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1.
J Transl Med ; 21(1): 93, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750892

RESUMO

BACKGROUND: Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to observe the characteristics of gut microbiota, lipid metabolism and neurotransmitters in Gut-Liver-Brain axis in depressed mice (DM), and identify some novel perceptions on relationships between gut microbiota and depression. METHODS: A mouse model of depression was built used chronic unpredictable mild stress (CUMS). Fecal samples (measuring gut microbiota compositions, microbial genes and lipid metabolites), liver samples (measuring lipid metabolites), and hippocampus (measuring neurotransmitters) were collected. Both univariate and multivariate statistical analyses were used to identify the differential gut microbiota, metabolic signatures and neurotransmitters in DM. RESULTS: There were significant differences on both microbial and metabolic signatures between DM and control mice (CM): 71 significantly changed operational taxonomic units (OTUs) (60.56% belonged to phylum Firmicutes) and 405 differential lipid metabolites (51.11% belonged to Glycerophospholipid (GP) metabolism) were identified. Functional analysis showed that depressive-like behaviors (DLB)-related differential microbial genes were mainly enriched in GP metabolism. Weighted correlation network analysis (WGCNA) showed that DLB-related differential metabolites mainly belonged to GPs. Meanwhile, seven differential neurotransmitters were identified. Comprehensive analysis found that Lachnospiraceae and gamma-aminobutyric acid (GABA) were significantly correlated with 94.20% and 53.14% differential GPs, respectively, and GABA was significantly correlated with three main DLB phenotypes. CONCLUSION: Our results provided novel perceptions on the role of Gut-Liver-Brain axis in the onset of depression, and showed that GP metabolism might be the bridge between gut microbiota and depression. "Lachnospiraceae-GP metabolism-GABA" held the promise as a potential way between gut microbiota and brain functions in DM.


Assuntos
Depressão , Multiômica , Camundongos , Animais , Depressão/metabolismo , Encéfalo/metabolismo , Metabolismo dos Lipídeos , Glicerofosfolipídeos/metabolismo , Lipídeos
2.
J Nat Prod ; 86(4): 1003-1009, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36858948

RESUMO

Three unreported ent-abietane-type norditerpene lactones, euphohelides A-C (1-3), and 11 known analogs (4-14) were isolated from the whole plants of Euphorbia helioscopia L. Euphohelide A (1) is an unprecedented 2-nor-ent-abietane lactone bearing a unique 5/6/6/5 tetracyclic system. Euphohelides B (2) and C (3) possess 2-nor-6/6/6/5 and 2,3-dinor-5/6/6/5 dilactone tetracyclic moieties, respectively. Their structures were established by spectroscopic methods, computational ECD, and X-ray crystallographic analyses. A biomimetic synthesis of 1 was achieved from precursor 4 based on the speculative biogenetic pathway. Compounds 1 and 5 significantly alleviated the release of LPS-induced NO with IC50 values of 32.98 ± 1.13 and 33.82 ± 3.25 µM, which might be related to the regulation of the NF-κB signaling pathway.


Assuntos
Diterpenos , Euphorbia , Abietanos/farmacologia , Euphorbia/química , Lactonas/farmacologia , Lactonas/química , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Estrutura Molecular
3.
Bioorg Chem ; 138: 106619, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37253310

RESUMO

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.


Assuntos
Diterpenos , Euphorbia , Estrutura Molecular , Euphorbia/química , Resistência a Múltiplos Medicamentos , Compostos Radiofarmacêuticos/farmacologia , Diterpenos/farmacologia , Diterpenos/química
4.
Chem Biodivers ; 20(12): e202301454, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37874779

RESUMO

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.


