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1.
Analyst ; 149(14): 3783-3792, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38845587

RESUMEN

Abrin toxin, highly dangerous with an estimated human lethal dose of 0.1-1 µg per kg body weight, has attracted much attention regarding criminal and terroristic misuse over the past decade. Therefore, developing a rapid detection method for abrin toxin is of great significance in the field of biosecurity. In this study, based on the specific dissociation method of an immobilized enzyme reactor, the trypsin immobilized reactor Fe3O4@CTS-GA-Try was prepared to replace free trypsin, and the immobilized enzyme digestion process was systematically investigated and optimized by using bovine serum albumin as the simulant of abrin. After 5 min one-step denaturation and reduction, a satisfactory peptide number and coverage were yielded with only 15 s assisted by an ultrasound probe to identify model proteins. Subsequently, abrin was rapidly digested using the established method, resulting in a stable and highly reproducible characteristic peptide number of 39, which can be analyzed by nanoelectrospray ionization coupled with high-resolution mass spectrometry. With the acquisition mode of full MS scan coupled with PRM, not only MS spectroscopy of total abrin peptides but also the corresponding MS/MS spectroscopy of specific abrin peptides can achieve the characteristic detection of abrin toxin and its different isoforms in less than 10 minutes, with high repeatability. This assay provides a universal platform and has great potential for the development of on-site detection and rapid mass spectrometric analysis techniques for macromolecular protein toxins and can further be applied to the integrated detection of chemical and biological agents.


Asunto(s)
Abrina , Enzimas Inmovilizadas , Albúmina Sérica Bovina , Tripsina , Abrina/análisis , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Tripsina/metabolismo , Tripsina/química , Albúmina Sérica Bovina/química , Animales , Bovinos , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Proteolisis
2.
Angew Chem Int Ed Engl ; 62(43): e202312698, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37682089

RESUMEN

The first coordination-saturated buckyball with a C60 molecule totally encased in an icosidodecahedral Cu30 in a (µ30 -(η2 )30 )-fashion, namely C60 @Cu30 @Cl36 N12 , has been successfully realized by a C60 -templated assembly. The 48 outmost coordinating atoms (36Cl+12N) comprise a new simple polyhedron that is described by a ccf topology. Charge transfer from (CuI , Cl) to C60 explains the expansion of the light absorption up to 700 nm, and accounts for an ultrafast photophysical process that underpins its high photothermal conversion efficiency. This work makes a giant step forward in exohedral metallofullerene (ExMF) chemistry.

3.
Clin Endocrinol (Oxf) ; 97(5): 612-621, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35384023

RESUMEN

BACKGROUND: Pituitary stalk interruption syndrome (PSIS), characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary, and an ectopic posterior pituitary, can lead to congenital combined pituitary hormone deficiency. There is a high prevalence of various metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), in this population. OBJECTIVE: To investigate the characteristics of NAFLD in Chinese adult patients with PSIS and its association with growth hormone deficiency. DESIGN: Retrospective cross-sectional study in a tertiary referral center of China. PATIENTS: Adult patients with PSIS diagnosed, followed up between September 2019 and August 2021, were consecutively enrolled. MEASUREMENTS: Abdominal ultrasonography images were evaluated and noninvasive fibrosis scores were determined to assess the severity of NAFLD. Anthropometric, clinical, and biochemical parameters were compared between patients with and without NAFLD. Logistic regression was performed to assess the independent effects of insulin-like growth factor-1 (IGF-1) on NAFLD. RESULTS: A total of 93 patients (77 men, 16 women, mean age: 29.6 ± 7.1 years) were included. The prevalence of NAFLD and advanced fibrosis/cirrhosis was 50.5% and 4.3%, respectively. Insufficient hormone therapy and prominent metabolic disorders, including central obesity, dyslipidemia, insulin resistance, and metabolic syndrome, were more common in the NAFLD (+) group. After adjusting for multiple variables, IGF-1 <-2 standard deviation score (SDS) was found to be associated with an increased prevalence of NAFLD (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 1.21-24.55, p = .035). Per 1 SDS increase in IGF-1 was associated with a 27% lower risk of NAFLD (OR: 0.73, 95% CI: 0.52-0.97, p = .042). CONCLUSION: NAFLD is a frequent comorbidity among Chinese adult patients with PSIS and is strongly associated with lower IGF-1 levels. Timely and appropriate hormone replacement, particularly growth hormone may contribute to decreasing the risk of NAFLD in these patients.


