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1.
Polymers (Basel) ; 16(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611124

RESUMO

The antioxidant activity of chitosan (CS) and three water-soluble derivatives was analyzed comparatively by in vitro and in vivo experiments, including hydroxypropyl chitosan (HPCS), quaternary ammonium salt of chitosan (HACC), and carboxymethyl chitosan (CMCS). The results show that chitosan and its water-soluble derivatives have a scavenging ability on DPPH radicals, superoxide radicals, and hydroxyl radicals, and a reducing ability. A remarkable difference (p < 0.05) was found for HACC and HPCS compared with CS on DPPH radicals, hydroxyl radicals, and reducing ability. The antioxidant ability of the four chitosan samples was in the order of HPCS > HACC > CMCS > CS. Furthermore, antioxidant activity of all samples increased gradually in a concentration-dependent manner. The in vivo result indicates that oral CS and its derivatives samples result in a decrease in lipid peroxides (LPO) and free fatty acids (FFA) levels in serum with an increase in superoxide dismutase (SOD) activity. Especially for the HPCS and HACC groups, the LPO, FFA, and SOD activity in serum was different significantly in comparison with the high-fat controlgroup (HF) (p < 0.05). These results indicate that chitosan and its derivatives can be used as good antioxidants, and the antioxidant activity might be related to the molecular structure of chitosan derivatives.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38512300

RESUMO

Background: Long noncoding RNAs (lncRNAs), as emerging regulators of a wide variety of biological processes via diverse mechanisms, have been demonstrated to be of increasing importance in biology. Genome-wide association studies of tumor samples have identified several lncRNAs as either oncogenes or tumor suppressors in various types of cancers. In recent years, the importance of lncRNAs, especially in endometrioid cancer (EEC), has become increasingly well understood. The lncRNA Forkhead box P4 antisense RNA 1 (FOXP4-AS1) has been reported to fulfill roles in several types of cancers; however, the main biological function and associated underlying molecular mechanism of FOXP4-AS1 in EEC have yet to be fully elucidated. Materials and Methods: The present study therefore aimed to investigate how RNA FOXP4-AS1 may participate in the development and progression of endometrioid carcinoma tissues. To meet this aim, in the present study, the expression level of FOXP4-AS1 was investigated in endometrioid carcinoma tissues and matching nearby normal endometrial tissues collected from patients receiving surgery at the hospital, and a series of molecular biological assays were performed to investigate the effect of FOXP4-AS1 on cell proliferation, cell migration, and cell invasion, and so on. Results: An increased concentration of FOXP4-AS1 was identified in endometrioid carcinoma samples and cell lines compared with the corresponding controls, and this lncRNA was found to be positively correlated with advanced FIGO stages in patients with endometrial cancer. Furthermore, knocking down endogenous FOXP4-AS1 led to a significant reduction in the colony formation number and a significant inhibition of cell proliferation, cell migration, and cell invasion in endometrioid carcinoma cells. Moreover, dual-specificity phosphatase 5 (DUSP5), which is lowly expressed in endometrioid carcinoma tissues cells and negatively modulated by FOXP4-AS1, was identified as the downstream target molecule of FOXP4-AS1. Subsequently, the mechanistic experiments confirmed that, through binding to enhancer of zeste homolog 2 (EZH2; one of the catalytic subunits of polycomb repressive complex 2 [PRC2]), FOXP4-AS1 could epigenetically suppress the expression of DUSP5. Finally, the oncogenic function of the FOXP4-AS1/EZH2/DUSP5 axis in endometrioid carcinoma was confirmed via rescue assays. Conclusions: The findings of the present study have highlighted how FOXP4-AS1 fulfills an oncogenic role in endometrioid carcinoma, and targeting FOXP4-AS1 and its pathway may provide new biomarkers for patients with endometrioid carcinoma.

