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1.
Int Arch Occup Environ Health ; 97(3): 231-251, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38356028

RESUMO

BACKGROUND: Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. METHODS: We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. RESULTS: We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. CONCLUSIONS: We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.


Assuntos
Neoplasias Colorretais , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Doenças Profissionais , Exposição Ocupacional , Neoplasias Gástricas , Humanos , Dióxido de Silício/efeitos adversos , Neoplasias Esofágicas/complicações , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Estudos de Coortes , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/complicações
2.
J Am Chem Soc ; 145(33): 18642-18648, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37562030

RESUMO

We disclose unified, protecting-group-free, bioinspired divergent total syntheses of eight allo-cedrane and seco-prezizaane Illicium sesquiterpenes and formal syntheses of five anislactone sesquiterpenes. The efficiency of our approach derives from rapid access to the 15-carbon tricyclic carboxylic acid through cationic epoxide-ene cyclization and HAT oxygenation, transformation of this intermediate into three distinct tricyclic precursors via Lewis acid-mediated skeletal reorganizations, subsequent programmed oxidation level enhancement, and a biomimetic oxidation-initiated skeletal rearrangement cascade. Consequently, we created a synthetic correlation map of the three most prevalent Illicium sesquiterpene families.


Assuntos
Illicium , Sesquiterpenos , Humanos , Ciclização , Oxirredução , Estrutura Molecular
3.
BMC Musculoskelet Disord ; 24(1): 402, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208648

RESUMO

BACKGROUND: Orthostatic state is maintained by harmonizing the spine, pelvis and lower extremities. In the past few decades, several studies have demonstrated the associations between spinal imbalance and generalized osteoarthritis. The compensatory mechanisms of pelvis translation and knee flexion, however, have not been fully assessed. METHODS: A total of 213 volunteers, over 40 years of age, were recruited. Radiological measurements were performed by EOS imaging system. Pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), global tilt (GT), hip-knee-angle (HKA), knee flexion angle (KFA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. On the basis of SRS-Schwab, the subjects were classified into decompensated group (PI-LL > 20°), compensated group(10° ≤ PI-LL ≤ 20°), and normal group (PI-LL < 10°). Differences in radiographic parameters among groups were evaluated. Data of Knee Society Score (KSS) and Oswestry Disability Index (ODI) score were collected via questionnaires. RESULTS: Decompensated group showed larger pelvic parameters (PT) and low extremity parameters (LDFA, MPTA, HKA and KFA) than normal group (P < 0.05). Pelvic parameter was larger in the compensated group (median = 31°) compared to the normal group (median = 17°) (P < 0.05). There was no difference in low extremity parameters between the compensated and normal groups. At the sagittal plane, the radiological parameters of spine were greater in subjects with patellofemoral joint pain (PFP) than without PFP (P = 0.058). Higher PI-LL values were observed in women (P < 0.05). CONCLUSIONS: A correlation between sagittal spinal imbalance and knee joint angles was recognized. The progression of knee and low back pain was associated with the severity of sagittal spinal imbalance. Pelvic retroversion was considered to be the probable compensatory mechanism.


Assuntos
Lordose , Osteoartrite do Joelho , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Coluna Vertebral , Lordose/diagnóstico por imagem , Pelve , Extremidade Inferior , Estudos Retrospectivos , Vértebras Lombares
4.
J Am Chem Soc ; 144(20): 8938-8944, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35576325

RESUMO

A concise and divergent synthesis of the polychlorinated marine steroids clionastatin A and B from inexpensive testosterone has been achieved through a unique two-stage chlorination-oxidation strategy. Key features of the two-stage synthesis include (1) conformationally controlled, highly stereoselective dichlorination at C1 and C2 and C4-OH-directed C19 oxygenation followed by a challenging neopentyl chlorination to install three chlorine atoms; (2) desaturation through one-pot photochemical dibromination-reductive debromination and anti-Markovnikov olefin oxidation by photoredox-metal dual catalysis to enhance the oxidation level of the backbone; and (3) Wharton transposition to furnish the D-ring enone. This synthesis proved that the introduction of the C19 chloride in the early stage of the synthesis secured the stability of the backbone against susceptibility to aromatization during the oxidation stage.