Asunto(s)
Hormona de Crecimiento Humana , Enfermedad del Hígado Graso no Alcohólico , Enfermedades de la Hipófisis , Adulto , Estudios Transversales , Femenino , Hormona del Crecimiento , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Cirrosis Hepática , Masculino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedades de la Hipófisis/patología , Hipófisis/patología , Estudios Retrospectivos , Adulto Joven
4.
Endocr Pract ; 28(11): 1118-1124, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35940470

RESUMEN

OBJECTIVE: This study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT). METHODS: Male patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites. RESULTS: Fifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009). CONCLUSION: Collectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non-recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.


Asunto(s)
Hormona de Crecimiento Humana , Enfermedades de la Hipófisis , Adulto , Humanos , Masculino , Adulto Joven , Densidad Ósea , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona de Crecimiento Humana/uso terapéutico , Testosterona , Hipófisis/diagnóstico por imagen
5.
Endocr Pract ; 28(5): 521-527, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35218954

RESUMEN

OBJECTIVE: Pulsatile gonadotropin-releasing hormone (GnRH), widely used to induce spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients, can restore the pituitary-testis axis function in men with pituitary stalk interruption syndrome (PSIS). This retrospective study aimed to compare the differences in the long-term efficacy of pulsatile GnRH therapy on PSIS and CHH. METHODS: Patients with PSIS (n = 25) or CHH (n = 64) who received pulsatile GnRH therapy for ≥3 months were included in this retrospective study. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, total testosterone, and testicular size were compared. RESULTS: Baseline characteristics were comparable except for the lower basal testosterone, triptorelin-stimulated peak luteinizing hormone (LH), and follicle-stimulating hormone in patients with PSIS. With similar duration of treatment and a significantly higher GnRH dose (P < .001), small increments in LH (2.82 [1.4, 4.55] vs 5.89 [3.88, 8.02] IU/L; P < .001), total testosterone (0.38 [0, 1.34] vs 2.34 [1.34, 3.66] ng/mL; P < .001), and testicular volume (5.3 ± 4.5 vs 8.8 ± 4.8 mL, P < .05) were observed. However, spermatogenesis rate (52.0% vs 70.3%, P > .05), median time of sperm appearance (14 vs 11 months, P > .05), sperm concentration, and progressive motility were comparable. Basal testicular volume (hazard ratio, 1.13; 95% CI, 1.01-1.27) and peak LH levels (hazard ratio, 1.11; 95% CI, 1.0-1.23) were predictors for early sperm appearance. CONCLUSIONS: Pulsatile GnRH therapy can improve gonad function and induce spermatogenesis in men with PSIS. However, its efficacy may be inferior to that in CHH.


Asunto(s)
Hipogonadismo , Enfermedades de la Hipófisis , Hormona Folículo Estimulante , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Hipogonadismo/tratamiento farmacológico , Hormona Luteinizante , Masculino , Hipófisis , Estudios Retrospectivos , Síndrome , Testículo , Testosterona
6.
Endocr Pract ; 27(9): 934-940, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34000389

RESUMEN

OBJECTIVE: This retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH). METHODS: In the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD. RESULTS: Our cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05). CONCLUSION: Sex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.


