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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(4): 370-373, 2022 Apr 10.
Artículo en Zh | MEDLINE | ID: mdl-35446968

RESUMEN

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION: The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.


Asunto(s)
Enanismo , Osteocondrodisplasias , China , Enanismo/genética , Humanos , Discapacidad Intelectual , Osteocondrodisplasias/congénito , Osteocondrodisplasias/genética , Linaje
2.
BMC Urol ; 19(1): 31, 2019 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-31053126

RESUMEN

BACKGROUND: To assess the technical feasibility and outcomes of robotic-assisted partial nephrectomy (RPN) with sequential segmental renal artery (SRA) clamping for multiple ipsilateral renal tumors (MIRTs). METHODS: From April 2016 to February 2018, consecutive eleven cases successfully underwent RPN with sequential SRA clamping under the guidance of dual-source computed tomography (DSCT). RESULTS: Ten cases had two lesions and two cases had three at the ipsilateral kidneys. The mean size and the mean R.E.N.A.L score for the dominant lesion of single case were 3.3 cm and 5.7, respectively. Twenty-two lesions (84.6%) had one target SRA and four (15.4%) had two target SRAs. Satisfactory ischemic areas were achieved by sequentially clamping two (81.8%) or three (18.2%) target SRAs with mean clamping time of 18.8 (15.0-27.0) min for single lesion, and the mean of total clamping time for single case was 37.5 (32.0-52.0) min. Only the complications of grade 1-2 were found and no positive surgical margin was discovered. The mean follow-up time was 5.4 months and no local recurrence or metastasis was found. The mean postoperative eGFR was 71.2 ml/minute/1.73m2 that was only an insignificant reduction (9.3%) compared with the preoperative baseline. CONCLUSION: This novel nephron-sparing technique, RPN with sequential SRA clamping, represents a good alternative for selected patients with MIRTs. With the guidance of DSCT and skilled robotic experience, this technique is feasible and can maximize renal function preservation. Large-scale multicenter clinical studies are still needed to further prove these initial outcomes.


Asunto(s)
Neoplasias Renales/cirugía , Nefrectomía/métodos , Arteria Renal/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Constricción , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Renal/diagnóstico por imagen , Resultado del Tratamiento
3.
Exp Cell Res ; 360(2): 105-112, 2017 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-28843961

RESUMEN

Activating transcription factor 4 (ATF4), an endoplasmic reticulum stress-inducible transcription factor, plays important roles in cancer progression and resistance to therapy. However, no report is available about its roles in endometrial cancer (EC). In this study, we found that ATF4 is commonly expressed in EC cell lines. Loss-of-function studies in two EC cell lines showed that ATF4 knockdown suppresses tumor growth of EC in vivo without influencing cell proliferation in vitro. And xenograft tumors derived from ATF4-knockdown cells had reduced M2 macrophage infiltration. In clinical specimens, ATF4-high expressing tumors indeed contained more macrophage infiltration compared to those with lower ATF4 expression. Moreover, we identified that ATF4-mediated chemokine CCL2 expression ultimately results in macrophage infiltration and tumor growth of EC. Taken together, our findings suggest that ATF4 contributes to tumor growth of EC by promoting CCL2 and subsequent recruitment of macrophage, and that ATF4/CCL2 axis might be a potential therapeutic target for EC.


Asunto(s)
Factor de Transcripción Activador 4/fisiología , Carcinoma Endometrioide/genética , Proliferación Celular/genética , Quimiocina CCL2/genética , Quimiotaxis de Leucocito/genética , Neoplasias Endometriales/genética , Macrófagos/fisiología , Factor de Transcripción Activador 4/antagonistas & inhibidores , Factor de Transcripción Activador 4/genética , Animales , Carcinoma Endometrioide/patología , Células Cultivadas , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Ratones , Ratones Desnudos , Escape del Tumor/genética
4.
Med Sci Monit ; 24: 6349-6358, 2018 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-30203815

RESUMEN

BACKGROUND This study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor), and IL-16 (interleukin-16) in different experimental groups, so as to understand the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a logistic regression analysis was utilized to investigate the survival status of recurrent AF in subjects harboring different genotypes of rs12976445. RESULTS The subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no obvious difference regarding all demographic characteristics that were collected in this study. In addition, 19 miRNAs were identified as potentially involved in the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13 were downregulated in the group with early recurrence. According to real-time PCR results, the expression of miR-125a was dramatically upregulated in LRAF (late recurrence of atrial fibrillation) as well as in subjects harboring the GG genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed as a candidate target of miR-125a by a luciferase reporter assay. CONCLUSIONS MicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the regulation of IL-6R.


