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1.
Toxicol Appl Pharmacol ; 484: 116857, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341106

RESUMO

Intestinal injury is one of the most debilitating side effects of many chemotherapeutic agents, such as irinotecan hydrochloride (CPT-11). Accumulating evidence indicates that neutrophil extracellular traps (NETs) play a critical role in the symptoms of ischemia and inflammation related to chemotherapy. The present study investigated the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating chemotherapeutic intestinal injury. CPT-11 induced robust neutrophil activation, as evidenced by increased NETs release, intestinal ischemia, and mRNA expression of inflammatory factors. PEITC prolonged the clotting time of chemotherapeutic mice, improved the intestinal microcirculation, inhibited the expression of inflammatory factors, and protected the tight junctions of the intestinal epithelium. Both in vivo and in vitro experiments revealed that PEITC directly suppresses CPT-11-induced NETs damage to intestinal cells, resulting in significant attenuation of epithelial injury. These results suggest that PEITC may be a novel agent to relieve chemotherapeutic intestinal injury via inhibition of NETs.


Assuntos
Armadilhas Extracelulares , Enteropatias , Animais , Camundongos , Irinotecano , Isotiocianatos/farmacologia , Isquemia
2.
Anal Bioanal Chem ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38839687

RESUMO

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme in the metabolism of xenobiotics, particularly in drug metabolism interactions (DDIs), making it a significant factor in clinical drug use. However, current assay techniques are both laborious and costly, making it difficult to construct a high-throughput monitoring method that can be used in conjunction with the clinic. This poses certain safety hazards for drug combination. Therefore, it is crucial to develop a synchronized monitoring method for the inhibition and induction of CYP3A4. In this study, we utilized 3D culture technology to develop a HepaRG cells spheroid model. The CYP450 and transporter expression, the albumin secretion, and urea synthesis capacity characteristics were analyzed. The NEN probe was utilized as a tracer molecule for CYP3A4. The fluorescence intensity of metabolites was characterized by laser confocal technique to determine the inhibition and expression of CYP3A4 in the HepaRG cell spheroid model by the antibiotics for sepsis. The results indicate that the HepaRG sphere model successfully possessed the physiological phenotype of the liver, which could be used for drug interaction monitoring. Through positive drug testing, NEN probe was able to achieve bidirectional characterization of CYP3A4 induction and inhibition. The monitoring method described in this paper was successfully applied to drug interaction monitoring of commonly used antibiotics in sepsis patients, which is a convenient and rapid monitoring method. The proposed method offers a new strategy for monitoring CYP3A4-mediated drug-drug interactions with a high-throughput assay, which will help to improve the safety of clinical drug combination.

3.
BMC Anesthesiol ; 24(1): 34, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254013

RESUMO

BACKGROUND: Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to endoscopic examinations such as electronic gastroscopy, and few adverse reactions have been reported. This article describes a patient who experienced a transient but severe disturbance of consciousness following oral dyclonine hydrochloride mucilage administration. CASE PRESENTATION: A 75-year-old female presenting with gastrointestinal bleeding was examined by electronic gastroscopy. Six minutes after oral dyclonine hydrochloride mucilage administration, the patient entered a comatose-like state accompanied by loss of limb muscle tone and profuse perspiration. This response was not accompanied by changes in cardiac rhythm, blood pressure, or respiration rate, suggesting an effect on higher brain centres. After ten minutes, the patient's symptoms were alleviated. CONCLUSION: We suggest that sites of dyclonine hydrochloride mucilage use be equipped with appropriate rescue devices for these rare events.