Asunto(s)
Densidad Ósea , Testosterona , Adulto , Estudios Transversales , Hormonas Esteroides Gonadales , Humanos , Hipogonadismo , Estudios Longitudinales , Masculino , Estudios Retrospectivos
7.
Endocr Pract ; 27(11): 1119-1127, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33915281

RESUMEN

OBJECTIVE: Hypogonadotropic hypogonadism (HH) can be caused by congenital HH (CHH), pituitary stalk interruption syndrome (PSIS), and pituitary injury (acquired HH). Gonadotropin therapy, typically administered every other day or twice a week, is commonly used to promote spermatogenesis. The aim of this retrospective study was to evaluate the efficacy of weekly gonadotropin therapy on spermatogenesis in patients with HH (n = 160). METHODS: The patients' diagnoses include Kallmann syndrome (KS) (n = 61), normosmic CHH (nCHH) (n = 34), PSIS (n = 48), and acquired HH (n = 17). The rate of successful spermatogenesis and median time to achieve spermatogenesis among these 4 subgroups were compared as well as between a weekly group (n = 95) and a twice-a-week group (n = 223) of CHH patients. RESULTS: Once-a-week gonadotropin therapy resulted in 74% (119/160) of HH patients achieving spermatogenesis with significantly increased testicular volume and total testosterone levels (P < .001). The median period of spermatogenesis was 13 (interquartile range[IQR] 11.4-14.6) months. Larger basal testicular volume (P = .0142) was an independent predictor for earlier sperm appearance. Six spontaneous pregnancies occurred. Compared with the twice-a-week regimen for spermatogenesis, the weekly injection group had a similar median time of sperm appearance (14 [IQR, 11.6-16.4] vs 15 [IQR, 13.5-16.5] months), success rate (78% [74/95] vs 64% [143/223]), sperm concentration (20.9 [IQR, 5.0-46.3] vs 11.7 [IQR, 2.1-24.4] million/mL), and progressive sperm motility (40.8 ± 27.3% vs 36.9% ± 20.2%). CONCLUSION: Weekly gonadotropin therapy is effective in inducing spermatogenesis, similar to that of twice-a-week therapy. A larger basal testicular size was a favorable indicator for earlier spermatogenesis.


Asunto(s)
Gonadotropina Coriónica , Hipogonadismo , Femenino , Humanos , Hipogonadismo/tratamiento farmacológico , Masculino , Embarazo , Estudios Retrospectivos , Motilidad Espermática , Espermatogénesis , Testículo
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(3): 297-301, 2020 05 25.
Artículo en Zh | MEDLINE | ID: mdl-32762157

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD). METHODS: Clinical data of 12 male DSD children with a mean age of 14.6±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients were treated with letrozole (1.25-2.5 mg, once a day) for 3 months or longer, and followed up for 0.5-2.5 years. Clinical manifestation and laboratory test findings were documented, and the efficacy and safety were evaluated. RESULTS: After half-year treatment, the blood luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels of patients increased (all P < 0.05), and estrogen levels decreased from baseline ( P < 0.05). After 1 year of treatment, the blood testosterone level was significantly higher ( P < 0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease, but there was no significant statistical difference ( P>0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant changes in biochemical results after treatment, and no significant adverse event was observed during the treatment. CONCLUSIONS: Letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.


Asunto(s)
Trastornos del Desarrollo Sexual/tratamiento farmacológico , Letrozol/uso terapéutico , Adolescente , Niño , Hormona Folículo Estimulante , Humanos , Hormona Luteinizante , Masculino , Estudios Retrospectivos , Testosterona
9.
Curr Microbiol ; 76(10): 1161-1167, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31278426

