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1.
Plant Physiol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743701

RESUMO

Maize (Zea mays L.) has very strong requirements for nitrogen. However, the molecular mechanisms underlying the regulations of nitrogen uptake and translocation in this species are not fully understood. Here, we report that an APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor ZmEREB97 functions as an important regulator in the N-signaling network in maize. Predominantly expressed and accumulated in main root and lateral root primordia, ZmEREB97 rapidly responded to nitrate treatment. By overlapping the analyses of differentially expressed genes and conducting a DAP-seq assay, we identified 1446 potential target genes of ZmEREB97. Among these, 764 genes were co-regulated in two lines of zmereb97 mutants. Loss of function of ZmEREB97 substantially weakened plant growth under both hydroponic and soil conditions. Physiological characterization of zmereb97 mutant plants demonstrated that reduced biomass and grain yield were both associated with reduced nitrate influx, decreased nitrate content and less N accumulation. We further demonstrated that ZmEREB97 directly targets and regulates the expression of six ZmNRT genes by binding to the GCC box-related sequences in gene promoters. Collectively, these data suggest that ZmEREB97 is a major positive regulator of the nitrate response and that it plays an important role in optimizing nitrate uptake, offering a target for improvement of nitrogen use efficiency in crops.

2.
J Hum Genet ; 69(8): 401-409, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38769386

RESUMO

Human infertility affects 10-15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein regulatory complex (N-DRC) is a large protein complex in the sperm flagellum that connects adjacent doublets of microtubules. Defects in the N-DRC can disrupt cilia/flagellum movement, resulting in primary ciliary dyskinesia and male infertility. Using whole-exome sequencing, we identified a pathological homozygous variant of the dynein regulatory complex subunit 3 (DRC3) gene, which expresses leucine-rich repeat-containing protein 48, a component of the N-DRC, in a patient with asthenozoospermia. The variant ENST00000313838.12: c.644dup (p. Glu216GlyfsTer36) causes premature translational arrest of DRC3, resulting in a dysfunctional DRC3 protein. The patient's semen count, color, and pH were normal according to the reference values of the World Health Organization guidelines; however, sperm motility and progressive motility were reduced. DRC3 protein was not detected in the patient's sperm and the ultrastructure of the patient's sperm flagella was destroyed. More importantly, the DRC3 variant reduced its interaction with other components of the N-DRC, including dynein regulatory complex subunits 1, 2, 4, 5, 7, and 8. Our data not only revealed the essential biological functions of DRC3 in sperm flagellum movement and structure but also provided a new basis for the clinical genetic diagnosis of male infertility.


Assuntos
Astenozoospermia , Homozigoto , Infertilidade Masculina , Humanos , Masculino , Astenozoospermia/genética , Astenozoospermia/patologia , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Motilidade dos Espermatozoides/genética , Adulto , Espermatozoides/metabolismo , Espermatozoides/patologia , Sequenciamento do Exoma , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/patologia , Dineínas/genética , Dineínas/metabolismo , Mutação
3.
J Vasc Surg ; 79(3): 623-631.e2, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37951514

