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1.
Bioelectrochemistry ; 160: 108768, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897000

RESUMO

2205 DSS is an excellent corrosion-resistant engineering metal material, but it is still threatened by microbiological corrosion. The addition of copper elements is a new approach to improving the resistance of 2205 DSS to microbiological corrosion. In this study, 2205-Cu DSS was compared with 2205 DSS to study its antimicrobial properties and resistance to microbiological corrosion in the presence of the electroactive bacterium Shewanella algae. The results showed that compared to 2205 DSS, the biofilm thickness and the number of live bacteria on the surface of 2205-Cu DSS were significantly reduced, demonstrating excellent antimicrobial properties against S. algae. Electrochemical tests and surface morphology characterization results showed that the corrosion rate and pitting of 2205-Cu DSS by S. algae were lower than that of 2205 DSS, indicating better resistance to microbiological corrosion. The good antimicrobial properties and resistance to microbiological corrosion exhibited by 2205-Cu DSS are attributed to the contact antimicrobial properties of copper elements in the 2205-Cu DSS matrix and the release of copper ions for antimicrobial effects. This study provides a new strategy for combating microbiological corrosion.

2.
BMC Gastroenterol ; 24(1): 187, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811868

RESUMO

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.


Assuntos
Aspirina , Mucosa Gástrica , Gastrinas , Omeprazol , Inibidores da Bomba de Prótons , Ratos Sprague-Dawley , Animais , Aspirina/efeitos adversos , Aspirina/administração & dosagem , Omeprazol/farmacologia , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastrinas/sangue , Masculino , Ratos , Esquema de Medicação , Humanos , Úlcera Péptica/prevenção & controle , Úlcera Péptica/induzido quimicamente , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
3.
J Colloid Interface Sci ; 662: 786-795, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382363

RESUMO

Copper-based tandem catalysts are effective candidates for yielding multi-carbon (C2+) products in electrochemical reduction of carbon dioxide (CO2RR). However, these catalysts still face a significant challenge regarding in the low selectivity for the production of a specific product. In this study, we report a high selectivity of 77.8 %±2 % at -1.0 V (vs RHE) for the production of C2H4 by using a Cu88Ag12NW catalyst which is primarily prepared through a combined Cu-Ag co-deposition and wet chemical method, employing an attractive strategy focused on regulating the microenvironment over Cu-Ag nanowires. The experimental and computational studies show that the higher *CO coverage and lower intermediate adsorption energy are important reasons for achieving the high C2H4 selectivity of Cu88Ag12NW catalyst. Comsol simulation results indicate that dense nanowires exhibit a nano-limiting effect on OH- ions, thereby leading to an increase in local pH and promoting coupling reactions. The catalyst demonstrates no noticeable decrease in current density or selectivity even after 12 h of continuous operation. The Cu-Ag nanowire composite exhibits remarkable catalytic activity, superior faradaic efficiency, excellent stability, and easy synthesis, which highlights its significant potential for electro-reducing carbon dioxide into valuable products.

4.
Environ Int ; 181: 108269, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37866238

RESUMO

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Antimônio , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Dinamarca/epidemiologia , Infarto do Miocárdio/epidemiologia , não Fumantes , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Estudos Prospectivos
5.
Ann Cardiothorac Surg ; 12(2): 128-129, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37035652
6.
J Thorac Cardiovasc Surg ; 166(4): 1234-1244.e13, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36965521

RESUMO

OBJECTIVES: To evaluate the feasibility and safety of sleeve lobectomy after neoadjuvant therapy by assessing the postoperative morbidity. METHODS: Patients who underwent sleeve lobectomy for non-small cell lung cancer (NSCLC) were retrospectively analyzed from January 2018 to December 2021. A total of 613 patients were enrolled, including 124 patients who received previous neoadjuvant therapy and 489 patients who did not. Propensity score matching was adopted to create a balanced cohort consisting of 97 paired cases. Patient demographics and perioperative outcomes were compared between the 2 groups, and logistic regression analysis was used to identify risk factors for postoperative complications. RESULTS: In the entire cohort, univariable logistic regression analysis showed that smoking history (odds ratio [OR], 1.501; 95% confidence interval [CI], 1.011-2.229, P = .044), open thoracotomy (OR, 1.748; 95% CI, 1.178-2.593, P = .006), and operation time more than 150 minutes (OR, 1.548; 95% CI, 1.029-2.328, P = .036) were risk factors for postoperative complications, and multivariable logistic regression analysis showed open thoracotomy was an independent risk factor (OR, 1.765; 95% CI, 1.178-2.643, P = .006). In the balanced cohort, the neoadjuvant group had a lower proportion of double-sleeve resections (3.1% vs 11.3%, P = .035) and longer postoperative chest tube drainage (6.67 ± 3.81 vs 5.13 ± 3.74 days, P < .001). However, no significant differences were observed in postoperative morbidity between the 2 groups (25.8% vs 24.7%, P = .869). The complete pathologic response of chemoimmunotherapy was significantly superior to chemotherapy alone (28.2% vs 4.1%, P < .001), and no significant differences were noted in postoperative morbidity in different neoadjuvant therapy modalities. CONCLUSIONS: After neoadjuvant therapy, sleeve lobectomy can be safely performed with no increased postoperative morbidity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Morbidade , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia
7.
J Colloid Interface Sci ; 631(Pt B): 173-181, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36401925

