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1.
Altern Ther Health Med ; 29(8): 650-655, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37678870

RESUMO

Objective: To investigate the effects of Moringa Oleifera Leaf Extract (MOLE) plus rosiglitazone (RSG) on glucose and lipid metabolism, serum leptin, and the Akt/GSK3ß/ß-Catenin signaling pathway in type 2 diabetic (T2D) rats. Methods: Sixty male Sprague-Dawley (SD) rats were randomly divided into six groups: the normal group, the model group, the RSG group, the low- and high-dose MOLE group, and the MOLE+RSG group. The normal group was fed a standard rat diet, while the other groups were given a single intraperitoneal injection of low-dose streptozomycin (STZ) (35 mg/kg) and fed a high-sugar and high-fat diet. After 8 weeks, the treatment outcomes were evaluated by measuring key parameters of blood glucose and lipid metabolism and the protein kinase B (AKT) / Glycogen synthase kinase 3beta (GSK3ß) /ß-Catenin signaling pathway in the T2D rats. Results: Compared with the normal group, the model group showed significantly increased levels of blood glucose, blood lipids, serum leptin, free fatty acid (FFA), and tumor necrosis factor-α (TNF-α). Compared with the model group, the RSG, low-dose MOLE, and high-dose MOLE groups displayed effective control of blood glucose, blood lipids, serum leptin, FFA, and TNF-α. The MOLE+RSG group surpassed the RSG group in regulating glucose, lipid metabolism, and serum leptin levels in T2D rats. In addition, the MOLE+RSG group also had superiority over the RSG group in activating the AKT/GSK3ß/ß-Catenin pathway. Conclusion: MOLE plus RSG can effectively reduce blood glucose and blood lipids in T2DM rats.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Moringa oleifera , Ratos , Masculino , Animais , Rosiglitazona/uso terapêutico , Glucose/metabolismo , Glicemia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , Moringa oleifera/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/metabolismo , beta Catenina/uso terapêutico , Leptina/metabolismo , Leptina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Metabolismo dos Lipídeos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Ratos Sprague-Dawley , Lipídeos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico
2.
Neurogenetics ; 23(1): 11-17, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34716526

RESUMO

The target of EGR1 protein 1 (TOE1) is a 3-exonuclease belonging to the Asp-Glu-Asp-Asp deadenylase family that plays a vital role in the maturation of a variety of small nuclear RNAs (snRNAs). Bi-allelic variants in TOE1 have been reported to cause a rare and severe neurodegenerative syndrome, pontocerebellar hypoplasia type 7 (PCH7) (OMIM # 614,969), which is characterized by progressive neurodegeneration, developmental delay, and ambiguous genitalia. Here, we describe the case of a 5-year-6-month-old female Chinese patient who presented with cerebral dysplasia, moderate intellectual disability, developmental delay, and dystonia. Trio whole-exome sequencing revealed two previously unreported heterozygous variants of TOE1 in the patient, including a maternal inherited splicing variant c.237-2A > G and a de novo missense variant c.551G > T, p.Arg184Leu. TA clone sequencing showed trans status of the two variants, indicating the missense variant occurred on the paternal strand in the patient. Clinical features of the patient were mostly concordant with previous reports but brain deformities (enlarged lateral ventricle and deepened cerebellum sulcus without microcephaly and reduced cerebellar volume) were less severe than in typical PCH7 patients. Moreover, the patient had no gonadal malformation, which is common and variable in patients with PCH7. In summary, we report the case of a Chinese patient with atypical PCH7 caused by a novel TOE1 compound variant. Our work suggests that variations in the TOE1 gene can lead to highly variable clinical phenotypes.