RESUMO

OBJECTIVE: There is a lack of consensus regarding the optimal strategy for evaluating the efficiency and safety of dual-pathway inhibition (DPI) in preventing femoropopliteal restenosis in patients undergoing repeated endovascular interventions. Despite several therapeutic interventions available for preventing femoropopliteal restenosis post repeated endovascular interventions, the ideal strategy, particularly evaluating the efficacy and safety of DPI, remains a matter of debate. METHODS: From January 2015 to September 2021, patients who underwent repeated endovascular interventions for femoropopliteal restenosis were compared with those who underwent DPI or dual antiplatelet therapy (DAPT) after surgery using a propensity score-matched analysis. The primary outcome was clinically driven target lesion revascularization (CD-TLR). The principal safety outcome was a composite of major bleeding and clinically relevant non-major (CRNM) bleeding. To further enhance the rigor, Kaplan-Meier plots, Cox proportional hazards modeling, and sensitivity analyses, as well as subgroup analyses were employed, reducing potential confounders. RESULTS: A total of 441 patients were included in our study, of whom 294 (66.7%) received DAPT and 147 (33.1%) received DPI, with 114 matched pairs (mean age, 72.21 years; 84.2% male). Cumulative probability of CD-TLR at 36 months in the DPI group (17%) trended lower than that in the DAPT group (32%) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.78; P =.004). The cumulative probability of freedom from CD-TLR at 36 months in the DPI group was 83%. No significant difference was observed in the composite outcome of major or CRNM bleeding between the DPI and DAPT groups (HR, 1.26; 95% CI, 0.34 to 4.69; P = .730). The DPI group was associated with significantly lower rates of CD-TLR in the main subgroup analyses of diabetes (P = .001), previous smoking history (P = .008), longer lesion length (>10 cm) (P = .003), and treatment with debulking strategy (P = .003). CONCLUSIONS: In our investigation focused on CD-TLR, we found that DPI exhibited a significant reduction in the risk of reintervention compared with other treatment modalities. This underscores the potential of DPI as a viable therapeutic strategy in preventing reinterventions. Moreover, our assessment of safety outcomes revealed that the bleeding risks associated with DPI were on par with DAPT, thereby not compromising patient safety. These findings pave the way for potential broader clinical implications, emphasizing the effectiveness and safety of DPI in the context of reducing reintervention risks.


Assuntos
Angioplastia com Balão , Doença Arterial Periférica , Humanos , Masculino , Idoso , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/patologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Artéria Poplítea/patologia , Inibidores da Agregação Plaquetária/efeitos adversos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/patologia , Resultado do Tratamento , Grau de Desobstrução Vascular , Fatores de Risco
4.
Ann Vasc Surg ; 102: 209-215, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37922962

RESUMO

BACKGROUND: This study aimed to assess the safety and efficacy of the transbrachial approach as a single or combined procedure for complex interventions in peripheral artery disease (PAD). METHODS: Between March 2011 and April 2021, 169 patients with PAD underwent endovascular therapy via the transbrachial approach as a single or dual procedure. Univariate and multivariate analyses were performed to evaluate the predictors of adverse events at the brachial puncture site. All demographic, clinical, and perioperative data were acquired from electronic medical records and retrospectively analyzed. RESULTS: Brachial artery access was used alone and in combination in 87 and 82 patients, respectively. Patients in the combined-approach group underwent more intraoperative stent implantations and had more vascular closure devices (VCD). Multivariate logistic regression analysis revealed that hypertension was an independent factor for higher rates of brachial puncture site adverse events (odds ratio, 4.76; 95% confidence interval, 1.33-16.97; P = 0.016). Brachial artery access-site complications occurred in 26 patients, including 6 (23.1%) major and 20 (76.9%) minor entry-site complications. Entry-site complications were observed in 21 (16.8%) and 5 (11.4%) patients assigned to manual compression and VCD groups, respectively. There were no significant intergroup differences in the incidence of major or minor complications. Interestingly, patients assigned to the VCD group did not experience major entry-site complications. CONCLUSIONS: The transbrachial approach, as a single or combined procedure, is a safe alternative to complex interventions in patients with PAD. Complications of brachial access progressively decrease with improved blood pressure control.


Assuntos
Cateterismo Periférico , Doença Arterial Periférica , Humanos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/métodos , Estudos Retrospectivos , Resultado do Tratamento , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/etiologia , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/cirurgia , Artéria Femoral
5.
Thromb J ; 20(1): 78, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527031