Asunto(s)
Fibrilación Atrial/genética , MicroARNs/genética , Receptores de Interleucina-6/genética , Anciano , Fibrilación Atrial/metabolismo , Fibrilación Atrial/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , Receptores de Interleucina-6/biosíntesis , Receptores de Interleucina-6/metabolismo , Recurrencia
5.
Zhonghua Nan Ke Xue ; 22(1): 77-81, 2016 Jan.
Artículo en Zh | MEDLINE | ID: mdl-26931032

RESUMEN

Sperm DNA fragmentation index (DFI) refers to the percentage of DNA strand breaks in the total sperm. Many studies suggest that elevated DFI can lead to male infertility and early spontaneous abortion. High-DFI patients are more likely to fail in assisted reproduction and preliminary treatment or prevention methods have been developed for this population. This review focuses on the impact of DFI on clinical pregnancy outcomes and progress in the studies of its treatment.


Asunto(s)
Fragmentación del ADN , Resultado del Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Aborto Espontáneo , Cromatina , Femenino , Humanos , Infertilidad Masculina , Masculino , Embarazo , Espermatozoides
6.
BMC Microbiol ; 14: 220, 2014 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-25163588

RESUMEN

BACKGROUND: Enterocin A is a classic IIa bacteriocin isolated firstly from Enterococcus faecium CTC492 with selective antimicrobial activity against Listeria strains. However, the application of enterocin A as an anti-Listeria agent has been limited due to its very low native yield. The present work describes high production of enterocin A through codon optimization strategy and its character study. RESULTS: The gene sequence of enterocin A was optimized based on preferential codon usage in Pichia pastoris to increase its expression efficiency. The highest anti-Listeria activity reached 51,200 AU/ml from 180 mg/l of total protein after 24 h of induction in a 5-L fermenter. Recombinant enterocin A (rEntA), purified by gel filtration chromatography, showed very strong activity against Listeria ivanovii ATCC 19119 with a low MIC of 20 ng/ml. In addition, the rEntA killed over 99% of tested L. ivanovii ATCC19119 within 4 h when exposed to 4 × MIC (80 ng/ml). Moreover, it showed high stability under a wide pH range (2-10) and maintained full activity after 1 h of treatment at 80°C within a pH range of 2-8. Its antimicrobial activity was enhanced at 25 and 50 mM NaCl, while 100-400 mM NaCl had little effect on the bactericidal ability of rEntA. CONCLUSION: The EntA was successfully expressed in P. pastoris, and this feasible system could pave the pre-industrial technological path of rEntA as a competent candidate as an anti-Listeria agent. Furthermore, it showed high stability under wide ranges of conditions, which could be potential as the new candidate of anti-Listeria agent.


Asunto(s)
Bacteriocinas/aislamiento & purificación , Bacteriocinas/farmacología , Listeria/efectos de los fármacos , Bacteriocinas/genética , Bacteriocinas/metabolismo , Cromatografía en Gel , Activadores de Enzimas/metabolismo , Expresión Génica , Vectores Genéticos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Pichia/genética , Pichia/metabolismo , Estabilidad Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Análisis de Secuencia de ADN , Cloruro de Sodio/metabolismo , Temperatura
7.
Biometals ; 27(5): 957-68, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25015218

