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1.
Planta ; 258(5): 100, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839056

RESUMO

MAIN CONCLUSION: Auto-fluorescent condensed tannins specifically accumulated in mesophyll cells of non-salt secretor mangroves are involved in the compartmentation of Na+ and osmotic regulation, contributing to their salt tolerance. Salinity is a major abiotic stress affecting the distribution and growth of mangrove plants. The salt exclusion mechanism from salt secretor mangrove leaves is quite known; however, salt management strategies in non-salt secretor leaves remain unclear. In this study, we reported the auto-fluorescent inclusions (AFIs) specifically accumulated in mesophyll cells (MCs) of four non-salt secretor mangroves but absent in three salt secretors. The AFIs increased with the leaf development under natural condition, and applied NaCl concentrations applied in the lab. The AFIs in MCs were isolated and identified as condensed tannin accretions (CTAs) using the dye dimethyl-amino-cinnamaldehyde (DMACA), specific for condensed tannin (CT), both in situ leaf cross sections and in the purified AFIs. Fluorescence microscopy and transmission electron microscope (TEM) analysis indicated that the CTAs originated from the inflated chloroplasts. The CTAs had an obvious membrane and could induce changes in shape and fluorescence intensity in hypotonic and hypertonic NaCl solutions, suggesting CTAs might have osmotic regulation ability and play an important role in the osmotic regulation in MCs. The purified CTAs were labeled by the fluorescent sodium-binding benzofuran isophthalate acetoxymethyl ester (SBFI-AM), confirming they were involved in the compartmentation of excess Na+ in MCs. This study provided a new view on the salt resistance-associated strategies in mangroves.


Assuntos
Células do Mesofilo , Proantocianidinas , Tolerância ao Sal , Cloreto de Sódio/farmacologia , Folhas de Planta/fisiologia , Salinidade
2.
J Immunol ; 206(5): 953-962, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33483349

RESUMO

IL-17-secreting Th17 cells play an important role in the pathogenesis of various inflammatory and autoimmune diseases. IL-17-targeted biologics and small molecules are becoming promising treatments for these diseases. In this study, we report that SZB120, a derivative of the natural compound 3-acetyl-ß-boswellic acid, inhibits murine Th17 cell differentiation by interacting with the α-subunit of eukaryotic initiation factor 2 (eIF2α). We showed that SZB120 directly interacts with eIF2α and contributes to serine 51 phosphorylation of eIF2α. The suppressive effect of SZB120 on Th17 cell differentiation was reversed by GSK2606414, an inhibitor of eIF2α phosphokinase. Phosphorylation of eIF2α induced by SZB120 decreased the protein expression of IκBζ, which is important for Th17 cell differentiation. Notably, interaction with eIF2α by SZB120 also impaired glucose uptake and glycolysis in T cells. In vivo, SZB120 treatment of C57BL/6 mice significantly attenuated IL-17/Th17-mediated autoimmune disease. Our study indicates that SZB120 is a promising drug candidate for IL-17/Th17-mediated inflammatory diseases.


Assuntos
Produtos Biológicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Fatores Imunológicos/farmacologia , Células Th17/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Células Cultivadas , Feminino , Interleucina-17/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Células Th17/metabolismo
3.
Reprod Biol Endocrinol ; 20(1): 139, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114509

