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PURPOSES: This study was designed to evaluate the effect of preoperative jaundice on long-term prognosis of gallbladder carcinoma (GBC) after radical resection (R0). METHODS: A total of 267 GBC patients who underwent R0 resection from January 2004 to December 2014 were enrolled, including 54 patients with preoperative jaundice and 213 patients without jaundice. The clinicopathological parameters between the two groups were compared, and the correlation between preoperative jaundice and the long-term prognosis was furtherly analyzed. RESULTS: Unilateral and multivariate analyses of 267 GBC patients showed that the depth of tumor invasion (pT stage), lymphatic metastasis, and hepatic invasion were independent prognostic factors. The univariate and multivariate analysis of 54 GBC patients with preoperative jaundice showed that only pT stage was an independent factor for prognosis. Furthermore, the intraoperative blood transfusion and pT stage were significant different between long-term survival (survive for more than 3 years) and those who died within 3 years (P < 0.05). CONCLUSION: Preoperative jaundice was not the independent factor resulting in the poor long-term prognosis of gallbladder carcinoma after R0 resection. The pT stage was the only long-term prognostic factor in all GBC patients regardless of preoperative jaundice.
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Neoplasias da Vesícula Biliar , Icterícia , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Icterícia/etiologia , Icterícia/patologia , Fígado/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Synovial fluid components, especially lipids, can trigger oxidation of ultrahigh-molecular-weight polyethylene (UHMWPE) artificial joint components in vivo. The use of antioxidants such as vitamin E effectively diminishes the oxidative cascade by capturing free radicals and reducing the oxidation potential of UHMWPE implants. Using a thermo-oxidative aging method, we recently found that tea polyphenols can enhance the oxidation resistance of irradiated UHMWPE in comparison with commercial vitamin E. However, it is yet unknown whether tea polyphenols can reduce lipid-induced oxidation. QUESTIONS/PURPOSES: We explored whether tea polyphenol-stabilized UHMWPE would exhibit (1) lower squalene absorption; (2) stronger oxidation resistance; and (3) lower content of free radicals than vitamin E-stabilized UHMWPE under a physiologically-motivated in vitro accelerated-aging model. METHODS: Tea polyphenol (lipid-soluble epigallocatechin gallate [lsEGCG]) and vitamin E were blended with UHMWPE powders followed by compression molding and electron beam irradiation at 100 and 150 kGy. Small cubes (n = 3, 60 mg, 4 × 4 × 4 mm) cut from the blocks were doped in squalene at 60°, 80°, 100°, and 120° C for 2 hours. Gravimetric change of the cubes after squalene immersion was measured to assess absorption. Thin films (n = 3, â¼60 µm) were also microtomed from the blocks and were doped at 120° C for 24 hours. Oxidation induction time (n = 3, 5 mg of material from the cubes) and incipient oxidation temperature (n = 3, thin films) were obtained to determine the oxidation stability. Signal intensity of the free radicals, obtained by electron spin resonance spectroscopy, was used to qualitatively rank the antioxidant ability of vitamin E and lsEGCG. RESULTS: Squalene absorption was comparable between lsEGCG/UHMWPE and vitamin E/UHMWPE at a given temperature and radiation dose. The oxidation induction time of 100 kGy-irradiated UHMWPE was increased with lsEGCG compared with vitamin E except at 120° C. For example, the oxidation induction time value of 100 kGy-irradiated lsEGCG/UHMWPE immersed at 60 C was 25.3 minutes (24.2-27.8 minutes), which was 8.3 minutes longer than that of 100 kGy-irradiated vitamin E/UHMWPE which was 17.0 minutes (15.0-17.1 minutes) (p = 0.040). After squalene immersion at 120° C, the incipient oxidation temperature of 100 and 150 kGy irradiated lsEGCG/UHMWPE was 234° C (227-240° C) and 227° C (225-229° C), which was higher than vitamin E-stabilized counterparts with value of 217° C (214-229° C; p = 0.095) and 216° C (207-218° C; p = 0.040), respectively. The electron spin resonance signal of 150 kGy irradiated lsEGCG/UHMWPE was qualitatively weaker than that of 150 kGy irradiated vitamin E/UHMWPE. CONCLUSIONS: lsEGCG-stabilized UHMWPE demonstrated higher oxidation resistance than vitamin E-stabilized UHMWPE after squalene immersion, likely because lsEGCG donates more protons to eliminate macroradicals than vitamin E. CLINICAL RELEVANCE: Our in vitro findings provide support that lsEGCG may be effective in protecting against oxidation that may be associated with synovial fluid-associated oxidation of highly crosslinked UHMWPE joint replacement components.