RESUMEN

The haloalkane dehalogenase DhaA can degrade sulfur mustard (2,2'-dichlorethyl sulfide; also known by its military designation HD) in a rapid and environmentally safe manner. However, DhaA is sensitive to temperature and pH, which limits its applications in natural or harsh environments. Spore surface display technology using resistant spores as a carrier to ensure enzymatic activity can reduce production costs and extend the range of applications of DhaA. To this end, we cloned recombinant Bacillus subtilis spores pHY300PLK-cotg-dhaa-6his/DB104(FH01) for the delivery of DhaA from Rhodococcus rhodochrous NCIMB 13064. A dot blotting showed that the fusion protein CotG-linker-DhaA accounted for 0.41% ± 0.03% (P < 0.01) of total spore coat proteins. Immunofluorescence analyses confirmed that DhaA was displayed on the spore surface. The hydrolyzing activity of DhaA displayed on spores towards the HD analog 2-chloroethyl ethylsulfide was 1.74 ± 0.06 U/mL (P < 0.01), with a specific activity was 0.34 ± 0.04 U/mg (P < 0.01). This is the first demonstration that DhaA displayed on the surface of B. subtilis spores retains enzymatic activity, which suggests that it can be used effectively in real-world applications including bioremediation of contaminated environments.


Asunto(s)
Bacillus subtilis/enzimología , Proteínas Bacterianas/metabolismo , Hidrolasas/metabolismo , Esporas Bacterianas/enzimología , Bacillus subtilis/genética , Proteínas Bacterianas/genética , Estabilidad de Enzimas , Expresión Génica , Hidrolasas/genética , Gas Mostaza/análogos & derivados , Gas Mostaza/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Rhodococcus/enzimología , Rhodococcus/genética , Esporas Bacterianas/genética , Especificidad por Sustrato
10.
Clin Endocrinol (Oxf) ; 89(5): 613-620, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30103258

RESUMEN

OBJECTIVE: To analyze nuclear receptor subfamily 5 group A member 1 (NR5A1) gene mutations in a cohort of Chinese patients with 46, XY Disorders of Sex Development (DSD). METHODS: Sixty 46, XY DSD patients were recruited at Peking Union Medical College Hospital. Targeted next-generation and Sanger sequencing were performed to investigate pathogenic gene variants and validate NR5A1 gene variants, respectively. In silico tools and in vitro function studies were used to analyze the pathogenicity of rare variants. The clinical and endocrinological characteristics of patients with NR5A1 variants were retrospectively analyzed. RESULTS: A total of four novel and three recurrent NR5A1 variants were identified in seven 46, XY DSD patients. These variants widely spread almost all the functional domains. Functional studies showed that novel mutations including p.S32N, p.N44del and p.G91D reduced transactivation of CYP11A1, while the other missense variant p.A168E did not impact protein function. All patients with NR5A1 rare variants had normal adrenal function and showed genital defects. Results of the genitalia examination showed female external genitalia (three patients), ambiguous external genitalia (two patients), female external genitalia with clitoromegaly (one patient), and hypospadias (one patient). All seven patients had bilateral testis and five of seven patients lacked Müllerian structures. CONCLUSIONS: Four novel mutations in the NR5A1 gene were identified in our cohort with 46, XY DSD, expanding the spectrum of NR5A1 gene mutations. All patients with NR5A1 rare variants had normal adrenal function and showed genital defects.


Asunto(s)
Trastorno del Desarrollo Sexual 46,XY/genética , Factor Esteroidogénico 1/genética , Adolescente , Adulto , Pueblo Asiatico , Niño , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Mutación/genética , Mutación Missense/genética , Plásmidos/genética , Estudios Retrospectivos , Adulto Joven
11.
Sensors (Basel) ; 16(3): 308, 2016 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-26927130

