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BACKGROUND: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China. METHODS: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed. RESULTS: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits. CONCLUSIONS: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China.
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Disfunção Cognitiva , Demência , Humanos , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Idoso , China/epidemiologia , Demência/epidemiologia , Demência/diagnóstico , Prevalência , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
STUDY OBJECTIVE: Any abnormality of the uterine cavity can result in reduced endometrial receptivity, which negatively affects embryo implantation and leads to lower clinical pregnancy rates. The effects of improved uterine cavity environment on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET) treatment outcome are unclear. This study aimed to investigate the impact of improved uterine cavity abnormalities on the pregnancy outcomes of infertile patients undergoing IVF/ICSI-ET. DESIGN: Retrospective study. SETTING: Single-center. PATIENTS: Women with infertility who underwent fresh cycles of IVF/ICSI-ET. INTERVENTIONS: We retrospectively analyzed the clinical data of 31 057 cycles of women with infertility undergoing IVF/ICSI-ET with hysteroscopy and treated at the First Affiliated Hospital of Zhengzhou University Reproductive Medicine Center from August 2009 to May 2018. According to the previous condition of their uterine cavity, patients were divided into the normal uterine cavity, single uterine cavity abnormality, and complex uterine cavity abnormality groups. Differences in general conditions and pregnancy-assisted outcomes were compared among the groups, which were screened according to propensity score matching. MEASUREMENTS AND MAIN RESULTS: In 3005 cycles after propensity score matching screening, there were no statistically significant differences in the implantation and clinical pregnancy rates of patients with successfully treated uterine cavity abnormalities and lesions (p > .05). The miscarriage rate was significantly higher in the complex uterine cavity abnormality group than in the normal (p = .001) and single uterine cavity abnormality groups (p = .002). Logistic regression analysis showed that the female partner's age (adjusted odds ratio, 1.12; 95% confidence interval, 1.05-1.19; p = .001) and history of intrauterine adhesions (adjusted odds ratio, 1.44; 95% confidence interval, 1.12-1.85; p = .005) were independent risk factors for miscarriage. CONCLUSION: The age of the female partner and history of intrauterine adhesions increased the miscarriage rate in patients undergoing IVF/ICSI-ET.
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Aborto Espontâneo , Infertilidade , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Feminino , Fertilização in vitro , Humanos , Infertilidade/etiologia , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Sêmen , Injeções de Esperma Intracitoplásmicas , Anormalidades Urogenitais/complicações , Útero/anormalidadesRESUMO
BACKGROUND: In recent years, some studies have shown that there is a positive association between the number of oocytes retrieved and the cumulative live birth rate (CLBR) after fresh and frozen cycles of one oocyte retrieval. However, almost no studies have examined the association between the number of oocytes retrieved and the CLBR when using the "freeze-all" strategy. We performed this study to investigate the effects of an extreme oocyte yield during the first "freeze-all" cycle on the cumulative live birth rate among patients younger than 35 years old. METHODS: This was a retrospective cohort study performed in a university-affiliated reproductive medicine centre. Data obtained from 3276 women aged younger than 35 years who underwent their first "freeze-all" cycle (IVF/ICSI) were collected between January 2009 and December 2016. In all, 5025 frozen cycles took place during the follow-up period from January 2009 to December 2018. Patients were divided into five groups according to oocytes retrieved (group 1: 4-10 oocytes; group 2: 11-20 oocytes; group 3: 21-30 oocytes; group 4: 31-40 oocytes; group 5: > 40 oocytes). The primary outcome was the cumulative live birth rate. RESULTS: Unadjusted results showed that the cumulative live birth rate significantly increased as the number of oocytes retrieved increased and reached up to 93.82% in cases with yields of 21-30 oocytes (P < 0.05), after which it did not have a significant increase (P > 0.05). After adjusting for confounders, our results showed that the number of oocytes retrieved is an independent positive predictor of cumulative live birth rate when using a "freeze-all" strategy. (P < 0.001). In addition, the fertilization rate and the gonadotropin dose also influenced the cumulative live birth rate (P<0.05). CONCLUSIONS: Among women younger than 35 years old who underwent the "freeze-all" strategy, the number of oocytes retrieved positively correlated with the cumulative live birth rate. Taking both efficacy and safety into account, ovarian stimulation should be rational, and the upper limit of the oocyte yield should be no more than 30.