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Antioxidantes/química , Catequina/análogos & derivados , Prótese Articular , Extratos Vegetais/química , Polietilenos/química , Vitamina E/química , Antioxidantes/isolamento & purificação , Camellia sinensis/química , Catequina/química , Catequina/isolamento & purificação , Radicais Livres/química , Oxirredução , Extratos Vegetais/isolamento & purificação , Polietilenos/efeitos da radiação , Falha de Prótese , Esqualeno/química , Fatores de TempoRESUMO
The effect of myeloid cell leukemia-1 (Mcl-1) inhibition on apoptosis of peritoneal macrophages in mice infected with Mycobacterium tuberculosis was investigated and the primary signaling pathway associated with the transcriptional regulation of Mcl-1 was identified. Real-time PCR and western blotting indicated that Mcl-1 transcript and protein expression are upregulated during infection with virulent M. tuberculosis H37Rv and Xinjiang strains but not with attenuated M. tuberculosis strain H37Ra or Bacillus Calmette-Guérin. Mcl-1 transcript and protein expression were downregulated by specific inhibitors of the Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways (AG490, PD98059 and LY294002, respectively). The strongest inhibitor of Mcl-1 expression was PD98059, the MAPK inhibitor. Flow cytometry demonstrated that the rate of apoptosis in peritoneal macrophages is significantly higher in mice infected with M. tuberculosis and the rate of apoptosis is correlated with the virulence of the strain of M. tuberculosis. Apoptosis was found to be upregulated by AG490, PD98059 and LY294002, whereas inhibition of the MAPK pathway sensitized the infected macrophages to apoptosis. Taken together, these results suggest that specific downregulation of Mcl-1 significantly increases apoptosis of peritoneal macrophages and that the MAPK signaling pathway is the primary mediator of Mcl-1 expression.
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Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Tuberculose/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Regulação para Baixo , Feminino , Flavonoides/metabolismo , Flavonoides/farmacologia , Fator Gênico 3 Estimulado por Interferon, Subunidade alfa/metabolismo , Janus Quinases/metabolismo , Macrófagos Peritoneais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/biossíntese , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Tuberculose/sangue , Tuberculose/patologia , Tirfostinas/metabolismo , Tirfostinas/farmacologia , Regulação para CimaRESUMO
Ferroptosis is a newly identified form of non-apoptotic regulated cell death (RCD) andplaysanimportantrole in epileptogenesis. The p38 mitogen-activated protein kinase (p38 MAPK) pathway has been confirmed to be involved in ferroptosis. The mitochondria-targeting antioxidant Elamipretide (SS-31) can reduce the generation of lipid peroxidation and the buildup of reactive oxygen species (ROS). Collectively, our present study was to decipher whether SS-31 inhibits ferroptosis via the p38 MAPK signaling pathway in the rat epilepsy model induced by pilocarpine (PILO).Adult male Wistar rats were randomly divided into four groups: control group (CON group), epilepsy group (EP group), SS-31 treatment group (SS group), and p38 MAPK inhibitor (SB203580) treatment group (SB group). Our results demonstrated that the rat hippocampal neurons after epilepsy were followed by accumulated iron and malondialdehyde (MDA) content, upregulated phosphorylated p38 MAPK protein (P-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels, reduced glutathione peroxidase 4 (Gpx4) content, and depleted glutathione (GSH) activity. Morphologically, mitochondrial ultrastructural damage under electron microscopy was manifested by a partial increase in outer membrane density, disappearance of mitochondrial cristae, and mitochondrial shrinkage. SS-31 and SB203580 treatment blocked the initiation and progression of ferroptosis in the hippocampus of epileptic rats via reducing the severity of epileptic seizures, reversing the expression of Gpx4, P-p38 , decreasing the levels of iron and MDA, as well as increasing the activity of GSH and Nrf2. To summarize, our findings proved that ferroptosis was coupled with the pathology of epilepsy, and SS-31 can inhibit PILO-induced seizures by preventing ferroptosis, which may be connected to the inhibition of p38 MAPK phosphorylation, highlighting the potential therapeutic value for targeting ferroptosis process in individuals with seizure-related diseases.