RESUMO

Enhancing the electrocatalytic oxygen evolution reaction (OER) performance is essential to realize practical energy-saving water electrolysis and CO2 electroreduction. Herein, we report a bimetallic co-doping engineering to design and fabricate nickel-cobalt-iron collaborative oxy-hydroxide on nickel foam that labeled as NiCoFeOxHy-NF. As expected, NiCoFeOxHy-NF exhibits an outstanding OER activity with current density of 10 mA cm-2 at 194 mV, Tafel slope of 53 mV dec-1, along with the robust long-term stability, which is significantly better than bimetallic NiCo and NiFe combinations. Comprehensive computational simulations and characterizations jointly unveil that the twisted ligand environment induced by heteroatoms ensures the balance strength between the metal-oxygen hybrid orbital states and the oxidized intermediates adsorption, thus lowering the oxygen cycling energy barriers for overcoming the sluggish OER kinetics. Moreover, a novel phase transition behavior is monitored by in-situ Raman spectra under OER operating conditions, which facilitates electron-mass transfer as well as boosts the exposure of activity sites. For practical applications, Ni2P-NF || NiCoFeOxHy-NF and Cu || NiCoFeOxHy-NF couples were constructed to realize high-efficiency water electrolysis and CO2 electrochemical reduction for the production of valuable H2 and C2H4, respectively. This work elucidates a novel mechanism by which bimetallic co-doping improves the electrocatalytic OER activity of nickel-based hydroxides.

8.
Front Immunol ; 13: 1029294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713425

RESUMO

Background: Reversible splenial lesion syndrome (RESLES) is a spectrum of disease radiologically characterized by reversible lesions caused by multiple factors, primarily involving the splenium of the corpus callosum (SCC). The most common causes of RESLES include infection, antiepileptic drug use and withdrawal, and severe metabolic disorders. Nevertheless, cases of autoimmune encephalitis (AE) are uncommon. Case presentation: A 26-year-old female computer programming engineer with no previous medical or psychiatric history reported to the psychiatric hospital due to a 3-day episode of irritability, babbling, limb stiffness, sleepwalking, hallucinations, and paroxysmal mania. Brain MRI revealed abnormal signals of the SCC. Lumbar puncture was performed and further testing for auto-antibodies was conducted in both the CSF and serum. CSF of the patient was positive for anti-NMDAR (titer of 1:3.2) antibodies, and serum was also positive for anti-NMDAR (titer of 1:32) as well as mGluR5 (titer of 1:10) antibodies. Enhanced CT of the pelvis showed an enlarged pelvic mass; bilateral ovarian teratomas (mature teratoma and immature teratoma) were evaluated, which were pathologically confirmed after transabdominal left adnexal resection, right ovarian biopsy, and ovarian cystectomy. The patient considerably improved after intravenous administration of steroids, immunoglobulin, oral prednisone, surgical treatment, and chemotherapy. A follow-up MRI revealed completely resolved lesions. During a 3-month follow-up, the patient experienced complete resolution of symptoms without any sign of recurrence and tumors. The titer of the anti-NMDAR antibody decreased to 1:10 in serum. Conclusion: Herein, we report a rare case of AE with overlapping auto-antibodies, along with RESLES and bilateral ovarian teratomas. The current case provides the possibility of the concurrence of mGluR5 antibodies in anti-NMDAR encephalitis. However, the underlying mechanism remains elusive. Furthermore, we provide additional evidence that overlapping antibodies-related pathology may be one of the many causes of RESLES. Nonetheless, caution should be observed in interpreting the observation, considering that this is a single-case study.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Neoplasias Ovarianas , Teratoma , Feminino , Humanos , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Anticorpos , Teratoma/complicações , Teratoma/diagnóstico
9.
Pharm Biol ; 59(1): 1351-1358, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34590530