3.
Cell Mol Biol (Noisy-le-grand) ; 70(1): 99-109, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38372107

RESUMO

This study aimed to explore the involvement of Transmembrane and coiled-coil domains 1 (TMCO1) in ovarian cancer progression and its regulatory mechanisms in cisplatin resistance. Using the GEPIA database, we analyzed TMCO1 expression in ovarian cancer and normal tissues. In a cohort of 99 ovarian cancer patients, immunohistochemistry and immunofluorescence were employed to assess TMCO1 expression in tumor and adjacent tissues, correlating findings with clinical and pathological characteristics. TMCO1 overexpression and knockout cell models were constructed, and their impact on non-cisplatin-resistant (SK-OV-3) and cisplatin-resistant (SK-OV-3-CDDP) ovarian cancer cells was investigated through cloning, wound healing, Fluo 4, and Transwell experiments. Knocking down CALR and VDAC1 was performed to examine their effects on TMCO1, cell proliferation, and malignant markers. Subcutaneous tumor models in nude mice elucidated the in vivo role of TMCO1 in tumor growth. Expression levels of CALR, VDAC1, angiogenesis indicators (CD34), and epithelial-mesenchymal transition (EMT) markers were evaluated. TMCO1 expression in ovarian cancer tissue significantly differed from normal tissue, correlating with survival rates. TMCO1 overexpression was associated with lymph node metastases, late FIGO stage, and larger tumors. TMCO1 promoted proliferation, calcium ion elevation, cytoskeletal remodeling, and metastasis in SK-OV-3 and SK-OV-3-CDDP cells, upregulating VDAC1, CALR, Vimentin, N-cadherin, ß-catenin, and downregulating E-cadherin. Silencing TMCO1 inhibited cell growth, proliferation, and angiogenesis in vivo, suppressing the expression of CALR, VDAC1, Vimentin, N-cadherin, and ß-catenin. Overall, this study highlighted TMCO1 as a crucial regulator in ovarian cancer progression, influencing VDAC1 through CALR and impacting diverse cellular processes, offering potential as a targeted therapeutic strategy for ovarian cancer.


Assuntos
Canais de Cálcio , Calreticulina , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , beta Catenina/metabolismo , Caderinas/metabolismo , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Transição Epitelial-Mesenquimal/genética , Camundongos Nus , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Vimentina/metabolismo , Calreticulina/genética , Calreticulina/metabolismo
4.
BMB Rep ; 57(2): 122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38416113

RESUMO

[Erratum to: BMB Reports 2023; 56(3): 184-189, PMID: 36617466, PMCID: PMC10068343] The BMB Reports would like to correct in BMB Rep. 56(3): 184-189, titled "circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis". The original version of this article unfortunately contained image error in the Fig. 3. This article has been updated to correct an error in the image in Fig. 3D. The author apologizes for any inconvenience or confusion this error may cause. Author information has been modified in the original PDF version.

5.
Open Med (Wars) ; 18(1): 20230870, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075032

RESUMO

In areas with high incidence of tuberculosis (TB), there are more infertile women who underwent in vitro fertilization (IVF) and have latent TB infection (LTBI), and thus, their potential risks should be paid enough attention. The purpose of our study aimed to analyze the relationship between LTBI and clinical pregnancy outcomes of IVF and fresh embryo transfer (IVF-FET). This was a retrospective study of 628 infertile women who had undergone IVF-FET in the Fourth Affiliated Hospital of Hebei Medical University from January 2019 to December 2021. The women experienced no clinical symptoms, negative imaging, and T-SPOT.TB-positive diagnosis of LTBI. We divided the study population into the LTBI group and the non-LTBI group. The clinical pregnancy rate in the LTBI group was significantly lower than that in the non-LTBI group (40.54% vs 49.51%, P = 0.031), and there was no significant difference in live birth rate and miscarriage rate between the two groups. Logistic regression analysis showed that LTBI was an independent risk factor for decreased clinical pregnancy rate in infertile women undergoing IVF-FET. In conclusion, LTBI affects clinical pregnancy rate of IVF-FET in infertile women, and therefore, clinicians (especially in countries with a high TB burden) need to pay attention to LTBI before IVF and embryo transfer.