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Epilepsia , Ferroptose , Hipocampo , Mitocôndrias , Ratos Wistar , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Masculino , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Ferroptose/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Ratos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Dipeptídeos/farmacologia , Pilocarpina , Imidazóis/farmacologia , Piridinas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , OligopeptídeosRESUMO
BACKGROUND: Nanoparticle polymeric micellar paclitaxel (NPMP) is a novel Cremophor EL (CrEL)-free nanoparticle micellar formulation of paclitaxel. This study evaluated the efficacy and toxicity of NPMP in the treatment of patients with advanced gastric cancer (AGC). METHODS: Patients with histologically confirmed AGC in Jiangsu Cancer Hospital were retrospectively collected and divided into two groups. Patients in group A received NPMP at a total dose of 360 mg/m2 each cycle, and patients in group B were given paclitaxel at a dose of 210 mg/m2 each cycle. In addition, all patients received 5-fluorouracil at a dose of 0.75 g/m2 on days 1-4 and leucovorin at a dose of 200 mg/m2 on days 1-4 for at least 2 cycles. RESULTS: From January 2021 to May 2023, 63 patients (32 in group A and 31 in group B) could be evaluated for treatment response. A marked disparity in the overall response was observed between groups A and B, indicating statistical significance. The overall response rate was 31% in group A (10/32) and 10% in group B (3/31) (P = 0.034). Disease control rate was 91% in group A (29/32) and 81% in group B (25/31) (P = 0.440). No statistically significant difference in adverse reactions was observed between the two groups. However, the incidence of anemia, leucopenia, nausea, vomiting, diarrhea, liver dysfunction, and allergy in group A was notably lower than that in group B. CONCLUSIONS: NPMP combined chemotherapy offers a new, active, and safe treatment for patients with AGC.
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Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×1010viral particles) and B.1.1.529 variant (5×1010viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×1010viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.
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COVID-19 , Vacinas , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , Vacinas Combinadas , Adenoviridae/genética , Anticorpos Neutralizantes , Imunogenicidade da Vacina , Anticorpos AntiviraisRESUMO
Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria.
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On the basis of the structure of nicotlactone A (L1), a series of novel α-methylene-γ-butyrolactone derivatives B1-B43 were designed and synthesized by structure simplification and active fragment replacement strategies, and their antiviral and antifungal activities were evaluated. The bioassay studies indicated that many target compounds possessed good to excellent antiviral activity against tobacco mosaic virus (TMV) and some of these compounds exhibited specific antifungal activities against Valsa mali and Fusarium graminearum. Compound B32 exhibited the best anti-TMV activity (inactivation effect, 88.9%; protection effect, 65.8%; curative effect, 52.8%) in vivo at 500 mg/L, which is significantly higher than that of commercial virucides ribavirin and ningnanmycin. The inhibition effect of compound B32 was also visualized by the inoculation test using green fluorescent protein (GFP)-labeled TMV. The preliminary antiviral mechanism of compound B32 was investigated. Transmission electron microscopy (TEM) showed that compound B32 could destroy the integrity of virus particles. Then, molecular docking and isothermal titration calorimetry (ITC) analysis further demonstrated that compound B32 exhibited a strong binding affinity to the TMV coat protein with a dissociation constant (Kd) of 3.06 µM, superior to ribavirin. Thus, we deduced that compound B32 may interfere with the self-assembly of TMV particles by binding TMV coat protein (CP). In addition, compound B28 showed good in vitro activity against F. graminearum with an inhibition rate of 90.9% at 50 mg/L, which was greater than that of fluxapyroxad (59.1%) but lower than that of the commercial fungicide carbendazim (96.8%). The present study provides support for the application of these α-methylene-γ-butyrolactone derivatives as novel antiviral and antifungal agents in crop protection.
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Antifúngicos , Vírus do Mosaico do Tabaco , 4-Butirolactona/análogos & derivados , Antifúngicos/química , Antifúngicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Benzaldeídos , Desenho de Fármacos , Simulação de Acoplamento Molecular , Ribavirina/farmacologia , Relação Estrutura-AtividadeRESUMO
Maternal diabetes adversely affects preimplantation embryo development and oocyte maturation. Thus, it is important to identify ways to eliminate the effects of maternal diabetes on preimplantation embryos and oocytes. The objectives of this study were to investigate whether islet transplantation could reverse the effects of diabetes on oocytes. Our results revealed that maternal diabetes induced decreased ovulation; increased the frequency of meiotic spindle defects, chromosome misalignment, and aneuploidy; increased the relative expression levels of Mad2 and Bub1; and enhanced the sensitivity of oocytes to parthenogenetic activation. Islet transplantation prevented these detrimental effects. Therefore, we concluded that islet transplantation could reverse the effects of diabetes on oocytes, and that this technique may be useful to treat the fundamental reproductive problems of women with diabetes mellitus.