Assuntos
Encéfalo , Estado de Consciência , Propiofenonas , Feminino , Humanos , Idoso , Administração Oral , Anestesia Local
4.
J Asian Nat Prod Res ; 26(6): 765-771, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38373226

RESUMO

To clarify the chemical basis of the total alkaloids of Uncaria rhynchophylla, HPLC-VWD chromatogram of total alkaloids was established. Under its guidance, modern chromatographic and spectroscopic techniques were used to track, isolate and identify the representative principal components. As a result, one new monoterpenoid indole alkaloid, 3S,15S-N4-methoxymethyl-geissoschizine methyl ether (1), together with 20 known alkaloids (2-21), and 5 other known compounds (22-26) were obtained. Meanwhile, sixteen characteristic peaks were identified from the total alkaloids using HPLC analysis. Then, the anti-neuroinflammatory effect of compounds 1-21 was assessed through inhibiting nitric ---oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among them, compounds 1, 3, 7, 8, 11, 12, 19 and 21 showed potent inhibitory activities with IC50 values of 5.87-76.78 µM.


Assuntos
Alcaloides , Anti-Inflamatórios , Alcaloides Indólicos , Lipopolissacarídeos , Microglia , Óxido Nítrico , Uncaria , Uncaria/química , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Animais , Camundongos , Cromatografia Líquida de Alta Pressão , Alcaloides de Triptamina e Secologanina/farmacologia , Alcaloides de Triptamina e Secologanina/química
5.
Invest New Drugs ; 41(1): 13-24, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36331675

RESUMO

Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has been approved for the treatment of HER2-positive (HER2+) early-stage and brain metastatic breast cancer. Thus far, the pharmacology effects and pharmacodynamics of neratinib have been well studied. However, the disposition of neratinib and its influencing factors in vivo remain unclear. P-glycoprotein (P-gp), one of the most extensively studied transporters, substantially restricts penetration of drugs into the body or deeper compartments (i.e., blood-brain barrier, BBB), regarding drug resistance and drug-drug interactions. Thereby, the aim of this study was to investigate the influence of verapamil (a P-gp inhibitor) on the pharmacokinetics of neratinib in rats. Here, we have established a high specific, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify plasma concentrations of neratinib in rats. Pharmacokinetic results showed that verapamil significantly increased the system exposure of neratinib, as Cmax increased by 2.09-fold and AUC0-t increased by 1.64-fold, respectively. Additionally, the in vitro transport of neratinib was evaluated using Madin-Darby canine kidney II (MDCK II) and human MDR1 gene overexpressed MDCK (MDCK-MDR1) cell line models. As a result, the net flux ratio was over than 2 and decreased over 50% by verapamil, suggesting that neratinib was a substrate of P-gp. Hence, our findings have highlighted the important role of P-gp in the system exposure of neratinib in vivo, and drug-drug interaction should be considered when coadministration of P-gp inhibitors with neratinib. These findings may support the further clinical development and application of neratinib.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Humanos , Ratos , Animais , Cães , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Verapamil/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
6.
BMC Cancer ; 23(1): 970, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828491

RESUMO

OBJECTIVE: CalliSpheres® is a microsphere that is already widely used for primary liver cancer treatment; however, its application in colorectal cancer liver metastasis (CRLM) is limited. The current study aimed to investigate the efficacy of CalliSpheres® drug-eluting bead (DEB) transarterial chemoembolization (TACE) therapy versus (vs.) conventional cTACE therapy in treating refractory CRLM (RCRLM) patients. METHODS: Twenty-two RCRLM patients who underwent CalliSpheres® DEB-TACE therapy (n = 11) or cTACE therapy (n = 11) were retrospectively analyzed. Data on clinical response, progression-free survival (PFS) and overall survival (OS) were retrieved. RESULTS: The objective response rate (36.4% vs. 18.2%, P = 0.338) and disease control rate (81.8% vs. 54.4%, P = 0.170) were both numerically (but not statistically) higher in the DEB-TACE group than in the cTACE group. Meanwhile, PFS was prolonged in the DEB-TACE group compared with the cTACE group [median: 12.0 (95% CI: 5.6-18.4) vs. 4.0 (95% CI: 0.9-7.1) months, P = 0.018]; OS was also longer in the DEB-TACE group compared with the cTACE group [median: 24.0 (95% CI: 18.3-29.7) vs. 14.0 (95% CI: 7.1-20.9) months, P = 0.040]. In addition, after adjustment by multivariate Cox analyses, DEB-TACE was superior to cTACE independently regarding PFS (HR: 0.110, 95% CI: 0.026-0.463, P = 0.003) and OS (HR: 0.126, 95% CI: 0.028-0.559, P = 0.006). CONCLUSION: CalliSpheres® DEB-TACE therapy may prolong survival profile than cTACE therapy in RCRLM patients, while further validation is still needed.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Estudos Retrospectivos , Microesferas , Resultado do Tratamento
7.
Lupus ; 32(9): 1084-1092, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37480363