RESUMO

CONTEXT: Sepsis is a systemic inflammatory disease; pristimerin exhibits strong antibacterial, anti-inflammatory and antioxidant properties. OBJECTIVES: We explored whether pristimerin protected against cognitive dysfunction and neuroinflammation in C57BL/6 J mice with sepsis-induced brain injuries. MATERIALS AND METHODS: Sepsis was induced by intraperitoneal administration of 2 mg/kg lipopolysaccharide (LPS). C57BL/6 J mice were separated into four groups (n = 10 per group): positive control, negative control, pristimerin 10 mg/kg and pristimerin 100 mg/kg. Pristimerin was administered orally for 28 days prior to LPS administration and for six days thereafter. Behavioural changes were assessed one day after LPS administration using the Morris water maze and via neurological dysfunction scoring. Molecular pathogenesis was explored by measurement of malondialdehyde, superoxide dismutase, reactive oxygen species and inflammatory cytokine levels in mouse brains. Neuronal apoptosis was evaluated using the TUNEL assay. The levels of p-Akt/Akt, p-PI3K/PI3K, mTOR, Bax, Bcl-2 and caspase-3 proteins were determined via Western blotting. RESULTS: Pristimerin improved cognitive function and reduces the neurological score to 1.15 ± 0.03. Pristimerin significantly reduced all cytokine levels: TNF-α by 18 ± 0.6 pg/mg, IL-1ß by 43 ± 1.3 pg/mg and IL-6 by 34 ± 1.12 pg/mg. There was significant (p < 0.01) improvement in PI3K/Akt signalling and histopathological changes in the brain tissue of sepsis induced brain injured rats. CONCLUSIONS: Pristimerin ameliorated neuronal injury by regulating PI3K/Akt signalling in mice with sepsis-induced brain injuries. Pristimerin may merit further development for clinical applications.


Assuntos
Lesões Encefálicas/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Triterpenos Pentacíclicos/farmacologia , Sepse/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/etiologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/prevenção & controle , Triterpenos Pentacíclicos/administração & dosagem , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Sepse/complicações , Transdução de Sinais/efeitos dos fármacos
10.
SSM Popul Health ; 15: 100856, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34277923

RESUMO

RATIONALE: Smoking prevalence is well known to vary socioeconomically but has been less studied in relation to political participation. Growing evidence suggests that health disparities and political nonparticipation are intertwined, but the underlying mechanism is unclear. OBJECTIVE: We investigated the relationship between smoking and voter registration, testing various forms of trust as possible mediators, in U.S. national survey data collected around the 2012 presidential election. METHODS: A random half (n = 9757) of adults who completed The Attitudes and Behaviors Survey on Health (TABS) in 2012 (response rate was 58.4% for landline and 24.3% for cell phone) also answered a section on voter registration, voting behavior, and trust in people and selected institutions. Multivariable logistic regression was used to examine the association between smoking and registering to vote and potential mediation by trust in people and various institutions, adjusted for covariates known to be associated with both. Analyses used design-based methods with weights to account for sampling probabilities, nonresponse, and calibration to the U.S. adult population in 2012. RESULTS: Compared with nonsmokers, daily smokers had significantly lower adjusted odds of being registered to vote (aOR: 0.33, 95% CI: 0.21-0.52) and higher adjusted odds of having low trust in people (aOR: 2.50, 95% CI: 1.29-4.83). Low trust in people predicted lower odds of registering to vote (aOR: 0.55, 95% CI: 0.36 to 0.84) and partially mediated the smoking-registration relationship. CONCLUSION: Lower electoral participation among daily smokers is partly attributable to lower trust in people, a factor that could also affect willingness to use cessation support resources such as quitlines. Low trust and low political participation among daily smokers may have important political and public health consequences.