6.
Medicine (Baltimore) ; 102(40): e35406, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800830

RESUMO

BACKGROUND: Endometriosis is a chronic inflammatory, benign disorder that often co-occurs with adenomyosis and/or leiomyoma. The overall incidence of endometriosis in reproductive period women was nearly 10%. However, the exact mechanisms of endometriosis-associated pathogenesis are still unknown. METHODS: In this study, we aimed to investigate whether Frizzled-7 (FZD7) would effectively promote the development of endometriosis. The microarray-based data analysis was performed to screen endometriosis-related differentially expressed genes. This process uncovered specific hub genes, and the nexus of vital genes and ferroptosis-related genes were pinpointed. Then, we collected human endometrial and endometriotic tissues from patients with endometriosis of the ovary (n = 39) and control patients without endometriosis (n = 10, who underwent hysterectomy for uterine fibroids) to compare the expression of FZD7. RESULTS: These findings indicated that the expression of FZD7 was high compared with normal endometrium, and FZD7 may promote the progression of endometriosis. CONCLUSION: FZD7 may serve as a potential therapeutic target for endometriosis treatment.


Assuntos
Endometriose , Feminino , Humanos , Biomarcadores/metabolismo , Endometriose/genética , Endometriose/metabolismo , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Leiomioma/patologia , Ovário/patologia
7.
Front Endocrinol (Lausanne) ; 14: 1234761, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822605

RESUMO

Objective: This study aimed to evaluate the effectiveness of total contact casts (TCCs) versus removable offloading interventions among patients with diabetic foot ulcers (DFUs). Methods: A comprehensive search was done in databases Embase, Cochrane Library, and, PubMed. The references of retrieved articles were reviewed, up until February 2023. Controlled trials comparing the effects of TCCs with removable offloading interventions (removable walking casts and footwear) in patients with DFUs were eligible for review. Results: Twelve studies were included in the meta-analysis, involving 591 patients with DFUs. Among them, 269 patients were in the intervention group (TCC), and 322 in the control group (removable walking casts/footwear). The analysis revealed that the TCC group had higher healing rates (Risk Ratio(RR)=1.22; 95% confidence interval(CI):1.11 to 1.34, p<0.001), shorter healing time (Standard Mean Difference(SMD)=-0.57; 95%CI: -1.01 to -0.13, P=0.010), and elevated occurrence of device-related complications (RR=1.70; 95%CI:1.01 to 2.88, P=0.047), compared with the control group. Subgroup analysis illustrated patients using TCCs had higher healing rates than those using removable walking casts (RR=1.20; 95%CI:1.08 to 1.34, p=0.001) and footwear (RR=1.25; 95%CI:1.04 to 1.51, p=0.019), but they required comparable time for ulcer healing compared with those using removable walking casts (SMD=-0.60; 95%CI: -1.22 to 0.02, P=0.058) or footwear group (SMD=-0.52; 95%CI: -1.17 to 0.12, P=0.110). Although patients using TCCs had significantly higher incidence of device-related complications than those using footwear (RR=4.81; 95%CI:1.30 to 17.74, p=0.018), they had similar one compared with those using the removable walking casts (RR=1.27; 95%CI:0.70 to 2.29, p=0.438). Conclusion: The use of TCCs in patients with DFUs resulted in improved rates of ulcer healing and shorter healing time compared to removable walking casts and footwear. However, it is important to note that TCCs were found to be associated with increased prevalence of complications.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/terapia , Moldes Cirúrgicos , Cicatrização , Caminhada
8.
BMB Rep ; 56(7): 416, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37500559

RESUMO

[Erratum to: BMB Reports 2023; 56(3): 184-189, PMID: 36617466, PMCID: PMC10068343] The BMB Reports would like to correct in BMB Rep. 56(3): 184-189, titled "circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis". This research has the wrong affiliation of the authors and number of affiliation. Since author's affiliation is incorrect, this information has now been corrected as follows. Kaiyun Qin1,3,#, Fenghua Zhang2,#, Hongxia Wang1, Na Wang1, Hongbing Qiu4, Xinzhuan Jia1,5, Shan Gong1 & Zhengmao Zhang1,* 1Department of Gynecology, Fourth Hospital of Hebei Medical University, Hebei Shijiazhuang 050011, 2Department of Breast & Thyroid Surgery, Hebei General Hospital, Hebei Shijiazhuang 050057, 3Department of Gynecology, Hebei General Hospital, Hebei Shijiazhuang 050057, 4Department of Gynecology, Hebei Xingtai People's Hospital, Hebei Shijiazhuang 054001, 5Department of Reproductive Medicine, Fourth Hospital of Hebei Medical University, Hebei Shijiazhuang 050011, China The author apologizes for any inconvenience or confusion this error may cause. Author information has been modified in the original PDF version.

