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1.
Infect Dis Poverty ; 13(1): 54, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982550

RESUMO

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.


Assuntos
Variação Genética , Filogenia , Rickettsiales , Carrapatos , China/epidemiologia , Animais , Prevalência , Rickettsiales/genética , Rickettsiales/isolamento & purificação , Rickettsiales/classificação , Carrapatos/microbiologia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Gado/microbiologia , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia , Infecções por Rickettsia/veterinária , Rickettsia/isolamento & purificação , Rickettsia/genética , Rickettsia/classificação , Mamíferos/microbiologia , Humanos
2.
One Health ; 18: 100735, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38711479

RESUMO

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

3.
J Am Chem Soc ; 146(4): 2333-2338, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38241610

RESUMO

Odd-electron bonds, i.e., the two-center, three-electron (2c/3e), or one-electron (2c/1e) bonds, have attracted tremendous interest owing to their novel bonding nature and radical properties. Herein, complex [K(THF)6][LSn:···Sn:L] (1), featuring the first and unsupported 2c/1e Sn···Sn σ-bond with a long distance (3.2155(9) Å), was synthesized by reduction of stannylene [LSn:] (L = N,N-dpp-o-phenylene diamide) with KC8. The one-electron Sn-Sn bond in 1 was confirmed by the crystal structure, DFT calculations, EPR spectroscopy, and reactivity studies. This compound can be viewed as a stabilized radical by delocalizing to two metal centers and can readily mediate radical reactions such as C-C coupling of benzaldehyde.

4.
Science ; 382(6674): 1056-1065, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38033072

RESUMO

The development of functionally distinct catalysts for enantioselective synthesis is a prominent yet challenging goal of synthetic chemistry. In this work, we report a family of chiral N-heterocyclic carbene (NHC)-ligated boryl radicals as catalysts that enable catalytic asymmetric radical cycloisomerization reactions. The radical catalysts can be generated from easily prepared NHC-borane complexes, and the broad availability of the chiral NHC component provides substantial benefits for stereochemical control. Mechanistic studies support a catalytic cycle comprising a sequence of boryl radical addition, hydrogen atom transfer, cyclization, and elimination of the boryl radical catalyst, wherein the chiral NHC subunit determines the enantioselectivity of the radical cyclization. This catalysis allows asymmetric construction of valuable chiral heterocyclic products from simple starting materials.

5.
Entropy (Basel) ; 25(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37895572

RESUMO

The underground pressure disaster caused by the exploitation of deep mineral resources has become a major hidden danger restricting the safe production of mines. Microseismic monitoring technology is a universally recognized means of underground pressure monitoring and early warning. In this paper, the wavelet coefficient threshold denoising method in the time-frequency domain, STA/LTA method, AIC method, and skew and kurtosis method are studied, and the automatic P-phase-onset-time-picking model based on noise reduction and multiple detection indexes is established. Through the effect analysis of microseismic signals collected by microseismic monitoring system of coral Tungsten Mine in Guangxi, automatic P-phase onset time picking is realized, the reliability of the P-phase-onset-time-picking method proposed in this paper based on noise reduction and multiple detection indexes is verified. The picking accuracy can still be guaranteed under the severe signal interference of background noise, power frequency interference and manual activity in the underground mine, which is of great significance to the data processing and analysis of microseismic monitoring.

6.
Org Lett ; 25(27): 5067-5072, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37387463

RESUMO

A metal-free electrophotochemical C(sp3)-H arylation was developed under mild conditions. This method enables a switchable synthesis of diaryl alcohols and diaryl alkanes from inactive benzylic carbons. More importantly, a cheap and safe mediator N-chlorosuccinimide (NCS) was developed, which was employed for the hydrogen atom transfer (HAT) process of the benzylic C-H bond. In addition, this active radical was captured and identified by electron paramagnetic resonance (EPR).


