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1.
Clin Transl Med ; 14(8): e1793, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39113232

RESUMEN

INTRODUCTION: Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. OBJECTIVES: N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. METHODS AND RESULTS: This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi-omics analysis revealed that HSC-specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split-1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%-62% and protein levels to 28%-35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%-38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. CONCLUSION: These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. KEY POINTS/HIGHLIGHTS: IGF2BP3 deficiency inactivates Jag1 signalling. IGF2BP3 deficiency-mediated m6A modifications promote HSC ferroptosis. IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis. IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis.


Asunto(s)
Ferroptosis , Células Estrelladas Hepáticas , Proteína Jagged-1 , Cirrosis Hepática , Proteínas de Unión al ARN , Receptores Notch , Transducción de Señal , Ferroptosis/genética , Células Estrelladas Hepáticas/metabolismo , Animales , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Ratones , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Transducción de Señal/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Ratones Noqueados , Masculino , Humanos
2.
BMC Med Imaging ; 24(1): 215, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143526

RESUMEN

BACKGROUND: Due to the increasing incidence of ischaemic cerebrovascular diseases, the accurate assessment of internal carotid artery (ICA) stenosis is crucial for the development of treatment plans. This systematic review and meta-analysis aimed to evaluate the diagnostic value of computed tomography angiography (CTA) for severe ICAstenosis, thereby providing support for clinical decision-making and promoting diagnostic updates. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical Literature (CBM) electronic databases were searched from inception to March 21, 2024, to identify publicly available research literature on the use of CTA to diagnose severe ICA stenosis. Literature screening, data extraction, and quality assessment were conducted based on the inclusion and exclusion criteria as well as the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) standards. Data analysis was performed using Stata 17.0 and Meta-Disc 1.4 software. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the included studies were calculated using Stata 17.0 software, and forest plots and summary receiver operating characteristic (SROC) curves were generated. The area under the curve (AUC) was calculated, and funnel plots were constructed to assess publication bias. RESULTS: A total of 16 studies with 2368 vascular segments were included. The meta-analysis revealed that the combined sensitivity and specificity of CTA for severe ICA stenosis were 0.93 (95% CI: 0.88 ~ 0.96) and 0.99 (95% CI: 0.96 ~ 1.00), respectively. The combined positive likelihood ratio and negative likelihood ratio were 92.0 (95% CI: 24.2 ~ 349.6) and 0.07 (95% CI: 0.04 ~ 0.13), respectively. The diagnostic odds ratio was 1302 (95% CI: 257 ~ 6606), and the AUC of the SROC curve was 0.98. The Deeks funnel plot suggested no publication bias among the included studies. CONCLUSION: CTA demonstrated high sensitivity and specificity for diagnosing severe ICA stenosis. Therefore, this study provided important evidence for the accurate diagnosis and treatment of severe ICA stenosis. However, there was considerable heterogeneity among the included studies, thus indicating the need for additional high-quality prospective studies to confirm the clinical applicability of CTA.


Asunto(s)
Arteria Carótida Interna , Estenosis Carotídea , Angiografía por Tomografía Computarizada , Sensibilidad y Especificidad , Humanos , Estenosis Carotídea/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Arteria Carótida Interna/diagnóstico por imagen , Curva ROC , Índice de Severidad de la Enfermedad
3.
Gynecol Endocrinol ; 40(1): 2381504, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39034637

RESUMEN

Endometriosis is a common gynecological condition in women of childbearing age that causes symptoms such as menstrual changes and dysmenorrhea, and is also a major cause of infertility. Therefore, women with endometriosis usually need to use assisted reproductive technology (ART), such as in vitro fertilization or intracytoplasmic sperm injection, to increase their chances of conceiving. Numerous clinical observations and studies have indicated that endometriosis can affect the success of ART, such that women with endometriosis who use ART have a lower live-birth rate than those without endometriosis who use ART. Therefore, this article reviews the impact of various controlled ovarian hyperstimulation protocols and surgery on the pregnancy outcomes of women with endometriosis using ART to explore the selection of individualized treatment.