Assuntos
Doenças Cerebelares , Microcefalia , Doenças Cerebelares/genética , Pré-Escolar , Feminino , Humanos , Microcefalia/genética , Proteínas Nucleares/genética , Fenótipo , Sequenciamento do Exoma
3.
Artigo em Inglês | MEDLINE | ID: mdl-35316174

RESUMO

Two novel, designated strains 29W222T and 2943T, were isolated from the marine sediment from Aoshan Bay, Jimo, PR China. Growth was observed at pH 6.0-8.5 (optimum, pH 7.5) for strain 29W222T, and pH 5.5-8.5 (pH 7.0) for strain 2943T. Both strains displayed growth in 0.5-6 % NaCl with an optimum at 1 % for 29W222T; 0.5 % for 2943T. Both strains grew optimally at 33 °C. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that 29W222T and 2943T represented members of the genus Fulvivirga and strain 29W222T was most closely related to Fulvivirga kasyanovii KMM 6220T (97.9 % sequence similarity) and Fulvivirga imtechensis AK7T (95.0 %), and 2943T to Fulvivirga imtechensis AK7T (95.7 %) and Fulvivirga kasyanovii KMM 6220T (94.8 %). The genomic DNA G+C contents of 29W222T and 2943T were 39.9 and 37.7 mol%, respectively. The results of chemotaxonomic analysis indicated that the sole respiratory quinone was menaquinone 7 (MK-7), and the major fatty acid was iso-C15 : 0 for both strains. Average nucleotide identity and average amino acid identity values between strain 29W222T and Fulvivirga kasyanovii KMM 6220T were 78.9 and 83.6 %, respectively; the corresponding values between 2943T and Fulvivirga imtechensis AK7T were 69.8 and 63.6 %, respectively. Therefore, strains 29W222T and 2943T represent to two novel species of the genus Fulvivirga, for which the names Fulvivirga marina sp. nov. (29W222T=KCTC 62848T=MCCC 1K05194T) and Fulvivirga sediminis sp. nov. (2943T=KCTC 62847T= MCCC 1K05144T) are proposed, respectively.


Assuntos
Ácidos Graxos , Água do Mar , Técnicas de Tipagem Bacteriana , Bacteroidetes , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
4.
Int J Syst Evol Microbiol ; 70(10): 5280-5286, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32881678

RESUMO

A Gram-stain-positive, rod-shaped, whitesmoke-coloured and aerobic bacterium, designated strain Co35T, was isolated from the intestine of Collichthys lucidus collected from the Jiangmen Guangdong Chinese White Dolphin Provincial Nature Reserve. Strain Co35T was able to grow at 15-35 °C (optimal 28 °C), at pH 7.0-8.5 (optimal 8.0) and with 0-9 % (w/v) NaCl (optimal 0.5-1 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Co35T was a member of the genus Aeromicrobium within the family Nocardioidaceae. The genomic DNA G+C content of strain Co35T was 68.4 mol%. Chemotaxonomic analysis showed that the sole respiratory quinone was menaquinone 9 (MK-9), and the major fatty acids included 10-methyl C18 : 0. The polar lipids were found to consist of phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), two unidentified phospholipids (PL1-2) and two unidentified glycolipids (GL1-2). On the basis of its phylogenetic, phenotypic, chemotaxonomic, genotypic and genomic characteristics presented in this study, strain Co35T represents a novel species in the genus Aeromicrobium, for which the name Aeromicrobium piscarium sp. nov. is proposed. The type strain is Co35T (=KCTC 49280T=MCCC 1K03754T).


Assuntos
Actinobacteria/classificação , Perciformes/microbiologia , Filogenia , Actinobacteria/isolamento & purificação , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Glicolipídeos/química , Intestinos/microbiologia , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Neurourol Urodyn ; 39(2): 688-694, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31804751

RESUMO

AIMS: To investigate the prevalence of overactive bladder (OAB) and assess its risk factors in 5- to 14-year-old Chinese children. METHODS: A cross-sectional study of OAB prevalence was performed by distributing 11 800 anonymous self-administered questionnaires to parents in five provinces of mainland China from July to October 2018. The questionnaires included questions on sociodemographics, history of urinary tract infection (UTI), lower urinary tract symptoms (LUTS), family history of LUTS, bowel symptoms, and details about the elimination communication (EC) start time. OAB was defined as urgency and increased the daytime frequency with or without urinary incontinence. RESULTS: A total of 10 133 questionnaires qualified for statistical analysis. The overall prevalence of OAB was 9.01% and decreased with age, from 12.40% at 5 years to 4.55% at 14 years (χ2 trend = 88.899; P < .001). The proportion of dry OAB increased with age, whereas the proportion of wet OAB decreased. A late-onset of EC was associated with a high OAB prevalence (χ2 trend = 39.802; P < .001). Children with obesity, a history of UTI, nocturnal enuresis (NE), a family history of LUTS, constipation, and fecal incontinence had a higher prevalence of OAB than did normal children (P < .05). CONCLUSION: Obesity, a history of UTI, NE, a family history of LUTS, and bowel symptoms are risk factors associated with OAB. Starting EC before 12 months of age might help reduce the prevalence of OAB in children.