Assuntos
Alcanos , Carbono , Hidrogênio
7.
ACS Appl Mater Interfaces ; 15(12): 15332-15343, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36940264

RESUMO

Accomplishments of enhanced activity and durability are a major concern in the design of catalysts for acidic water oxidation. To date, most studied supported metal catalysts undergo fast degradation in strongly acidic and oxidative environments due to improper controlling of the interface stability caused by their lattice mismatches. Here, we evaluate the activity-stability trends of in situ crystallized antimony-doped tin oxide (Sb-SnO2)@RuOx (Sb-SnO2@RuOx) heterostructure nanosheets (NSs) for acidic water oxidation. The catalyst prepared by atomic layer deposition of a conformal Ru film on antimony-doped tin sulfide (Sb-SnS2) NSs followed by heat treatment highlights comparable activity but longer stability than that of the ex situ catalyst (where Ru was deposited on Sb-SnO2 followed by heating). Air calcination for in situ crystallization allows the formation of hierarchical mesoporous Sb-SnO2 NSs from as-prepared Sb-SnS2 NSs and parallel in situ transformation from Ru to RuOx, resulting in a compact heterostructure. The significance of this approach significantly resists corrosive dissolution, which is justified by the enhanced oxygen evolution reaction (OER) stability of the catalyst compared to most of the state-of-the-art ruthenium-based catalysts including Carbon@RuOx (which shows ∼10 times higher dissolution) as well as Sb-SnO2@Com. RuOx and Com. RuO2. This study demonstrates the controlled interface stability of heterostructure catalysts toward enhancing OER activity and stability.

8.
J Am Chem Soc ; 145(2): 811-821, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36596224

RESUMO

The catalytic transformation of N2 to NH3 by transition metal complexes is of great interest and importance but has remained a challenge to date. Despite the essential role of vanadium in biological N2 fixation, well-defined vanadium complexes that can catalyze the conversion of N2 to NH3 are scarce. In particular, a V(NxHy) intermediate derived from proton/electron transfer reactions of coordinated N2 remains unknown. Here, we report a dinitrogen-bridged divanadium complex bearing POCOP (2,6-(tBu2PO)2-C6H3) pincer and aryloxy ligands, which can serve as a catalyst for the reduction of N2 to NH3 and N2H4. Low-temperature protonation and reduction of the dinitrogen complex afforded the first structurally characterized neutral metal hydrazido(2-) species ([V]═NNH2), which mediated 15N2 conversion to 15NH3, indicating that it is a plausible intermediate of the catalysis. DFT calculations showed that the vanadium hydrazido complex [V]═NNH2 possessed a N-H bond dissociation free energy (BDFEN-H) of as high as 59.1 kcal/mol. The protonation of a vanadium amide complex ([V]-NH2) with [Ph2NH2][OTf] resulted in the release of NH3 and the formation of a vanadium triflate complex, which upon reduction under N2 afforded the vanadium dinitrogen complex. These transformations model the final steps of a vanadium-catalyzed N2 reduction cycle. Both experimental and theoretical studies suggest that the catalytic reaction may proceed via a distal pathway to liberate NH3. These findings provide unprecedented insights into the mechanism of N2 reduction related to FeV nitrogenase.


Assuntos
Amônia , Vanádio , Amônia/química , Oxirredução , Nitrogenase/metabolismo , Prótons , Catálise
9.
Chem Sci ; 13(33): 9560-9568, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36091900

RESUMO

Developing highly efficient catalytic protocols for C-sp(3)-H bond aerobic oxidation under mild conditions is a long-desired goal of chemists. Inspired by nature, a biomimetic approach for the aerobic oxidation of C-sp(3)-H by galactose oxidase model compound CuIIL and NHPI (N-hydroxyphthalimide) was developed. The CuIIL-NHPI system exhibited excellent performance in the oxidation of C-sp(3)-H bonds to ketones, especially for light alkanes. The biomimetic catalytic protocol had a broad substrate scope. Mechanistic studies revealed that the CuI-radical intermediate species generated from the intramolecular redox process of CuIILH2 was critical for O2 activation. Kinetic experiments showed that the activation of NHPI was the rate-determining step. Furthermore, activation of NHPI in the CuIIL-NHPI system was demonstrated by time-resolved EPR results. The persistent PINO (phthalimide-N-oxyl) radical mechanism for the aerobic oxidation of C-sp(3)-H bond was demonstrated.