9.
J Ovarian Res ; 16(1): 142, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37468993

RESUMO

BACKGROUND: Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. METHODS: In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. RESULTS: Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. CONCLUSION: Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy.


Assuntos
Carcinoma , MicroRNAs , Neoplasias Ovarianas , RNA Circular , Fatores de Transcrição SOX9 , Feminino , Humanos , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , RNA Circular/genética , Fatores de Transcrição SOX9/genética
10.
Open Med (Wars) ; 18(1): 20230729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333452

RESUMO

The miR-141-3p has been reported to participate in regulating autophagy and tumor-stroma interactions in ovarian cancer (OC). We aim to investigate whether miR-141-3p accelerates the progression of OC and its effect on macrophage 2 polarization by targeting the Kelch-like ECH-associated protein1-Nuclear factor E2-related factor2 (Keap1-Nrf2) pathway. SKOV3 and A2780 cells were transfected with miR-141-3p inhibitor and negative control to confirm the regulation of miR-141-3p on OC development. Moreover, the growth of tumors in xenograft nude mice treated by cells transfected with miR-141-3p inhibitor was established to further testify the role of miR-141-3p in OC. The expression of miR-141-3p was higher in OC tissue compared with non-cancerous tissue. Downregulation of miR-141-3p inhibited the proliferation, migration, and invasion of ovarian cells. Furthermore, miR-141-3p inhibition also suppressed M2-like macrophage polarization and in vivo OC progression. Inhibition of miR-141-3p significantly enhanced the expression of Keap1, the target gene of miR-141-3p, and thus downregulated Nrf2, while activation of Nrf2 reversed the reduction in M2 polarization by miR-141-3p inhibitor. Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

11.
BMB Rep ; 56(2): 184-189, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36617466

RESUMO

Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC. [BMB Reports 2023; 56(3): 184-189].


Assuntos
Ferroptose , MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , RNA Circular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Ferroptose/genética , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Sistema y+ de Transporte de Aminoácidos/genética
12.
J Sci Food Agric ; 103(4): 2175-2185, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36541582

RESUMO

BACKGROUND: In recent years, an increasing interest in healthy functional foods has been documented among health-conscious consumers. Steam explosion (SE)-treated black-grained wheat (BGW) bran was explored for the development of chiffon cakes with high nutritional and functional value. RESULTS: The content of crude fat and total starch decreased with increasing SE pressure, whereas water-holding capacity and antioxidant activity increased, suggesting SE at 0.6-1.0 MPa could be an effective technique for enhancing the nutritional and functional properties of wheat bran. The protein, iron, zinc, manganese, selenium, and soluble dietary fiber contents, the water-holding, oil-binding, swelling, cholesterol binding, and cation-exchange capacities, and antioxidant activity of SE BGW bran were better than those of SE white-grained wheat bran. The addition of SE bran (0.8 MPa) to flour significantly decreased the peak viscosity, final viscosity, and setback and increased the pasting temperature. The effect of SE bran on the pasting properties of low-gluten and medium-gluten flour was stronger than that of high-gluten flour. SE BGW bran altered the physicochemical properties of chiffon cakes. When 6% SE BGW bran (0.8 MPa) was added, chiffon cakes exhibited good specific volume, hardness, chewiness, and other sensory qualities. CONCLUSIONS: These results indicate that SE at 0.6-1.0 MPa is an effective technique for enhancing the nutritional and functional properties of wheat bran. SE BGW bran can be alternatives to food materials for developing health functional cereal-based products. © 2022 Society of Chemical Industry.


Assuntos
Fibras na Dieta , Vapor , Fibras na Dieta/análise , Antioxidantes , Água , Farinha/análise , Glutens
13.
Diagn Microbiol Infect Dis ; 104(4): 115789, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36122486