RESUMO

BACKGROUND: This study aimed to explore risk factors for lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and establish a Nomogram prediction model based on LASSO-logistic regression. METHODS: The clinical and laboratory data of SLE patients in Meishan People's Hospital from July 2012 to December 2021 were analyzed retrospectively. All SLE patients were divided into two groups with or without LN. Risk factors were screened based on LASSO-logistic regression analysis, and a Nomogram prediction model was established. The receiver operating characteristic curve, calibration curves, and decision curve analysis were adopted to evaluate the performance of the Nomogram model. RESULTS: A total of 555 SLE patients were enrolled, including 303 SLE patients with LN and 252 SLE patients without LN. LASSO regression and multivariate logistic regression analyses showed that ESR, mucosal ulcer, proteinuria, and hematuria were independent risk factors for LN in SLE patients. The four clinical features were incorporated into the Nomogram prediction model. Results showed that calibration curve was basically close to the diagonal dotted line with slope 1 (ideal prediction case), which proved that the prediction ability of the model was acceptable. In addition, the decision curve analysis showed that the Nomogram prediction model could bring net clinical benefits to patients when the threshold probability was 0.12-0.54. CONCLUSION: Four clinical indicators of ESR, mucosal ulcer, proteinuria, and hematuria were independent risk factors for LN in SLE patients. The predictive power of the Nomogram model based on LASSO-logistic regression was acceptable and could be used to guide clinical work.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/complicações , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Nomogramas , Hematúria/complicações , Úlcera , Biomarcadores , Proteinúria/complicações , Fatores de Risco
8.
J Sci Food Agric ; 103(1): 450-456, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36205212

RESUMO

BACKGROUND: Nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide, plays an important in anti-aging and disease. Lactococcus lactis, an important probiotic lactic acid bacteria (LAB), has shown great potential for the biosynthesis of NMN, which will significantly affect the probiotic effects of the dairy products. RESULTS: We used the CRISPR/nCas9 technique to knockout nadR gene of L. lactis NZ9000 to enhance the accumulation of NMN by 61%. The nadE* gene from Francisella tularensis with codon optimization was heterologous in L. lactis NZ9000ΔnadR and has a positive effect on NMN production. Combined with optimization of the concentration of substrate nicotinamide, a final intracellular NMN titer was 2289 µmol L-1  mg-1 with 10 g L-1 nicotinamide supplement, which was 5.7-fold higher than that of the control. The transcription levels of key genes (pncA, nadD and prs1) involved in NMN biosynthesis were up-regulated by more than two-fold, indicating that the increase of NMN titer was attributed to FtnadE* heterologous expression. CONCLUSION: Our study provides a better understanding of the NMN biosynthesis pathway in L. lactis, and can facilitate NMN production in LAB via synthetic biology approaches. © 2022 Society of Chemical Industry.