10.
Front Pharmacol ; 13: 876550, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35496312

RESUMO

Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, quercetin was reported to be capable of inhibiting ferroptosis, which is a recognized type of regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression of NAFLD, but experimental evidence is limited. Hence, our study aimed to investigate the effect of quercetin on hepatic ferroptosis in high-fat diet (HFD)-induced NAFLD and further elucidate the underlying molecular mechanism. Methods: C57BL/6J mice were fed either a normal diet (ND), an HFD, or an HFD supplemented with quercetin for 12 weeks. Hepatic lipid peroxidation, steatosis, ferroptosis and iron overload were examined. In vitro, steatotic L-02 cells was used to study the potential mechanism. Results: We found that the HFD caused lipid peroxidation, lipid accumulation and ferroptosis in the liver, which were rescued by quercetin supplementation. Consistent with the in vivo results, quercetin alleviated lipid droplet accumulation and reduced the levels of lipid reactive oxygen species (ROS) and ferroptosis in steatotic L-02 cells. Using a mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) and ferroptosis specific inhibitor (Fer-1), we found that quercetin remarkably alleviated lipid droplet accumulation and lipid peroxidation by reducing MtROS-mediated ferroptosis in steatotic L-02 cells. Conclusion: Our data showed that HFD consumption induced lipid accumulation and triggered ferroptosis in liver, ultimately leading to hepatic lipotoxicity, which can be alleviated by quercetin. Findings from this study provide new insight into the mechanism by which quercetin can be used for the prevention and treatment of NAFLD.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-932901

RESUMO

Objective:To evaluate the influence of telomerase reverse transcriptase (TERT) promoter mutation on radioiodine uptake status of radioactive iodine refractory papillary thyroid cancer (RAIR-PTC) and radioiodine therapy response by analyzing the mutation frequency of TERT promoter in RAIR-PTC.Methods:A total of 37 patients with RAIR-PTC (15 males, 22 females, age (49.8±16.1) years) and 40 PTC patients with effective radioiodine therapy (13 males, 27 females, age (39.8±10.9) years) between January 2005 and June 2020 in JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine were retrospectively analyzed. TERT promoter mutation and B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation of patients were observed. The differences across genotype patterns on radioiodine uptake status and therapy response were compared. The Fisher′s exact test and independent-sample t test were used for data analysis. Results:The incidence rate of TERT promoter mutation in the RAIR-PTC group was 40.54% (15/37, all C228T), which was significantly higher than that in the effective radioiodine therapy group (0, 0/40; P<0.001). No statistically significant difference was found for the mutation rate of BRAF V600E between the RAIR group (64.86%, 24/37) and the effective radioiodine therapy group (72.50%, 29/40; P=0.858). Patients with TERT promoter mutation were older ( t=3.76, P=0.001) and the non-intake rate of radioiodine in distant metastases of those patients was higher ( P=0.037). Furthermore, 2/3 of patients who received targeted therapies and 3/4 deaths had TERT promoter mutation. Among 35 patients with negative thyroglobulin antibody (TgAb), 11/14 of patients with TERT mutation had a rising stimulated thyroglobulin (sTg), while the percentage of the non-TERT mutation group was 57.1% (12/21; P=0.357). Conclusion:The TERT promoter mutation rate is significantly increased in RAIR-PTC patients and can serve as a prognostic predictor in RAIR.

12.
Neurochem Res ; 46(11): 3012-3024, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34309775

RESUMO

Sinensetin (SIN) is an important active compound that exists widely in citrus plants, and has been reported to exhibit various pharmacological properties, including anti-oxidative, anti-inflammatory, and anti-tumor. This study was designed to examine whether SIN can protect against amyloid beta (Aß)-induced neurotoxicity and to elucidate the underlying mechanism. Our results showed that pretreatment with SIN for 1 h, followed by co-treatment with Aß plus SIN for 24 h, attenuated Aß25-35-induced cell viability reduction, oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Aß25-35-induced upregulation of Toll-like receptor 4 (TLR4) expression and nuclear translocation of nuclear factor-kappaB (NF-κB) p65 subunit were inhibited by pretreatment with SIN. Furthermore, the protective effect of SIN was abrogated by TLR4 overexpression. Hence, our data suggested that SIN attenuated Aß25-35-induced neurotoxicity through the TLR4/NF-κB pathway.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Apoptose/fisiologia , Flavonoides/farmacologia , NF-kappa B/biossíntese , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/toxicidade , Receptor 4 Toll-Like/biossíntese , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , NF-kappa B/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/antagonistas & inibidores
13.
Phytother Res ; 35(6): 3390-3405, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33856743