Asunto(s)
Endometriosis , Infertilidad Femenina , Inducción de la Ovulación , Resultado del Embarazo , Humanos , Femenino , Embarazo , Endometriosis/cirugía , Endometriosis/complicaciones , Inducción de la Ovulación/métodos , Infertilidad Femenina/terapia , Infertilidad Femenina/etiología , Índice de Embarazo , Técnicas Reproductivas Asistidas , Fertilización In Vitro/métodos
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 763-767, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38926964

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of daratumumab on stem cell collection and engraftment. METHODS: The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis. RESULTS: All 43 RRMM patients were treated with daratumumab-based combination regimens, including Dd, DVd, DRd, Dkd, DId, and Dara-DECP. With median follow-up time 10.1 (2.1-36.6) months, the best overall response rate (ORR) was 74.4% and a best complete response rate (CR) was 25.6%. 1-year overall survival rate (OS) was 84.5%. The most common severe hematologic adverse events (Grade>3) are 3/4 grade leukopenia(18.6%), and the most common severe non-hematologic adverse events were infusion-related reactions (IRRs, 20.9%) and infections(7.0%). Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS (P =0.004). The use of daratumumab has no effect on stem cell collection, or engraftment. CONCLUSION: Daratumumab is safe and effective in RRMM.


Asunto(s)
Anticuerpos Monoclonales , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento
5.
J Craniofac Surg ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38838369

RESUMEN

Autologous adipose tissue was recognized as a promising therapeutic option for soft tissue defects owing to its regenerative potential and ability to facilitate tissue reconstruction. However, the mechanisms by which autologous fat grafting (AFG) promotes healing remain unclear, hindering its potential applications. This study aimed to investigate the distribution and phenotypic transition of infiltrating macrophages in transplanted adipose tissue, as well as their correlation with diabetic skin defect remodeling. Streptozotocin-induced diabetic rats with full-thickness dorsal skin defects were included in this study. The transplanted adipose tissue at the skin defects was collected and analyzed using flow cytometry to determine macrophage proportion and phenotype. The healing of skin defects was evaluated, and treatment was continued until day 14 as the designated endpoint of healing, followed by histopathologic examinations. Immunostaining with CD31 and lymphatic vessel endothelial receptor-1 was performed on wound tissues to analyze angiogenesis and lymphangiogenesis, respectively. Western blot and quantitative polymerase chain reaction analyses were used to assess the expression of the representative genes involved in the healing process. The results showed early polarization of M2 macrophages in the transplanted adipose tissue, concomitant with the upregulation of growth factors and downregulation of inflammatory factors. In vivo experiments revealed that AFG significantly promoted macrophage infiltration and M2 transformation in diabetic skin defects compared to the control groups, thereby promoting tissue extracellular matrix remodeling and lymphatic and vascular regeneration. However, the beneficial effects of AFG were inhibited by macrophage depletion. This study further demonstrated the potential of AFG for treating diabetic skin defects.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 293-296, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38686728

RESUMEN

Hereditary protein C deficiency is a chromosomal genetic disease caused by mutations in the protein C gene,which can lead to venous thrombosis and is mostly related to mutations in exons 4-9 and intron 8.Fatal pulmonary embolism caused by mutations in the protein C gene is rare,and the treatment faces great challenges.This article reports a case of fatal pulmonary embolism caused by a frameshift mutation in exon 8 of the protein C gene and summarizes the treatment experience of combining extracorporeal membrane oxygenation (for respiratory and circulatory support) with interventional thrombectomy,providing a basis for the diagnosis and treatment of this disease.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Deficiencia de Proteína C , Embolia Pulmonar , Trombectomía , Humanos , Masculino , Oxigenación por Membrana Extracorpórea/métodos , Mutación del Sistema de Lectura , Deficiencia de Proteína C/complicaciones , Embolia Pulmonar/terapia , Embolia Pulmonar/etiología , Trombectomía/métodos , Persona de Mediana Edad
7.
Int J Pharm ; 654: 123991, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38471578