Assuntos
Lactococcus lactis , Mononucleotídeo de Nicotinamida , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , NAD/metabolismo , Niacinamida/metabolismo
9.
Environ Geochem Health ; 45(7): 4867-4881, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36959429

RESUMO

The use of solid fuels for heating and cooking in rural Northeast China has led to severe indoor metal element pollution in particulate matter (PM), posing a direct threat to human health and creating immense pressure on the sustainability of residential environments. To investigate the levels, sources, and potential health hazards of indoor metal element pollution in this region, we conducted a year-long sampling and monitoring campaign in actual residential settings and used ICP-OES to measure six metal elements (Mn, Cr, Zn, Cu, Pb, and Ni). This study's findings reveal that indoor metal element pollution levels in PM (33,513.65 mg/kg per year) are higher in rural Northeast China compared to other rural areas. Straw burning is the primary source of metal element pollution, followed by motor vehicle emissions and natural soil sources. It is crucial to note that our results indicate a total carcinogenic risk greater than 10-4 according to the US EPA health risk model assessment, highlighting the high risk posed to human health by indoor metal elements in rural areas. By using a seriously polluted area in Northeast China as a case study, this research provides initial insights into the characteristics and sources of indoor metal pollution in rural areas, offering a reference for future prevention and control of indoor pollution in these regions. Ultimately, this work can help improve the rural habitat and enhance the health of the rural population.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Humanos , Material Particulado/análise , Monitoramento Ambiental/métodos , Poluição do Ar em Ambientes Fechados/análise , População Rural , Metais , China , Medição de Risco , Poluentes Atmosféricos/análise
10.
Mol Cancer ; 21(1): 37, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130920

RESUMO

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
11.
Cell Commun Signal ; 20(1): 175, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348350

RESUMO

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/patologia , Antígeno B7-H1/metabolismo , beta Catenina , Neoplasias Hepáticas/patologia , Espermina/farmacologia , Proteínas Proto-Oncogênicas c-akt , Linhagem Celular Tumoral , Microambiente Tumoral
12.
J Fish Dis ; 45(6): 895-905, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35445749

RESUMO

Micropterus salmoides rhabdovirus (MSRV) is an significant pathogen that causes high mortality and related economic losses in bass aquaculture. There is no effective or approved therapy to date. In this study, we evaluated the anti-MSRV effects of 22 quinoline derivatives in grass carp ovary (GCO) cells. Among these compounds, 8-hydroxyquinoline exhibited valid inhibition in decreasing MSRV nucleoprotein gene expression levels of 99.3% with a half-maximal inhibitory concentrations (IC50 ) value of 4.66 µM at 48 h. Moreover, 8-hydroxyquinoline significantly enhanced a protective effect in GCO cells by reducing the cytopathic effect (CPE). By comparing the anti-MSRV activity of 22 quinoline derivatives, we found that 8-hydroxyquinoline possessed the efficient active site of 8-hydroxyl and inhibited MSRV infection in vitro. For in vivo studies, 8-hydroxyquinoline via intraperitoneal injection exhibited an antiviral effect in MSRV-infected largemouth bass by substantially enhancing the survival rate by 15.0%. Importantly, the viral loads in the infected largemouth bass notably reduced in the spleen on the third days post-infection. Overall, 8-hydroxyquinoline was considered to be an efficient agent against MSRV in aquaculture.


Assuntos
Bass , Carpas , Doenças dos Peixes , Quinolinas , Infecções por Rhabdoviridae , Rhabdoviridae , Animais , Domínio Catalítico , Feminino , Oxiquinolina/farmacologia , Quinolinas/farmacologia , Rhabdoviridae/genética , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/veterinária
13.
Psychol Health Med ; : 1-7, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36260478