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Coeficiente de Natalidade , Fertilização in vitro/métodos , Recuperação de Oócitos/métodos , Indução da Ovulação/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Criopreservação/métodos , Transferência Embrionária/métodos , Feminino , Gonadotropinas/administração & dosagem , Humanos , Recuperação de Oócitos/estatística & dados numéricos , Oócitos/citologia , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND Worldwide, the treatment of complications associated with type 2 diabetes mellitus, including diabetic foot ulcer (DFU), results in an economic burden for patients and healthcare systems. This study aimed to use high-throughput 16S rRNA gene sequencing to investigate the changes in foot skin microbiome of patients with diabetes mellitus from a single center in China. MATERIAL AND METHODS Fifty-two participants were divided into 4 study groups: healthy controls (n=13); patients with short-term diabetes (<2 years; n=13); patients with intermediate-term diabetes (5-8 years; n=13); and patients with long-term diabetes (>10 years; n=13). Swabs were analyzed from the intact skin of the foot arch using high-throughput 16S ribosomal RNA sequencing. RESULTS Microbiome phylogenic diversity varied significantly between the study groups (whole tree, P<0.01; Chao1, P<0.01), but were similar within the same group. The findings were supported by non-parametric multidimensional scaling (stress=0.12) and principal component analysis (principal component 1, 8.38%; principal component 2, 5.28%). In patients with diabetes mellitus, the dominant skin microbial phyla were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. CONCLUSIONS High-throughput 16S rRNA gene sequencing showed dynamic changes in the skin microbiome from the foot during the progression of diabetes mellitus. These findings support the importance of understanding the role of the skin microbiota in the pathogenesis of DFU.
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Diabetes Mellitus Tipo 2/microbiologia , Pé Diabético/microbiologia , Microbiota/genética , Adulto , Bactérias/genética , Estudos de Casos e Controles , China , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Pé Diabético/genética , Progressão da Doença , Feminino , Pé/microbiologia , Genes de RNAr , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes , RNA Ribossômico 16S/genética , Pele/microbiologiaRESUMO
The standard terms of infant incubators with high clinical risk and high incidence of adverse events has been tested through the introduction of YY/T 0841-2011 standard, an on-site inspection scheme for using infant incubators has been proposed, the problems existing in the inspection are analyzed and reasonable suggestions are put forward, this paper provides a certain technical reference for the whole life cycle management of the infant incubator.
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Incubadoras para Lactentes , Exame Físico , Humanos , LactenteRESUMO
Wogonoside, a bioactive flavonoid component derived from Scutellaria baicalensis Georgi, has been reported to inhibit tumor growth in mice bearing various types of cancer cells such as breast cancer, lung cancer, and leukemia cells. However, whether wogonoside could inhibit tumor growth of endometrial cancer has not been elucidated. In this study, we explored the function of wogonoside on tumor growth and the underlying mechanism on endometrial cancer. Firstly, we investigated the effect of wogonoside on endometrial cancer cells and found that wogonoside could significantly decrease cell proliferation and metastasis. Mechanistically, wogonoside could aggravate the extent of ER stress and upregulate the phosphorylation level of Mammalian Ste20-like kinase 1, leading to the activation of the Hippo signaling pathway. Taken together, in vitro and in vivo data demonstrated that wogonoside could be a potent inducer of ER stress and could be further developed into a promising therapy for endometrial cancer.
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Neoplasias do Endométrio/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Flavanonas/farmacologia , Glucosídeos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Via de Sinalização Hippo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Scutellaria baicalensis/metabolismoRESUMO
BACKGROUND: Endometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied. METHODS/DESIGN: Eligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis. TRIAL REGISTRATION: This trial has been assigned the following registry number: NCT03006406 .