RESUMEN

The tri-hybrid peptide-LHP7 has the potent activity against Gram-positive and Gram-negative as well as fungi, but its mechanism of action has remained elusive. The effluences of LHP7 on the Staphylococcus aureus cell membrane and targets of intracellular action were investigated. LHP7 exhibited an inhibitory effect on the S. aureus growth, similar to those achieved by plectasin, vancomycin and gramicidin. The membrane integrity studies confirmed that LHP7 disrupted the cell membrane, indicating a membrane permeabilizing killing action. A marginal decline in the intensity fluorescence indicated no significant depolarization of the membrane potential following LHP7 treatment. Furthermore, electron microscopy showed that cell shrinkage, cell wall thickening, cellular content leakage, and cell disruption were observed in the cells treated with LHP7. A gel retardation assay showed that LHP7 bound to the genomic DNA of S. aureus or plasmid DNA at a mass ratio of 2.5­10 (peptide/DNA). Circular dichroism indicated that LHP7 inserted into the groove of DNA. The cell cycle analysis showed that after the treatment with LHP7 for 30 and 60 min, the proportion of cells in I-phase increased from 8.71 to 12.09 % and from 8.71 to 15.68 %, indicating that LHP7 induced arrest of cells in the I-phase. These results would conduce to elucidate its underlying antibacterial mechanism.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Lactoferrina/química , Lactoferrina/farmacología , Péptidos/química , Péptidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de los fármacos , ADN Bacteriano/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Microscopía Electrónica , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/farmacología , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/metabolismo
8.
Appl Microbiol Biotechnol ; 98(2): 681-94, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23624708

RESUMEN

NZ2114, a new variant of plectasin, was overexpressed in Pichia pastoris X-33 via pPICZαA for the first time. The total secreted protein of fermentation supernatant reached 2,390 mg/l (29 °C) and 2,310 mg/l (25 °C), and the recombinant NZ2114 (rNZ2114) reached 860 mg/l (29 °C) and 1,309 mg/l (25 °C) at 96 h induction in a 5-l fermentor, respectively.The rNZ2114 was purified by cation exchange chromatography, and its yield was 583 mg/l with 94.8 % purity. The minimal inhibitory concentration (MIC) of rNZ2114 to four ATCC strains of Staphyloccocus aureus was evaluated from 0.028 to 0.90 µM. Meanwhile, it showed potent activity (0.11-0.90 µM) to 20 clinical isolates of MRSA. The rNZ2114 killed over 99.9 % of tested S. aureus (ATCC 25923 and ATCC 43300) in Mueller-Hinton medium within 6 h when treated with 4 × MIC. The postantibiotic effect of rNZ2114 to S. aureus ATCC 25923 and ATCC 43300 was 18.6-45.6 and 1.7-3.5 h under 1×, 2×, and 4× MIC, respectively. The fractional inhibitory concentration index (FICI) indicated a synergistic effect between rNZ2114 and kanamycin, streptomycin, and vancomycin against S. aureus ATCC 25923 (FICI = 0.125), and additivity between rNZ2114 and ampicillin, spectinomycin (FICI = 0.625), respectively. To S. aureus ATCC 43300 [methicillin-resistant S. aureus (MRSA)], rNZ2114 showed a synergistic effect (FICI = 0.125-0.3125) with kanamycin, ampicillin, streptomycin, and vancomycin, and antagonism with spectinomycin (FICI = 8.0625). The rNZ2114 caused only less than 0.1 % hemolytic activity in the concentration of 128 µg/ml, and showed a good thermostability from 20 to 80 °C. In addition, it exhibited the highest activity at pH 8.0. These results suggested that large-scale production of NZ2114 is feasible using the P. pastoris expression system, and it could be a new potential antimicrobial agent for the prevention and treatment of S. aureus especially for MRSA infections.


Asunto(s)
Antibacterianos/farmacología , Sinergismo Farmacológico , Péptidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/aislamiento & purificación , Cromatografía por Intercambio Iónico , Expresión Génica , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Péptidos/genética , Péptidos/aislamiento & purificación , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología
9.
Appl Microbiol Biotechnol ; 98(19): 8313-25, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24981062

RESUMEN

The food-borne bacterial gastrointestinal infection is a serious public health threat. Defensins are evolutionarily conserved innate immune components with broad-spectrum antibacterial activity that do not easily induce resistance. AvBD103b, an avian defensin with potent activity against Salmonella enteritidis, was isolated from the stomach contents of the king penguin (Aptenodytes patagonicus). To elucidate further the antibacterial mechanism of AvBD103b, its effect on the S. enteritidis CVCC3377 cell membrane and intracellular DNA was researched. The cell surface hydrophobicity and a N-phenyl-1-naphthylamine uptake assay demonstrated that AvBD103b treatment increased the cell surface hydrophobicity and outer membrane permeability. Atomic absorption spectrometry, ultraviolet spectrophotometry, flow cytometry, and transmission electron microscopy (TEM) indicated that AvBD103b treatment can lead to the release of the cellular contents and cell death through damage of the membrane. DNA gel retardation and circular dichroism analysis demonstrated that AvBD103b interacted with DNA and intercalated into the DNA base pairs. A cell cycle assay demonstrated that AvBD103b affected cellular functions, such as DNA synthesis. Our results confirmed that AvBD103b exerts its antibacterial activity by damaging the cell membrane and interfering with intracellular DNA, ultimately causing cell death, and suggested that AvBD103b may be a promising candidate as an alternative to antibiotics against S. enteritidis.