RESUMO

BACKGROUND: To assess the immediate effect and factors affecting the efficacy of rotational thrombectomy (RT) in patients with thrombus-containing lower-limb ischaemic lesions. METHODS: Patients were retrospectively divided into two groups: RT and RT+ CDT (Catheter-directed thrombolysis). The RT group included patients in whom intraoperative thrombus aspiration was successful, while the RT + CDT group included patients in whom intraoperative thrombus aspiration was less effective and remedial CDT treatment was used. The primary outcome was the immediate effect of RT on thrombus-containing lower-limb ischaemic lesions. RESULTS: From May 2015 to July 2021, 170 patients (113 men, 57 women; mean age, 74.0 years) with thrombus-containing lower-limb ischaemic lesions were treated in our centre. Of these patients, 113 received RT only, while 57 received RT + CDT. There were no significant intergroup differences in terms of age, disease duration, or comorbidities, but a higher proportion of male patients and higher preoperative plasma D-dimer levels (1.23 vs. 0.84; p = .017) was observed in the RT + CDT group. There were no significant intergroup differences in terms of diagnosis, lesion characteristics, lesion location, or lesion length. Multivariate logistic regression analysis revealed that male sex (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.098-6.410; p = .030) and poor distal runoff (OR, 2.94; 95% CI, 1.439-5.988; p = .003) were associated with higher rates of additional CDT. Male patients also had a significantly longer onset time, more thrombotic occlusions, and a greater frequency of in-stent restenosis. CONCLUSIONS: RT alone or with CDT is a feasible primary treatment option for thrombus debulking. Sex significantly influences the effect of RT on thrombus-containing lower-limb ischaemic lesions.

6.
Biochem Genet ; 60(6): 2455-2470, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35482130

RESUMO

Ischemic stroke is a disease with high mortality. Circular RNA_0010729 (hsa_circ_0010729) has been reported to be involved in ischemic heart disease. However, it is not clear whether hsa_circ_0010729 is involved in the regulation of ischemic stroke. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R) to stimulate human brain microvascular endothelial cells (HBMECs) model to investigate the potential role of hsa_circ_0010729 in stroke in vitro. The expression levels of hsa_circ_0010729, miR-665, and ING5 in ischemic stroke were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HBMECs proliferation was detected by CCK-8. Cell apoptosis was detected by flow cytometry. The levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the related protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to examine the target relationship between miR-665 and hsa_circ_0010729 or ING5. Compared with the control group, hsa_circ_0010729 and ING5 were highly expressed in OGD/R-induced HBMECs, while miR-665 was lowly expressed. Hsa_circ_0010729 silencing promoted OGD/R-induced cell proliferation and inhibited apoptosis. However, the effect of hsa_circ_0010729 down-regulation on OGD/R-induced cell was partially restored after co-transfection with miR-665 inhibitor. Overexpression of miR-665 can promote the proliferation and inhibit apoptosis of OGD/R-induced HBMECs by inhibiting ING5 expression. In OGD/R-induced HBMECs, hsa_circ_0010729 silencing decreased ING5 expression by upregulating miR-665. Hsa_circ_0010729 regulated miR-665/ING5 axis in OGD/R-induced HBMECs. Therefore, hsa_circ_0010729 may be a new therapeutic target for ischemic stroke.


Assuntos
AVC Isquêmico , MicroRNAs , RNA Circular , Humanos , Apoptose/genética , Proliferação de Células/genética , Células Endoteliais/metabolismo , Glucose/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Oxigênio/metabolismo , Fatores de Transcrição , Proteínas Supressoras de Tumor/genética , RNA Circular/genética
7.
BMC Genomics ; 21(1): 353, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393171

RESUMO

BACKGROUND: The fluctuation of nitrogen (N) contents profoundly affects the root growth and architecture in maize by altering the expression of thousands of genes. The differentially expressed genes (DEGs) in response to N have been extensively reported. However, information about the effects of N variation on the alternative splicing in genes is limited. RESULTS: To reveal the effects of N on the transcriptome comprehensively, we studied the N-starved roots of B73 in response to nitrate treatment, using a combination of short-read sequencing (RNA-seq) and long-read sequencing (PacBio-sequencing) techniques. Samples were collected before and 30 min after nitrate supply. RNA-seq analysis revealed that the DEGs in response to N treatment were mainly associated with N metabolism and signal transduction. In addition, we developed a workflow that utilizes the RNA-seq data to improve the quality of long reads, increasing the number of high-quality long reads to about 2.5 times. Using this workflow, we identified thousands of novel isoforms; most of them encoded the known functional domains and were supported by the RNA-seq data. Moreover, we found more than 1000 genes that experienced AS events specifically in the N-treated samples, most of them were not differentially expressed after nitrate supply-these genes mainly related to immunity, molecular modification, and transportation. Notably, we found a transcription factor ZmNLP6, a homolog of AtNLP7-a well-known regulator for N-response and root growth-generates several isoforms varied in capacities of activating downstream targets specifically after nitrate supply. We found that one of its isoforms has an increased ability to activate downstream genes. Overlaying DEGs and DAP-seq results revealed that many putative targets of ZmNLP6 are involved in regulating N metabolism, suggesting the involvement of ZmNLP6 in the N-response. CONCLUSIONS: Our study shows that many genes, including the transcription factor ZmNLP6, are involved in modulating early N-responses in maize through the mechanism of AS rather than altering the transcriptional abundance. Thus, AS plays an important role in maize to adapt N fluctuation.