11.
Am J Transl Res ; 12(6): 2793-2804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655810

RESUMO

The purpose of the current study was to investigate the differences in knee kinematics and kinetics in patients with semilunar lateral meniscus (SLM) and discoid lateral meniscus (DLM) injuries before and after arthroscopic partial meniscectomy during level walking. Fifteen healthy volunteers (control group), thirteen patients with SLM injury (SLM group) and nine patients with DLM injury (DLM group) were enrolled in our study. Gait analyses were performed pre- and post-operatively during level walking at a self-selected walking speed. Our results showed that compared to the control group before surgery, the SLM and DLM groups showed significantly lower walking speed, shorter stride length, lower maximum knee flexion during stance phase and swing phase, lower first peak knee flexion moment, and smaller adduction-abduction range of motion (ROM) during the gait cycle. Compared to the control group, only the DLM group showed significantly decreased flexion-extension ROM and maximum abduction angle. The first peak knee adduction moment was lower in the SLM group than in the control group. Significant difference was observed in first peak knee flexion moment between SLM and DLM groups. After surgery, there were no significant differences in gait spatiotemporal parameters, knee kinematics, and kinetics between the three groups, indicating that meniscectomy is an effective treatment for both types of injury. By using three-dimensional gait analysis, the current results revealed that lateral meniscus types influence gait patterns after injury, which may further impact clinical treatment choice and long-term prognosis.

12.
Biomed Pharmacother ; 125: 109859, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32036209

RESUMO

In this study, we identified prognostic biomarkers for lung squamous cell carcinoma (LUSC) by integrating multiple sets of DNA copy number variants (CNV) and methylation variant (MET) data, and performing qPCR and immunohistochemical identification. We examined the expression of CNV and MET in 368 LUSC patients. Gene expression associated with DNA copy number or DNA methylation was identified and four LUSC gene subtypes were defined based on these correlations. The prognosis overall survival (OS) of the iC1 subtype was significantly lower than that in the iC2 and iC4 subtypes. We assessed the immune scores of each subtype and found that the six immune cell scores of the iC3 subtype were significantly higher than the other subtypes (p < 0.01). Three genes associated with prognosis, NFE2L2, ASAH2, and RIMBP2, were identified by comparing the expression of CNV and MET in subtypes. Analysis of mutational differences between subtypes revealed a group of genes with significant mutations between the iC1 and iC4 subtypes. The number of mutations in the NFE2L2 gene in LUSC was significantly higher than that in other genes, and the gene was prognostic. The number of mutations was significantly higher in the best iC4 subtype than the iC1 subtype with the worst prognosis; the other two genes, ASAH2 and RIMBP2, were only found in the worst prognosis of the iC1 subtype. This comprehensive multi-omics analysis of genomics, epigenomics, and transcriptomics data provides new insights into the molecular mechanisms of LUSC and may be helpful in identifying biomolecular markers for early disease diagnosis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Biologia Computacional , Epigênese Genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Transcriptoma , Biomarcadores Tumorais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Metilação de DNA , Epigenômica , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico
13.
J Addict Med ; 14(1): 48-55, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30939501

RESUMO

OBJECTIVES: Marijuana's evolving legality may change marijuana use patterns in adults. Co-use of marijuana and tobacco are strongly associated, and populations with mental health disorders are disproportionately likely to use either substance, but neither association has been assessed in the context of legal recreational marijuana. We assessed the associations of tobacco smoking with marijuana use and with mental health disorders in Colorado in 2015. METHODS: Data came from a population-based survey of adults (n = 8023). Multiple logistic regressions were used with current tobacco smoking as the primary outcome. Past 30-day marijuana use and mental health status were the independent variables of interest. Covariates included age, sex, ethnicity, poverty level, and education. RESULTS: Adults who used marijuana in the past 30 days had 3.4 (95% confidence interval [CI] 2.7, 4.2) greater odds of currently smoking tobacco compared to adults who had not recently used marijuana, after adjusting for sociodemographic and economic factors. A mental health disorder was independently associated with tobacco smoking (adjusted odds ratio [OR] 1.7, 95% CI 1.4, 2.1). Prevalence of co-use among adults self-reporting a mental health disorder was significantly higher compared those without a mental health disorder (11.1% vs 4.3%; P < 0.0001). CONCLUSIONS: This study examined the associations between mental health, marijuana use, and tobacco smoking after the legalization of recreational marijuana in Colorado. Adults using marijuana and/or self-reporting a mental health disorder were more likely to smoke tobacco and should be targeted for cessation interventions.