Asunto(s)
Antibacterianos/farmacología , Proteínas Aviares/farmacología , Membrana Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Defensinas/farmacología , Salmonella enteritidis/efectos de los fármacos , Salmonella enteritidis/genética , Spheniscidae/genética , Animales , Membrana Celular/química , Permeabilidad de la Membrana Celular/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Proteínas Hemolisinas/farmacología , Humanos , Salmonella enteritidis/química
10.
Appl Microbiol Biotechnol ; 98(17): 7387-98, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24816779

RESUMEN

The candidacidal mechanisms of NZ17074, which is a variant of arenicin-3 from Arenicola marina, against human pathogenic fungus Candida albicans are reported in this work. The minimum inhibitory concentration (MIC) of NZ17074 toward C. albicans was 4 µg/ml, and this peptide exerted marked candidacidal activity in an energy-dependent and salt-sensitive manner. The flow cytometric analysis using propidium iodide (PI) showed that the plasma membrane of cells treated with NZ17074 was perturbed and that the cells were arrested in the G2/M phase. The dihydrorhodamine-123 (DHR-123) staining showed that the reactive oxygen species (ROS) production of C. albicans increased after exposure to NZ17074. Typical cellular disruption events, such as mitochondrial degradation, nuclear fragmentation, nuclear membrane disruption, and chromatin condensation, were further revealed through rhodamine 123 (RH123) staining, 4',6-diamidino-2-phenylindole (DAPI) staining, and transmission electron microscopy. In addition, the intracellular localization of this peptide was concentration dependent: it was located in the membrane at low concentrations (4 to 8 µg/ml) and penetrated into the cytoplasm at high concentrations (16 to 32 µg/ml). Our results suggested that NZ17074 exerts its candidacidal effects by disrupting the cell membrane, inducing apoptosis, and interrupting the cell cycle. These findings showed the potential of NZ17074 as a new candidacidal peptide, in addition to its antibacterial activities.


Asunto(s)
Antifúngicos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Candida albicans/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Animales , Antifúngicos/aislamiento & purificación , Péptidos Catiónicos Antimicrobianos/aislamiento & purificación , Apoptosis , Candida albicans/metabolismo , Candida albicans/ultraestructura , Ciclo Celular/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión , Poliquetos/química , Especies Reactivas de Oxígeno/metabolismo , Coloración y Etiquetado
11.
Zhonghua Nan Ke Xue ; 20(11): 999-1003, 2014 Nov.
Artículo en Zh | MEDLINE | ID: mdl-25577835

RESUMEN

OBJECTIVE: To investigate the association of erectile dysfunction (ED) with metabolic syndrome ( MS) and the total testosterone ( tT) level in young and middle-aged men. METHODS: This study included 154 organic ED outpatients aged 20 -59 years and 103 age-matched men with normal sexual life. We obtained their waist circumference ( WC) , blood pressure ( BP) , fasting blood glucose ( FBG) , triglyceride ( TG) , high density lipoprotein ( HDL) , tT, IIEF -5 score, erectile function indexes and other relevant variables, and compared them between the ED and non-ED groups as well as between the ED patients with MS and those without MS. RESULTS: The prevalence of MS was significantly higher in the ED patients than in the non-ED males ( 40. 9 vs 17.4%, P < 0. 01). Statistically significant differences were found between the ED and non-ED groups in WC ( [90. 80 ±4. 90] vs [87. 70 ±4. 60] em, P <0.01), SBP ([134.40±14.40] vs [129.90±12.40] mmHg, P

Asunto(s)
Disfunción Eréctil/etiología , Síndrome Metabólico/complicaciones , Adulto , Estudios de Casos y Controles , Colesterol/sangre , Disfunción Eréctil/sangre , Humanos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Erección Peniana/fisiología , Prevalencia , Testosterona/sangre , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto Joven
12.
Reprod Sci ; 31(4): 1017-1027, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37815748