Assuntos
Nitrogênio/metabolismo , Proteínas de Plantas/metabolismo , Zea mays/genética , Processamento Alternativo , Regulação da Expressão Gênica de Plantas , Nitrogênio/deficiência , Fenótipo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo
8.
Int J Mol Sci ; 21(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093344

RESUMO

Plants have evolved complex mechanisms to respond to the fluctuation of available nitrogen (N) in soil, but the genetic mechanisms underlying the N response in crops are not well-documented. In this study, we generated a time series of NO3--mediated transcriptional profiles in roots of maize and sorghum, respectively. Using weighted gene co-expression network analysis, we identified modules of co-expressed genes that related to NO3- treatments. A cross-species comparison revealed 22 conserved modules, of which four were related to hormone signaling, suggesting that hormones participate in the early nitrate response. Three other modules are composed of genes that are mainly upregulated by NO3- and involved in nitrogen and carbohydrate metabolism, including NRT, NIR, NIA, FNR, and G6PD2. Two G2-like transcription factors (ZmNIGT1 and SbNIGT1), induced by NO3- stimulation, were identified as hub transcription factors (TFs) in the modules. Transient assays demonstrated that ZmNIGT1 and SbNIGT1 are transcriptional repressors. We identified the target genes of ZmNIGT1 by DNA affinity-purification sequencing (DAP-Seq) and found that they were significantly enriched in catalytic activity, including carbon, nitrogen, and other nutrient metabolism. A set of ZmNIGT1 targets encode transcription factors (ERF, ARF, and AGL) that are involved in hormone signaling and root development. We propose that ZmNIGT1 and SbNIGT1 are negative regulators of nitrate responses that play an important role in optimizing nutrition metabolism and root morphogenesis. Together with conserved N responsive modules, our study indicated that, to encounter N variation in soil, maize and sorghum have evolved an NO3--regulatory network containing a set of conserved modules and transcription factors.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Nitratos/farmacologia , Proteínas de Plantas/biossíntese , Raízes de Plantas/metabolismo , Sorghum/metabolismo , Zea mays/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Sorghum/genética , Especificidade da Espécie , Zea mays/genética
9.
Cancer Sci ; 110(5): 1573-1586, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30815935

RESUMO

The testis-specific protein, Y-linked 1 (TSPY1), a newly recognized cancer/testis antigen, has been suggested to accelerate tumor progression. However, the mechanisms underlying TSPY1 cancer-related function remain limited. By mining the RNA sequencing data of lung and liver tumors from The Cancer Genome Atlas, we found frequent ectopic expression of TSPY1 in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC), and the male-specific protein was associated with higher mortality rate and worse overall survival in patients with LUAD and LIHC. Overexpression of TSPY1 promotes cell proliferation, invasiveness, and cycle transition and inhibits apoptosis, whereas TSPY1 knockdown has the opposite effects on these cancer cell phenotypes. Transcriptomic analysis revealed the involvement of TSPY1 in PI3K/AKT and RAS signaling pathways in both LUAD and LIHC cells, which was further confirmed by the increase in the levels of phosphorylated proteins in the PI3K-AKT and RAS signaling pathways in TSPY1-overexpressing cancer cells, and by the suppression on the activity of these two pathways in TSPY1-knockdown cells. Further investigation identified that TSPY1 could directly bind to the promoter of insulin growth factor binding protein 3 (IGFBP3) to inhibit IGFBP3 expression and that downregulation of IGFBP3 increased the activity of PI3K/AKT/mTOR/BCL2 and RAS/RAF/MEK/ERK/JUN signaling in LUAD and LIHC cells. Taken together, the observations reveal a novel mechanism by which TSPY1 could contribute to the progression of LUAD and LIHC. Our finding is of importance for evaluating the potential of TSPY1 in immunotherapy of male tumor patients with TSPY1 expression.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Transdução de Sinais , Células A549 , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Análise de Sequência de RNA , Análise de Sobrevida , Proteínas ras/metabolismo
10.
Biomed Chromatogr ; 33(9): e4581, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31077417