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Transplante das Ilhotas Pancreáticas/fisiologia , Oócitos/fisiologia , Gravidez em Diabéticas/terapia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Aneuploidia , Animais , Glicemia/análise , Glicemia/fisiologia , Peso Corporal , Aberrações Cromossômicas/embriologia , Aberrações Cromossômicas/estatística & dados numéricos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/terapia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/metabolismo , Oócitos/patologia , Ovulação/fisiologia , Gravidez , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/patologia , Gravidez em Diabéticas/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/genética , Fuso Acromático/genética , Fuso Acromático/metabolismo , Fuso Acromático/patologia , EstreptozocinaRESUMO
To avoid catastrophic bacterial infection in prosthesis failure, ultrahigh molecular weight polyethylene (UHMWPE), a common bearing material of artificial joints, has been formulated with antibiotics to eliminate bacteria locally at the implant site. However, the pressing issues regarding cytotoxic effects and evolution of drug resistant bacteria necessitates the development of bio-friendly bacteriostat with long bacteriostatic efficacy. Herein, tea polyphenol extracted from nature source was introduced in UHMWPE as a biogenic antimicrobial. Controlled antimicrobial activity was achieved by chemical crosslinking to regulate the release of the tea polyphenol. In addition, the crosslinking efficiency of UHMWPE blends with high loaded tea polyphenol was significantly improved in comparison to radiation crosslinking. The immobilized tea polyphenols also enhanced the oxidation stability of the UHMWPE, which is essential to prolong the service life in vivo and the storage time in vitro. The blends presented good biocompatibility, despite cell repellent on the highly crosslinked surface. Chemically crosslinked tea polyphenol/UHMWPE exhibited feasible properties for total joint implants, which is promising for clinical application.
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Artroplastia de Substituição , Polifenóis , Teste de Materiais , Peso Molecular , Polietilenos , Polifenóis/farmacologia , Chá , TiramRESUMO
Highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) bearings are wear-resistant to reduce aseptic loosening but are susceptible to oxidize in vivo/in vitro, as reported in clinical studies. Despite widespread acceptance of antioxidants in preventing oxidation, the crosslinking efficiency of UHMWPE is severely impacted by antioxidants, the use of which was trapped in a trace amount. Herein, we proposed a new strategy of polyphenol-assisted chemical crosslinking to facilitate the formation of a crosslinking network in high-loaded tea polyphenol/UHMWPE blends. Epigallocatechin gallate (EGCG), a representative of tea polyphenol, was mixed with UHMWPE and peroxide. Multiple reactive phenolic hydroxyl groups of tea polyphenol coupled with the nearby free radicals to form extra crosslinking sites. The crosslinking efficiency was remarkably enhanced with increasing tea polyphenol content, even at a concentration of 8 wt %. Given by the hydrogen donation principle, the high-loaded tea polyphenol also enhanced the oxidation stability of the crosslinked UHMWPE. The antioxidative performance was preserved even after tea polyphenol elution. Moreover, superior antibacterial performance was achieved by the in situ tea polyphenol release from the interconnected pathways in the present design. The strategy of polyphenol-assisted chemical crosslinking is applicable for producing highly crosslinked, antioxidative, and antibacterial UHMWPE, which has promising prospects in clinical applications.
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Antioxidantes , Artroplastia de Substituição , Antibacterianos , Polietilenos , Polifenóis , Vitamina ERESUMO
Periprosthetic joint infection (PJI) is one of the main causes for the failure of joint arthroplasty. In view of the limited clinical effect of oral/injectable antibiotics and the drug resistance problem, there is a pressing need to develop antibacterial implants with therapeutic antimicrobial properties. In this work, we prepared a highly antibacterial ultrahigh molecular weight polyethylene (UHMWPE) implant by incorporating tea polyphenols. The presence of tea polyphenols not only improved the oxidation stability of irradiated UHMWPE, but also gave it the desirable antibacterial property. The potent antibacterial activity was attributed to the tea polyphenols that produced excess intracellular reactive oxygen species and destroyed the bacterial membrane structure. The tea polyphenol-blended UHMWPE had no biological toxicity to human adipose-derived stem cells and effectively reduced bacteria-induced inflammation in vivo. These results indicate that tea polyphenol-blended UHMWPE is promising for joint replacement prostheses with multifunctionality to meet patient satisfaction.