RESUMEN

Accumulating evidence has shown that inflammation is a key process in polycystic ovary syndrome (PCOS). Nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) inflammasomes play an essential role in inflammation. We investigated the expression of NLRP3 inflammasome in PCOS and its underlying mechanisms. Human granulosa cells (GCs) were isolated from patients with PCOS and control women who underwent in vitro fertilization and embryo transfer. Ovarian specimens were collected from mice with polycystic ovarian changes induced by a high-fat diet and letrozole. RNA sequencing (RNA-Seq) was performed on a granulosa cell line (KGN) overexpressing NLRP3. Polymerase chain reaction (PCR) was performed to quantify the differentially expressed genes of interest. NLRP3 and caspase-1 expression was significantly higher in GCs from patients with PCOS than in GCs from the control group. Increased NLRP3 and caspase-1 expression was also detected by immunohistochemistry in the GCs of a mouse model of polycystic ovarian changes. The serum IL-18 concentration in PCOS-like mice was significantly higher than that in control mice. Following NLRP3 overexpression in KGN cells, the genes involved in N-glycan processing, steroidogenesis, oocyte maturation, autophagy, and apoptosis were upregulated. The RT-qPCR results revealed that the expression levels of GANAB, ALG-5, HSD3B2, ULK1, PTK2B, and Casp7 in KGN cells after NLRP3 overexpression were significantly higher than those in control cells, which was consistent with the RNA-Seq results. Taken together, the NLRP3 inflammasome-dependent pathway is involved in the pathogenesis of PCOS not only by mediating pyroptosis, but also by regulating glycan synthesis, sex hormone synthesis, autophagy, and apoptosis in GCs.


Asunto(s)
Inflamasomas , Síndrome del Ovario Poliquístico , Animales , Femenino , Humanos , Ratones , Caspasas/metabolismo , Células de la Granulosa/metabolismo , Inflamasomas/metabolismo , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Polisacáridos/metabolismo
13.
Nat Med ; 30(5): 1489-1498, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38528168

RESUMEN

Aging populations are susceptible to heat-related mortality because of physiological factors and comorbidities. However, the understanding of individual vulnerabilities in the aging population is incomplete. In the Chinese Longitudinal Healthy Longevity Survey, we assessed daily heatwave exposure individually for 13,527 participants (median age = 89 years) and 3,249 summer mortalities during follow-up from 2008 to 2018. The mortality risk during heatwave days according to relative temperature is approximately doubled (hazard ratio (HR) range = 1.78-1.98). We found that heatwave mortality risks were increased for individuals with functional declines in mobility (HR range = 2.32-3.20), dependency in activities of daily living (HR range = 2.22-3.27), cognitive impairment (HR = 2.22) and social isolation reflected by having nobody to ask for help during difficulties (HR range = 2.14-10.21). Contrary to current understanding, older age was not predictive of heatwave mortality risk after accounting for individual functional declines; no statistical differences were detected according to sex. Beyond age as a risk factor, our findings emphasize that functional aging is an underlying factor in enhancing heatwave resilience. Assessment of functional decline and implementing care strategies are crucial for targeted prevention of mortality during heatwaves.


Asunto(s)
Actividades Cotidianas , Humanos , Masculino , Anciano , Femenino , Factores de Riesgo , Anciano de 80 o más Años , China/epidemiología , Calor Extremo/efectos adversos , Calor/efectos adversos , Estudios Longitudinales , Envejecimiento/fisiología , Pueblo Asiatico , Pueblos del Este de Asia
14.
Plasmid ; 69(1): 108-13, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23085154

RESUMEN

Standard reference molecules play a significant role for the detection of genetically modified (GM) crops and products. The newest reference molecules should catch up with the rapid development of GM crops in the world. In this work, a reference plasmid containing ten targets from GM soybean, maize and cotton was constructed on the basis of the pTLE8 harboring eight targets only from GM soybean and cotton. Three target segments of the Bt176 event-specific 3'-junction (Bt176G3'), MON810 event-specific 3'-junction (MON810G3') and the endogenous maize Hmg genes, were fused into the 890 bp fragment by overlap extension PCR. The CP4 EPSPS gene in the plasmid pTLE8 previously constructed in our laboratory was replaced with above fusion fragment, thus generating a new plasmid pTLH10 containing ten target genes from GM soybean, maize and cotton. The PCR efficiencies with pTLH10 as a calibrator ranged from 93.3% to 99.9% for the standard curves of the Bt176G3', MON810G3' and Hmg genes. The standard deviation (SD) values of repeatability were from 0.04 to 0.8 for three different days and from 0.12 to 1.14 for one day, respectively. These results indicated that the reference plasmid constructed in this work is also suitable for the identification of GM maize, and would be an important tool to establish a feasible identification management for various GM crops components.