Assuntos
Bexiga Urinária Hiperativa/epidemiologia , Adolescente , Fatores Etários , Povo Asiático , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , População , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários
6.
Small ; 15(20): e1805544, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30924285

RESUMO

Many candidate anticancer drugs have suffered from their intrinsic hydrophobicity, which poses several obstacles for clinical application. To overcome this challenge and further improve the performance, herein a nanocrystal-based biomimetic formulation with a sandwich structure is developed. As the core, flake shaped nanocrystals (NCs) with high loading of the hydrophobic drug hydroxycamptothecin (HCPT) are synthesized via a mild nanoprecipitation process by exploring the template effect of serum albumin. Meanwhile, the camouflaged cancer cell membrane (CM) composed of plentiful membrane proteins endows the NCs with homotypic targeting capacity at tumor sites. In addition, the photosensitizer indocyanine green sandwiched between NCs and CM not only converts near infrared light to heat for photothermal treatment but also improves the dissolution of HCPT NCs for chemotherapy. These features corporately achieve the orchestration of chemo-photothermal combination therapy and completely inhibit tumor growth with few adverse effects, showing promise as a new modality for the utilization of hydrophobic drugs to treat cancer.


Assuntos
Membrana Celular/química , Interações Hidrofóbicas e Hidrofílicas , Hipertermia Induzida , Nanopartículas/química , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Humanos , Verde de Indocianina/uso terapêutico , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Distribuição Tecidual
7.
Genet Med ; 21(10): 2231-2238, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30890784

RESUMO

PURPOSE: The benefits of concurrent newborn hearing and genetic screening have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of newborns with genetic screening results. METHODS: Newborns in China were screened for 20 hearing-loss-related genetic variants from 2012 to 2017. Genetic results were categorized as positive, at-risk, inconclusive, or negative. Hearing screening results, risk factors, and up-to-date hearing status were followed up via phone interviews. RESULTS: Following up 12,778 of 1.2 million genetically screened newborns revealed a higher rate of hearing loss by three months of age among referrals from the initial hearing screening (60% vs. 5.0%, P < 0.001) and a lower rate of lost-to-follow-up/documentation (5% vs. 22%, P < 0.001) in the positive group than in the inconclusive group. Importantly, genetic screening detected 13% more hearing-impaired infants than hearing screening alone and identified 2,638 (0.23% of total) newborns predisposed to preventable ototoxicity undetectable by hearing screening. CONCLUSION: Incorporating genetic screening improves the effectiveness of newborn hearing screening programs by elucidating etiologies, discerning high-risk subgroups for vigilant management, identifying additional children who may benefit from early intervention, and informing at-risk newborns and their maternal relatives of increased susceptibility to ototoxicity.


Assuntos
Testes Genéticos/métodos , Perda Auditiva/genética , Triagem Neonatal/métodos , China/epidemiologia , Surdez/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos/tendências , Genética Populacional , Perda Auditiva Neurossensorial/diagnóstico , Testes Auditivos , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal/tendências
8.
Neurourol Urodyn ; 38(5): 1423-1429, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30998267