RESUMO

Shanghai is one of the largest cities in China and has the highest proportion of inbound travelers in the world. The HIV (human immunodeficiency virus) infection status of this population can reflect the global HIV epidemic trend to a certain extent. Therefore, we conducted a retrospective epidemic survey to clarify the prevalence and characteristics of HIV-1 infection among inbound travelers applying for Shanghai residency. The retrospective cohort analysis included a total of 50,830 inbound tourists/travelers who applied for Shanghai residency from 2005 to 2016. HIV-1 infection rates were determined based on HIV-1 antibody testing. Among all the recruited inbound travelers, 245 were HIV-1 positive, with an infection rate of 0.48%. The detection rate of HIV in males was significantly higher than in females (χ2 = 62.584, P < 0.0001). Those aged 18-30 years, 31-40 years, and >40 years accounted for 34.3%, 39.6%, and 26.1% of the infected population, respectively. Although the annual detection rates were different, the trend analysis results showed no increase in HIV-1 prevalence rates among the sampling years (Cochran-Armitage Z = 2.543, P = 0.111). Proportions of individuals infected through homosexual transmission increased over the study period (Cochran-Armitage Z = 5.41, P < 0.001), while the proportion infected through heterosexual declined over time (Cochran-Armitage Z = 3.38, P = 0.001). The rate and characteristics of HIV-1 infection among foreign applicants for residency in Shanghai were identified in the study. The results provide the necessary epidemiological data for monitoring the HIV-1 epidemic among international entry travelers and contribute to establishing relevant policies and regulations for HIV control and prevention.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 797-805, 2022 Jul 15.
Artigo em Zh | MEDLINE | ID: mdl-35894196

RESUMO

OBJECTIVES: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. RESULTS: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). CONCLUSIONS: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.


Assuntos
Aminoidrolases , Cardiopatias Congênitas , Metilenotetra-Hidrofolato Desidrogenase (NADP) , Enzimas Multifuncionais , Aminoidrolases/genética , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Cardiopatias Congênitas/genética , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Antígenos de Histocompatibilidade Menor/genética , Mães , Enzimas Multifuncionais/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
15.
Eur J Neurosci ; 53(1): 140-150, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491043

RESUMO

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyse the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail.


Assuntos
Depressão , Transtornos Mentais , Fatores de Crescimento de Fibroblastos/genética , Humanos , Receptores de Fatores de Crescimento de Fibroblastos
16.
Anal Bioanal Chem ; 413(14): 3725-3735, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33851226

RESUMO

In this study, for the first time, we propose a sensitive colloidal gold-based lateral flow immunoassay (LFIA) that can be used to detect carbendazim residues in functional foods. The adoption of inline cleanup LFIA strips effectively improved background interference to reduce misjudgment of results. First, the hapten 2-(methylamino)-1H-benzo[d]imidazole-5-carboxylic acid was used to establish the carbendazim immunoassay method. Subsequently, colloidal gold-mAb preparation and LFIA detection conditions were systematically optimized. For root and fruit samples (ginseng, ginger, jujube, and Chinese wolfberry), the designed strips had a cutoff value of 8 ng/mL. For flower and seed samples (chrysanthemum, coix seed, and malt), the cutoff value was 12 ng/mL. Even in a complex matrix, the established LFIA method demonstrates satisfactory sensitivity and anti-interference ability. This method was successfully applied in detection of carbendazim residues in complex functional foods, and the assay results are consistent with those obtained via liquid chromatography-tandem mass spectrometry. In short, the proposed method is fast and sensitive and has strong anti-interference ability. Furthermore, it provides a new technical method highly relevant to the on-site rapid detection of carbendazim residues in complex sample matrix.


Assuntos
Benzimidazóis/análise , Carbamatos/análise , Contaminação de Alimentos/análise , Alimento Funcional/análise , Fungicidas Industriais/análise , Coloide de Ouro/química , Imunoensaio/métodos , Desenho de Equipamento , Imunoensaio/economia , Imunoensaio/instrumentação , Limite de Detecção , Fatores de Tempo
17.
Adv Exp Med Biol ; 3233: 197-216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34053029