RESUMO

BACKGROUND: Infertile men with higher sexual dysfunction risk and increased psychological burden, were also associated with more inclined to timed intercourse. Decreased semen quality may have adverse effects on male sexual function. However, it is also likely that many of these sequences do not play a direct role, those negative consequences may depend mainly on the later failed attempting pregnancy. Research is limited in this area. METHODS: This cross-sectional study was based on a group of 509 men who were assessed for couple's infertility at the First Hospital of Jilin University between June 2021 and October 2021. All the men completed a comprehensive questionnaire, and then were divided in two groups. Group A included patients who either never received a routine infertility work-up or done so recently within the last 6 months. Group B included patients who previously received a sperm quality assessment at least 6 months or more prior. Patients were further categorized into three subgroups according to the severity of the decreases in their sperm parameters: severe, mild-moderate, and normozoospermic. RESULTS: The prevalence of erectile dysfunction was higher in Group B Mild-Moderate and Group B Severe in comparison to Group A (OR=1.86 [1.07-3.24], P = 0.027; OR=5.312 [2.69-10.49], P < 0.001, respectively). No significant differences were found between Group A and Group B-normozoospermic. Similar results were observed in the prevalence of premature ejaculation between the groups. Timed intercourse was seen in 11.8% (20/170) of men in Group A and 16.2% (19/117) in Group B-normozoospermic. It was more commonly practiced among infertile men in Group B-Mild-Moderate and Group B Severe, as 28.2% (44/156) and 25.7% (17/66) of these couples had attempted to conceive through timed intercourse (P < 0.001). CONCLUSIONS: Our findings indicate that the severity of sperm quality impairment was negatively associated with sexual dysfunction only in infertile men who with known impairment of sperm quality for a long period. Timed intercourse was more common among these couples. For those individuals had never test their sperm quality, although more than half of these patients showed a decrease in sperm quality, the incidence of sexual dysfunction is relatively low and were comparable to those men examined previously known as normozoospermic.


Assuntos
Infertilidade Masculina , Disfunções Sexuais Fisiológicas , Estudos Transversais , Hospitais , Humanos , Incidência , Masculino , Sêmen , Análise do Sêmen , Disfunções Sexuais Fisiológicas/epidemiologia , Espermatozoides
4.
Clin Lab ; 68(6)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704733

RESUMO

BACKGROUND: Although rare, several mutations in the gene VSX2 (visual system homeobox 2, formerly CHX10) have been associated with congenital autosomal recessive anophthalmia (absence of one or both eyes). This report describes a proband, who at presentation was gravida 2, para 0, and 30 weeks pregnant. METHODS: A 30-year-old woman with congenital bilateral anophthalmia was 30 weeks pregnant at the time of presentation. Her parents were fourth-generation collateral blood relatives, and the familial congenital disease history suggested a possible genetic cause for her anophthalmia. Next generation sequencing and Sanger sequencing of blood samples of the patient, her parents, and her husband were conducted. The fetus was examined via ultrasound. RESULTS: The woman patient had a homozygous variation of the VSX2 gene (NM_182894.2) c.634delC (p.R211 Gfs*90). Both of her parents carried a heterozygous variation of this locus. The husband showed no pathogenic variation in VSX2. The fetal ultrasound revealed bilateral eyeball lenses. A healthy girl was delivered at 41 weeks gestation, with bilateral eyeballs visible. CONCLUSIONS: Homogenous mutation of VSX2 c.634delC (p.R211Gfs*90) has not been reported previously. The patient's congenital bilateral anophthalmia was due to this homogenous mutation, the result of familial inbreeding. Avoiding near-relative marriage is an important means of preventing such diseases.


Assuntos
Anoftalmia , Adulto , Anoftalmia/genética , Anoftalmia/patologia , Feminino , Proteínas de Homeodomínio/genética , Homozigoto , Humanos , Mutação , Linhagem , Gravidez , Fatores de Transcrição/genética
5.
Clin Lab ; 68(5)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536067

RESUMO

BACKGROUND: Amniocentesis was performed on a pregnant woman with a deletion of exon 45 of the Duchenne Muscular Dystrophy (DMD) gene. METHODS: Fetal Xp21.1 (31944831-32030363) x 0 was found by chromosome microarray analysis (CMA), i.e., 0.086 Mb hemizygote deletion was detected in the Xp21.1 region of the fetal X chromosome, which contained exon 45 of the DMD gene. RESULTS: The results verified by MLPA were consistent with those of CMA, which indicated that CMA was accurate in a single exon deletion in this fetus. This case suggests that CMA may become an essential method for the prenatal diagnosis of a fetus with DMD gene deletion/duplication. CONCLUSIONS: It can routinely detect chromosome copy number variation and analyze DMD diseases caused by exon duplication or deletion, which is enormously significant for new DMD exon deletion or duplication.