RESUMO

AIMS: A pilot survey shows that primary nocturnal enuresis (PNE) prevalence has increased significantly during the past decade in Mainland China. Whether it is related to the delay of elimination communication (EC) is unclear. This study retrospectively investigated the influence of delayed EC on the PNE prevalence in children and adolescents in mainland China. METHODS: A cross-sectional study of PNE prevalence was performed by distributing 19 500 anonymous self-administered questionnaires to parents in five provinces of mainland China from July 2017 to October 2017. The questionnaires included sociodemographic data, family caregivers' information, and details about the disposable diapers (DD) usage, EC commencement date, psychological disorders, lower urinary tract symptoms, and family history of PNE in children and adolescents. The 2017 PNE prevalence was compared with that of 2006 in Mainland China. RESULTS: The total response rate was 97.04% (18 631 of 19 500) and 92.39% (18 016 of 19 500) qualified for statistical analysis. The PNE prevalence in 2017 has increased significantly compared to that of 2006 (7.30% vs 4.07%, P < 0.001). The PNE prevalence in children with EC starting before 6 months of age was significantly lower than those who start after 12 months of age. The longer DD were used and the later the beginning of EC, the higher the PNE prevalence was found. CONCLUSIONS: The PNE prevalence in Mainland China has increased significantly during the past 10 years. A longer use of DD and later onset of EC may be risk factors for PNE.


Assuntos
Enurese Noturna/epidemiologia , Treinamento no Uso de Banheiro , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pais , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários
9.
Sheng Li Xue Bao ; 70(5): 489-496, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30377687

RESUMO

The purpose of the present study was to investigate the effects and underlying mechanism of gonadotropin-releasing hormone agonist (GnRHa) controlled ovarian hyperstimulation (COH) on embryo implantation in mice. Forty female Kunming mice aged 9 weeks were randomly divided into two groups (control and COH groups). The COH group received intraperitoneal (i.p.) injections of aminocyclin acetate (GnRHa), human menopausal gonadotropin (HMG) and human chorionic gonadotropin (hCG), while the control group was given equal amount of physiological saline by i.p. injection. One male mouse and two female mice were put into the same cage at 16:00 on the hCG injection day, and on the fourth day of pregnancy, 10 mice from each group were killed. The levels of serum estradiol (E2) and progesterone (P) were measured by radioimmunoassay; HE staining was used to observe the morphology of ovarian and endometrial tissues. The protein expression levels of endometrial leukemia inhibitory factor (LIF), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and glycodelin A were detected by Western blot and immunohistochemistry. Ten mice from each group were sacrificed on the eighth day of pregnancy, and the status of the uterus and the average number of blastocysts were observed. The results showed that, compared with control group, the serum E2 level in COH group was significantly decreased (P < 0.05), while the P level was increased significantly (P < 0.05); the ovarian follicles at different developmental stages were rare, corpus lutea (CL) were visible and multiple, the endometrium was thinned, and the number of endometrial glands was reduced (P < 0.05); the contents of LIF, p-STAT3, HB-EGF and glycodelin A in the endometrium were decreased significantly (P < 0.05) on the fourth day of pregnancy; mouse blastocysts developed slowly and were decreased in number on the eighth day of pregnancy (P < 0.05). The above results suggest that GnRHa COH can affect embryo implantation in mice. The mechanism may be related to the imbalance of gonadal hormone, the changes in the structure of the endometrium and the expressions of LIF, p-STAT3, HB-EGF and glycodelin A in the implantation stage, which may lead to the decrease of endometrial receptivity and the abnormal dialogue between the embryo and the uterus.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/agonistas , Minociclina/farmacologia , Indução da Ovulação , Animais , Gonadotropina Coriônica/farmacologia , Endométrio/efeitos dos fármacos , Estradiol/sangue , Feminino , Glicodelina/metabolismo , Humanos , Fator Inibidor de Leucemia/metabolismo , Menotropinas/farmacologia , Camundongos , Folículo Ovariano/efeitos dos fármacos , Gravidez , Progesterona/sangue , Distribuição Aleatória , Fator de Transcrição STAT3/metabolismo
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(5): 534-538, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-28506344

RESUMO

OBJECTIVE: To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology. METHODS: A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the distribution of mutations in families. RESULTS: Both patients had novel mutations in the PHEX gene; one patient had a frameshift mutation, c.931dupC, which caused early termination of translation and produced the truncated protein p.Gln311Profs*13; the other patient had a splice site mutation, IVS14+1G>A, which caused the skipping of exon 15 and produced an incomplete amino acid chain. Their parents had normal gene phenotypes. CONCLUSIONS: c.931dupC and IVS14+1G>A are two novel mutations of the PHEX gene and might be the new pathogenic mutations of XLH.