RESUMO

We evaluated the performance of SARS-CoV-2 TaqMan real-time reverse-transcription PCR (RT-qPCR) assays (ThermoFisher) for detecting 2 nonsynonymous spike protein mutations, E484K and N501Y. Assay accuracy was evaluated by whole genome sequencing (WGS). Residual nasopharyngeal SARS-CoV-2 positive samples (N = 510) from a diverse patient population in New York City submitted for routine SARS-CoV-2 testing during January-April 2020 were used. We detected 91 (18%) N501Y and 101 (20%) E484K variants. Four samples (0.8%) were positive for both variants. The assay had nearly perfect concordance with WGS in the validation subset, detecting B.1.1.7 and B.1.526 variants among others. Sensitivity and specificity ranged from 0.95 to 1.00. Positive and negative predictive values were 0.98-1.00. TaqMan genotyping successfully predicted the presence of B.1.1.7, but had significantly lower sensitivity, 62% (95% CI, 0.53, 0.71), for predicting B.1.526 sub-lineages lacking E484K. This approach is rapid and accurate for detecting SARS-CoV-2 variants and can be rapidly implemented in routine clinical setting.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Teste para COVID-19 , Polimorfismo de Nucleotídeo Único , Genótipo , COVID-19/diagnóstico , Mutação
14.
Tissue Cell ; 79: 101903, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36081320

RESUMO

OBJECTIVE: Ovarian cancer (OC) is one of the common gynecological malignant tumors. Cell division cycle-associated protein-3 (CDCA3) is involved in the regulation of cell cycle progression. The role of CDCA3 in OC was explored in this study. METHODS: The expression of CDCA3 in OC was evaluated in the Gene Expression Omnibus (GEO) database and further verified by qRT-PCR and Western blot (WB). Subsequently, we established lentivirus-mediated CDCA3 knockdown in OC cell lines HO-8910 and A2780. The biological roles of CDCA3 on proliferation, sensitivity to cisplatin, apoptosis, migration and tumor formation of OC were investigated using loss-of-function assays. RESULTS: CDCA3 was frequently up-regulated in OC. Knockdown of CDAC3 inhibited proliferation and migration, and enhanced apoptosis as well as sensitivity of OC cells to cisplatin. In vivo results further confirmed the inhibitory effect of CDCA3 knockdown on tumor growth. CONCLUSIONS: Our findings indicated that CDCA3 may play an important role in OC progression, and may serve as a potential therapeutic target for the OC treatment.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Cisplatino/farmacologia , Linhagem Celular Tumoral , Carcinoma Epitelial do Ovário , Apoptose/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
15.
Clin Genet ; 102(6): 483-493, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36029107

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 and PKD2 (PKD1/2), has unexplained phenotypic variability likely affected by environmental and other genetic factors. Approximately 10% of individuals with ADPKD phenotype have no causal mutation detected, possibly due to unrecognized risk variants of PKD1/2. This study was designed to identify risk variants of PKD genes through population genetic analyses. We used Wright's F-statistics (Fst) to evaluate common single nucleotide variants (SNVs) potentially favored by positive natural selection in PKD1 from 1000 Genomes Project (1KG) and genotyped 388 subjects from the Rogosin Institute ADPKD Data Repository. The variants with >90th percentile Fst scores underwent further investigation by in silico analysis and molecular genetics analyses. We identified a deep intronic SNV, rs3874648G> A, located in a conserved binding site of the splicing regulator Tra2-ß in PKD1 intron 30. Reverse-transcription PCR (RT-PCR) of peripheral blood leukocytes (PBL) from an ADPKD patient homozygous for rs3874648-A identified an atypical PKD1 splice form. Functional analyses demonstrated that rs3874648-A allele increased Tra2-ß binding affinity and activated a cryptic acceptor splice-site, causing a frameshift that introduced a premature stop codon in mRNA, thereby decreasing PKD1 full-length transcript level. PKD1 transcript levels were lower in PBL from rs3874648-G/A carriers than in rs3874648-G/G homozygotes in a small cohort of normal individuals and patients with PKD2 inactivating mutations. Our findings indicate that rs3874648G > A is a PKD1 expression modifier attenuating PKD1 expression through Tra2-ß, while the derived G allele advantageously maintains PKD1 expression and is predominant in all subpopulations.