RESUMEN

Using the multiple advantages of the ultra-highly sensitive electrochemiluminescence (ECL) technique, Staphylococcus protein A (SPA) functionalized gold-magnetic nanoparticles and phage displayed antibodies, and using gold-magnetic nanoparticles coated with SPA and coupled with a polyclonal antibody (pcAb) as magnetic capturing probes, and Ru(bpy)3(2+)-labeled phage displayed antibody as a specific luminescence probe, this study reports a new way to detect ricin with a highly sensitive and specific ECL immunosensor and amplify specific detection signals. The linear detection range of the sensor was 0.0001~200 µg/L, and the limit of detection (LOD) was 0.0001 µg/L, which is 2500-fold lower than that of the conventional ELISA technique. The gold-magnetic nanoparticles, SPA and Ru(bpy)3(2+)-labeled phage displayed antibody displayed different amplifying effects in the ECL immunosensor and can decrease LOD 3-fold, 3-fold and 20-fold, respectively, compared with the ECL immunosensors without one of the three effects. The integrated amplifying effect can decrease the LOD 180-fold. The immunosensor integrates the unique advantages of SPA-coated gold-magnetic nanoparticles that improve the activity of the functionalized capturing probe, and the amplifying effect of the Ru(bpy)3(2+)-labeled phage displayed antibodies, so it increases specificity, interference-resistance and decreases LOD. It is proven to be well suited for the analysis of trace amounts of ricin in various environmental samples with high recovery ratios and reproducibility.


Asunto(s)
Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Ricina/aislamiento & purificación , Proteína Estafilocócica A/química , Anticuerpos/química , Bacteriófagos/química , Oro/química , Luminiscencia , Nanopartículas de Magnetita/química
12.
Sensors (Basel) ; 15(2): 3896-910, 2015 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-25671509

RESUMEN

In this research, super-paramagnetic Fe3O4 nanoparticles (magnetic particles) were coated with Staphylococcus protein A (SPA) and coupled with polyclonal antibody (pcAb) to construct magnetic capturing probes, and HRP-conjugated phage antibody was then used as specific detecting probe to design a labeled immunosensor for trace detection of Staphylococcus aureus enterotoxin B (SEB). The linear detection range of the sensor was 0.008~125 µg/L, the regression equation was Y = 0.487X + 1.2 (R = 0.996, N = 15, p < 0.0001), the limit of detection (LOD) was 0.008 µg/L, and the limit of quantification (LOQ) was 0.008 µg/L. HRP-conjugated phage antibody, SPA and magnetic particles can enhance the sensitivity 4-fold, 3-fold and 2.6-fold higher, respectively. Compared with conventional double-antibody sandwich ELISA, the detection sensitivity of the sensor was 31-fold higher resulting from the integrated amplifying effect. The immunosensor integrates the unique advantages of SPA-oriented antibody as magnetic capturing probe, HRP-conjugated phage antibody as detecting probe, magnetic separation immunoassay technique, and several other advanced techniques, so it achieves high sensitivity, specificity and interference-resistance. It is proven to be well suited for analysis of trace SEB in various environmental samples with high recovery rate and reproducibility.


Asunto(s)
Técnicas Biosensibles , Enterotoxinas/aislamiento & purificación , Nanopartículas de Magnetita/química , Staphylococcus aureus/aislamiento & purificación , Anticuerpos/química , Anticuerpos/inmunología , Bacteriófagos/química , Enterotoxinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Oro/química , Humanos , Límite de Detección , Proteína Estafilocócica A/química , Staphylococcus aureus/inmunología
13.
J Hepatol ; 61(6): 1297-303, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25016226