Assuntos
Alcenos , Cloro , Catálise , Oxirredução , Estereoisomerismo
5.
J Virol ; 95(16): e0076021, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037418

RESUMO

Pseudorabies virus (PRV) is the causative pathogen of Aujeszky's disease in pigs. Although vaccination is currently applied to prevent the morbidity of PRV infection, new applications are urgently needed to control this infectious disease. Poly(ADP-ribose) polymerase 1 (PARP1) functions in DNA damage repair. We report here that pharmacological and genetic inhibition of PARP1 significantly influenced PRV replication. Moreover, we demonstrate that inhibition of PARP1 induced DNA damage response and antiviral innate immunity. Mechanistically, PARP1 inhibition-induced DNA damage response resulted in the release of double-stranded DNA (dsDNA) into the cytosol, where dsDNA interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS). cGAS subsequently catalyzed cGAMP production to activate the STING/TBK1/IRF3 innate immune signaling pathway. Furthermore, challenge of mice with PARP1 inhibitor stimulated antiviral innate immunity and protected mice from PRV infection in vivo. Our results demonstrate that PARP1 inhibitors may be used as a new strategy to prevent Aujeszky's disease in pigs. IMPORTANCE Aujeszky's disease is a notifiable infectious disease of pigs and causes economic losses worldwide in the pig industry. The causative pathogen is PRV, which is a member of the subfamily Alphaherpesvirinae of the family Herpesviridae. PRV has a wide range of hosts, such as ruminants, carnivores, and rodents. More seriously, recent reports suggest that PRV can cause human endophthalmitis and encephalitis, which indicates that PRV may be a potential zoonotic pathogen. Although vaccination is currently the major strategy used to control the disease, new applications are also urgently needed for the pig industry and public health. We report here that inhibition of PARP1 induces DNA damage-induced antiviral innate immunity through the cGAS-STING signaling pathway. Therefore, PARP1 is a therapeutic target for PRV infection as well as alphaherpesvirus infection.


Assuntos
Antivirais/imunologia , Dano ao DNA/imunologia , Imunidade Inata/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Pseudorraiva/tratamento farmacológico , Animais , Antivirais/farmacologia , Linhagem Celular , Herpesvirus Suídeo 1/efeitos dos fármacos , Herpesvirus Suídeo 1/fisiologia , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Nucleotidiltransferases/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Pseudorraiva/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Suínos , Replicação Viral/efeitos dos fármacos
6.
Arch Virol ; 167(12): 2623-2631, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36269412

RESUMO

Next-generation sequencing enables the evaluation of gene expression changes resulting from virus-host interactions at the RNA level. Pseudorabies virus (PRV) causes substantial economic loss in the swine industry. Recent research has revealed that PRV can be transmitted to and infect humans as well. To identify physiopathological and pathological responses post-PRV infection, we characterized transcriptomic changes in the murine RAW 264.7 cell line over the course of 36 h. In total, 156, 153, and 190 differentially expressed genes were identified at 2 h, 12 h, and 36 h, respectively. Seven differentially expressed genes (Trim27, Ccdc117, Mrps12, Ccl4, Cerkl, Ubald1, and Hmga1-rs1) were present across all treatment groups. Our findings expand our knowledge of gene regulation and immune response following PRV infection. These differentially expressed genes can subsequently improve our understanding of PRV pathogenesis.


Assuntos
Herpesvirus Suídeo 1 , Pseudorraiva , Doenças dos Suínos , Humanos , Animais , Suínos , Camundongos , Herpesvirus Suídeo 1/genética , Células RAW 264.7 , Perfilação da Expressão Gênica , Fosfotransferases (Aceptor do Grupo Álcool)
7.
Indoor Air ; 32(7): e13081, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35904392

RESUMO

The complex and uncertain causes of sick building syndrome (SBS) have become one of the most challenging and hot issues worldwide. Studies on the correlation between indoor environment and SBS based on local characteristics are relatively limited in China. We studied typical SBS risk factors related to the indoor environment and lifestyle in two northern Chinese cities. The study population was drawn from parents of pre-school children in randomized daycare centers in Taiyuan, Shanxi, and Urumqi, Xinjiang, China (N = 6838). Data on SBS and indoor environment were obtained from cross-sectional questionnaires. Odds ratios (OR) were estimated by multilevel logistic regression and adjusted using gender, atopy, own smoking, home size, and dampness index. Results showed that location, homeownership, year of construction completion, changes in the indoor environment (new furniture and decorations), and changes in indoor air (smoking, burning mosquito repellent and incense, cooking fuels including electricity, natural gas, coal, and wood) might contribute to different levels of SBS in Chinese adults, including eye, nasal, throat, dermal symptoms, and headache and tiredness. The results of the subgroup analysis suggest city and gender differences in susceptibility. Daily cleaning, window opening, and improved ventilation effectively improved SBS. People should improve their indoor environment and lifestyles based on sensitivity factors, gender, and geographic characteristics to reduce SBS risks.