Assuntos
Rim Policístico Autossômico Dominante , Canais de Cátion TRPP , Humanos , Íntrons , Mutação , Nucleotídeos , Rim Policístico Autossômico Dominante/genética , Sítios de Splice de RNA , Canais de Cátion TRPP/genética
16.
Front Public Health ; 10: 892756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784204

RESUMO

Multiple high-powered magnetic Buckyball ingestions may lead to a high risk of severe complications. Great concerns have been raised by public health workers, and it remains challenging for clinicians to solve this troublesome problem. We report a large case series of children with Buckyball ingestion from six tertiary medical centers. The clinical data, including demographics, medical history, diagnosis tools, management options, intraoperative or endoscopic findings, and outcomes, were retrospectively analyzed. Seventy-one children aged 1-13 years ingested 2-41 Buckyballs. Among them, Buckyballs passed spontaneously on 2-10 days post-ingestion in seven cases; gastroscopic removal was performed in 14 cases; laparoscopic removal in 13 cases; laparoscopic-assisted surgical removal in 6 cases; and open surgical removal in 31 cases. Surgical indications included small bowel obstruction, perforation, peritonitis, acute abdominal pain, or along with ingestion of other metallic foreign bodies. Among those who underwent a surgical procedure, primary intestinal repair was performed in 44 cases, enterectomy with primary anastomosis in 6 cases. The postoperative hospital stay ranged from 5 to 28 days. No major complications occurred. In unwitnessed cases, a vague medical history and nonspecific symptoms usually make the diagnosis difficult. The treatment options should include the watch-and-wait approach, endoscopic, laparoscopic-assisted, or open surgical removal of Buckyballs, with primary intestinal repair or anastomosis. Preventive measures, including children's not having access to Buckyballs, are essential to protect children from this kind of unintentional injury.


Assuntos
Fulerenos , Criança , Ingestão de Alimentos , Hospitais , Humanos , Fenômenos Magnéticos , Estudos Retrospectivos
17.
Front Surg ; 9: 1055008, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36760670

RESUMO

Background and aims: Both casts and braces can be used for post-operational immobilization of ankle fractures. This meta-analysis aimed to assess the complications and functional effects of the two types of immobilization. Material and methods: PubMed, Embase, Cochrane, and CNKI was searched for randomized controlled trials (published between Jan 1, 1950, and March 2022). Relative risk (RR) or standard mean difference (SMD) with a 95% confidence interval (CI) was used to present the outcomes. The pooled data were assessed by using the fixed-effects model or random-effects model. Results: A total of 5 randomized controlled studies involving 930 subjects were included according to our inclusion criteria. On the ankle score at 6w,12w and 52w, there was no statistically significant difference between the two groups. In terms of 6w, the brace group showed better ankle dorsiflexion (MD = 6.78, 95% CI 0.56-13.00, p = 0.03) and plantar flexion (MD = 6.58, 95% CI 1.60-11.55, p = 0.01) than the cast group. The wound complications (RR = 3.49, 95% CI 1.32 to 9.24, p = 0.01) and total complications (RR = 3.54, 95% CI 1.92 to 6.50, p < 0.0001) in the brace group were three times more than that in the cast group. There was no statistically significant difference between the two groups in the non-wound complications. There was no statistically significant difference between the two groups in the time of going back to work, swelling of the ankle, and atrophy of the calf muscle. Conclusion: The short-term and long-term functional outcomes after postoperative treatment of adult ankle fractures with braces are similar to those with casts. The usage of braces may cause three times more wound complications than that of casts.

18.
Front Plant Sci ; 12: 748523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733304

RESUMO

In Se-deficient populations, Selenium- (Se-) enriched wheat is a source of Se supplementation, and Se content can be improved by agronomic biofortification. Thus, black-grained wheat (BGW) and white-grained wheat (WGW) (as the control) were grown in Se naturally contained soils at different concentrations (11.02, 2.21, 2.02, and 0.20 mg·kg-1). Then, a field experiment was conducted to assess agronomic performance, the concentration of microelements and heavy metals, and the uptake and distribution of Se in the BGW under the application of Se ore powder. The results showed that the grain yield and grain Se concentration of wheat respectively show a significant increase and decrease from high Se to low Se areas. Higher grain yield and crude protein content were observed in Se-rich areas. The soil application of Se ore powder increased wheat grain yield and its components (biomass, harvest index, grain number, and 1,000 kernels weight). The concentrations of Zn, Fe, Mn, total Se, and organic Se in the grains of wheat were also increased, but Cu concentration was decreased. The concentrations of Pb, As, Hg, and Cr in wheat grains were below the China food regulation limits following the soil application of Se ore powder. Compared with the control, Se ore powder treatment increased the uptake of Se in various parts of wheat plants. More Se accumulation was observed in roots following Se ore powder application, with a smaller amount in grains. In addition, compared with the control, BGW had significantly higher concentrations of Zn, Fe, and Mn and accumulated more Se in grains and shoots and less Se in roots. The results indicate that wheat grown in Se-rich areas increases its grain yield and crude protein content. The soil application of Se ore powder promotes wheat growth and grain yield. Compared with WGW, BGW accumulated more Se in grains and had a higher concentration of organic Se in grains. In conclusion, the application of Se ore powder from Ziyang as Se-enriched fertilizer could be a promising strategy for Se biofortification in the case of wheat, and BGW is the most Se-rich potential genotype.