Assuntos
Uso da Maconha/epidemiologia , Transtornos Mentais/epidemiologia , Uso de Tabaco/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colorado/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
14.
Cell Biol Int ; 42(2): 205-215, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29024399

RESUMO

Magnesium, as a physiological calcium antagonist, plays a vital role in the bone metabolism and the balance between magnesium and calcium is crucial in bone physiology. We recently demonstrated that matrix mineralization in human bone marrow-derived mesenchymal stem cells (hBMSCs) can be suppressed by high Mg2+ . However, a complete understanding of the mechanisms involved still remains to be elucidated. As mitochondrial calcium phosphate granules depletion manifests concurrently with the appearance of matrix vesicles (MVs) and autophagy are associated with matrix mineralization, we studied the effect of high extracellular Mg2+ on these pathways. Our results first demonstrated that high Mg2+ has a significant inhibitory effect on the generalization of extracellular mineral aggregates and the expression of collagen 1 along which the mineral crystals grow. Transmission electron microscope results showed that less amount of MVs were observed inside hBMSCs treated with high Mg2+ and high Mg2+ inhibited the release of MVs. In addition, high Mg2+ significantly suppressed mitochondrial Ca2+ accumulation. Autophagy is promoted as a response to osteogenesis of hBMSCs. High Mg2+ inhibited the level of autophagy upon osteogenesis and autophagy inhibitor 3-MA significantly suppressed mineralization. Exogenous ATP can reverse the inhibitory effect of high Mg2+ by increasing the level of autophagy. Taken together, our results indicate that high Mg2+ may modulate MVs-mediated mineralization via suppressing mitochondrial Ca2+ intensity and regulates autophagy of hBMSCs upon osteogenesis, resulting in decreased extracellular mineralized matrix deposition. Our results contribute to the understanding of the role of magnesium homeostasis in osteoporosis and the design of magnesium alloys.


Assuntos
Autofagia , Calcificação Fisiológica , Vesículas Extracelulares/metabolismo , Magnésio/fisiologia , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Trifosfato de Adenosina/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/metabolismo , Células Cultivadas , Vesículas Extracelulares/ultraestrutura , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos
16.
Mol Cell ; 66(3): 332-344.e4, 2017 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-28475869

RESUMO

Skeletal muscle is a major site of postprandial glucose disposal. Inadequate insulin action in skeletal myocytes contributes to hyperglycemia in diabetes. Although glucose is known to stimulate insulin secretion by ß cells, whether it directly engages nutrient signaling pathways in skeletal muscle to maintain systemic glucose homeostasis remains largely unexplored. Here we identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improved postprandial glucose disposal in mice, whereas its muscle-specific ablation impaired insulin action and led to postprandial glucose intolerance. Mechanistically, glucose triggers KATP channel-dependent calcium signaling, which promotes HDAC5 phosphorylation and nuclear exclusion, leading to Baf60c induction and insulin-independent AKT activation. This pathway is engaged by the anti-diabetic sulfonylurea drugs to exert their full glucose-lowering effects. These findings uncover an unexpected mechanism of glucose sensing in skeletal myocytes that contributes to homeostasis and therapeutic action.


Assuntos
Glicemia/metabolismo , Metabolismo Energético , Fibras Musculares Esqueléticas/metabolismo , Transdução de Sinais , Animais , Glicemia/efeitos dos fármacos , Linhagem Celular , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Metabolismo Energético/efeitos dos fármacos , Ativação Enzimática , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Homeostase , Humanos , Hipoglicemiantes/farmacologia , Insulina/sangue , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Canais KATP/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Musculares Esqueléticas/efeitos dos fármacos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Período Pós-Prandial , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Compostos de Sulfonilureia/farmacologia , Fatores de Tempo , Técnicas de Cultura de Tecidos
17.
Med Sci Monit ; 22: 3523-3528, 2016 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-27694796