RESUMEN

BACKGROUND & AIMS: Liver cancer has a very dismal prognosis due to lack of effective therapy. Here, we studied the therapeutic effects of hyper-interleukin15 (hyper-IL-15), which is composed of IL-15 and the sushi domain of the IL-15 receptor α chain, on metastatic and autochthonous liver cancers. METHODS: Liver metastatic tumour models were established by intraportally injecting syngeneic mice with murine CT26 colon carcinoma cells or B16-OVA melanoma cells. Primary hepatocellular carcinoma (HCC) was induced by diethylnitrosamine (DEN). A hydrodynamics-based gene delivery method was used to achieve sustained hyper-IL-15 expression in the liver. RESULTS: Liver gene delivery of hyper-IL-15 robustly expanded CD8(+) T and NK cells, leading to a long-term (more than 40 days) accumulation of CD8(+) T cells in vivo, especially in the liver. Hyper-IL-15 treatment exerted remarkable therapeutic effects on well-established liver metastatic tumours and even on DEN-induced autochthonous HCC, and these effects were abolished by depletion of CD8(+) T cells but not NK cells. Hyper-IL-15 triggered IL-12 and interferon-γ production and reduced the expression of co-inhibitory molecules on dendritic cells in the liver. Adoptive transfer of T cell receptor (TCR) transgenic OT-1 cells showed that hyper-IL-15 preferentially expanded tumour-specific CD8(+) T cells and promoted their interferon-γ synthesis and cytotoxicity. CONCLUSIONS: Liver delivery of hyper-IL-15 provides an effective therapy against well-established metastatic and autochthonous liver cancers in mouse models by preferentially expanding tumour-specific CD8(+) T cells and promoting their anti-tumour effects.


Asunto(s)
Linfocitos T CD8-positivos/patología , Proliferación Celular/efectos de los fármacos , Interleucina-15/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Neoplasias del Colon/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Interleucina-15/farmacología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/patología , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia/patología , Proteínas Recombinantes de Fusión/farmacología , Resultado del Tratamiento
14.
Rapid Commun Mass Spectrom ; 28(15): 1764-8, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-24975257

RESUMEN

RATIONALE: The pivotal challenge associated with miniature mass analyzers is their proper design and construction without sacrificing performance. In order to analyze and improve the performance of a miniature linear ion trap with odd and even multipole fields, we designed a novel asymmetrical arc-shaped electrode ion trap (AAEIT), and tested the properties of AAEITs with different dimensions. METHODS: A series of asymmetrical ion traps using arc-shaped electrodes were designed to optimize the properties (resolutions and intensity) of the coupling effects between odd and even multipole fields. Using arginine and reserpine, we evaluated the performance of mass resolution, ion intensity ratio and deduced the collision-induced dissociation (CID) efficiency using a self-constructed electrospray ionization mass spectrometry (ESI-MS) platform. RESULTS: An AAEIT with field radius dimensions of 5 mm × 5.75 mm exhibits a good performance: its maximum resolution of 833 (FWHM) at m/z 175 was achieved for the side of small electrode. With this AAEIT, a tandem mass (MS/MS) capability with 91.0% CID efficiency was obtained with reserpine (m/z 609). CONCLUSIONS: The results indicated that the AAEIT, comprising both odd and even multipole fields, could act as a qualified linear ion trap mass analyzer with compact structure, high resolution, and high tandem mass analysis efficiency. It has a great potential in miniature mass spectrometry.


Asunto(s)
Arginina/análisis , Microelectrodos , Reserpina/análisis , Espectrometría de Masa por Ionización de Electrospray/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Miniaturización
15.
Anal Sci ; 40(8): 1409-1419, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38687414

RESUMEN

Mustard gas, a representative of blister agents, poses a severe threat to human health. Although the structure of 2-chloroethyl ethyl sulfide (2-CEES) is similar to mustard gas, 2-CEES is non-toxic, rendering it a commonly employed simulant in related research. ZnFe2O4-based semiconductor gas sensors exhibit numerous advantages, including structural stability, high sensitivities, and easy miniaturization. However, they exhibit insufficient sensitivity at low concentrations and require high operating temperatures. Owing to the effect of electronic and chemical sensitization, the gas-sensing performance of a sensor may be remarkably enhanced via the sensitization method of noble metal loading. In this study, based on the morphologies of ZnFe2O4 hollow microspheres, a solvothermal method was adopted to realize different levels of Au loading. Toward 1 ppm of 2-CEES, the gas sensor based on 2 wt.% Au-loaded ZnFe2O4 hollow microspheres exhibited a response sensitivity twice that of the gas sensor based on pure ZnFe2O4; furthermore, the response/recovery times decreased. Additionally, the sensor displayed excellent linear response to low concentrations of 2-CEES, outstanding selectivity in the presence of several common volatile organic compounds, and good repeatability, as well as long-term stability. The Au-loaded ZnFe2O4-based sensor has considerable potential for use in detecting toxic chemical agents and their simulants.