Assuntos
Diterpenos , Euphorbia , Euphorbia/química , Diterpenos/farmacologia , Diterpenos/química , Espectroscopia de Ressonância Magnética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Estrutura Molecular
5.
Chem Biodivers ; 20(3): e202201180, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36785981

RESUMO

Two new azaphilones, penimultiones A and B, together with seven known analogs were isolated from the culture of Penicillium multicolor LZUC-S2. Their structures were elucidated by detailed spectroscopic data analysis and chemical transformation. Penimultiones A and B belong to a rare class of azaphilones possessing a 1,3-dioxolane moiety. In addition, all compounds were evaluated for their antibacterial activity against five clinically bacterial strains in vitro, and three compounds showed potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 12.5 to 50.0 µg/mL.


Assuntos
Penicillium , Estrutura Molecular , Penicillium/química , Antibacterianos/química , Fungos , Testes de Sensibilidade Microbiana
6.
Eur Arch Otorhinolaryngol ; 280(8): 3707-3720, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36939907

RESUMO

OBJECTIVES: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. METHODS: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. RESULTS: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. CONCLUSIONS: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/diagnóstico , Rinite/metabolismo , Proteína Catiônica de Eosinófilo/metabolismo , Peroxidase , Doença Crônica , Sinusite/diagnóstico , Sinusite/metabolismo , Biomarcadores , Pólipos Nasais/diagnóstico , Pólipos Nasais/metabolismo
7.
ORL J Otorhinolaryngol Relat Spec ; 85(3): 128-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37019094

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.


Assuntos
Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêutico
8.
Chem Biodivers ; 19(11): e202200762, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36177989

RESUMO

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.


Assuntos
Ligularia , Sesquiterpenos , Camundongos , Animais , Sesquiterpenos Policíclicos , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Células RAW 264.7 , Óxido Nítrico
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 759-764, 2022 Jul 15.
Artigo em Zh | MEDLINE | ID: mdl-35894190

RESUMO

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS: Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neuroblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Humanos , Lactente , Neuroblastoma/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Cintilografia , Estudos Retrospectivos , Resultado do Tratamento
10.
J Virol ; 94(6)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31896589

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV), an important pathogen that affects the pig industry, is a highly genetically diverse RNA virus. However, the phylogenetic and genomic recombination properties of this virus have not been completely elucidated. In this study, comparative analyses of all available genomic sequences of North American (NA)-type PRRSVs (n = 355, including 138 PRRSV genomes sequenced in this study) in China and the United States during 2014-2018 revealed a high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and the GP2 to GP3 regions. Lineage 1 (L1) PRRSV was found to be susceptible to recombination among PRRSVs both in China and the United States. The recombinant major parent between the 1991-2013 data and the 2014-2018 data showed a trend from complex to simple. The major recombination pattern changed from an L8 to L1 backbone during 2014-2018 for Chinese PRRSVs, whereas L1 was always the major backbone for US PRRSVs. Intralineage recombination hot spots were not as concentrated as interlineage recombination hot spots. In the two main clades with differential diversity in L1, NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, NADC34-like PRRSVs have been relatively stable in population genetic diversity for years. Systematic analyses of insertion and deletion (indel) polymorphisms of NSP2 divided PRRSVs into 25 patterns, which could generate novel references for the classification of PRRSVs. The results of this study contribute to a deeper understanding of the recombination of PRRSVs and indicate the need for coordinated epidemiological investigations among countries.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases. However, the phylogenetic and genomic recombination properties of the PRRS virus (PRRSV) have not been completely elucidated. In this study, we systematically compared differences in the lineage distribution, recombination, NSP2 polymorphisms, and evolutionary dynamics between North American (NA)-type PRRSVs in China and in the United States. Strikingly, we found high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and in the GP2 to GP3 region. Also, intralineage recombination hot spots were scattered across the genome between Chinese and US strains. Furthermore, we proposed novel methods based on NSP2 indel patterns for the classification of PRRSVs. Evolutionary dynamics analysis revealed that NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, suggesting that a dominant population may occur and cause an outbreak. Our findings offer important insights into the recombination of PRRSVs and suggest the need for coordinated international epidemiological investigations.