Asunto(s)
Genes de Plantas , Plantas Modificadas Genéticamente/genética , Plásmidos/genética , ADN de Plantas/genética , Fusión Génica , Gossypium/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Glycine max/genética
15.
Appl Microbiol Biotechnol ; 97(9): 3991-4002, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23095942

RESUMEN

A novel specifically targeted antimicrobial peptide (STAMP) that was especially effective against methicillin-resistant Staphylococcus aureus (MRSA) was designed by fusing the AgrD1 pheromone to the N-terminal end of plectasin. This STAMP was named Agplectasin, and its gene was synthesized and expressed in Pichia pastoris X-33 via pPICZαA. The highest amount of total secreted protein reached 1,285.5 mg/l at 108 h during the 120-h induction. The recombinant Agplectasin (rAgP) was purified by cation exchange chromatography and hydrophobic exchange chromatography; its yield reached 150 mg/l with 94 % purity. The rAgP exhibited strong bactericidal activity against S. aureus but not Staphylococcus epidermidis or other types of tested bacteria. A bactericidal kinetics assay showed that the rAgP killed over 99.9 % of tested S. aureus (ATCC 25923 and ATCC 43300) in both Mueller-Hinton medium and human blood within 10 h when treated with 4× minimal inhibitory concentration. The rAgP caused only approximately 1 % hemolysis of human blood cells, even when the concentration reached 512 µg/ml, making it potentially feasible as a clinical injection agent. In addition, it maintained a high activity over a wide range of pH values (2.0-10.0) and demonstrated a high thermal stability at 100 °C for 1 h. These results suggested that this STAMP has the potential to eliminate MRSA strains without disrupting the normal flora.


Asunto(s)
Antibacterianos/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Péptidos Cíclicos/metabolismo , Péptidos/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Proteínas Bacterianas/genética , Pruebas de Sensibilidad Microbiana , Péptidos/genética , Péptidos Cíclicos/genética , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes de Fusión/genética
16.
Mol Genet Genomic Med ; 10(10): e2040, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35975393

RESUMEN

BACKGROUND: Premature ovarian insufficiency (POI) is a clinical syndrome occurring in women before 40 with decreased ovarian function. Up to 25% of POI cases result from genetic factors that remain largely unknown. The Excision repair cross-complementing, group 6 (ERCC6) variant has been found to cause POI, which is hardly ever diagnosed in adolescents. METHODS: Whole-exome sequencing was performed on a 19-year-old proband with non-syndromic POI and her parents. Sanger sequencing was used to confirm the identified variant. The effect of the variant on the protein was analyzed in silico and Swiss-MODEL. RESULTS: A novel heterozygous missense variant, c.2444G > A (p. GLy815Asp) of ERCC6 was identified in the proband who inherited the variant from her father. The variant was confirmed in another POI patient from the pedigree and was absent in the proband's mother and sister who presented normally. In silico analysis predicted this variant was deleterious. Swiss-Model revealed that the mutant amino acid formed multiple H-bonds with adjacent residues, which may lead to a dysfunction of ERCC6 protein. CONCLUSION: We firstly diagnosed an adolescent POI case associated with a novel heterozygous ERCC6 variant. The results expanded the variants spectrum of ERCC6 and provided guidance for POI diagnosis and genetic counselling.


Asunto(s)
Insuficiencia Ovárica Primaria , Adolescente , Adulto , Aminoácidos/genética , China , ADN Helicasas/genética , Reparación del ADN , Enzimas Reparadoras del ADN/genética , Femenino , Heterocigoto , Humanos , Proteínas de Unión a Poli-ADP-Ribosa/genética , Insuficiencia Ovárica Primaria/genética , Adulto Joven
17.
Zhonghua Nan Ke Xue ; 16(1): 84-8, 2010 Jan.
Artículo en Zh | MEDLINE | ID: mdl-20180411