16.
Endocrine ; 83(2): 488-493, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37749390

RESUMEN

PURPOSE: Kallmann syndrome is a rare disease characterized by delayed puberty, infertility and anosmia. We report the clinical and genetic characteristics of three patients with Kallmann syndrome who presented with Klinefelter syndrome and defined this neglected combined form of hypogonadism as mixed hypogonadism. METHODS: Clinical data and examinations were obtained, including laboratory examination and magnetic resonance imagination (MRI) of the olfactory structures. Congenital hypogonadotropic hypogonadism (CHH) related genes were screened by next generation sequencing (NGS). RESULTS: Three patients with Kallmann syndrome were included. They had co-existence with Klinefelter syndrome and showed hypogonadotropic hypogonadism. Patient 1 was complicated with germinoma. CONCLUSION: Mixed hypogonadism was defined as hypogonadotropic hypogonadism in Klinefelter syndrome or primary testicular disease. Clinicians should be alert to mixed hypogonadism when spermatogenesis induction failed in patients with CHH or gonadotropin levels decrease in patients with Klinefelter syndrome.


Asunto(s)
Hipogonadismo , Infertilidad , Síndrome de Kallmann , Síndrome de Klinefelter , Masculino , Humanos , Síndrome de Kallmann/complicaciones , Síndrome de Klinefelter/complicaciones , Hipogonadismo/etiología , Testículo
17.
Protein Pept Lett ; 30(11): 959-965, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37946356

RESUMEN

BACKGROUND: LinB, as a Haloalkane dehalogenase, has good catalytic activity for many highly toxic and recalcitrant compounds, and can realize the elimination of chemical weapons HD in a green non-toxic mode. OBJECTIVES: In order to display Haloalkane dehalogenase LinB on the surface of Bacillus subtilis spore. METHODS: We have constituted the B. subtilis spore surface display system of halogenated alkanes dehalogenase LinB by gene recombination. RESULTS: Data revealed that LinB can display on spore surface successfully. The hydrolyzing HD analogue 2-chloroethyl ethylsulfide (2-CEES) activity of displayed LinB spores was 4.30±0.09 U/mL, and its specific activity was 0.78±0.03U/mg. Meanwhile, LinB spores showed a stronger stress resistance activity on 2-CEES than free LinB. This study obtained B. subtilis spores of LinB (phingobium japonicum UT26) with enzyme activity that was not reported before. CONCLUSION: Spore surface display technology uses resistance spore as the carrier to guarantee LinB activity, enhances its stability, and reduces the production cost, thus expanding the range of its application.


Asunto(s)
Bacillus subtilis , Esporas Bacterianas , Bacillus subtilis/genética , Esporas Bacterianas/genética , Hidrolasas/genética , Hidrolasas/química , Proteínas Bacterianas/genética
18.
Anal Methods ; 15(25): 3084-3091, 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37326453