Assuntos
Distrofia Muscular de Duchenne , Cromossomos , Variações do Número de Cópias de DNA , Distrofina/genética , Éxons/genética , Feminino , Feto , Deleção de Genes , Humanos , Análise em Microsséries , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Gravidez
6.
Exp Ther Med ; 26(2): 372, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37415841

RESUMO

The present study aimed to investigate clinical phenotype and genotype characteristics of a male child with SATB2-associated syndrome (SAS) and analyzed the relationship between these characteristics and the possible underlying genetic mechanism. His clinical phenotype was analyzed. Using a high-throughput sequencing platform, his DNA samples were subjected to medical exome sequencing, screened for suspected variant loci and analyzed for chromosomal copy number variations. The suspected pathogenic loci were verified by Sanger sequencing. He presented with phenotypic anomalies of delayed growth, delayed speech and mental development, facial dysmorphism showing the typical manifestation of SAS and motor retardation symptoms. Gene sequencing result analyses revealed a de novo heterozygous repeat insertion shift mutation in the SATB2 gene (NM_015265.3) c.771dupT (p.Met258Tyrfs*46), resulting in a frameshift mutation from methionine to tyrosine at the amino acid site 258 and a truncated protein with 46 amino acids missing. The parents showed no mutation at this locus. This mutation was identified as the nosogenesis of this syndrome in children. To the best of the authors' knowledge, this is the first report on this mutation. The clinical manifestations and gene variation characteristics of 39 previously reported SAS cases were analyzed together with this case. The findings of the present study suggested severely impaired language development, facial dysmorphism and varying degrees of delayed intellectual development as the characteristic clinical manifestations of SAS.

7.
J Cosmet Dermatol ; 21(10): 4818-4835, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35080093

RESUMO

BACKGROUND: Integrated information on the global prevalence and incidence of bullous pemphigoid (BP) is lacking. OBJECTIVE: To estimate the incidence and prevalence of BP in a systematic review and meta-analysis. METHODS: Observational studies were included by using databases of Medline, EMBASE, and Cochrane Library. Subgroup analysis was by continent, age, sex, and country income level. Random-effects model was used. Between-study heterogeneity was assessed using the I2  statistic. RESULTS: The global incidence was 0.0419 per 1000 person-years (95% CI: 0.0414-0.0424). The incidence was 0.047 per 1000 person-years (95% CI: 0.0462-0.0477), 0.0419 per 1000 person-years (95% CI: 0.0411-0.0426), 0.0072 per 1000 person-years (95% CI: 0.0067-0.0078), 0.003 per 1000 person-years (95% CI: 0.0023-0.0039) in North America, Europe, Asia, and Africa, respectively; 0.0202 per 1000 person-years (95% CI: 0.0196-0.0208) and 0.0181 per 1000 person-years (95% CI: 0.0175-0.0188) females and males; 0.001 per 1000 person-years (95% CI: 0.001-0.001), 0.002 per 1000 person-years (95% CI: 0.001-0.002), 0.004 per 1000 person-years (95% CI: 0.004-0.004); 0.007 per 1000 person-years (95% CI: 0.007-0.008), 0.011 per 1000 person-years (95% CI: 0.011-0.012), 0.017 per 1000 person-years (95% CI: 0.015-0.018) for age <50, 50-59, 60-69, 70-79, 80-89, and ≥90 years; 0.0038 per 1000 person-years (95% CI: 0.0036-0.004112) (I2  = 99%, p < .05) and 0.0456 per 1000 person-years (95% CI: 0.0450-0.0462) (I2  = 100%, p < .05). The pooled clinic-based prevalence was 0.79% (95% CI: 0.75%-0.84%), 1.13% (95% CI: 1.06%-1.21%), 0.21% (95% CI: 0.17%-0.26%), and 0.13% (95% CI: 0.1%-0.15%) for Asia, Africa, and Europe. CONCLUSIONS: This study identified the global incidence and prevalence of BP in terms of spatial and population distributions and among various income level. A relatively higher incidence was in Europe, females, older people, and high-income level country. The prevalence was higher in Asia. These findings should be interpreted with caution due to high heterogeneity of included studies.