Assuntos
Polimorfismo Genético , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Recombinação Genética , Proteínas Virais/genética , Animais , China/epidemiologia , Filogeografia , Síndrome Respiratória e Reprodutiva Suína/epidemiologia , Síndrome Respiratória e Reprodutiva Suína/genética , Suínos , Estados Unidos/epidemiologia
11.
J Nat Prod ; 84(8): 2111-2120, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34197108

RESUMO

A bioactivity-guided study on the leaves of Picrasma javanica led to the isolation of 19 quassinoids, including 13 new compounds. The structures of the new compounds were elucidated by a combination of spectroscopic data analysis, X-ray crystallography studies, and electronic circular dichroism (ECD) data interpretation. Compounds 1-7 are rare examples of quassinoids with a keto carbonyl group at C-12. The biological activities of 11 of the more abundant isolates were evaluated against five phytopathogenic fungi in vitro, and several of them including 6 and 15 showed moderate inhibitory effects that were comparative to those of the positive control, carbendazim. In addition, the preliminary structure-activity relationships (SARs) of these quassinoids were also investigated.


Assuntos
Fungos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Picrasma/química , Quassinas/farmacologia , China , Fungos/patogenicidade , Fungicidas Industriais/química , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Picrasma/microbiologia , Extratos Vegetais/química , Folhas de Planta/química , Quassinas/química , Relação Estrutura-Atividade
12.
Inorg Chem ; 59(23): 17276-17281, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33231077

RESUMO

A biocompatible Y(III)-based metal-organic framework [Y4(TATB)2]·(DMF)3.5·(H2O) (ZJU-16, H3TATB= 4,4',4''-(1,3,5-triazine-2,4,6-triyl) tribenzoic acid) was synthesized, and it was adopted to load Mn2+ for chemodynamic therapy. Meanwhile, ibuprofen sodium (IBUNa), an anti-inflammatory drug, was introduced to increase the amount of Mn2+ (about 5.66 wt %) due to the low loading capacity of Mn2+. Mn&IBUNa@ZJU-16 which was loaded by Mn2+ and IBUNa exhibited significant effects of chemodynamic therapy and excellent inhibition of the 4T1 tumor cell growth, implying its long-term prospects in chemodynamic therapy and its possibility in bimodal cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Neoplasias da Mama/tratamento farmacológico , Estruturas Metalorgânicas/farmacologia , Ítrio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Camundongos , Células Tumorais Cultivadas , Ítrio/química
13.
Chin J Traumatol ; 23(6): 336-340, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32768290

RESUMO

PURPOSE: To assess the clinical efficacy of converting partial articular supraspinatus tendon avulsion (PASTA) lesions to full-thickness tears through a small local incision of the bursal-side supraspinatus tendon followed by repair. METHODS: We retrospectively analyzed 41 patients with Ellman grade 3 PASTA lesions and an average age of (54.7 ± 11.4) years from March 2013 to July 2017. Patients without regular conservative treatment and concomitant with other shoulder pathologies or previous shoulder surgery were excluded from the study. The tears were confirmed via arthroscopy, and a polydioxanone suture was placed to indicate the position of each tear. A small incision of approximately 6 mm was made using a plasma scalpel on the bursal-side supraspinatus tendon around the positioned suture to convert the partial tear into a full-thickness tear. The torn rotator cuff was sutured through the full thickness using a suture passer after inserting a 4.5-mm double-loaded suture anchor. Data were analyzed using a paired Student's t-test with statistical significance defined as p <0.05. RESULTS: At the final follow-up of 2 years, the pain-free shoulder joint range of motion and visual analog scale score were significantly improved compared to those before surgery (p < 0.001). The postoperative American Shoulder and Elbow Surgeons shoulder score was (90.6 ± 6.2), which was significantly higher than the preoperative score of (47.9 ± 8.3) (p < 0.001). The University of California at Los Angeles shoulder rating scale score increased from (14.7 ± 4.1) prior to surgery to (32.6 ± 3.4) points after surgery (p < 0.001). No patient had joint stiffness. CONCLUSION: This modified tear completion repair, by conversion to full-thickness tears through a small incision, has less damage to the supraspinatus tendon on the side of the bursa compared to traditional tear completion repair in the treatment of PASTA lesions. This surgical method is a simple and effective treatment that can effectively alleviate pain and improve shoulder joint function.