Assuntos
Poluição do Ar em Ambientes Fechados , Estilo de Vida , Síndrome do Edifício Doente , Adulto , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , China/epidemiologia , Estudos Transversais , Humanos , Síndrome do Edifício Doente/epidemiologia , Síndrome do Edifício Doente/etiologia
8.
Neurol Sci ; 43(6): 3551-3563, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35314911

RESUMO

OBJECTIVE: The current meta-analysis aimed to investigate the efficacy and safety of direct endovascular treatment (EVT) and bridging therapy (EVT with prior intravenous thrombolysis (IVT)) in patients with acute anterior circulation large vessel occlusion (LVO) stroke. METHODS: This meta-analysis followed PRISMA guidelines. Eligible RCTs were identified through a systemic search of electronic databases (PubMed, Ovid, Web of Science, and Cochrane Library) from the inception dates to January 10, 2022. The pooled analyses were performed using RevMan 5.3 software. The primary outcome was functional outcome on the modified Rankin Scale (mRS) (range 0 to 5) at 90 days. The secondary outcomes included successful reperfusion, intracranial hemorrhage, and mortality (mRS 6) within 90 days. RESULTS: A total of 4 RCTs involving 1633 patients were finally included. Findings of pooled analyses indicated that neither the primary outcomes (no disability (mRS 0), no significant disability despite some symptoms (mRS 1), slight disability (mRS 2), moderate disability (mRS 3), moderately severe disability (mRS 4), severe disability (mRS 5), excellent outcome (mRS 0-1), functional independence outcome (mRS 0-2), and poor outcome (mRS 3-5)) nor the secondary outcomes (successful reperfusion, intracranial hemorrhage, and mortality) in the EVT groups were not statistically significant compared with the IVT plus EVT groups (P > 0.05). In addition, the outcomes of sensitivity analysis implied that the findings of meta-analysis were credible. CONCLUSIONS: Among patients with acute ischemic stroke due to LVO of anterior circulation, EVT alone yielded efficacy and safety outcomes similar to IVT plus EVT.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Procedimentos Endovasculares/efeitos adversos , Fibrinolíticos/efeitos adversos , Humanos , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/etiologia , AVC Isquêmico/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
9.
Ecotoxicol Environ Saf ; 230: 113148, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34995912

RESUMO

Aflatoxin B1 (AFB1) is a common mycotoxin in food and in the environment that lead to multi-organ injury in humans and animals. The objective of this study was to evaluate the detoxification properties of dietary total flavonoids of Rhizoma drynariae (TFRD), a Chinese herbal, on aflatoxin B1 (AFB1)-induced hepatic oxidative damage and apoptosis of liver of broiler chickens. A total of 160 healthy specific pathogen free (SPF) 21-day-old broilers were randomly allocated to 4 groups, including the CON group (basal diet), TFRD group (basal diet with 125 mg/kg TFRD), AFB1 group (100 µg/kg body weight), and AFB1 (100 µg/kg body weight) + TFRD (basal diet with 125 mg/kg TFRD) group. The exposure of AFB1 continued for seven days. The results showed that TFRD treatment alleviated the abnormal changes of growth performance and liver morphology, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Moreover, TFRD promoted the antioxidant capacity of serum, increased the activities of total superoxide dismutase (T-SOD), oxidized glutathione (GSSG) and glutathione (GSH) (p < 0.05), while decreased MDA contents (p > 0.05). Meanwhile, supplementation of TFRD significantly increased the expression of antioxidant-related genes (SOD, CAT, GST, and GPX1) in liver (p < 0.05). Furthermore, we found that AFB1 was involved in the regulation of PI3K/AKT signaling pathway, leading to hepatocyte apoptosis. At the same time, TFRD treatment inhibited AFB1-induced apoptosis and significantly changed mRNA expression of apoptosis-related genes, including PI3K, AKT, Bax, and Bcl-2 (p < 0.05). The results indicated that TFRD could alleviate AFB1-induced liver injury in broiler chickens.