RESUMEN

The degradation of peptide drugs limits the application of peptide drug microspheres. Structural changes of peptides at the water-oil interface and the destruction of their spatial structure in the complex microenvironment during polymer degradation can affect drug release and in vivo biological activity. This study demonstrates that adding hydroxyethyl starch (HES) to the internal aqueous phase (W1) significantly enhances the stability of semaglutide and optimizes its release behavior in PLGA microspheres. The results showed that this improvement was due to a spontaneous exothermic reaction (ΔH = -132.20 kJ mol-1) facilitated by hydrogen bonds. Incorporating HES into the internal aqueous phase using the water-in-oil-in-water (W1/O/W2) emulsion method yielded PLGA microspheres with a high encapsulation rate of 94.38 %. Moreover, microspheres with HES demonstrated well-controlled drug release over 44 days, unlike the slower and incomplete release in microspheres without HES. The optimized h-MG2 formulation achieved a more complete drug release (83.23 %) and prevented 30.65 % of drug loss compared to the HES-free microspheres within the same period. Additionally, the optimized semaglutide microspheres provided nearly three weeks of glycemic control with adequate safety. In conclusion, adding HES to the internal aqueous phase improved the in-situ drug stability and release behavior of semaglutide-loaded PLGA microspheres, effectively increasing the peptide drug payload in PLGA microspheres.


Asunto(s)
Péptidos Similares al Glucagón , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Láctico/química , Ácido Poliglicólico/química , Estabilidad de Medicamentos , Microesferas , Composición de Medicamentos/métodos , Tamaño de la Partícula , Péptidos , Agua , Almidón/química
8.
J Craniofac Surg ; 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38315768

RESUMEN

BACKGROUND: The mentalis muscle is a significant component of the lower lip; its injury could impair appearance and function. This study presents a surgical strategy for treating mentalis muscle rupture to restore muscle tension and improve function. METHODS: Medical records and photographs of 2 patients with mentalis muscle rupture were reviewed. After physical examinations, 3-dimensional computed topographies were conducted to evaluate chin appearance further. The surgical strategy was designed according to individual malformations and requests. RESULTS: Both patients injured their mentalis muscles in childhood and presented to our clinic with a concave deformity at the center of the chin and impaired mentalis muscle function. The surgical procedure involved the reconstruction of the mentalis muscle by reassembling the muscle flaps and releasing the scarred soft tissue. Both patients were satisfied with the outcome. CONCLUSIONS: Mentalis muscle rupture requires surgical correction. The study proposes an innovative approach that enables patients to achieve a more harmonious appearance and improve function.

9.
Oncogene ; 43(12): 839-850, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38355808

RESUMEN

Medulloblastoma is one of the most common malignant pediatric brain tumors derived from posterior fossa. The current treatment includes maximal safe surgical resection, radiotherapy, whole cranio-spinal radiation and adjuvant with chemotherapy. However, it can only limitedly prolong the survival time with severe side effects and relapse. Defining the intratumoral heterogeneity, cellular origin and identifying the interaction network within tumor microenvironment are helpful for understanding the mechanisms of medulloblastoma tumorigenesis and relapse. Due to technological limitations, the mechanisms of cellular heterogeneity and tumor origin have not been fully understood. Recently, the emergence of single-cell technology has provided a powerful tool for achieving the goal of understanding the mechanisms of tumorigenesis. Several studies have demonstrated the intratumoral heterogeneity and tumor origin for each subtype of medulloblastoma utilizing the single-cell RNA-seq, which has not been uncovered before using conventional technologies. In this review, we present an overview of the current progress in understanding of cellular heterogeneity and tumor origin of medulloblastoma and discuss novel findings in the age of single-cell technologies.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Cerebelosas , Meduloblastoma , Niño , Humanos , Meduloblastoma/genética , Meduloblastoma/terapia , Meduloblastoma/patología , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/terapia , Neoplasias Cerebelosas/patología , Recurrencia Local de Neoplasia , Neoplasias Encefálicas/patología , Recurrencia , Carcinogénesis , Microambiente Tumoral/genética
10.
Br J Cancer ; 130(5): 852-860, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38212482

RESUMEN

BACKGROUND: Cyclin-dependent kinase 6 (CDK6) was proved to be an important regulator in the progression of cell cycle and has been a promising therapeutic target in cancer treatment. However, the clinical significance of CDK6 in muscle-invasive bladder cancer (MIBC) remains obscure. Herein, we attempt to explore the clinical relevance of CDK6 and assess the feasibility of the integrative model to predict immune checkpoint blockade (ICB) response. METHODS: This study enrolled 933 patients with muscle-invasive bladder cancer (MIBC) from Zhongshan Hospital (ZSHS), The Cancer Genome Atlas (TCGA), Chemo, IMvigor210 and UC-GENOME cohorts. Kaplan-Meier survival and Cox regression analyses were performed to assess clinical outcomes based on CDK6 expression. RESULTS: High CDK6 expression conferred poor prognosis and superior response to platinum-based chemotherapy but inferior response to ICB in MIBC. Furthermore, the integrative model named response score based on CDK6, PD-L1 and TMB could better predict the response to ICB and chemotherapy. Patients with higher response scores were characterised by inflamed immune microenvironment and genomic instability. CONCLUSIONS: CDK6 expression was correlated with prognosis and therapy response in MIBC. Integration of CDK6, PD-L1 and TMB could better identify patients who were most likely to benefit from ICB and chemotherapy.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias de la Vejiga Urinaria , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/uso terapéutico , Platino (Metal)/uso terapéutico , Antígeno B7-H1 , Quinasa 6 Dependiente de la Ciclina/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Músculos/metabolismo , Microambiente Tumoral
12.
Urol Oncol ; 41(10): 433.e9-433.e18, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37625906