RESUMO

The chemical fingerprinting and metabolite profile in a rat plasma sample after intragastric administration of Yangyin qingfei decoction (YYQFD, 14 g/kg) were investigated. First, YYQFD was analyzed by UPLC/Q-TOF MS to establish the chemical composition database by comparing their retention behavior, accurate molecular mass and MS2 data with those of references or known compounds in the literature. In this database, 100 chemical constituents with information on retention time, molecular mass, molecular formula, MS2 data and compound name were identified, which can provide compound information for further metabolite profiling studies. Furthermore, 64 compounds including 37 prototypes and 27 metabolites were detected in the dosed rat plasma sample, and the metabolic pathways of YYQFD were hydrolyzation, hydroxylation, dehydrogenation, glucuronidation, glucosylation, sulfation and mixed modes. Among the five component herbs in the YYQFD, Glycyrrhizae Radix et Rhizome and Fritillariae Thunbergii bulbs were actively metabolized, contributing 16 and 7 metabolites, respectively. It is suggested that chemical characterization and metabolite profiling studies are valuable to elucidate the material basis of herbal preparations.


Assuntos
Bases de Dados de Compostos Químicos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 817-820, 2019 Aug 10.
Artigo em Zh | MEDLINE | ID: mdl-31400136

RESUMO

OBJECTIVE: To explore clinical and genetic features of a pedigree affected with autosomal recessive neuromyotonia and axonal neuropathy (NMAN). METHODS: For the proband and her parents, clinical data was collected, genomic DNA was extracted from peripheral blood samples. Triplet primed-PCR was carried out to detect dynamic mutation of DMPK and ZNF9 genes, which are responsible for myotonic dystrophy, by capillary electrophoresis. High-throughput sequencing was used to screen variants of candidate genes for Mendelian disorders involving the nervous system. Candidate variants were confirmed by Sanger sequencing. The genotype of the variant was determined in the parents and 100 healthy controls. Pathogenicity of the variant was assessed by ACMG criterion. RESULTS: Mutation of DMPK and ZNF9 genes was excluded. DNA sequencing has identified a homozygous missense variant (c.335C>T, p.R119W) in the HINT1 gene. Both parents were found to carry the variant. The same variant was not found among the healthy controls. According to the ACMG criterion, the missense variant was classified as a pathogenic variant. CONCLUSION: The c.335C>T (p.R119W) of the HINT1 gene probably underlie the disease in this pedigree. Above finding provided further evidence for the connection between HINT1 and NMAN and enriched the mutation spectrum of HINT1 gene.


Assuntos
Síndrome de Isaacs/genética , Proteínas do Tecido Nervoso/genética , Feminino , Genótipo , Homozigoto , Humanos , Linhagem
12.
Reprod Fertil Dev ; 30(3): 555-562, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28847364