Assuntos
Raquitismo Hipofosfatêmico Familiar/genética , Mutação , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Estudos Retrospectivos
11.
Biomed Chromatogr ; 29(8): 1146-66, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25545370

RESUMO

Xiao Chai Hu Decoction (XCHD), named Sho-saiko-to in Japanese, is a well-known traditional Chinese medicine formula used in Asia. However, the characterization methods used in the past have lacked sensitivity and the nature of the active constituents of XCHD remains unclear. This study was carried out to establish the hyphenated method of bioactivity-guided fractionation and liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOFMS/MS) in order to identify the major bioactive constituents of XCHD. D101 macroporous resin was used to separate and enrich the material base into four fractions, XCHD-1, XCHD-2, XCHD-3 and XCHD-4. Each fraction was then evaluated for its antidepressant effect using depression-related parameters. An LC-ESI-QTOFMS/MS method in both positive and negative ion mode was also applied for separation and identification of the biological active fractions of XCHD. As a result, 79 compounds including polysaccharides, flavonoids, saikosaponins, ginsenosides, licoricesaponins and gingerols were detected, 69 of them were identified or tentatively characterized. Based on our preliminary characterization investigations, polysaccharides, gingerols and flavonoids in XCHD may contribute to the antidepressant effect of XCHD. In conclusion, the hyphenated method of bioactivity-guided fractionation and LC-ESI-QTOFMS/MS was meaningful for the isolation and preliminary identification of the biological active components in complex matrices of traditional Chinese medicine.


Assuntos
Bupleurum/química , Medicamentos de Ervas Chinesas/química , Extratos Vegetais/química , Catecóis/análise , Cromatografia Líquida de Alta Pressão/métodos , Álcoois Graxos/análise , Flavonoides/análise , Ginsenosídeos/análise , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análise , Polissacarídeos/análise , Saponinas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
13.
Cell Mol Neurobiol ; 34(6): 871-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24794794

RESUMO

Leptin is a multifunctional hormone produced by the ob gene and is secreted by adipocytes that regulate food intake and energy metabolism. Numerous studies demonstrated that leptin is a novel neuroprotective effector, however, the mechanisms are largely unknown. Herein, we demonstrate the protective activities of leptin after ischemic stroke and provide the first evidence for the involvement of the connexin 43 (Cx43) in leptin-mediated neuroprotection. We found that leptin treatment reduces the infarct volume, improves animal behavioral parameters, and inhibits the elevation of Cx43 expression in vivo. In vitro, leptin reverses ischemia-induced SY5Y and U87 cells Cx43 elevation, secreted glutamate levels in medium and SY5Y cell death, these roles could be abolished by leptin receptor blocker. Additionally, leptin administration upregulated the extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. Moreover, ERK1/2 inhibitors pretreatment reversed the effects of leptin on Cx43 expression, glutamate levels and cell apoptosis. In conclusion, the present study demonstrated that leptin can reduce the Cx43 expression and cell death both in vivo and in vitro via ERK1/2 signaling pathway. This result provides a novel regulatory signaling pathway of the neuroprotective effects of leptin and may contribute to ischemic brain injury prevention and therapy.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Conexina 43/metabolismo , Leptina/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Masculino , Camundongos , Neurônios/metabolismo , Receptores para Leptina/efeitos dos fármacos
15.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(3): 317-23, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-24758084