Assuntos
Artroscopia/métodos , Manguito Rotador , Técnicas de Sutura , Traumatismos dos Tendões/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Traumatismos dos Tendões/fisiopatologia , Resultado do Tratamento
14.
J Nat Prod ; 82(9): 2568-2579, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31503485

RESUMO

Thirteen new labdane-type diterpenoids 1-6, 9-11, 13, 14, 18, and 19 and seven known ones were isolated from the aerial parts of Leonurus japonicus. Compounds 1-5 represent rare examples of labdane-type diterpenoids, of which compounds 1-4 carry an N-chain linked at C-7 in their B-ring and compound 5 featured an α,ß-unsaturated-γ-lactam moiety. The structures and absolute configurations of these new diterpenoids were characterized by a combination of spectroscopic techniques, X-ray crystallography, electronic circular dichroism, and calculated specific rotations. The plant-growth regulatory activity of these compounds on the growth of the roots and shoots of Lactuca sativa and Lolium perenne seedlings were evaluated. Compound 3 showed a broad-spectrum inhibitory activity with the inhibition rates ranging from 60 to 83.5% at a concentration of 200 µg/mL, which were as active as those of glyphosate. Compound 8 had a selective inhibitory activity against the growth of the roots of L. perenne seedlings with an inhibition rate of 81.7%. However, compounds 11 and 16 exhibited significant stimulation effects on the roots of L. sativa with stimulation rates of 59.8 and 65.3%, respectively. In addition, compounds 3 and 8 exhibited inhibitory effects on the germination of L. perenne seeds.


Assuntos
Diterpenos/farmacologia , Leonurus/química , Reguladores de Crescimento de Plantas/farmacologia , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Estrutura Molecular , Reguladores de Crescimento de Plantas/isolamento & purificação , Análise Espectral/métodos
15.
BMC Ophthalmol ; 19(1): 10, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621664

RESUMO

BACKGROUND: This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese family with autosomal dominant aniridia. METHODS: The recruited family members underwent comprehensive routine and ophthalmic examinations, and Sanger sequencing was performed to screen the mutation in PAX6. RESULTS: A novel heterozygous PAX6 deletion c.435_445delTAGCGAAAAGC (p.Ser146ThrfsX9) in exon 7 was identified in all affected individuals, but this was absent in any of the unaffected family members and in the 200 unrelated controls. CONCLUSION: A novel deletion in the PAX6 gene was identified in a Chinese family associated with aniridia, which expands the spectrum of the PAX6 mutation and its associated phenotype.


Assuntos
Aniridia/genética , Povo Asiático/genética , Proteínas do Olho/genética , Predisposição Genética para Doença/genética , Fator de Transcrição PAX6/genética , Deleção de Sequência , Adulto , Pré-Escolar , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Cell Physiol Biochem ; 45(5): 1975-1985, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29529599

RESUMO

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. METHODS: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. RESULTS: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. CONCLUSION: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , MicroRNAs/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Idoso , Antagomirs/metabolismo , Apoptose , Sequência de Bases , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Intervalo Livre de Doença , Feminino , Glioma/genética , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Regulação para Cima
17.
Artigo em Inglês | MEDLINE | ID: mdl-29580941

RESUMO

BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The concentration of EETs was higher in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues (1.91 ±â€¯0.98 ng/mg vs. 0.96 ±â€¯0.77 ng/mg, mean ±â€¯SD, P < 0.01). As shown by immunohistochemistry, sEH was present in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues. Western blot analyses showed reduced sEH expression in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in ulcerative colitis tissues (P < 0.05). However, there was no statistically significant difference observed in CYP2C8 and CYP2C9 protein expression between them (P > 0.05). CONCLUSION: Our data suggest that the increase in EET levels may be part of a protective mechanism in ulcerative colitis. Furthermore, the concentration of EETs could be a key factor for drug therapy for ulcerative colitis.