Assuntos
Penfigoide Bolhoso , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Incidência , Prevalência , Penfigoide Bolhoso/epidemiologia , América do Norte/epidemiologia , Ásia/epidemiologia , Estudos Observacionais como Assunto
8.
PLoS One ; 17(7): e0270828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35802641

RESUMO

The association between methionine synthase (MTR) A2756G (rs1805087) polymorphism and the susceptibility to congenital heart disease (CHD) has not been fully determined. A meta-analysis of case-control studies was performed to systematically evaluate the above association. Studies were identified by searching the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang databases from inception to June 20, 2021. Two authors independently performed literature search, data extraction, and quality assessment. Predefined subgroup analyses were carried out to evaluate the impact of the population ethnicity, source of healthy controls (community or hospital-based), and methods used for genotyping on the outcomes. A random-effects model was used to combine the results, and 12 studies were included. Results showed that MTR A2756G polymorphism was not associated with CHD susceptibility under the allele model (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.86 to 1.07, P = 0.43, I2 = 4%), heterozygote model (OR: 0.95, 95% CI: 0.84 to 1.07, P = 0.41, I2 = 0%), homozygote model (OR: 1.00, 95% CI: 0.64 to 1.55, P = 0.99, I2 = 17%), dominant genetic model (OR: 0.95, 95% CI: 0.84 to 1.07, P = 0.41, I2 = 0%), or recessive genetic model (OR: 0.94, 95% CI: 0.62 to 1.43, P = 0.32, I2 = 13%). Consistent results were found in subgroup analyses between Asian and Caucasian populations in studies with community and hospital-derived controls as well as in studies with PCR-RFLP and direct sequencing (all P values for subgroup differences > 0.05). In conclusion, current evidence does not support an association between MTR A2756G polymorphism and CHD susceptibility.


Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase , Cardiopatias Congênitas , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Povo Asiático/genética , Predisposição Genética para Doença , Cardiopatias Congênitas/genética , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
9.
Front Cell Dev Biol ; 10: 999174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105363

RESUMO

Long noncoding RNAs (lncRNAs) have been characterized to play an essential role in ovarian tumorigenesis via controlling a variety of cellular processes, such as cell proliferation, invasion, apoptotic death, metastasis, cell cycle, migration, metabolism, immune evasion, and chemoresistance. The one obstacle for the therapeutic efficacy is due to the development of drug resistance in ovarian cancer patients. Therefore, in this review article, we describe the role of lncRNAs in chemoresistance in ovarian cancer. Moreover, we discuss the molecular mechanism of lncRNAs-involved drug resistance in ovarian cancer. We conclude that lncRNAs could be useful targets to overcome chemoresistance and improve therapeutic outcome in ovarian cancer patients.

10.
Front Chem ; 10: 900482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615317

RESUMO

In this study, a novel sulfonic acid-modified catalyst for MOFs (UIO-66-SO3H) was synthesized using chlorosulfonic acid as a sulfonating reagent and first used as efficient heterogeneous catalysts for the one-pot conversion of fructose into biofuel 5-ethoxymethylfurfural (EMF) in a cosolvent free system. The physicochemical properties of this catalyst were characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and powder X-ray diffraction (XRD). The characterization demonstrated that the sulfonic acid group was successfully grafted onto the MOF material and did not cause significant changes to its morphology and structure. Furthermore, the effects of catalyst acid amount, reaction temperature, reaction time, and catalyst dosage on reaction results were investigated. The results showed that the conversion of fructose was 99.7% within 1 h at 140°C, while the EMF yield reached 80.4%. This work provides a viable strategy by application of sulfonic acid-based MOFs for the efficient synthesis of potential liquid fuel EMF from renewable biomass.