RESUMO

Glioblastoma multiforme (GBM) is the most frequent, lethal, and aggressive tumor of the central nervous system in adults. In this study, we found for the first time that moschamindole (MCD), a rare phenolic amide with 8/6/6/5/5 rings, is a major bioactive constituent derived from Phragmites communis Trin (Poaceae) that exhibits a potential cytotoxic effect on both TMZ-resistant GBM cell lines and xenograft models. MCD-induced intrinsic apoptosis signals and mitochondrial dysfunction were confirmed by cell cycle arrest, caspase-3/7 activation, and membrane potential depolarization. Furthermore, investigations exploring the mechanism showed that MCD specifically inhibits Mia40-mediated oxidative folding of mitochondrial intermembrane space (IMS) proteins via PCR assay and immunoblot analysis. MCD relies on its positive charge to associate with mitochondrial oxidative respiration, thus blocking energy metabolism and inducing apoptosis. Overexpression and upregulation of Mia40 were proven to reverse MCD-induced apoptosis and were correlated with the chemoresistance of GBM in vitro and in vivo, respectively. Taken together, our study demonstrates that Mia40 is a potential target of the chemoresistance of glioblastoma and suggests that MCD might be a potential agent for the individualized treatment of chemoresistant GBM based on mitochondrial metabolic characteristics and Mia40 expression.


Assuntos
Apoptose/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Mitocôndrias/metabolismo , Animais , Glioblastoma/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Dalton Trans ; 49(43): 15190-15194, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33112318

RESUMO

Bismuth(iii) oxidation of 3,5-di-substituted-1,2,4-triazolato anions afforded a paddlewheel 1,2,4-triazolato dibismuth complex [L2(Bi-Bi)L2] (L = η1,η1-3,5-R2tz, R = Ph (3), iPr (4)) with very short Bi(ii)-Bi(ii) bonds (2.8650(4)-2.8721(3) Å). The reaction involved the intermediates of the organobismuth radical [Bi(R2tz)2]˙ and neutral N-1,2,4-triazolyl radical [3,5-R2tz]˙. The dimerization of the former produced the corresponding dibismuth complex while the latter was trapped by using spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) to give the radical adduct of {(3,5-R2tz)(DMPO)}˙ which was unambiguously evidenced by EPR analysis.

15.
Int J Clin Exp Pathol ; 13(5): 979-988, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509069

RESUMO

EP300-interacting inhibitor of differentiation 3 (EID3) is a member of the IED family and has been associated with tumorigenesis and tumor development in different cancer types. However, the role of EID3 in glioblastoma multiforme (GBM) prognosis is not clear. Whole transcriptome sequencing data of 249 and 149 GBM patients were collected from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) database respectively. The correlation between EID3 expression and overall survival (OS)/clinical pathologic features of GBM patients was investigated. Based on the Wilcoxon rank-sum test, EID3 expression in GBM tissues was significantly lower than in normal brain tissues (P < 0.001), and significantly higher than in LGG (low-grade glioma) (P < 0.001).There was a significant correlation between high EID3 expression with poor OS in CGGA (P = 0.049) and TCGA data (P = 0.024). Gene set enrichment analysis (GSEA) data analysis revealed a significant difference (FDR < 0.25, NOM p-value < 0.05) in the enrichment of MSigDB Collection (h.all.v6.2.symbols.gmt). A total of eight enriched pathways were identified in the high EID3 expression group, including Myc Targets V1, Kras signaling DN, and DNA repair pathways. Multivariate Cox regression analysis indicated that high expression of EID3 correlated with poor OS (P = 0.032, HR = 1.41, CI: 1.03-1.90). We conclude that EID3 could serve as an independent factor for predicting the prognosis of patients with GBM. Moreover, it is associated with GBM development through the regulation of the Myc Targets, Kras signaling DN, and DNA repair pathways.