RESUMO

OBJECTIVE: To explore the potential molecular mechanisms for Bushen Tiaojing Recipe (BTR) improving the endocrine function of ovarian granular cells by observing the effect of BTR containing serum on follicle stimulating hormone/cyclic adenosine monophosphate-protein kinase A (FSH/ cAMP-PKA) pathway in in vitro cultured human ovarian granular cells. METHODS: The primary ovarian granular cells collected from in vitro fertilization-embryo transfer patients were cultured for 24 h. The human and rat serum containing different concentrations of BTR (low, medium, high dose), and their normal serums were co-incubated with ovarian granular cells for 48 h respectively, and then they were divided into the low, medium, high dose BTR groups and the control group. The levels of estradiol (E2), progesterone (P), and cyclic adenosine monophosphate (cAMP) in the culture medium were measured by radioimmunoassay. The protein expression of FSHR in ovarian granular cells was detected by Western Blot. The mRNA expression of follicle stimulating hormone receptor (FSHR) and P450 aromatase (P450arom) in ovarian granular cells were detected by Real-time PCR. RESULTS: In human BTR containing serum groups: Compared with control group, the levels of E2 and cAMP in the culture medium were higher (both P < 0.05) in the medium and high dose BTR groups; the levels of P in the culture medium decreased in the medium dose BTR group (P < 0.01). The protein and mRNA expression of FSHR in ovarian granular cells increased (all P < 0.01), the mRNA expressions of P450arom in ovarian granular cells were higher (P < 0.05, P< 0.01) in the medium and high dose BTR groups. In rat BTR containing serum groups: Compared with the control group, the levels of E2 in the culture medium were higher (all P < 0.01), cAMP in the culture medium were higher (P < 0.05, P < 0.01) in the medium and high dose BTR group; the levels of P in the culture medium decreased in the medium dose BTR group (P < 0.01). The protein and mRNA expression of FSHR in ovarian granular cells were higher (all P < 0.01), the mRNA expression of P450arom in ovarian granular cells increased in the medium and high dose BTR groups (P < 0.05, P < 0.01). CONCLUSION: BTR could possibly improve the endocrine function of ovarian granular cells by regulating main effector molecules FSHR, cAMP, P450arom, and E2 in FSH/cAMP-PKA pathway of ovarian granular cells.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Células Cultivadas , Proteína Quinase Tipo I Dependente de AMP Cíclico/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/citologia , Humanos , Soro/química , Transdução de Sinais/efeitos dos fármacos
16.
Orphanet J Rare Dis ; 19(1): 146, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580983

RESUMO

Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression of the maternal ubiquitin protein ligase E3A gene (UBE3A). As one of the most challenging symptoms and important focuses of new treatment, sleep disturbance is reported to occur in 70-80% of patients with AS and has a serious impact on the lives of patients and their families. Although clinical studies and animal model studies have provided some clues, recent research into sleep disorders in the context of AS is still very limited. It is generally accepted that there is an interaction between neurodevelopment and sleep; however, there is no recognized mechanism for sleep disorders in AS patients. Accordingly, there are no aetiologically specific clinical treatments for AS-related sleep disorders. The most common approaches involve ameliorating symptoms through methods such as behavioural therapy and symptomatic pharmacotherapy. In recent years, preclinical and clinical studies on the targeted treatment of AS have emerged. Although precision therapy for restoring the UBE3A level and the function of its signalling pathways is inevitably hindered by many remaining obstacles, this approach has the potential to address AS-related sleep disturbance.


Assuntos
Síndrome de Angelman , Transtornos do Sono-Vigília , Animais , Humanos , Síndrome de Angelman/genética , Sono , Ubiquitina-Proteína Ligases/genética
17.
Quant Imaging Med Surg ; 14(1): 144-159, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223047