11.
J Cosmet Dermatol ; 21(10): 4482-4489, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35182003

RESUMO

The efficacy and safety of commercial low-concentration glycolic acid products on acne were evaluated by recruiting volunteers accompanying mild to moderate acne of different ages and genders, which is a clinical practice for acne. We recruited a total of 30 volunteers according to the inclusion criteria, conducting clinical evaluation and skin physiological index testing, VISIA skin analysis, distributing products, and informing the trial method. Clinical testing and assessment will be carried out in weeks 0, 1, 2, and 4. 27 acne volunteers finished the entire trial. After 4 weeks of using low-concentration glycolic acid products, most subjects experienced a significant improvement in their skin lesions and the GAGS score. At the same time, the VISIA test showed that the subjects had an obvious amelioration in facial porphyrins, which was statistically significant, and there was a slight improvement in residual spots and erythema. The skin physiological indexes showed that the skin hydration value increased from 236.2 ± 98.05 to 278.2 ± 90.26 after 14 days. At the end of the test, the skin hydration value dropped to 234.6 ± 81.88. Regarding the melanin and erythema, the value decreased in the 4th week significantly. Repeated use of 5% low-concentration glycolic acid improves the appearance and chromaticity of the treatment site. It increases the brightness L* and reduces the redness a*. This study shows that low concentrations of glycolic acids have a good effect on the treatment of mild to moderate acne. It may pay the way to carry out further large-scale clinical research.


Assuntos
Acne Vulgar , Feminino , Humanos , Masculino , Acne Vulgar/terapia , Eritema/etiologia , Eritema/tratamento farmacológico , Glicolatos/efeitos adversos , Resultado do Tratamento
12.
Biomed Pharmacother ; 142: 112013, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34388526

RESUMO

Uterine lipoleiomyomas are variants of uterine leiomyomas and are characterized by progressive enlargement that can occur even after menopause. These tumors can produce serious clinical symptoms and are difficult to diagnosis preoperatively. The growth rate of uterine lipoleiomyomas after menopause is comparatively higher than that of conventional uterine leiomyomas, and lipoleiomyosarcomas as well as tumor-to-tumor metastasis associated with lipoleiomyomas have been reported. However, detailed histogenic mechanisms of the tumor remain unclear. Surgical treatments are the current choice for the management of lipoleiomyomas. The purpose of this review is to promote greater awareness of lipoleiomyoma characteristics with a focus on histogenesis, diagnosis, and treatment. We performed an exhaustive literature review and have summarized the available data. We assessed the interpretation of auxiliary examinations to help physicians in making an early accurate diagnosis of the disease and to help with treatment decision-making, particularly regarding whether surgery should be performed or avoided.


Assuntos
Leiomioma/diagnóstico , Neoplasias Uterinas/diagnóstico , Tomada de Decisões , Diagnóstico Precoce , Feminino , Humanos , Leiomioma/patologia , Leiomioma/terapia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia
13.
Front Pharmacol ; 12: 748102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776965

RESUMO

Tumor microenvironment-responsive polypeptide nanogels belong to a biomaterial with excellent biocompatibility, easily adjustable performance, biodegradability, and non-toxic properties. They are developed for selective delivery of antitumor drugs into target organs to promote tumor cell uptake, which has become an effective measure of tumor treatment. Endogenous (such as reduction, reactive oxygen species, pH, and enzyme) and exogenous (such as light and temperature) responsive nanogels can release drugs in response to tumor tissues or cells to improve drug distribution and reduce drug side effects. This article systematically introduces the research progress in tumor microenvironment-responsive polypeptide nanogels to deliver antitumor drugs and provides a reference for the development of antitumor nanoformulations.

14.
Biomed Pharmacother ; 125: 109984, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32066042

RESUMO

Melanoma is a life-threatening cancer with limited treatments. Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) crucial to RNA virus sensing, interferon production, and tumor suppression. Quercetin, a natural flavonoid, has particularly therapeutic interests to prevent and treat cancer, for its pharmacological effects against oxidant, inflammation, and angiogenesis. Quercetin was investigated for its anti-melanoma activity and potential mechanisms in this study. We found that quercetin inhibited mouse melanoma growth in vivo, and suppressed proliferation and promoted apoptosis of both B16 and A375 cells in vitro. Quercetin upregulated IFN-α and IFN-ß expression through activating RIG-I promoter in B16 cells. The induction of IFN-α and IFN-ß, which could be severely impaired by silencing RIG-I induced interferon stimulated genes (ISGs). Moreover, RIG-I likely amplifies antitumor effects by activating signal transduction and activator of transcription 1 (STAT1) in the IFN-JAK-STAT pathway in an autocrine and paracrine manner. Our study provided novel insights regarding biological and anti-proliferative activities of quercetin against melanoma, and we identified RIG-I as a potential target in anti-tumor therapies.