RESUMEN

OBJECTIVE: To investigate the effects of curcumin on the expressions of TNF-alpha, IL-6 and IL-8 in rats with chronic nonbacterial prostatitis. METHODS: Sixty healthy adult male SD rats with the body weight of 200 -220 g were equally and randomly divided into a normal control, a positive control, a model, an oral curcumin and an intraperitoneal curcumin group. The rat models of chronic nonbacterial prostatitis were made by hypodermic injection of estradiol benzoate at the dose of 0.25 mg/(kg x d) for 30 days after castration, and then treated with curcumin at 200 mg/(kg x d) by gavage or intraperitoneal injection. The positive controls received oral celebrex at 250 mg/(kg x d), while the normal control and model groups were given saline by gavage. After a week of treatment, the levels of TNF-alpha, IL-6 and IL-8 in the serum and prostate tissues of the rats were detected by ELISA assay. RESULTS: The levels of TNF-alpha and IL-8 in the serum and prostate tissues were significantly lower in the intraperitoneal curcumin than in the positive control group (P < 0.05), but the expression of IL-6 showed no significant difference between the two groups (P > 0.01). CONCLUSION: Curcumin is efficacious for chronic nonbacterial prostatitis in rats, and the action mechanism may be associated with its decreasing effect on the proinflammatory cytokines IL-8 and TNF-alpha in the blood and tissues.


Asunto(s)
Curcumina/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Prostatitis/tratamiento farmacológico , Prostatitis/metabolismo , Animales , Enfermedad Crónica , Curcumina/farmacología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo
18.
Int J Clin Exp Pathol ; 13(8): 2137-2142, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922611

RESUMEN

Desbuquois dysplasia (DBQD) is a severe chondrodysplasia characterized by short stature, retarded development, multiple joint dislocations, and a distinct radiological appearance of the proximal femur. Pathogenic variants in the calcium-activated nucleotidase 1 (CANT1) or xylosyltransferase 1 (XYLT1) gene have been previously reported to cause DBQD. Here we present a 12-year-old boy manifesting the typical features of DBQD type 1 caused by a homozygous intronic variant c.836-9G>A of CANT1. To our knowledge, this is the first DBQD case described in China revealing that a CANT1 variant was also responsible for DBQD in the Chinese population and further emphasizing the role of CANT1 variants in the etiology of DBQD type 1. Our finding provides certainty for the DBQD clinical diagnosis of this patient and expands the spectrum of known DBQD genetic risk factors. On the basis of this study, amniocentesis-based prenatal diagnosis or preimplantation genetic diagnosis (PGD)-based assisted reproduction could be a helpful aristogenesis strategy to avoid the birth of a DBQD affected child.

19.
Artículo en Inglés | MEDLINE | ID: mdl-31438583

RESUMEN

The urban environment is a complex ecosystem influenced by strong human disturbances in multi-environmental media, so it is necessary to analyze urban environmental pollutants through the comprehensive analysis of different media. Soil, road dust, foliar dust, and camphor leaves from 32 sample sites in Shanghai were collected for the analysis of mercury contamination in soil-road dust-leaves-foliar dust systems. Mercury concentrations in surface soils in Shanghai were the highest, followed by road dust, foliar dust, and leaves, successively. The spatial distribution of mercury in the four environmental media presented different distribution patterns. Except for the significant correlation between mercury concentrations in road dust and mercury concentrations in leaves (r = 0.56, p < 0.001), there was no significant correlation between the other groups in the four media. Besides this, there was no significant correlation between mercury concentrations and land types. The LUR (Land use regression) model was used to assess the impact of urbanization factors on mercury distribution in the environment. The results showed that soil mercury was affected by factories and residential areas. Foliar dust mercury was affected by road density and power plants. Leaf mercury was affected by power plants and road dust mercury was affected by public service areas. The highest average HI (Hazard index) value of mercury in Shanghai was found in road dust, followed by surface soil and foliar dust. The HI values for children were much higher than those for adults. However, the HI values of mercury exposure in all sampling sites were less than one, suggesting a lower health risk level. The microscopic mechanism of mercury in different environmental media was suggested to be studied further in order to learn the quantitative effects of urbanization factors on mercury concentrations.


Asunto(s)
Polvo/análisis , Mercurio/análisis , Contaminantes del Suelo/análisis , Adulto , Niño , China , Monitoreo del Ambiente , Humanos , Centrales Eléctricas , Medición de Riesgo
20.
Nat Med ; 29(7): 1613-1614, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37464046
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