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Endometriose/fisiopatologia , Infertilidade/tratamento farmacológico , Luteolíticos/uso terapêutico , Injeções de Esperma Intracitoplásmicas/métodos , Pamoato de Triptorrelina/uso terapêutico , Adulto , Coeficiente de Natalidade , Feminino , Humanos , Infertilidade/etiologia , Luteolíticos/sangue , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Método Simples-Cego , Pamoato de Triptorrelina/sangueRESUMO
ß-N-Acetylglucosaminidases (GlcNAcases) are important for many biological functions and industrial applications. In this study, a glycoside hydrolase family 20 GlcNAcase from Shinella sp. JB10 was expressed in Escherichia coli BL21 (DE3). Compared to many GlcNAcases, the purified recombinant enzyme (rJB10Nag) exhibited a higher specificity activity (538.8 µmol min-1 mg-1) or V max (1030.0 ± 82.1 µmol min-1 mg-1) toward p-nitrophenyl ß-N-acetylglucosaminide and N,N'-diacetylchitobiose (specificity activity of 35.4 µmol min-1 mg-1) and a higher N-acetylglucosaminide tolerance (approximately 50% activity in 70.0 mM N-acetylglucosaminide). The degree of synergy on enzymatic degradation of chitin by a commercial chitinase and rJB10Nag was as high as 2.35. The enzyme was tolerant to most salts, especially 3.0-15.0% (w/v) NaCl and KCl. These biochemical characteristics make the JB10 GlcNAcase a candidate for use in many potential applications, including processing marine materials and the bioconversion of chitin waste. Furthermore, the enzyme has the highest proportions of alanine (16.5%), glycine (10.5%), and random coils (48.8%) with the lowest proportion of α-helices (24.9%) among experimentally characterized GH 20 GlcNAcases from other organisms.
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Acetilglucosaminidase/metabolismo , Rhizobiaceae/enzimologia , Acetilglucosaminidase/química , Acetilglucosaminidase/genética , Sequência de Aminoácidos , Clonagem Molecular , Hidrólise , Homologia de Sequência de Aminoácidos , Especificidade por SubstratoRESUMO
BACKGROUND/AIM: Pelvic floor dysfunctions (PFDs), which encompass pelvic organ prolapse (POP), stress urinary incontinence (SUI), and anal incontinence (AI), are common degenerative diseases in women. Bone marrow mesenchymal stem cells (BMSCs) hold promise for the treatment of PFDs. Extracellular vesicles (EVs) derived from BMSCs, have displayed an extensive role in intercellular communication and tissue repair. However, efficacy of the treatment using EVs originated from BMSCs on mouse models of PFD remains unknown. This study investigated the therapeutic potential of BMSC-derived EVs in a female PFD mouse model induced by vaginal distension (VD). MATERIALS AND METHODS/RESULTS: Flow cytometry analysis confirmed the positive expression of BMSC-related markers, and successful induction of multilineage differentiation further validated their characteristics. As expected, the EVs extracted from BMSCs exhibited typical cup-shaped and circular-shaped structures. In the PFD model, BMSC-derived EVs significantly reduced the levels of inflammatory cytokines (p<0.05), improved tissue repair, and mitigated neutrophil infiltration. Furthermore, EVs promoted cell proliferation, decreased expression of relaxin receptors, increased expression of elastin, and elevated collagen content in the anterior vaginal wall tissue (p<0.05), suggesting beneficial effects on tissue regeneration and connective tissue restoration in PFD. CONCLUSION: BMSC-derived EVs effectively reduce tissue inflammation, promote tissue regeneration and connective tissue reconstruction, and improve pelvic support deficiency, thereby alleviating PFD induced by vaginal distension (VD) in vivo.