Assuntos
Proteína DEAD-box 58/metabolismo , Interferon Tipo I/metabolismo , Melanoma/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Apoptose/genética , Linhagem Celular Tumoral , Proteína DEAD-box 58/genética , Modelos Animais de Doenças , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/tratamento farmacológico , Melanoma/etiologia , Melanoma/patologia , Melanoma Experimental , Camundongos , Regiões Promotoras Genéticas , Receptores Imunológicos , Ativação Transcricional
15.
Sci Adv ; 6(21): eaaz2059, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32671205

RESUMO

Many annotated long noncoding RNAs (lncRNAs) harbor predicted short open reading frames (sORFs), but the coding capacities of these sORFs and the functions of the resulting micropeptides remain elusive. Here, we report that human lncRNA MIR155HG encodes a 17-amino acid micropeptide, which we termed miPEP155 (P155). MIR155HG is highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacts with the adenosine 5'-triphosphate binding domain of heat shock cognate protein 70 (HSC70), a chaperone required for antigen trafficking and presentation in dendritic cells (DCs). P155 modulates major histocompatibility complex class II-mediated antigen presentation and T cell priming by disrupting the HSC70-HSP90 machinery. Exogenously injected P155 improves two classical mouse models of DC-driven auto inflammation. Collectively, we demonstrate the endogenous existence of a micropeptide encoded by a transcript annotated as "non-protein coding" and characterize a micropeptide as a regulator of antigen presentation and a suppressor of inflammatory diseases.


Assuntos
RNA Longo não Codificante , Animais , Apresentação de Antígeno , Proteínas de Choque Térmico HSP70/genética , Humanos , Inflamação/genética , Camundongos , Fases de Leitura Aberta , RNA Longo não Codificante/genética
16.
EBioMedicine ; 39: 575-590, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30591370

RESUMO

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-ß-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease. METHODS: To explore the targets and molecular mechanism of AKBA, we performed affinity purification, metabolomics analysis of HaCaT cells treated with AKBA, and epidermis of imiquimod (IMQ) induced mouse model of psoriasis and psoriasis patients. FINDINGS: AKBA directly interacts with methionine adenosyltransferase 2A (MAT2A), inhibited its enzyme activity, decreased level of S-adenosylmethionine (SAM) and SAM/SAH ratio, and reprogrammed one­carbon metabolism in HaCaT cells. Untargeted metabolomics of epidermis showed one­carbon metabolism was activated in psoriasis patients. Topical use of AKBA improved inflammatory phenotype of IMQ induced psoriasis-like mouse model. Molecular docking and site-directed mutagenesis revealed AKBA bound to an allosteric site at the interface of MAT2A dimer. INTERPRETATION: Our study extends the molecular mechanism of AKBA by revealing a new interacting protein MAT2A. And this leads us to find out the dysregulated one­carbon metabolism in psoriasis, which indicates the therapeutic potential of AKBA in psoriasis. FUND: The National Natural Science Foundation, the National Program on Key Basic Research Project, the Shanghai Municipal Commission, the Leading Academic Discipline Project of the Shanghai Municipal Education Commission.


Assuntos
Carbono/metabolismo , Metabolômica/métodos , Metionina Adenosiltransferase/antagonistas & inibidores , Psoríase/tratamento farmacológico , Triterpenos/administração & dosagem , Administração Tópica , Sítio Alostérico/efeitos dos fármacos , Animais , Linhagem Celular , Regulação para Baixo , Humanos , Imiquimode/efeitos adversos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Metionina Adenosiltransferase/química , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Psoríase/induzido quimicamente , Psoríase/metabolismo , Triterpenos/farmacologia
17.
Artigo em Zh | MEDLINE | ID: mdl-17287573