10.
J Environ Sci (China) ; 122: 25-40, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35717088

RESUMO

Fine particulate matter (PM2.5) is associated with increased risks of Alzheimer's disease (AD), yet the toxicological mechanisms of PM2.5 promoting AD remain unclear. In this study, wild-type and APP/PS1 transgenic mice (AD mice) were exposed to either filtered air (FA) or PM2.5 for eight weeks with a real-world exposure system in Taiyuan, China (mean PM2.5 concentration in the cage was 61 µg/m3). We found that PM2.5 exposure could remarkably aggravate AD mice's ethological and brain ultrastructural damage, along with the elevation of the pro-inflammatory cytokines (IL-6 and TNF-α), Aß-42 and AChE levels and the decline of ChAT levels in the brains. Based on high-throughput sequencing results, some differentially expressed (DE) mRNAs and DE miRNAs in the brains of AD mice after PM2.5 exposure were screened. Using RT-qPCR, seven DE miRNAs (mmu-miR-193b-5p, 122b-5p, 466h-3p, 10b-5p, 1895, 384-5p, and 6412) and six genes (Pcdhgb8, Unc13b, Robo3, Prph, Pter, and Tbata) were evidenced the and verified. Two miRNA-target gene pairs (miR-125b-Pcdhgb8 pair and miR-466h-3p-IL-17Rα/TGF-ßR2/Aß-42/AChE pairs) were demonstrated that they were more related to PM2.5-induced brain injury. Results of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways predicted that synaptic and postsynaptic regulation, axon guidance, Wnt, MAPK, and mTOR pathways might be the possible regulatory mechanisms associated with pathological response. These revealed that PM2.5-elevated pro-inflammatory cytokine levels and PM2.5-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising miRNA and mRNA biomarkers and potential miRNA-mRNA interaction networks of PM2.5-promoted AD.


Assuntos
Doença de Alzheimer , MicroRNAs , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Camundongos , Camundongos Transgênicos , MicroRNAs/metabolismo , Material Particulado/toxicidade , RNA Mensageiro/genética
11.
J Am Chem Soc ; 143(27): 10275-10281, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34165963

RESUMO

Halide double perovskites A2B(I)B(III)X6, in which monovalent B(I) and trivalent B(III) cations are arranged in the B-sites of the perovskite structure with a rock-salt ordering, have attracted substantial interest in the field of optoelectronics. However, the rock-salt ordering generally leads to low electronic dimensionality, with relatively large bandgaps and large carrier effective masses. In this work, we demonstrate, by density functional theory (DFT) calculations, that the electronic dimensionality and thus the electronic properties of halide double perovskites can be effectively modulated by manipulating the arrangement of the B-site cations. Through symmetry analysis and DFT calculations, we propose a family of halide double perovskites A2B(I)B(II)X5 where the B-site cations adopt a columnar-ordered arrangement. Among the considered compounds, Cs2AgPdCl5, Cs2AgPdBr5, and Cs2AgPtCl5 were successfully synthesized as the first examples of the B-site columnar-ordered halide double perovskites. These compounds exhibit small bandgaps of 1.33-1.77 eV that are suitable for visible light absorption, small carrier effective masses along the octahedra chains, and good thermal and air stability. Our work provides a prototype double perovskite structure to incorporate cations in +1 and +2 oxidation states, which may significantly expand the large family of the halide double perovskites and offer a platform to explore prospective optoelectronic semiconductors.

12.
Vet Res ; 52(1): 95, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174954

RESUMO

Pseudorabies, caused by pseudorabies virus (PRV) variants, has broken out among commercial PRV vaccine-immunized swine herds and resulted in major economic losses to the pig industry in China since late 2011. However, the mechanism of virulence enhancement of variant PRV is currently unclear. Here, a recombinant PRV (rPRV HN1201-EGFP-Luc) with stable expression of enhanced green fluorescent protein (EGFP) and firefly luciferase as a double reporter virus was constructed on the basis of the PRV variant HN1201 through CRISPR/Cas9 gene-editing technology coupled with two sgRNAs. The biological characteristics of the recombinant virus and its lethality to mice were similar to those of the parental strain and displayed a stable viral titre and luciferase activity through 20 passages. Moreover, bioluminescence signals were detected in mice at 12 h after rPRV HN1201-EGFP-Luc infection. Using the double reporter PRV, we also found that 25-hydroxycholesterol had a significant inhibitory effect on PRV both in vivo and in vitro. These results suggested that the double reporter PRV based on PRV variant HN1201 should be an excellent tool for basic virology studies and evaluating antiviral agents.