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Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Materiais Biocompatíveis/farmacologia , Prótese Articular , Polietilenos/farmacologia , Polifenóis/farmacologia , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artroplastia de Substituição/efeitos adversos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular , Humanos , Prótese Articular/efeitos adversos , Prótese Articular/microbiologia , Masculino , Polietilenos/uso terapêutico , Polifenóis/uso terapêutico , Ratos Sprague-Dawley , Chá/químicaRESUMO
Three-dimensional excitation emission matrix was applied to characterize the fluorescence properties of dissolved organic matter in various waters of Shilong coal-mining area. Fluorescence peak I (fulvic-like) and peak II (humic-like) were strong, while peak IV and peak V (protein-like) were weak or even undetected in some samples. Fluorescence peaks in various waters and different zones showed great difference in intensities and the fluorescence peaks in underground water tended to be much lower than those of surface waters. Furthermore, the fluorescence peaks of rivers and lakes were higher than those of mine drainage, and also the fluorescence peaks in coking zone and coal mining zone were higher than those in sewage-irrigated zone, or even much higher than those in farming zone. The reason may be that coal mining activities and coal industry can bring plenty of organic matter from coal to surroundings. Meanwhile, surface water would accept mine drainage, waste water of coal-washing and sewage from daily life easier than underground water, so surface water can be polluted seriously. Fluorescence peaks in waters from coal mining area are little influenced by pH of the water but can be influenced by the content of Ca2+ to water in some extent.
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Autophagy is an adaptive response to cardiomyocytes survival under stress conditions. MicroRNAs (miRNAs, miR) have been described to act as potent modulators of autophagy. To investigate whether and how miR-199a modulated autophagy in vitro, primary cardiomyocytes were treated under starvation to induce autophagy. Results showed that down-regulation of miR-199a was sufficient to activate cardiomyocytes autophagy. MiR-199a suppressed cardiomyocytes autophagy through direct inhibiting heat shock protein family A member 5 (Hspa5). Forced overexpression of Hspa5 recovered the inhibitory effect of miR-199a in autophagy activation. Our results suggested miR-199a as an effective suppressor of starvation-induced cardiomyocytes autophagy and that Hspa5 was a direct target during this process. These results extend the understanding of the role and pathway of miR-199a in cardiomyocytes autophagy, and may introduce a potential therapeutic strategy for the protection of cardiomyocytes in myocardial infarction or ischemic heart disease.
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Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.
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Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/microbiologia , Macrófagos/microbiologia , Mycobacterium tuberculosis/fisiologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , RNA Interferente Pequeno/genética , Animais , Apoptose , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Regulação da Expressão Gênica , Macrófagos/citologia , Macrófagos/metabolismo , Macrófagos Peritoneais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Viabilidade Microbiana , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células RAW 264.7 , Interferência de RNA , Regulação para Cima , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
The aim of this study was to investigate the osseous characteristics of Chinese temporomandibular joint (TMJ) and detect the size clusters for total joint prostheses design.Computer tomography (CT) data from 448 Chinese adults (226 male and 222 female, aged from 20 to 83 years, mean age 39.3 years) with 896 normal TMJs were chosen from the Department of Radiology in the Shanghai 9th People's Hospital. Proplan CMF 1.4 software was used to reconstruct the skulls. Three-dimensional (3D) measurements of the TMJ fossa and condyle-ramus units with 13 parameters were performed. Size clusters for prostheses design were determined by hierarchical cluster analyses, nonhierarchical (K-means) cluster analysis, and discriminant analysis.The glenoid fossa was grouped into 3 clusters, and the condyle-ramus units were grouped into 4 clusters. Discriminant analyses were capable of correctly classifying 97.24% of the glenoid fossa and 94.98% of the condyle-ramus units. The means and standard deviations for the parameter values in each cluster were determined.Fossa depth and angles between the condyle and ramus were important parameters for Chinese TMJ prostheses design. 3D measurements and cluster analysis of the osseous morphology of the TMJ provided an anatomical reference and identified the dimensions of the minimum numbers of prosthesis sizes required for Chinese TMJ replacement.