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Modelos Animais de Doenças , Vesículas Extracelulares , Inflamação , Células-Tronco Mesenquimais , Distúrbios do Assoalho Pélvico , Regeneração , Animais , Camundongos , Células-Tronco Mesenquimais/metabolismo , Feminino , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Distúrbios do Assoalho Pélvico/terapia , Distúrbios do Assoalho Pélvico/metabolismo , Inflamação/terapia , Inflamação/metabolismo , Inflamação/patologia , Diafragma da Pelve , Transplante de Células-Tronco Mesenquimais/métodos , Diferenciação Celular , Humanos , Proliferação de CélulasRESUMO
Background: Sophora flavescens, a traditional Chinese medicine for treating conditions associated with abnormal skin pigmentation, contains flavonoids with inhibitory effects on tyrosinase. However, their mechanisms of action and their modulatory effects on melanogenesis remain unclear. Methods: Herein, a group of prenylated flavonoids was identified from S. flavescens extracts and their inhibitory activities on mushroom tyrosinase were evaluated. The anti-melanogenesis effects of these prenylated flavonoids were investigated in cellular (with murine melanoma cells) and animal (with zebrafish) models. Results: Prenylated flavonoids including isoanhydroicaritin (IAI), kurarinone (KR), and sophoraflavanone G (SG) were the major active constituents in S. flavescens extracts with anti-tyrosinase activity (IC50 = 0.7, 7.1, and 6.7 µM, respectively). Enzyme kinetic assays showed that IAI, KR, and SG had a mixed type of tyrosinase inhibition, supported by data from computational docking. Notably, KR at concentrations of 5 and 10 µM enhanced intracellular tyrosinase activity and stimulated melanin production in B16F10 cells, whereas SG and IAI did not exhibit significant activity. Further studies with the zebrafish model showed that IAI (80 and 160 µM) inhibited melanin biosynthesis by about 30.0% while KR (20 µM) stimulated melanogenesis by 36.9%. Furthermore, a zebrafish depigmentation model supported the anti-melanogenesis effect of IAI (80 and 160 µM) by 33.0% and 34.4%, respectively. Conclusion: In summary, IAI was identified as a tyrosinase inhibitor with an anti-melanogenic effect and KR was an enhancer for melanin production in B16F10 cells and zebrafish. Findings from the current study suggest that IAI and KR from S. flavescens may exert contrasting effects in the modulation of melanin production, providing important insights into the development of S. flavescens as a cosmeceutical or medicinal ingredient.
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BACKGROUND: Patients with polycystic ovary syndrome (PCOS) have a higher risk of obstetric complications. The association between anti-Müllerian hormone (AMH) and gestational hypertension in these patients is poorly understood. OBJECTIVE: To determine the association between serum AMH levels and gestational hypertension in patients with PCOS undergoing fresh embryo transfer. METHODS: This retrospective study included 649 patients with PCOS who had singleton live births after undergoing fresh embryo transfers. The association of AMH with gestational hypertension in these patients was estimated before and after propensity score matching (PSM). RESULTS: Patients with gestational hypertension had higher AMH levels than those without gestational hypertension. In single-factor logistic regression, the odds of gestational hypertension increased by 11.7% and 18.6% for every 1â ng/mL increase in AMH before and after adjusting for confounding factors [OR 1.117, 95% CI(1.025, 1.217), P = 0.012; adjusted OR 1.186, 95% CI(1.061, 1.327), adjusted P = 0.003], respectively. The odds of gestational hypertension increased more than 100% [adjusted OR 2.635, 95% CI(1.132, 6.137), adjusted P = 0.025] in the 75th percentile group (>9.30â ng/ml) and more than thrice [adjusted OR 4.75, 95% CI(1.672, 13.495), adjusted P = 0.003] in the 90th percentile group (>12.31â ng/ml) as compared to the without-gestational hypertension group. AMH level was still associated with gestational hypertension after PSM. The area under the curve of AMH predicting gestational hypertension was 0.654 [95% CI (0.532, 0.776), P = 0.011] with an optimal cutoff value of 11.975â ng/mL. CONCLUSIONS: High serum AMH level pre-pregnancy (especially at levels > 9.30â ng/mL) indicates a high odds of gestational hypertension in patients with PCOS undergoing fresh embryo transfer.