Assuntos
Sistemas CRISPR-Cas , Herpesvirus Suídeo 1/fisiologia , Herpesvirus Suídeo 1/patogenicidade , Animais , Feminino , Herpesvirus Suídeo 1/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Pseudorraiva/virologia , Virulência
13.
Virol J ; 17(1): 19, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014014

RESUMO

BACKGROUND: Porcine parvovirus (PPV) and pseudorabies virus (PRV) are the important etiological agents of swine infectious diseases, resulting in huge economic losses to the Chinese swine industry. Interleukin-6 (IL-6) has the roles to support host immune response to infections as a pleiotropic cytokine. It is essential to construct a live attenuated vaccine-based recombinant PRV that expresses PPV VP2 protein and porcine IL-6 for prevention and control of PRV and PPV. METHODS: The recombinant plasmid, pGVP2-IL6, was constructed by porcine IL-6 gene substituting for EGFP gene of the PRV transfer plasmid pGVP2-EGFP containing VP2 gene of PPV. Plasmid pGVP2-IL6 was transfected into swine testicle cells pre-infected with the virus rPRV-VP2-EGFP strain through homologous recombination and plaque purification to generate a recombinant virus rPRV-VP2-IL6. The recombinant PRV was further identified by PCR and DNA sequencing, and the expression of the VP2 protein and porcine IL-6 was analyzed by reverse transcription-PCR (RT-PCR) and Western blot. The virus titer was calculated according to Reed and Muench method. The immunogenicity of the recombinant virus was preliminarily evaluated in mice by intramuscular administration twice with the rPRV-VP2-IL6 at 4-week intervals. RESULTS: A recombinant virus rPRV-VP2-IL6 was successfully constructed and confirmed in this study. The properties of rPRV-VP2-IL6 were similar to the parental virus HB98 in terms of growth curve, morphogenesis and virus plaque sizes, and rPRV-VP2-IL6 was proliferated in different cell types. It induced specific antibodies against PPV as well as a strong increase of PPV-specific lymphocyte proliferation responses in mice immunized with rPRV-VP2-IL6, and provided partial protection against the virulent PPV challenge. rPRV-VP2-IL6 also induced a high level of neutralizing antibodies against PRV, and significantly reduced the mortality rate of (1 of 10) following virulent PRV challenge compared with the control (10 of 10). CONCLUSIONS: The recombinant rPRV-VP2-IL6 might be a potential candidate vaccine against PRV and PPV infections in pigs.


Assuntos
Antígenos Virais/genética , Proteínas do Capsídeo/genética , Herpesvirus Suídeo 1/genética , Interleucina-6/genética , Infecções por Parvoviridae/veterinária , Pseudorraiva/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Proteínas do Capsídeo/imunologia , Esquema de Medicação , Feminino , Herpesvirus Suídeo 1/imunologia , Imunogenicidade da Vacina , Injeções Intramusculares , Interleucina-6/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/prevenção & controle , Pseudorraiva/imunologia , Suínos , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Virais/genética
14.
Neurochem Res ; 45(12): 3021-3033, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33095440

RESUMO

Treatment for epilepsy, particularly temporal lobe epilepsy, is challenging. Baicalein has multiple effects, including anti-inflammatory action. However, little is known about its efficacy in treatment of epilepsy. In this study, we established a pilocarpine-induced rat model and used it for assessment of baicalein efficacy in vivo. We predicted the pharmacological mechanism of baicalein by network pharmacology and RNA sequencing analyses. Pilocarpine epileptic rats treated with baicalein exhibited improved average seizure severity, seizure frequency, seizure duration, and survival time. Network pharmacology and RNA sequencing identified the differentially expressed genes between the baicalein treatment and epileptic groups. Insulin-like growth factor 1 receptor (IGF1R) was chosen as the top candidate target because of its overlapping findings in RNA sequencing and network pharmacology data. Western blotting, immunofluorescence, and polymerase chain reaction analyses showed that baicalein inhibited microglial proliferation, IGF1R, and inflammatory cytokine expression. Moreover, baicalein improved epilepsy symptoms. Inhibition of IGF1R function by blocking with AXL1717 enhanced baicalein treatment efficacy both in vivo and in vitro. In conclusion, baicalein exerted antiepileptic effects by regulation of IGF1R in a pilocarpine-induced rat model.