RESUMEN

Mustard gas, an erosive chemical agent, is primarily used as a chemical weapon, which seriously threatens human life and health. Therefore, detecting mustard gas and its simulant, 2-chloroethyl ethyl sulfide (2-CEES), is a very important task. As a binary metal oxide with a spinel structure, ZnFe2O4 is widely used for fabricating gas sensors because of its stable chemical structure and abundant oxygen vacancies. In this study, gas-sensing ZnFe2O4 microspheres with a hierarchical core-shell nanosheet structure were prepared via a simple one-step solvothermal method. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and N2 adsorption analyses were performed to characterize the morphology, structure, and chemical composition of these microspheres. A gas sensor was fabricated from the as-synthesized material, and its gas sensing performance was evaluated, using 2-CEES as a target gas. The obtained ZnFe2O4-based sensor exhibited a high sensitivity of 9.07 to 1 ppm 2-CEES at the optimal working temperature of 250 °C. The sensor response and recovery times were 18 and 546 s, respectively, and its detection sensitivity of 2.87 achieved at a 2-CEES concentration of 0.01 ppm was within an acceptable range. Additionally, the sensor demonstrated sufficiently high 2-CEES selectivity, repeatability, and long-term stability.

19.
Minerva Surg ; 77(3): 221-228, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34160177

RESUMEN

BACKGROUND: The anatomical structure of pulmonary segments is complex, and there are many anatomical variations, making the operation more difficult, so we used Mimics Medical 21.0 software for three-dimensional computed tomography bronchography and angiography (3D-CTBA), carefully formulated the surgical plan and on this basis completed the video-assisted thoracoscopic anatomical sublobectomy. METHODS: A total of 38 patients with pulmonary nodules were selected and received video-assisted thoracoscopic anatomical sublobectomy after using Mimics Medica 21.0 software for 3D-CTBA. RESULTS: The mean operative duration was 158.42±20.21 minutes, and the operative hemorrhage was 97.66±22.37 mL. In pathological diagnoses, there were 5 benign cases (13.2%), 9 cases with atypical adenomatous hyperplasia (23.7%), 12 cases with adenocarcinoma in situ (31.6%), 11 cases with minimally invasive adenocarcinoma (28.9%) and 1 case with invasive adenocarcinoma (2.6%); 8.29±0.98 lymph nodes sampled had no metastasis. The chest tube drainage duration and postoperative hospital stay were 2.47±0.73 days and 5.47±0.73 days, respectively. CONCLUSIONS: Using Mimics Medical 21.0 software can quickly and accurately complete 3D-CTBA, which is beneficial to formulate a personalized anatomical sublobectomy surgical plan.


Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagen , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neumonectomía/métodos , Estudios Retrospectivos , Programas Informáticos , Cirugía Torácica Asistida por Video/métodos
20.
Front Endocrinol (Lausanne) ; 13: 868047, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35528001

RESUMEN

Background: Gonadotropins are effective in inducing spermatogenesis in patients with congenital combined pituitary hormone deficiency (CCPHD). Data on recombinant human growth hormone(rhGH) adjuvant treatment to improve gonadotropin-induced spermatogenesis are limited. Design and Setting: This retrospective study included 60 male patients with CCPHD on a relatively large case series in a single center from mainland China. Twenty-nine patients who received gonadotropin therapy alone were defined as the Gn group, while 31 patients treated with a combination of rhGH and gonadotropins were defined as GH/Gn group. Results: Spermatogenesis rate was 96.77% (30/31) and 62.07% (18/29) in the GH/Gn and Gn group, respectively (P < 0.001). The time for initial sperm appearance in the GH/Gn group was shorter than in the Gn group (14 versus 23 months, P < 0.001). A higher level of serum testosterone was achieved in the GH/Gn group than in the Gn group (4.79 versus 3.38 ng/mL, P = 0.026). After adjustment for potential confounders, rhGH supplementation was an independent beneficial factor on spermatogenesis (HR = 2.294, 95% CI: 1.143-4.604, P = 0.019). Conclusions: rhGH induces earlier spermatogenesis in patients with CCPHD, which encourages the co-treatment with rhGH and gonadotropins in CCPHD patients.


Asunto(s)
Hormona de Crecimiento Humana , Hipopituitarismo , Espermatogénesis , Adulto , Gonadotropinas/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hipopituitarismo/tratamiento farmacológico , Masculino , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Testosterona
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