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Object. The existing diagnostic paradigm for diabetic retinopathy (DR) greatly relies on subjective assessments by medical practitioners utilizing optical imaging, introducing susceptibility to individual interpretation. This work presents a novel system for the early detection and grading of DR, providing an automated alternative to the manual examination.Approach. First, we use advanced image preprocessing techniques, specifically contrast-limited adaptive histogram equalization and Gaussian filtering, with the goal of enhancing image quality and module learning capabilities. Second, a deep learning-based automatic detection system is developed. The system consists of a feature segmentation module, a deep learning feature extraction module, and an ensemble classification module. The feature segmentation module accomplishes vascular segmentation, the deep learning feature extraction module realizes the global feature and local feature extraction of retinopathy images, and the ensemble module performs the diagnosis and classification of DR for the extracted features. Lastly, nine performance evaluation metrics are applied to assess the quality of the model's performance.Main results. Extensive experiments are conducted on four retinal image databases (APTOS 2019, Messidor, DDR, and EyePACS). The proposed method demonstrates promising performance in the binary and multi-classification tasks for DR, evaluated through nine indicators, including AUC and quadratic weighted Kappa score. The system shows the best performance in the comparison of three segmentation methods, two convolutional neural network architecture models, four Swin Transformer structures, and the latest literature methods.Significance. In contrast to existing methods, our system demonstrates superior performance across multiple indicators, enabling accurate screening of DR and providing valuable support to clinicians in the diagnostic process. Our automated approach minimizes the reliance on subjective assessments, contributing to more consistent and reliable DR evaluations.
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Aprendizado Profundo , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Algoritmos , Redes Neurais de Computação , ComputadoresRESUMO
Current research on tumor fibrosis has focused on cancer-associated fibroblasts, which may exert dual functions of tumor promotion and inhibition. Little attention has been paid to whether tumor cells themselves can undergo fibrotic transformation and whether they can inhibit parenchymal cells similar to pulmonary fibrosis, thus achieving the goal of inhibiting the malignant progression of tumors. To explore the significance of inducing tumor fibrosis for cancer treatment. This study utilizes mesoporous silica nanoparticles (MSN) loaded with Trehalose dimycolate (TDM) to induce tumor cell fibrosis through the dual effects of TDM-induced inflammatory granuloma and MSN-induced foreign body granuloma. The results show that TDM/MSN (TM) can effectively induce tumor fibrosis, manifested specifically by collagen internalization, and suppression of proliferation and invasion capabilities, suggesting the potential role of tumor fibrosis therapy. However, further investigation reveals that extrachromosomal DNA (ecDNA) mediates resistance to fibrosis induction. To comprehensively enhance the efficacy, WRN exonuclease is conjugated to TM to form new nanoparticles (TMW) capable of effectively eliminating ecDNA, globally promoting tumor cell fibroblast-like transformation, and validated in a PDX model to inhibit cancer progression. Therefore, TMW, through inducing tumor cell fibrosis to inhibit its malignant progression, holds great potential as a clinical treatment strategy.
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Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Nanopartículas/química , Camundongos , Animais , Humanos , Helicase da Síndrome de Werner/genética , Helicase da Síndrome de Werner/metabolismo , Modelos Animais de Doenças , DNA/metabolismo , DNA/genética , Linhagem Celular Tumoral , Fibrose , Trealose/farmacologia , Trealose/químicaRESUMO
BACKGROUND: The incidence and mortality rates of primary hepatocellular carcinoma (HCC) are high, and the conventional treatment is radiofrequency ablation (RFA) with transcatheter arterial chemoembolization (TACE); however, the 3-year survival rate is still low. Further, there are no visual methods to effectively predict their prognosis. AIM: To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model. METHODS: Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded. We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software (version 4.1.2). Internal verification was performed using the bootstrapping technique. The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index (CI), calibration curve, and receiver operating characteristic curve. RESULTS: Of the 150 patients treated with RFA and TACE, 92 (61.33%) developed recurrence and metastasis. Logistic regression analysis identified six variables, and a predictive model was created. The internal validation results of the model showed a CI of 0.882. The correction curve trend of the prognosis prediction model was always near the diagonal, and the mean absolute error before and after internal validation was 0.021. The area under the curve of the prediction model after internal verification was 0.882 [95% confidence interval (95%CI): 0.820-0.945], with a specificity of 0.828 and sensitivity of 0.656. According to the Hosmer-Lemeshow test, χ 2 = 3.552 and P = 0.895. The predictive model demonstrated a satisfactory calibration, and the decision curve analysis demonstrated its clinical applicability. CONCLUSION: The prognosis of patients with HCC after RFA and TACE is affected by several factors. The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.
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The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.