RESUMO

Testis-specific protein, Y-encoded, 1 (TSPY1) is involved in the regulation of spermatogenic efficiency via highly variable copy dosage, with dosage deficiency of the multicopy gene conferring an increased risk of spermatogenic failure. TSPY-like 1 (TSPYL1) and TSPY-like 5 (TSPYL5), two autosomal homologous genes originating from TSPY1, share a core sequence that encodes a functional nucleosome assembly protein (NAP) domain with TSPY1. To explore the potential effects of TSPYL1 and TSPYL5 on the TSPY1-related spermatogenic phenotype, we investigated the expression of these genes in 15 healthy and nonpathological human tissues (brain, kidney, liver, pancreas, thymus, prostate, spleen, muscle, leucocytes, placenta, intestine, ovary, lung, colon and testis) and explored associations between their variations and spermatogenic failure in 1558 Han Chinese men with different spermatogenic conditions, including 304 men with TSPY1 dosage deficiency. TSPYL1 and TSPYL5 were expressed in many different tissues, including the testis. An unreported rare variant that is likely pathogenic (c.1057A>G, p.Thr353Ala) and another of uncertain significance (c.1258C>T, p.Arg420Cys) in the NAP-coding sequence of TSPYL1 were observed in three spermatogenesis-impaired patients with heterozygous status. The distribution differences in the alleles, genotypes and haplotypes of eight TSPYL1- and TSPYL5-linked common variants did not reach statistical significance in comparisons of patients with spermatogenic failure and controls with normozoospermia. No difference in sperm production was observed among men with different genotypes of the variants. Similar results were obtained in men with TSPY1 dosage deficiencies. Although the distribution of missense variants of TSPYL1 found in the present and other studies suggests that patients with spermatogenic failure may have a statistically significant greater burden of rare variations in TSPYL1 relative to normozoospermic controls, the functional evidence suggests that TSPYL1 contributes to impaired spermatogenesis. Moreover, the present study suggests that the effects of TSPYL1 and TSPYL5 on the spermatogenic phenotype of TSPY1 dosage deficiency are limited, which may be due to the stability of their function resulting from high sequence conservation.


Assuntos
Proteínas de Ciclo Celular/genética , Dosagem de Genes , Infertilidade Masculina/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Espermatogênese/genética , Povo Asiático/genética , Estudos de Casos e Controles , China , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etnologia , Infertilidade Masculina/fisiopatologia , Masculino , Fenótipo , Fatores de Risco , Transcriptoma
13.
Biol Reprod ; 96(3): 610-616, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339631

RESUMO

Spermatogenic failure characterized by impaired sperm production is a common multifactorial disease with molecular and cytogenetic causes for its extreme phenotype that include azoospermia and severe oliogzoospermia. Recently, a high-resolution array-comparative genomic hybridization analysis of the X chromosome and a subsequent cohort study revealed three X-linked microdeletions (CNV64, CNV67, and CNV69) that were associated with decreased sperm production in a mixed group that included Spanish and Italian males. To confirm their spermatogenic effect, we examined the hemizygous deletions and copy dosage of the MAGE family member A9 (MAGEA9) gene, which is a potential X-linked candidate for the CNV67-related spermatogenic phenotype, to investigate their association with spermatogenic failure in 1722 Han males from southwest China. The individuals in this group consisted of 884 patients with idiopathic azoospermia/oliogzoospermia and 838 controls with normozoospermia. Our results showed that both CNV64 and CNV69 were more common in patients than in controls. Similar to that reported previously, the CNV67 was also identified as being specific to spermatogenic failure in our population, although it was rare. More importantly, the paralog ratio tests and sequence family variant analyses provided evidence that the CNV67 might cause a partial deletion of the proximal copy of the MAGEA9 and suggests that CNV67-related spermatogenic failure may be attributed to the functional defect of the Cancer/Testis gene. Our findings highlight the potential of the Xq-linked CNV67 to serve as a novel detection target in the etiological diagnosis of spermatogenic failure and male infertility, although its pathogenic mechanism remains to be elucidated.


Assuntos
Antígenos de Neoplasias/genética , Proteínas de Neoplasias/genética , Espermatogênese/genética , Adulto , China , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Med Sci Monit ; 23: 2684-2691, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28572562

RESUMO

BACKGROUND We investigated the influence of Resolvin D1 (RvD1) on the inflammatory response in PC12 cells (a cell model of Parkinson disease, PD). MATERIAL AND METHODS 4 mmol/L 1-methyl-4-phenylpyridinium ion (Mpp+) was used in PC12 cells for an in vitro PD model. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to explore PC12 cell viability. Western blot (WB) experiments were used to identify nuclear factor-κB (NF-κB), phosphorylated extracellular signal-regulated kinase (p-ERK)/p-Jun N-terminal kinase (JNK)/p-P38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 protein levels. Transcription levels of inflammatory factors, for instance, TNF-α and IL-6, were explored by real-time quantitative polymerase chain reaction (RT-QPCR). Lactic dehydrogenase (LDH) level was detected by enzyme-linked immunosorbent (ELISA). Cell apoptosis was assessed by Annexin-V Fluorescein (FITC) kit. RESULTS RvD1 dose-dependently inhibited MPP+ induced upregulation of PC12 cell apoptosis/cellular damage/TNF-α and p-P38/p-ERK/NF-κB as well as downregulation of PC12 cell viability. CONCLUSIONS We can draw the conclusion that RvD1 attenuates PD via inhibiting Mpp+-induced inflammation in PC12 cells.


Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Inflamação/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , 1-Metil-4-fenilpiridínio , Animais , Apoptose , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Citometria de Fluxo , Interleucina-6/metabolismo , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Células PC12 , Doença de Parkinson/metabolismo , Fosforilação , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Immun Inflamm Dis ; 12(2): e1187, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38353388

RESUMO

BACKGROUND: Sepsis is a severe complication that results in increased morbidity and mortality after intestinal obstruction surgery. This study examined the role of preoperative systemic immune inflammation index (SII) for postoperative sepsis in intestinal obstruction patients. METHODS: Data on patients who underwent intestinal obstruction surgery were collected. SII was determined and separated into two groups (≤1792.19 and >1792.19) according to the optimal cut-off value of SII for postoperative sepsis. The odds ratio (OR) is calculated for the correlation between SII and postoperative sepsis. Additional analyses were used to estimate the robustness of SII. RESULTS: A total of 371 intestinal obstruction patients undergoing surgery were included in the final cohort, and 60 (16.17%) patients developed postoperative sepsis. Patients with an SII >1792.19 had a significantly higher risk for developing postoperative sepsis after multivariable adjustment [adjusted odds ratio = 2.12, 95% confidence interval: [1.02-4.40]]. The analysis of interaction showed no correlation between the preoperative SII and postoperative sepsis regarding age, hypertension, American Society of Anesthesiologists classification, blood loss, albumin, hemoglobin, creatinine, and leukocyte (all interactions p > .05). In subgroup analysis, all statistically significant subgroups showed that SII was a risk factor for postoperative sepsis (all p < .05). The analyses of subgroups and interactions revealed that the interaction effect of a preoperative SII >1792.19 and postoperative sepsis remained significant. A sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: A preoperative SII > 1792.19 was a risk factor for postoperative sepsis in patients undergoing intestinal obstruction surgery.


Assuntos
Obstrução Intestinal , Sepse , Humanos , Estudos Retrospectivos , Inflamação , Fatores de Risco , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Sepse/complicações
16.
Int J Dev Neurosci ; 84(2): 143-153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38323913

RESUMO

Explore the differences in behavioral and pathological manifestations of rat models of cerebral palsy made by different methods and discuss what types of studies these models are suitable for. Behavioral evaluation and pathological section observation were used to observe and evaluate the model. Conclusion: except for the absence of data of bilateral common carotid artery ligation rats, the other three methods could all achieve a successful cerebral palsy disease model for both behavioral and pathological. For researchers, the selection of intraperitoneal infection model in pregnant rats or unilateral ischemia and hypoxia model in infant rats is sufficient to meet the experimental needs, whereas the selection of the combined method for modeling does not show enough advantages, which not only causes the waste of financial and human resources but also increases the possibility of experimental error made by intervention factors.


Assuntos
Paralisia Cerebral , Humanos , Feminino , Gravidez , Ratos , Animais , Modelos Animais de Doenças , Hipóxia/complicações
17.
Syst Biol Reprod Med ; 70(1): 91-100, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38630599