Assuntos
Epilepsia/tratamento farmacológico , Flavanonas/uso terapêutico , Receptor IGF Tipo 1/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Epilepsia/induzido quimicamente , Epilepsia/complicações , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Microglia/metabolismo , Pilocarpina , Ratos Sprague-Dawley
15.
Ecotoxicol Environ Saf ; 192: 110325, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078839

RESUMO

Fine particulate matter (PM2.5) was a risk factor for neurological disorders when emerging studies revealed that PM2.5 affected the bacterial community structure of gut in Alzheimer's disease (AD) patients. The purpose of this study was to explore the effects of PM2.5 on intestinal and brain injury and on bacterial community structure in the intestine and feces of APP/PS1 transgenic mice exposed to PM2.5 for eight weeks with a real-world whole-body inhalation exposure system in Taiyuan, China. The brain and intestinal tissues were collected to evaluate histopathological changes by HE staining. TNF-α and IL-6 levels in intestines, brains, and serums, and Aß-42 levels in brains were detected. Intestinal and fecal samples were subjected to 16S rRNA gene sequencing. Results showed that PM2.5 significantly aggravated the pathological injury in intestines and brains in AD mice with elevated pro-inflammatory cytokine levels. The estimators of Shannon, Simpson, Chao1, and ACE indexes reflected the diversity and richness of the bacterial community. Compared with the FA-WT group, the FA-AD group had lower diversity and richness when the PM2.5-AD group had the highest ones. PCA and NMDS revealed the specific influence of PM2.5 on the bacterial community of intestine and feces because that the PM2.5-FA and PM2.5-AD group clumped visibly closer than the other groups in both bacterial communities of intestine and feces. The KEGG pathway analysis predicted the vital functional genes and metabolic pathways in the bacterial community of PM2.5-AD mice. This study indicated the histopathological changes and inflammation in the intestine and brain were seriously caused in PM2.5-AD mice when the α-diversity of the bacterial community in intestine and feces was visibly changed.


Assuntos
Doença de Alzheimer/microbiologia , Bactérias/isolamento & purificação , Encéfalo/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Material Particulado/toxicidade , Doença de Alzheimer/patologia , Animais , Bactérias/genética , Encéfalo/patologia , Fezes/microbiologia , Inflamação/metabolismo , Exposição por Inalação , Interleucina-6/metabolismo , Intestinos/patologia , Masculino , Camundongos , Camundongos Transgênicos , RNA Ribossômico 16S/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500132

RESUMO

Parkinson's disease is a progressive neurodegenerative disorder resulting from the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta. It induces a series of functional modifications in the circuitry of the basal ganglia nuclei and leads to severe motor disturbances. The amino acid glutamate, as an excitatory neurotransmitter, plays a key role in the disruption of normal basal ganglia function regulated through the interaction with its receptor proteins. It has been proven that glutamate receptors participate in the modulation of neuronal excitability, transmitter release, and long-term synaptic plasticity, in addition to being related to the altered neurotransmission in Parkinson's disease. Therefore, they are considered new targets for improving the therapeutic strategies used to treat Parkinson's disease. In this review, we discuss the biological characteristics of these receptors and demonstrate the receptor-mediated neuroprotection in Parkinson's disease. Pharmacological manipulation of these receptors during anti-Parkinsonian processes in both experimental studies and clinical trials are also summarized.


Assuntos
Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Receptores de Glutamato/metabolismo , Animais , Ensaios Clínicos como Assunto , Descoberta de Drogas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Humanos , Terapia de Alvo Molecular , Neurotransmissores/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Receptores de Glutamato/genética , Transdução de Sinais/efeitos dos fármacos , Substância Negra/metabolismo , Transmissão Sináptica , Resultado do Tratamento
17.
Opt Express ; 26(19): 25031-25036, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30469611

RESUMO

An electricity-mediated plasmonic engineering was applied on a single Ag nanowire to engineer its tip for surface-enhanced Raman scattering (SERS). Under this constant photoelectric field treatment, a significant sharpening of the tip and reduction of the surface fluctuation was observed for the Ag nanowire tip via in situ atomic force microscopy. A significant SERS signal enhancement was thus obtained after the tip engineering. The relevant dynamic mechanisms of the tip engineering, including the light-induced plasmonic phase transition and electrostatic force driven flow on the Ag nanowire tip are discussed in detail. It is expected that this type of tip engineering will greatly enhance the signal of single metal nanowire SERS probes and provide new insights into fabrication technologies for metal nanostructures.