RESUMEN

BACKGROUND: Muscle-invasive bladder cancer (MIBC) patients have benefitted greatly from immune checkpoint blockade (ICB) therapy. However, there is a pressing need to identify factors underlying the heterogeneity of clinical responses to ICB. METHODS: We conducted a study on 848 MIBC patients from 4 independent cohorts to investigate the key biological characteristics affecting ICB responses. The IMvigor210 cohort (n = 234) was used to identify the key factor, followed by exploration of the correlation between tumor angiogenesis and immune suppression in the IMvigor210, TCGA (n = 391), and UNC-108 (n = 89) cohorts. The ZSHS cohort (n = 134) was used for validation. Additionally, we integrated angiogenesis signature with tumor mutation burden (TMB) to decipher the heterogeneity of clinical outcomes to ICB in MIBC patients. RESULTS: Our analysis revealed that nonresponders to PD-L1 blockade were enriched with angiogenesis signature. Furthermore, we observed a correlation between angiogenesis signature and decreased neoantigen load, downregulated T-cell antigen recognition, and noninflamed immunophenotype. We identified a subgroup of patients resistant to ICB, characterized by high angiogenesis signature and low tumor mutation burden (TMB), and found the activation of TGF-ß signaling and downregulation of T-cell cytolytic signatures in this subgroup. CONCLUSIONS: The study concluded that angiogenesis signature is closely associated with an immunosuppressive microenvironment, leading to resistance to ICB therapy in MIBC patients. The study further suggested that the combination of angiogenesis signature and TMB can serve as an integrated biomarker for better stratification of patients' clinical outcomes to ICB therapy.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias de la Vejiga Urinaria , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Muerte Celular , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Mutación , Músculos , Biomarcadores de Tumor/genética , Microambiente Tumoral
13.
Science ; 381(6656): eadf3363, 2023 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-37499010

RESUMEN

He et al. dispute our anatomical interpretations on the structures of cellular chambers and microfibrils in yunnanozoan branchial arches and put forward alternative interpretations on these structures. Zhang and Pratt argue that the microfibrils we identified in yunnanozoans are more likely modern organic contamination. Here we provide additional evidence to support our interpretations and dismiss the alternative interpretations.


Asunto(s)
Faringe , Vertebrados , Animales
14.
BMC Cancer ; 23(1): 661, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452272

RESUMEN

BACKGROUND: V domain Immunoglobulin suppressor of T cell activation (VISTA) has been proved to be a novel immune checkpoint molecule that positively regulates T cell infiltration in several malignancies. However, the clinical impact of VISTA on muscle-invasive bladder cancer (MIBC) patients remains relatively obscure. METHODS: This study enrolled 135 MIBC patients from Zhongshan Hospital (ZSHS) and 391 patients from The Cancer Genome Atlas (TCGA) to examine the VISTA expression and immune contexture based on immunohistochemistry (IHC) staining and CIBERSORT algorithm. Additionally, IMvigor210 Cohort included 195 bladder-derived urothelial carcinoma patients to evaluate the efficacy of immunotherapy. Kaplan-Meier curve and Cox regression analyses were conducted to assess clinical outcomes. RESULTS: MIBC patients with high VISTA+ immune cells (ICs) possessed poor overall survival and inferior therapeutic responsiveness to adjuvant chemotherapy (ACT), but superior responsiveness to PD-L1 inhibitor. VISTA+ ICs infiltration shaped an immunoevasive context featured by regulatory T cells (Tregs), M2 macrophages, mast cells and exhausted CD8+ T cells infiltration, with increased interleukin 10 (IL-10), transforming growth factor-ß (TGF-ß) and interferon-γ (IFN-γ), but also elevated T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and ITIM domain (TIGIT), which was also mainly presented in basal-squamous and luminal-infiltrated subtypes of MIBC. CONCLUSION: VISTA+ ICs infiltration could be an independent predictor to identify poor prognosis and therapeutic responses (PD-L1 blockade and ACT) in MIBC patients, which was associated with immunoevasive contexture. The novel immune checkpoint VISTA might be utilized as a candidate treatment biomarker in MIBC patients.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Pronóstico , Linfocitos T CD8-positivos , Carcinoma de Células Transicionales/patología , Activación de Linfocitos , Músculos/patología , Microambiente Tumoral
15.
Int Immunopharmacol ; 121: 110515, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37379706