16.
Radiol Case Rep ; 15(7): 846-849, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32382364

RESUMO

Craniopharyngioma is an uncommon intracranial tumor that primarily occurs in the sella turcica. Giant cystic craniopharyngioma is rare in general and extremely rare in adults. We report a rare case of giant cystic craniopharyngioma in the anterior pontine cisterna and suprasellar cisterna. A 27-year-old man presented with double vision, and craniocerebral MRI revealed cystic masses in the anterior pontine cisterna and suprasellar cisterna. The masses were removed surgically and diagnosed as large cystic craniopharyngiomas by pathology and MRI. Giant cystic craniopharyngioma is rare in adults. Through this case report, we hope to increase awareness of this disease among various clinicians, including radiologists.

17.
Inflammation ; 43(5): 1759-1771, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32445069

RESUMO

Alzheimer's disease (AD) is a serious neuropathologic disease characterized by aggregation of amyloid-ß (Aß) peptide. Aß-mediated oxidative stress and neuroinflammation play crucial role in the development of AD. Engeletin is a flavononol glycoside that possesses anti-inflammatory effect. However, the effects of engeletin on AD have not been investigated. In the present study, we investigated the role of engeletin in AD using an in vitro AD model. Murine microglia BV-2 cells were stimulated with Aß1-42 (5 µM) for 24 h to induce oxidative stress and inflammation. Our results showed that treatment with engeletin suppressed Aß1-42-induced viability reduction and lactate dehydrogenase (LDH) release in BV-2 cells. Engeletin attenuated Aß1-42-induced oxidative stress in BV-2 cells, as proved by decreased production of reactive oxygen species (ROS) and malonaldehyde (MDA) and increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Aß1-42-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were inhibited by engeletin treatment. Besides, engeletin inhibited Aß1-42-induced production and mRNA levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Engeletin enhanced Aß1-42-induced activation of Kelch-like ECH-associated protein 1 (Keap1)/nuclear transcription factor E2-related factor 2 (Nrf2) signaling pathway in BV-2 cells. Inhibition of Keap1/Nrf2 signaling pathway reversed the inhibitory effects of engeletin on Aß1-42-induced oxidative stress and inflammation in BV-2 cells. Taken together, engeletin attenuated Aß1-42-induced oxidative stress and inflammation in BV-2 cells via regulating the of Keap1/Nrf2 pathway. These findings indicated that engeletin might be served as a therapeutic agent for the treatment of AD.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Flavonóis/farmacologia , Glicosídeos/farmacologia , Mediadores da Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Peptídeos beta-Amiloides/antagonistas & inibidores , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Flavonóis/uso terapêutico , Glicosídeos/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Camundongos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/antagonistas & inibidores
18.
Acad Radiol ; 27(12): e263-e271, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31983532

RESUMO

RATIONALE AND OBJECTIVES: The World Health Organization 2016 classification of central nervous system tumors added the molecular classification of gliomas and has guiding significance for the operation and prognosis of glioma patients. At present, the perfusion technique plays an important role in judging the malignant degree of glioma. To evaluate the performance of dynamic susceptibility contrast (DSC)- and dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) histogram analyses in discriminating the states of molecular biomarkers and survival in glioma patients. MATERIALS AND METHODS: Forty-three glioma patients who underwent DCE- and DSC-MRI were enrolled. Relevant molecular test results, including those on isocitrate dehydrogenase (IDH), O6-methylguanine-DNA methyltransferase (MGMT) and telomere reverse transcriptase (TERT), were collected. The mean relative cerebral blood volume of DSC-MRI and histogram parameters derived from DCE-MRI (volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (Ve), fractional blood plasma volume (Vp), rate constant between the extravascular extracellular space and blood plasma (Kep) and area under the curve (AUC)) were calculated. Differences in each parameter between gliomas with different expression states (IDH, MGMT, and TERT) were evaluated. The diagnostic efficiency of each parameter was analyzed. The overall survival of all patients was assessed. RESULTS: The 10th percentile AUC (AUC = 0.830, sensitivity = 0.78, specificity = 0.80), the 90th percentile Ve (AUC = 0.816, sensitivity = 0.84, specificity = 0.79), and the mean Kep (AUC = 0.818, sensitivity = 0.76, specificity = 0.78) provided the highest differential efficiency for IDH, MGMT, and TERT, respectively. Kaplan-Meier curves showed a significant difference between subjects with a 10th percentile AUC higher or lower than 0.028 (log-rank = 7.535; p = 0.006) for IDH and between subjects with different 90th percentile Ve values (log-rank = 6.532; p = 0.011) for MGMT. CONCLUSION: Histogram DCE-MRI demonstrates good diagnostic performance in identifying different molecular types and for the prognostic assessment of glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Telomerase , Biomarcadores , Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/diagnóstico por imagem , Humanos , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética , Gradação de Tumores , Proteínas Supressoras de Tumor
19.
Artigo em Inglês | MEDLINE | ID: mdl-31642797