19.
J Am Soc Nephrol ; 32(12): 3114-3129, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34716216

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development of multiple cysts in the kidneys. It is often caused by pathogenic mutations in PKD1 and PKD2 genes that encode polycystin proteins. Although the molecular mechanisms for cystogenesis are not established, concurrent inactivating germline and somatic mutations in PKD1 and PKD2 have been previously observed in renal tubular epithelium (RTE). METHODS: To further investigate the cellular recessive mechanism of cystogenesis in RTE, we conducted whole-genome DNA sequencing analysis to identify germline variants and somatic alterations in RTE of 90 unique kidney cysts obtained during nephrectomy from 24 unrelated participants. RESULTS: Kidney cysts were overall genomically stable, with low burdens of somatic short mutations or large-scale structural alterations. Pathogenic somatic "second hit" alterations disrupting PKD1 or PKD2 were identified in 93% of the cysts. Of these, 77% of cysts acquired short mutations in PKD1 or PKD2 ; specifically, 60% resulted in protein truncations (nonsense, frameshift, or splice site) and 17% caused non-truncating mutations (missense, in-frame insertions, or deletions). Another 18% of cysts acquired somatic chromosomal loss of heterozygosity (LOH) events encompassing PKD1 or PKD2 ranging from 2.6 to 81.3 Mb. 14% of these cysts harbored copy number neutral LOH events, while the other 3% had hemizygous chromosomal deletions. LOH events frequently occurred at chromosomal fragile sites, or in regions comprising chromosome microdeletion diseases/syndromes. Almost all somatic "second hit" alterations occurred at the same germline mutated PKD1/2 gene. CONCLUSIONS: These findings further support a cellular recessive mechanism for cystogenesis in ADPKD primarily caused by inactivating germline and somatic variants of PKD1 or PKD2 genes in kidney cyst epithelium.


Assuntos
Cistos , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/genética , Mutação , Células Epiteliais , Canais de Cátion TRPP/genética
20.
Front Plant Sci ; 12: 689502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163516

RESUMO

Psathyrostachys huashanica Keng, a wild relative of common wheat with many desirable traits, is an invaluable source of genetic material for wheat improvement. Few wheat-P. huashanica translocation lines resistant to powdery mildew have been reported. In this study, a wheat-P. huashanica line, E24-3-1-6-2-1, was generated via distant hybridization, ethyl methanesulfonate (EMS) mutagenesis, and backcross breeding. A chromosome karyotype of 2n = 44 was observed at the mitotic stage in E24-3-1-6-2-1. Genomic in situ hybridization (GISH) analysis revealed four translocated chromosomes in E24-3-1-6-2-1, and P. huashanica chromosome-specific marker analysis showed that the alien chromosome fragment was from the P. huashanica 4Ns chromosome. Moreover, fluorescence in situ hybridization (FISH) analysis demonstrated that reciprocal translocation had occurred between the P. huashanica 4Ns chromosome and the wheat 3D chromosome; thus, E24-3-1-6-2-1 carried two translocations: T3DS·3DL-4NsL and T3DL-4NsS. Translocation also occurred between wheat chromosomes 2A and 4A. At the adult stage, E24-3-1-6-2-1 was highly resistant to powdery mildew, caused by prevalent pathotypes in China. Further, the spike length, numbers of fertile spikelets, kernels per spike, thousand-kernel weight, and grain yield of E24-3-1-6-2-1 were significantly higher than those of its wheat parent 7182 and addition line 24-6-3-1. Thus, this translocation line that is highly resistant to powdery mildew and has excellent agronomic traits can be used as a novel promising germplasm for breeding resistant and high-yielding cultivars.

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