONCLUSION: The better clinical efficacy has been achieved for IBS-D treated with needling depth recorded in Lingshu (Miraculous Pivot) in Germany. The longer session of treatment is, the better efficacy is obtained.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Diarreia/terapia , Síndrome do Intestino Irritável/terapia , Terapia por Acupuntura/instrumentação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
16.
J Pineal Res ; 51(4): 426-33, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21797922

RESUMO

Recent studies suggest that oxidative stress and mitochondrial dysfunction play important roles in the neurotoxicity of nickel. Because mitochondrial DNA (mtDNA) is highly vulnerable to oxidative stress and melatonin can efficiently protect mtDNA against oxidative damage in various pathological conditions, the aims of this study were to determine whether mtDNA oxidative damage was involved in the neurotoxicity of nickel and to assay the neuroprotective effects of melatonin in mtDNA. In this study, we exposed mouse neuroblastoma cell lines (Neuro2a) to different concentrations of nickel chloride (NiCl(2), 0.125, 0.25, and 0.5 mm) for 24 hr. We found that nickel significantly increased reactive oxygen species (ROS) production and mitochondrial superoxide levels. In addition, nickel exposure increased mitochondrial 8-hydroxyguanine (8-OHdG) content and reduced mtDNA content and mtDNA transcript levels. Consistent with this finding, nickel was found to destroy mtDNA nucleoid structure and decrease protein levels of Tfam, a key protein component for nucleoid organization. However, all the oxidative damage to mtDNA induced by nickel was efficiently attenuated by melatonin pretreatment. Our results suggest that oxidative damage to mtDNA may account for the neurotoxicity of nickel. Melatonin has great pharmacological potential in protecting mtDNA against the adverse effects of nickel in the nervous system.


Assuntos
DNA Mitocondrial/efeitos dos fármacos , Melatonina/farmacologia , Níquel/toxicidade , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Linhagem Celular Tumoral , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
17.
Toxicol Appl Pharmacol ; 253(1): 38-44, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21419151

RESUMO

Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl2) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ(m)), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.


Assuntos
Carnitina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Níquel/toxicidade , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Camundongos , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/prevenção & controle , Níquel/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(10): 1891-3, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18971195

RESUMO

OBJECTIVE: To investigate the effect of Changyanqing decoction, a traditional Chinese medicinal preparation, on the expressions of interleukin-10 (IL-10) and intercellular adhesion molecule-1 (ICAM-1) in the colon mucosa of rats with ulcerative colitis. METHODS: The rats with ulcerative colitis induced by trinitrobenzene sulphonic acid and ethanol enema were randomly divided into 3 groups, namely the model group, sulfasalazine (SASP) group, and Changyanqing decoction group. Daily treatment with intragastric administration and enema of normal saline, SASP (100 mg/kg), and Changyanqing decoction (39.75 mg/kg), respectively, were administered 24 h after the establishment of colitis till the end of the experiment. Another group of rats was used as the normal control group. The disease activity index (DAI) and colon mucosa damage index (CMDI) of the rats were calculated. The activity of myeloperoxidase (MPO) was measured by biochemical method, and the expressions of IL-10 and ICAM-1 protein were measured by ELISA and immunohistochemistry, respectively. RESULTS: Compared with the normal group, the model group showed significantly increased DAI, CMDI, HS score and MPO activity in the colon tissues (P < 0.01), with also significantly increased expression of ICAM-1 (P < 0.01) and decreased expression of IL-10 in the rat colon mucosa (P < 0.01). Treatment with Changyanqing decoction resulted in a significant reduction in DAI, CMDI, HS score and MPO activity (P < 0.01), and decreased the expression of ICAM-1 (P < 0.01) and increased the expression of IL-10 (P < 0.01) in the colon mucosa. The expression of ICAM-1 in the colon mucosa was positively correlated to that of IL-10 (r = 0.927, P < 0.01) and the activity of MPO (r = 0.621, P < 0.01). CONCLUSIONS: Changyanqing decoction has protective effect against rat ulcerative colitis, mediated probably by enhancement of IL-10 expression and reduction in ICAM-1 expression and neutrophil infiltration.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Molécula 1 de Adesão Intercelular/biossíntese , Interleucina-10/biossíntese , Fitoterapia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Feminino , Mucosa Intestinal/metabolismo , Ratos , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico
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