RESUMO

Conventional semen parameters have long been considered fundamental in male fertility analyses. However, doubts have been raised regarding the clinical utility of the assessment of spermatozoa (sperm) DNA damage. In this retrospective study, we investigated the potential correlation between conventional semen parameters and semen DNA fragmentation (SDF) assessed as sperm DNA damage, in 11,339 semen samples collected between January 2019 and June 2022. We observed significant negative correlations between the DNA fragmentation index (DFI) and sperm viability (correlation coefficient [r] = -0.514) as well as progressive sperm motility (r = -0.512, p < 0.05). Samples were categorized into three groups according to DFI levels (Groups A, B, and C: ≤15%, 15 < DFI ≤30%, and >30%, respectively). Furthermore, the percentage of semen samples with normal sperm conventional parameters in Groups A, B, and C was 76.7% (4369/5697), 61.4% (2351/3827), and 39.7% (721/1815), respectively. Moreover, according to the reference values of conventional sperm parameters, the samples were divided into Groups F, G, and H with all normal, only one abnormal, and > two abnormal parameters, respectively. In addition, the proportions of samples with abnormal DFI values (>30) in Groups F, G, and H were 9.7% (721/7441), 23.1% (618/2676), and 39.0% (476/1222), respectively. Multivariate logistic regression models demonstrated that sperm vitality, progressive sperm motility, normal sperm form, total sperm count, semen volume, age, and some sperm kinematics collectively improved the area under the receiver operating characteristic curve (AUROC) to 0.861, surpassing the predictive value of a single predictor of pathologically damaged sperm DNA. Our study suggests that samples with abnormal sperm parameters may have a higher likelihood of high DNA fragmentation. Furthermore, certain semen parameters could be potential indicators of sperm DNA fragmentation, aiding sperm selection in assisted reproductive procedures.


Assuntos
Infertilidade Masculina , Sêmen , Masculino , Humanos , Fragmentação do DNA , Estudos Retrospectivos , Motilidade dos Espermatozoides , Espermatozoides , Análise do Sêmen , Infertilidade Masculina/genética
18.
Drug Des Devel Ther ; 18: 2381-2392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911034

RESUMO

Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.


Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.


Assuntos
Anestesia Epidural , Raquianestesia , Cesárea , Dexmedetomidina , Ketamina , Dor Visceral , Humanos , Dexmedetomidina/administração & dosagem , Ketamina/administração & dosagem , Método Duplo-Cego , Feminino , Adulto , Dor Visceral/prevenção & controle , Dor Visceral/tratamento farmacológico , Gravidez , Quimioterapia Combinada , Procedimentos Cirúrgicos Eletivos
19.
PLoS One ; 18(1): e0280318, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36701394

RESUMO

Internet use has an important impact on the elderly health. Based on the data of China General Social Survey (CGSS) in 2017, Model 4 and Model 14 in PROCESS were used to test the mechanism of Internet use on the mental health of the elderly, and further compare the differences between urban and rural elderly. The results are that Internet can positively predict the mental health of the whole sample and the urban elderly, but it has no significant predictive effect on the rural elderly; Internet can negatively predict the alienation of whole sample and urban and rural elderly; Alienation has a partly mediated effect between internet use and mental health of the whole elderly; "Internet using-alienation-mental health" the second path was moderated by embodied cultural capital in the whole sample and in the urban elderly. The conclusions are that Internet has a protective effect on the mental health of the elderly, and the mental health can be improved by reducing alienation. Increasing the use of the Internet and embodied cultural capital is an effective way to improve the mental health of the elderly. It is necessary to provide more internet access opportunities for the elderly, especially those in rural areas, increase the accessibility of embodied cultural capital, and bridge the digital divide between urban and rural elderly.


Assuntos
Uso da Internet , Saúde Mental , Humanos , Idoso , Emoções , Acesso à Internet , População Rural , China , População Urbana
20.
Sci Bull (Beijing) ; 68(11): 1119-1126, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37193612

RESUMO

An experiment of 12C(16O,16O → 4α)12C was performed at a beam energy of 96 MeV. A large number of 4-α events were recorded in coincidence and with full particle identification (PID). This was made possible by employing a series of silicon-strip-based telescopes that provided excellent position and energy resolutions. Four narrow resonances just above the 15.1 MeV state were firmly identified in the α + 12C(7.65 MeV; Hoyle state) decay channel. Combined with the theoretical predictions, these resonant states provide new evidence for the predicted possible Hoyle-like structure in 16O above the 4-α separation threshold. Some very high-lying 4-α resonant states have also been observed and need to be further investigated.


Assuntos
Registros , Telescópios , Silício , Vibração
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