RESUMO

BACKGROUND The purpose of this study was to determine the effect of mild hypothermia therapy on gastric mucosa after cardiopulmonary resuscitation (CPR) and the underlying mechanism. MATERIAL AND METHODS Ventricular fibrillation was induced in pigs. After CPR, the surviving pigs were divided into mild hypothermia-treated and control groups. The changes in vital signs and hemodynamic parameters were monitored before cardiac arrest and at intervals of 0.5, 1, 2, 4, 6, 12, and 24 h after restoration of spontaneous circulation. Serum IL-6 was determined at the same time, and gastroscopy was performed. The pathologic changes were noted, and the expression of IL-6 was determined by hematoxylin and eosin (HE) staining and immunohistochemistry under light. RESULTS The heart rate, mean arterial blood pressure, and cardiac output in both groups did not differ significantly. The gastric mucosa ulcer index evaluated by gastroscopy 2 h and 24 h after restoration of spontaneous circulation (ROSC) in the mild hypothermic group was lower than that the control group (P<0.05). The inflammatory pathologic score of gastric mucosa in the mild hypothermic group 6-24 h after ROSC was lower than that in the control group (P<0.05). Serum and gastric mucosa IL-6 expression 0.5-4 h and 6, 12, and 24 h after ROSC was lower in the mild hypothermic group than in the control group (P<0.05). CONCLUSIONS Mild hypothermia treatment protects gastric mucosa after ROSC via inhibiting IL-6 production and relieving the inflammatory reaction.


Assuntos
Reanimação Cardiopulmonar/métodos , Mucosa Gástrica/fisiologia , Hipotermia Induzida/métodos , Interleucina-6/antagonistas & inibidores , Fibrilação Ventricular/terapia , Animais , Pressão Arterial/fisiologia , Débito Cardíaco/fisiologia , Modelos Animais de Doenças , Parada Cardíaca/terapia , Frequência Cardíaca/fisiologia , Hemodinâmica , Interleucina-6/metabolismo , Masculino , Distribuição Aleatória , Suínos , Porco Miniatura , Fibrilação Ventricular/fisiopatologia
18.
Biochem Biophys Res Commun ; 478(1): 314-322, 2016 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-27402270

RESUMO

Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg(2+)/Ca(2+) balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP-P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg(2+) ([Mg(2+)]e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 µM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg(2+)]e levels. A high [Mg(2+)]e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg(2+) and Ca(2+) is therefore contradictory, Mg(2+) inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca(2+). JC-1 staining verified the protective effect of Mg(2+) on mitochondrial membrane potential and the decrease induced by Ca(2+). Taken together, these results indicate that high [Mg(2+)]e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg(2+) and Ca(2+) influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs.


Assuntos
Calcificação Fisiológica/fisiologia , Matriz Extracelular/metabolismo , Magnésio/administração & dosagem , Mitocôndrias/metabolismo , Células-Tronco/metabolismo , Tendões/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Matriz Extracelular/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Tendões/citologia
19.
Am J Prev Med ; 51(2): 232-239, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27020316

RESUMO

INTRODUCTION: Most smokers who try to quit do not use an evidence-based treatment (EBT), and in 2001, Hispanic/Latino quit-attempters were about half as likely as non-Hispanic white (NHW) quit-attempters to use one. This study analyzed the patterns of EBT use in Colorado across a recent decade, 2001-2012. METHODS: Data were from The Attitudes and Behaviors Survey, a random cross-sectional population-level telephone survey. Data included NHW and English-speaking Hispanic/Latino respondents from 2001 (n=11,872), 2005 (n=10,952), 2008 (n=12,323), and 2012 (n=13,265). Statistical analyses were conducted in 2014-2015. EBT measures included nicotine-replacement therapy, prescription cessation medication, telephone quit-line coaching, and other counseling. Bivariate and multiple logistic regression analyses evaluated associations across years between EBT use and ethnicity, adjusting for covariates. RESULTS: Any EBT use increased with each successive survey year, and the relative increase from 2001 to 2012 was greater among Hispanic/Latino than NHW quit-attempters (75.7% vs 38.7%). However, adjusted for covariates, Hispanic/Latino quit-attempters in 2012 were still 54% less likely to use any EBT (AOR=0.46, 95% CI=0.34, 0.63), 45% less likely to use nicotine-replacement therapy (AOR=0.55, 95% CI=0.39, 0.77), and 50% less likely to use a prescription cessation medication (AOR=0.50, 95% CI=0.30, 0.85). Ethnicity was unrelated to use of a quit-line or other counseling service. CONCLUSIONS: EBT use for smoking cessation has increased over the past decade, with more rapid increase among English-speaking Hispanics/Latinos compared with NHWs, but a large use gap remains. Healthcare and public health efforts are needed to clarify and overcome factors contributing to this ongoing disparity.


Assuntos
Prática Clínica Baseada em Evidências/métodos , Hispânico ou Latino/estatística & dados numéricos , Abandono do Hábito de Fumar/etnologia , População Branca/estatística & dados numéricos , Adulto , Idoso , Colorado , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/psicologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Inquéritos e Questionários , Telefone
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