RESUMO

OBJECTIVE: To investigate the relationship between Interleukin-1beta (IL-1beta) and diabetic peripheral neuropathy (DPN) using animal models. METHODS: The rat model of diabetic neuropathy was induced by intraperitoneal injection of a single dose of streptozotocin (STZ) at 65mg/kg. Diabetic rats were randomly divided into two groups (10 each), one treated with 0.9% saline (DMS group) and the other with interleukin-1 receptor antagonist (IL-1RA) at 50mg/kg (DMI group) twice a day for 5 weeks. Ten normal rats matched for weight, age and sex served as normal controls (Con group) and were treated with saline. Morphologic studies of sciatic nerves were achieved using light and transmission electron microscopy. RESULTS: Transmission electron microscopy of the sciatic nerve showed the ultrastructure of myelin and the axon in the IL-1RA group was highly protected compared to diabetic controls. CONCLUSION: High levels of circulating IL-1beta may be associated with the risk of DPN and anti-IL-1 treatment may provide a potential strategy for the prevention of diabetic neuropathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Interleucina-1beta/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/metabolismo , Neuropatias Diabéticas/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento
20.
J Clin Hypertens (Greenwich) ; 21(11): 1654-1663, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603618

RESUMO

A subgroup analysis of the nationwide, cross-sectional 3B STUDY was performed to understand the current blood pressure (BP) control status and treatment patterns in Chinese diabetes patients as well as to identify factors associated with BP control. The demographic data, anthropometric parameters, and laboratory results were collected from 24 512 type 2 diabetes patients. The BP goal was a systolic BP <130 mm Hg and a diastolic BP <80 mm Hg regardless of a history of hypertension or current antihypertensive treatment. The overall prevalence of hypertension was 59.9% with geographical differences. Among the diabetes patients with hypertension, 76.9% received antihypertensive medicines. Calcium channel blockers (39.3%), angiotensin II receptor antagonists (26.6%), and then ß-blockers (14.0%) or angiotensin-converting enzyme inhibitors (13.6%) were frequently used for BP control. Only 17.5% (n = 2658) of diabetes patients with hypertension reached the recommended target BP. Body mass index <24 kg/m2 , urban resident, frequent physical activity, good adherence to medication, comorbidity with cardiovascular disease, achieving glycemic goal (HbA1c <7.0%), achieving lipid goal (low-density lipoprotein cholesterol <2.59 mmol/L) were independent factors that predicted achievement of target BP goal. On the contrary, comorbidity with chronic kidney disease predicted failure to achieve target BP goal. Patients who were treated in a cardiology department or lived in the North were more likely to achieve BP goals. A considerable proportion of diabetic patients failed to achieve guideline-recommended BP targets. More aggressive efforts should be made to overcome the diverse barriers and facilitate the optimization of diabetes management.


Assuntos
Anti-Hipertensivos , Determinação da Pressão Arterial , Diabetes Mellitus Tipo 2 , Hipertensão , Insuficiência Renal Crônica , Anti-Hipertensivos/classificação , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/normas , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/normas , Planejamento de Assistência ao Paciente/normas , Cooperação do Paciente , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia
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