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Diferenciação Celular , Proteína 3 de Resposta de Crescimento Precoce , Melanoma , Células de Schwann , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Proteína 3 de Resposta de Crescimento Precoce/genética , Proteína 3 de Resposta de Crescimento Precoce/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Melanoma/genética , Células de Schwann/metabolismoRESUMO
Background: Migraine is a common primary headache that has a significant impact on patients' quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background. Objective: The aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort. Methods: In this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom's MALDI-TOF iPLEX platform. Results: In univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS). Conclusion: The study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.
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Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation of MTA1 expression by RNAi in A2780 ovarian cancer cells could affect proliferation, anoikis, migration, invasion and adhesion of the cells and to research the potential for MTA1 gene therapy of ovarian cancer. After transfection with effective Mta1 gene siRNA, the effects on proliferation, anoikis, migration, invasion and adhesion of A2780 cells were tested by MTT assay, flow cytometry, wound-healing assay, Transwell assay and adhesion assay. Expression levels of PTEN, beta 1 integrin, MMP-9, phosphor-AKT (Ser473), and total AKT activity were evaluated in control and transfected cells. The results showed that inhibition of MTA1 mediated by Mta1-siRNA transfection decreased the cell invasion, migration and adhesion, and induced the increased cell anoikis, but no significant difference was found in proliferation of A2780 cancer cells. In addition, beta 1 integrin, MMP-9, and phosphor-AKT protein levels were significantly down-regulated, while PTEN was significantly up-regulated. These results demonstrated that MTA1 played an important role in the cell metastasis in ovarian cancer. MTA1 could serve as another novel potential therapeutic target in ovarian cancer.
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Carcinoma/genética , Carcinoma/secundário , Histona Desacetilases/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética , Apoptose/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Marcação de Genes/métodos , Terapia Genética/métodos , Humanos , Neoplasias Ovarianas/terapia , RNA Interferente Pequeno/uso terapêutico , Transativadores , Resultado do TratamentoRESUMO
Resistance to chemotherapy is a major obstacle for the effective treatment of advanced ovarian cancer. The mechanism of chemoresistance is still poorly understood. Recently, more and more evidence showed microRNAs (miRNAs) modulated many key molecules and pathways involved in chemotherapy. microRNA-106a (miR-106a) has been implicated in many cancers, but its role in ovarian cancer and drug resistance still remains unexplored. This study was to investigate whether miR-106a mediated resistance of the ovarian cancer cell line A2780 to the chemotherapeutic agent cisplatin (DDP). The different levels of miR-106a in A2780 cells and their resistant variant A2780/DDP cells were identified by using real-time PCR. MTT assay and flow cytometry were used to analyze the effect of miR-106a on cisplatin resistance of these paired cells. Real-time PCR, Western blotting and luciferase reporter assay were applied to explore whether Mcl-1 was a target of miR-106a. As compared to A2780 cells, the expression of miR-106a was down-regulated in the cisplatin resistant cell line A2780/DDP. Moreover, knockdown of miR-106a dramatically decreased antiproliferative effects and apoptosis induced by cisplatin in A2780 cells, while overexpression of miR-106a significantly increased antiproliferative effects and apoptosis induced by cisplatin in A2780/DDP cells. Furthermore, miR-106a inhibited cell survival and cisplatin resistance through downregulating the expression of Mcl-1. Mcl-1 was a direct target of miR-106a. These results suggest that miR-106a may provide a novel mechanism for understanding cisplatin resistance in ovarian cancer by modulating Mcl-1.
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Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Linhagem Celular Tumoral , Feminino , HumanosRESUMO
BACKGROUND: Cerebral mucormycosis is an infectious disease of the brain caused by fungi of the order Mucorales. These infections are rarely encountered in clinical practice and are often misdiagnosed as cerebral infarction or brain abscess. Increased mortality due to cerebral mucormycosis is closely related to delayed diagnosis and treatment, both of which present unique challenges for clinicians. CASE SUMMARY: Cerebral mucormycosis is generally secondary to sinus disease or other disseminated disease. However, in this retrospective study, we report and analyze a case of isolated cerebral mucormycosis. CONCLUSION: The constellation of symptoms including headaches, fever, hemiplegia, and changes in mental status taken together with clinical findings of cerebral infarction and brain abscess should raise the possibility of a brain fungal infection. Early diagnosis and prompt initiation of antifungal therapy along with surgery can improve patient survival.