RESUMO

Optical coherence tomography (OCT) is a depth-resolved imaging modality, which is able to achieve micrometer-scale resolution within biological tissue noninvasively. In the past 30 years, researchers all around the world had made several essential efforts on techniques relevant to OCT. OCT has become a routine process for eye diseases with different types. In this chapter, the three important stages in the development of OCT are briefly illustrated, including the time domain OCT (TD-OCT), the frequency domain OCT (FD-OCT) and the optical coherence tomography angiography (OCTA). Each of the technique has made great progress for use on living human eye imaging in clinical applications. TD-OCT was first proposed and commercialized, which is able to achieve acceptable 2D depth-resolved cross-sectional images of human retina in vivo. FD-OCT was the upgraded OCT technique compared with TD-OCT. By capturing the coherent signal within the Fourier space, the FD-OCT could improve the image sensitivity compared with TD-OCT, and achieve dozens of kilo hertz imaging speed. OCTA is the newest developments of OCT technique, which is able to visualize the micro vasculature networks of human retina in vivo. With OCTA technique, the newest ophthalmologic OCT system is able to achieve detailed diagnosis for both micro-structure and vasculature abnormalities for clinical applications. The further development of OCT technique on imaging speed, contrast, resolution, field of view, and so on will make OCT to be a more powerful tool for clinical usages.


Assuntos
Oftalmopatias , Oftalmologia , Estudos Transversais , Humanos , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica
18.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5861-5866, 2021 Nov.
Artigo em Zh | MEDLINE | ID: mdl-34951176

RESUMO

The indirect competitive enzyme-linked immunosorbent assay(ic-ELISA) and direct competitive enzyme-linked immunosorbent assay(dc-ELISA) were performed for the rapid detection of aflatoxin B_1(AFB_1) in Astragali Radix, Zingiberis Rhizoma Recens, Jujubae Fructus, and Nelumbinis Semen with self-made antigens and antibodies. Different extraction methods were investigated to reduce the matrix effects of different medicinal parts in Chinese herbal medicines. The sensitivity of dc-ELISA method was improved by optimizing the molar ratio of AFB_1 to horseradish peroxidase(HRP). In this study, the sensitivity(IC_(50)) of ic-ELISA and dc-ELISA was 0.046 and 0.023 ng·mL~(-1), with the limit of detection(LOD) of 0.007 and 0.004 ng·mL~(-1), respectively. The detection time was 3 h and 50 min for ic-ELISA and dc-ELISA, respectively. The recovery rates were within the range of 62.96%-104.4%, with RSDs of less than 10%. Confirmed by LC-MS/MS, three positive samples of Nelumbinis Semen were detected from 53 samples. Two ELISA methods established in this study were accurate, rapid and sensitive, and can be used for rapid screening of AFB_1 in Chinese herbal medicines such as Astragali Radix, Zingiberis Rhizoma Recens, Jujubae Fructus, and Nelumbinis Semen. In addition, the advantages and limitations of the two methods were compared and discussed, which can provide a reference for the testing institutions to choose the proper method.


Assuntos
Aflatoxina B1 , Espectrometria de Massas em Tandem , Aflatoxina B1/análise , China , Cromatografia Líquida , Ensaio de Imunoadsorção Enzimática
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(11): 1141-1148, 2021 Nov 15.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-34753546

RESUMO

OBJECTIVES: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province. METHODS: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019. RESULTS: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019. CONCLUSIONS: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.


Assuntos
Doença de Mão, Pé e Boca , Criança , Pré-Escolar , China/epidemiologia , Análise por Conglomerados , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Incidência , Lactente , Análise Espaço-Temporal
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(12): 1242-1249, 2021 Dec 15.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-34911607

RESUMO

OBJECTIVES: To investigate the incidence of preterm birth and risk factors for preterm birth. METHODS: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth. RESULTS: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (P<0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth (P<0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth (P<0.05). CONCLUSIONS: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.


Assuntos
Nascimento Prematuro , Poluição por Fumaça de Tabaco , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Fatores de Risco
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