18.
Neurochem Res ; 42(8): 2154-2166, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28299629

RESUMO

FK506, a calcineurin inhibitor, shows neuroprotective effects and has been associated with neurodegenerative diseases. Calcineurin A (CaNA), a catalytic subunit of calcineurin, mediates the dephosphorylation of various proteins. N-methyl-D-aspartate receptor (GluN) is closely related to epileptogenesis, and various phosphorylation sites of GluN2B, a regulatory subunit of the GluN complex, have different functions. Thus, we hypothesized that one of the potential anti-epileptic mechanisms of FK506 is mediated by its ability to promote the phosphorylation of GluN2B and reduce the expression of GluN2B in membrane fraction by down-regulating CaNA. CaNA expression was increased in the cortex of patients with temporal lobe epilepsy and pentylenetetrazol (PTZ)-induced epileptic models. CaNA was shown to be expressed in neurons using immunofluorescence staining. According to our behavioral observations, epileptic rats exhibited less severe seizures and were less sensitive to PTZ after a systemic injection of FK506. The levels of phosphorylated GluN2B were decreased in epileptic rats but increased after the FK506 treatment. Moreover, there was no difference in the total GluN2B levels before and after FK506 treatment. However, the expression of GluN2B in membrane fraction was suppressed after FK506 treatment. Based on these results, FK506 may reduce the severity and frequency of seizures by reducing the expression of GluN2B in membrane fraction.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Membrana Celular/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/biossíntese , Convulsões/metabolismo , Tacrolimo/uso terapêutico , Adolescente , Adulto , Animais , Calcineurina/metabolismo , Inibidores de Calcineurina/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Pré-Escolar , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Convulsões/tratamento farmacológico , Convulsões/genética , Tacrolimo/farmacologia , Adulto Jovem
19.
Neurochem Res ; 41(11): 3020-3031, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27502938

RESUMO

E3 ubiquitin ligases are important protein-modifying enzymes involved in the pathogenesis of a variety of neurodegenerative diseases. F-box and leucine-rich repeat protein 20 (FBXL20), an E3 ubiquitin ligase widely expressed in the central nervous system, plays an important role in the ubiquitin-dependent degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an important factor in the release of synaptic vesicles. FBXL20 has been associated with a variety of neurodegenerative diseases; thus, we hypothesized that FBXL20 is involved in the development of epilepsy. Herein, we used immunofluorescence staining, immunohistochemistry and western blotting to determine the expression pattern of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced epilepsy animal models. We also injected SD rats with lentivirus-vector mediated overexpression of FBXL20. The results showed that FBXL20 is expressed in the membrane and the cytoplasm of cortical neurons, and overexpression of FBXL20 decreased the onset level of spontaneous seizure, the frequency and duration of seizures. Additionally, FBXL20 protein level was decreased but RIM1 protein level was increased in the epileptic group compared with the LV-FBXL20 and LV-GFP group. These findings in humans were consistent with the results from a pilocarpine-induced animal model of chronic epilepsy. Thus, abnormal expression of FBXL20 might play an important role in the development of epilepsy.


Assuntos
Epilepsia/metabolismo , Proteínas F-Box/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Pilocarpina/farmacologia , Vesículas Sinápticas/metabolismo , Adolescente , Adulto , Animais , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Feminino , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/metabolismo , Ratos Sprague-Dawley , Adulto Jovem
20.
Appl Opt ; 55(1): 117-21, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26835630

RESUMO

Although nanowire (NW) antireflection coating can enhance light trapping capability, which is generally used in crystal silicon (CS) based solar cells, whether it can improve light absorption in the CS body depends on the NW geometrical shape and their geometrical parameters. In order to conveniently compare with the bare silicon, two enhancement factors E(T) and E(A) are defined and introduced to quantitatively evaluate the efficient light trapping capability of NW antireflective layer and the effective light absorption capability of CS body. Five different shapes (cylindrical, truncated conical, convex conical, conical, and concave conical) of silicon NW arrays arranged in a square are studied, and the theoretical results indicate that excellent light trapping does not mean more light can be absorbed in the CS body. The convex conical NW has the best light trapping, but the concave conical NW has the best effective light absorption. Furthermore, if the cross section of silicon NW is changed into a square, both light trapping and effective light absorption are enhanced, and the Eiffel Tower shaped NW arrays have optimal effective light absorption.

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