RESUMO

ISSR (inter-simple sequence repeat) and RAPD (random-amplified polymorphic DNA) markers were used to detect genetic diversity of 4 different ecotypes of reed (Phragmites communis Trin.) growing in Hexi Corridor, Gansu province. Nine effective primers were screened from 30 ISSR arbitrary primers, and a total of 99 DNA bands were amplified, among which 51 (51.5%) were polymorphic. Thirteen effective primers were screened from 45 RAPD 10-oligonucleotide arbitrary primers, and a total of 195 DNA bands were amplified, among which 87 (44.6%) were polymorphic. Genetic identity based on ISSR and RAPD data showed a positive correlation (r=0.845, P<0.05). Based on unweighted pair-group method with arithmetic averages (UPGMA) cluster analysis on DNA bands amplified, together with the correlation analysis between genetic distance and soil water contents and soluble salt contents as well, the present results suggest that the genetic diversity occurs among the four ecotypes of reed in adaptation to long term natural drought and salinity, showing an obvious evolutional tendency from swamp reed via salt meadow reed to dune reed.


Assuntos
DNA de Plantas/análise , Poaceae/genética , Polimorfismo Genético , Técnica de Amplificação ao Acaso de DNA Polimórfico , Ecossistema , Variação Genética , Genética Populacional , Genoma de Planta , Genótipo , Técnicas de Sonda Molecular , Filogenia
18.
Biomed Res Int ; 2014: 527030, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25133165

RESUMO

Hepatitis C virus (HCV) infections spontaneously clear in approximately 15-45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.


Assuntos
Povo Asiático , Hepacivirus/fisiologia , Hepatite C/virologia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
19.
Hepatol Int ; 7(3): 798-804, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26201916

RESUMO

Interferon-γ-inducible protein 10 (IP-10), or C-X-C motif chemokine (CXCL10), is a small cytokine belonging to the non-ELR CXC chemokine family. By binding to its specific receptor CXCR3, IP-10 recruits activated CXCR3+ T cells to the liver parenchyma and plays a pivotal role in liver disease initiation and progression. IP-10 is mainly secreted by hepatocytes and liver sinusoidal endothelium. Different IP-10 forms exert different functions: long-length IP-10 directs CXCR3+ T cell migration and is associated with inflammation, while short IP-10 is a CXCR3 antagonist, thereby playing protective role in liver injury. IP-10 levels are positively associated with the severity of liver inflammation, fibrosis stage and acute graft rejection. High IP-10 levels are closely related to anti-HCV therapy failure. Thus, IP-10 may be both a potential prognostic tool and a therapeutic target for the treatment of patients with HCV or HIV/HCV co-infection. The purpose of this review is to highlight the growing advances in basic knowledge and clinical interest of IP-10 in liver disease.

20.
Plant Cell Rep ; 24(7): 401-7, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15843934

RESUMO

Callus culture has, to date, been reported only in a few species of Narcissus. We used anthers of Chinese narcissus (Narcissus tazetta L. var. chinensis Roem) as explants for callus induction and plant regeneration. A high percentage of anthers at the early- to mid-uninucleate microspore stage were responsive on the basal MS medium supplemented with 0.5-1 mg l(-1) 2,4-dichlorophenoxyacetic acid and 0.5-2 mg l(-1) 6-benzyladenine under dark conditions. Calli were initiated from anther connective tissue or anther wall tissue, and no division of microspores occurred during callus formation, as determined by histological observation. Using 20 random amplified polymorphic DNA primers, we verified the genetic integrity of the anther-derived plants of Chinese narcissus with respect to the donor plants. These results suggest that anther culture in vitro can provide an efficient new micropropagation technique for Chinese narcissus as well as a new strategy for in vitro mass propagation of other daffodils.


Assuntos
Flores/crescimento & desenvolvimento , Narcissus/crescimento & desenvolvimento , Regeneração/fisiologia , Ácido 2,4-Diclorofenoxiacético/farmacologia , Agricultura/métodos , Compostos de Benzil , Técnicas de Cultura de Células/métodos , Células Cultivadas , Flores/efeitos dos fármacos , Flores/genética , Genoma de Planta , Genótipo , Cinetina/farmacologia , Narcissus/efeitos dos fármacos , Narcissus/genética , Purinas , Regeneração/efeitos dos fármacos , Esporos/efeitos dos fármacos , Esporos/genética , Esporos/crescimento & desenvolvimento
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