Assuntos
Ácido 8,11,14-Eicosatrienoico/metabolismo , Colite Ulcerativa/metabolismo , Sistema Enzimático do Citocromo P-450/biossíntese , Epóxido Hidrolases/biossíntese , Regulação Enzimológica da Expressão Gênica , Adulto , Idoso , Colite Ulcerativa/patologia , Citocromo P-450 CYP2J2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Nat Prod ; 81(8): 1777-1785, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30106297

RESUMO

Ten new triterpenoids, ailanaltiolides A-J (1-10), and three known analogues (11-13) were isolated from the roots of Ailanthus altissima. Compounds 1-7 are apotirucallane-type, compounds 8 and 9 are tirucallane-type, and compound 10 is a trinordammarane-type triterpenoid. This is the first study indicating the genus Ailanthus as a potential source for apotirucallane derivatives, which contain an α,ß-unsaturated-ε-lactone A-ring and diversely modified C-17 side chains. Spectroscopic data interpretation, electronic circular dichroism analysis, and X-ray crystallographic data defined the structures and absolute configurations of these triterpenoids. Compounds 2, 7, and 8 showed cytotoxicity against four tumor cell lines (HeLa, 786-O, HepG2, and A549). In particular, compound 2 exhibited the highest activity against 786-O cells with an IC50 value of 8.2 µM in vitro.


Assuntos
Ailanthus/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Raízes de Plantas/química , Triterpenos/química , Triterpenos/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Difração de Raios X
19.
J Nat Prod ; 81(4): 791-797, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29469575

RESUMO

A high-content imaging assay was used to screen the fraction collection of the Natural Product Library at The Scripps Research Institute for inhibitors of Cryptosporidium parvum. A chemical investigation of one strain, Streptomyces sp. CB01388, resulted in the isolation of six herbicidins (1-6), one of which is new (herbicidin L, 1). Five of the six herbicidins (1-3, 5, 6) showed moderate inhibitory activity against C. parvum, with 1 and 6 comparable to the FDA-approved drug nitazoxanide, and 2-6 showed no toxicity to the host HCT-8 cells and human HEK293T and HepG2 cells. These findings highlight the herbicidin scaffold for anti- Cryptosporidium drug development.


Assuntos
Antibacterianos/farmacologia , Cryptosporidium parvum/efeitos dos fármacos , Nucleosídeos de Purina/farmacologia , Streptomyces/química , Antibacterianos/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Células Hep G2 , Humanos , Nitrocompostos , Nucleosídeos de Purina/química , Tiazóis/química , Tiazóis/farmacologia
20.
Cell Mol Biol (Noisy-le-grand) ; 63(11): 111-115, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-29208186

RESUMO

Many studies have been examined the association of platelet glycoprotein (GP) Ia C807T polymorphism with ischemic stroke (IS) susceptibility. However, the results of these studies are inconsistent. To further assess the effects of GP Ia C807T polymorphism on the risk of IS, a meta-analysis was performed in a separate ethnic group. Relevant studies were identified using PubMed and Chinese databases through January 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, 13 studies contained 2438 IS cases and 2308 controls included. In the total analyses, a significantly elevated risk of IS was associated with all variants of GP Ia C807T in the Chinese population (T vs C: OR = 1.24, 95% CI = 1.09-1.40; TT vs CC: OR = 1.59, 95% CI = 1.17-2.15; TT and CT combined vs CC: OR = 1.32, 95% CI = 1.09-1.59; TT vs CC and CT: OR = 1.35, 95% CI = 1.04-1.76). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han and in South China. This meta-analysis provides the evidence that GP Ia C807T polymorphism may contribute to the IS development in the Chinese population, especially in South China, and further studies in other ethic groups are required for definite conclusions.


Assuntos
Integrina alfa2/genética , Polimorfismo Genético/genética , Acidente Vascular Cerebral/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Razão de Chances
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