RESUMO

Background: In 2020, our center established a Tanner-Whitehouse 3 (TW3) artificial intelligence (AI) system using a convolutional neural network (CNN), which was built upon 9059 radiographs. However, the system, upon which our study is based, lacked a gold standard for comparison and had not undergone thorough evaluation in different working environments. Methods: To further verify the applicability of the AI system in clinical bone age assessment (BAA) and to enhance the accuracy and homogeneity of BAA, a prospective multi-center validation was conducted. This study utilized 744 left-hand radiographs of patients, ranging from 1 to 20 years of age, with 378 boys and 366 girls. These radiographs were obtained from nine different children's hospitals between August and December 2020. The BAAs were performed using the TW3 AI system and were also reviewed by experienced reviewers. Bone age accuracy within 1 year, root mean square error (RMSE), and mean absolute error (MAE) were statistically calculated to evaluate the accuracy. Kappa test and Bland-Altman (B-A) plot were conducted to measure the diagnostic consistency. Results: The system exhibited a high level of performance, producing results that closely aligned with those of the reviewers. It achieved a RMSE of 0.52 years and an accuracy of 94.55% for the radius, ulna, and short bones series. When assessing the carpal series of bones, the system achieved a RMSE of 0.85 years and an accuracy of 80.38%. Overall, the system displayed satisfactory accuracy and RMSE, particularly in patients over 7 years old. The system excelled in evaluating the carpal bone age of patients aged 1-6. Both the Kappa test and B-A plot demonstrated substantial consistency between the system and the reviewers, although the model encountered challenges in consistently distinguishing specific bones, such as the capitate. Furthermore, the system's performance proved acceptable across different genders and age groups, as well as radiography instruments. Conclusions: In this multi-center validation, the system showcased its potential to enhance the efficiency and consistency of healthy delivery, ultimately resulting in improved patient outcomes and reduced healthcare costs.

18.
Nat Commun ; 15(1): 3301, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671004

RESUMO

Diphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient's mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient's mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21 , Histidina , Histidina/análogos & derivados , Antígenos de Histocompatibilidade Menor , Crista Neural , Fator 2 de Elongação de Peptídeos , Proteína Supressora de Tumor p53 , Proteínas Supressoras de Tumor , Animais , Crista Neural/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Humanos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Camundongos , Fator 2 de Elongação de Peptídeos/metabolismo , Fator 2 de Elongação de Peptídeos/genética , Histidina/metabolismo , Ribossomos/metabolismo , Mutação , Proliferação de Células , Xenopus laevis , Feminino , Técnicas de Introdução de Genes , Xenopus , Masculino , Camundongos Knockout
19.
J Thorac Dis ; 16(1): 773-797, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38410605

RESUMO

Background: The epidemiology and severity of asthma vary by sex and age. The diagnosis, treatment, and management of asthma in female patients are quite challenging. However, there is hitherto no comprehensive and standardized guidance for female patients with asthma. Methods: Corresponding search strategies were determined based on clinical concerns regarding female asthma. Search terms included "sex hormones and lung development", "sex hormone changes and asthma", "hormones and asthma immune response", "women, asthma", "children, asthma", "puberty, asthma", "menstruation, asthma", "pregnancy, asthma", "lactation, asthma", "menopause, asthma", "obesity, asthma", and "women, refractory, severe asthma". Literature was retrieved from PubMed/Medline, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Data with the search date of July 30, 2022 as the last day. This consensus used the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the strength of recommendation and quality of evidence. Results: We collected basic research results and clinical evidence-based medical data and reviewed the effects of sex hormones, classical genetics, and epigenetics on the clinical presentation and treatment response of female patients with asthma under different environmental effects. Based on that, we formulated this expert consensus on the management of female asthma throughout the life cycle. Conclusions: This expert consensus on the management of asthma in women throughout the life cycle provides diagnosis, treatment, and research reference for clinical and basic medical practitioners.

20.
Psychol Res Behav Manag ; 16: 535-548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860350

RESUMO

Aim: This study aims to examine financial literacy's impact on individual investors' financial behaviour while also investigating the mediating role of financial risk tolerance and the moderator effect of emotional intelligence. Methods: The study collects time-lagged data from 389 financially independent individual investors from leading educational institutes in Pakistan. Data are analysed using SmartPLS (v 3.3.3) to test the measurement and structural models. Results: The findings reveal that financial literacy significantly impacts the financial behaviour of individual investors. In addition, financial risk tolerance partially mediates the relationship between financial literacy and financial behaviour. Besides, the study found a significant moderating role of emotional intelligence in the direct relationship between financial literacy and financial risk tolerance and an indirect relationship between financial literacy and financial behaviour. Discussion: The study examined a hitherto unexplored relationship between financial literacy and financial behaviour, mediated by financial risk tolerance and moderated by emotional intelligence.

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