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Imageamento Tridimensional , Prótese Articular , Desenho de Prótese , Articulação Temporomandibular/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ajuste de Prótese , SoftwareRESUMO
BACKGROUND: Lack of fluoroscopic landmarks can make valve deployment more difficult in patients with absent aortic valve (AV) calcification. The goal of this article was to evaluate the feasibility and effectiveness of transcatheter implantation of a valved stent into the AV position of a goat, assisted with a microcatheter which provides accurate positioning of coronary artery ostia to help valved stent deployment. METHODS: The subjects were 10 healthy goats in this study. A microcatheter was introduced into the distal site of right coronary artery (RCA) through femoral artery sheath. A minimal thoracic surgery approach was used to access the apex of the heart. The apex of the left ventricle was punctured; a delivery catheter equipped with the valved stent was introduced over a stiff guidewire into the aorta arch. We could accurately locate the RCA ostia through the microcatheter placed in the RCA under fluoroscopy. After correct valve position was confirmed, the valved stent was implanted after rapid inflation of the balloon. The immediate outcome of the function of the valved stents was evaluated after implantation. RESULTS: All ten devices were successfully implanted into the AV position of the goats. Immediate observation after the procedure showed that the valved stents were in the desired position after implantation by angiography, echocardiogram. No obstruction of coronary artery ostia occurred, and no moderate to severe aortic regurgitation was observed. CONCLUSIONS: When the procedure of transcatheter implantation of a balloon-expandable valved stent into the AV position of goats is assisted with microcatheter positioning coronary artery ostia, the success rate of operation can be increased in those with noncalcified AV.
Assuntos
Substituição da Valva Aórtica Transcateter/métodos , Animais , Valva Aórtica/cirurgia , Feminino , Cabras , Implante de Prótese de Valva Cardíaca/métodos , MasculinoRESUMO
BACKGROUND: Permanent atrial fibrillation (AF) is the most common form of dysrhythmia associated with atrial septal defects (ASDs) in patients older than 40 years. However, little is known about cardiac remodeling after transcatheter closure in patients with permanent AF. This study was designed to compare cardiac events and remodeling effects after transcatheter closure in such patients. METHODS: Clinical data of 289 adult patients older than 40 years who underwent ASD closure at our center were analyzed retrospectively. Of them, 63 patients with permanent AF were assigned to the case group, and the other 226 patients without permanent AF were assigned to the control group. Cardiac events and changes in left and right cardiac cavity dimensions before the procedure and 6 months after the procedure were compared between the two groups. RESULTS: Patients in the case group were significantly older than those in the control group. The right ventricular (RV) volume and right atrial (RA) volume were decreased significantly in both the groups during a median follow-up period of 6 months after closure (P < 0.001). The left atrial dimensions, left ventricular end-systolic dimensions, left ventricular end-diastolic dimensions and left ventricular ejection fraction showed no significant change before and after the procedure in both the groups. Changes of the RV volume and RA volume in the case group were significantly smaller than those in the control group (P = 0.005 and P < 0.001). The New York Heart Association cardiac function was improved in both the groups during the 6 months follow-up period. CONCLUSIONS: The transcatheter closure of ASD can improve the cardiac remodeling and cardiac function in patients with or without AF.
Assuntos
Fibrilação Atrial/terapia , Comunicação Interatrial/terapia , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the feasibility and satefy of transcatheter aortic valve implantation in animals by using a new balloon-expanding valved stent. METHODS: The balloon-expandable stent is made from cobalt-based alloy material and designed with a tubular, slotted structure. Fresh bovine pericardium was treated, sutured and fixed on the balloon-expandable stent. Ten healthy sheep (five males and five females), weighing an average of (25.16 ± 1.83) kg, were selected to undergo transcatheter implantation of the valve stents. The function of the valve stent was evaluated by angiography, echocardiography, and histology six months after the procedure. RESULTS: Of the ten experimental sheep, two sheep died during the operation because the higher position of the artificial valve affected the opening of the coronary artery. We successfully implanted the aortic valve stent in other eight sheep; however, one sheep died of heart failure two weeks after the operation due to the lower position of the valve stent. The valve stents were implanted in the desired position in seven sheep. Ascending aortic angiographic and autoptic findings immediately after the operation confirmed the satisfactory location and function of the valved stent. Echocardiography, angiography, and histology at six postoperative months confirmed the satisfactory location and function of the valve stent. CONCLUSION: We successfully implanted our new valve stent as a replacement of native aortic valve via the transcatheter route with satisfactory outcome.