RESUMEN

BACKGROUND: BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It can cause morbidity and may increase treatment-related mortality. Previous studies showed that the occurrence of BKV-HC was related to various factors. However, there are still many controversial factors. It is not clear whether BKV-HC will affect the long-term prognosis of patients. OBJECTIVE: We aimed to identify risk factors for BKV-HC after allo-HSCT and evaluate the effect of BKV-HC on overall survival (OS) and progression- free survival (PFS) of patients. STUDY DESIGN: We retrospectively analyzed the clinical data of 93 patients who underwent allo-HSCT. Univariate and multivariate analysis were used to identify risk factors for BKV-HC. The Kaplan-Meier method was used to estimate OS and PFS. A difference was considered statistically significant if P < 0.05. RESULTS: A total of 24 patients developed BKV-HC. The median occurrence time of BKV-HC was 30 (range:8-89) days after transplantation, and the median duration was 25.5 (range:6-50) days. Multivariate logistic regression analysis indicated that peripheral blood lymphocyte count <1 × 109/L before conditioning (OR = 4.705, P = 0.007) and haploidentical transplantation (OR = 13.161, P = 0.018) were independent risk factors for BKV-HC. The 3-year OS rate was 85.9% (95%CI:62.1%-95.2%) in the BKV-HC group and 73.1% (95%CI: 58.2%-88.0%) in the non-BKV-HC group. There was no significant difference between the two groups (P = 0.516). The 3-year PFS rate was 76.3% (95%CI: 57.9%-94.7%) in the BKV-HC group and 58.1% (95%CI: 39.5%-76.7%) in the non-BKV-HC group. There was no significant difference in the two groups (P = 0.459). The severity of BKV-HC was not related to the OS and PFS of the patients (P value was 0.816 and 0.501, respectively). CONCLUSION: Haploidentical transplantation and decreased peripheral blood lymphocyte count before conditioning increased the risk of BKV-HC after allo-HSCT. The occurrence of BKV-HC after allo-HSCT and the severity of which did not affect OS and PFS of the patients.


Asunto(s)
Virus BK , Cistitis , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia , Factores de Riesgo , Acondicionamiento Pretrasplante/efectos adversos
16.
Ecotoxicol Environ Saf ; 256: 114889, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37079940

RESUMEN

Heat stress (HS) triggers mammary gland degradation, accompanied by apoptosis and autophagy in bovine mammary epithelial cells, negatively affecting milk performance and mammary gland health. Ferroptosis is iron-mediated regulated cell death caused by over production of lipid peroxides, however, the relationship between ferroptosis and HS in bovine mammary epithelial cells has not been clarified. Methionine (Met) plays a notable role in alleviating HS affecting the mammary glands in dairy cows, but the underlying mechanisms require further exploration. Therefore, we evaluated the regulatory effect and mechanism of Met in alleviating HS-induced ferroptosis by using bovine mammary epithelial cell line (MAC-T) as an in vitro model. The results showed that Met improved cell vitality, restored mitochondrial function; reduced the content of various reactive oxygen species (ROS), especially hydrogen peroxide (H2O2) and superoxide anion (O2·-); had positive effects on antioxidant enzyme activity, namely glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). More importantly, Met reduced labile iron protein (LIP) levels; increased iron storage and simultaneously decreased the levels of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA), which all caused by HS in MAC-T. Mechanistically, Met increased the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7, member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1) by activating nuclear factor E2-related factor 2 (Nrf2) expression. Additionally, the protection effect of Met was cut off in MAC-T cells after interference with Nrf2, manifesting in decresing the protein expression levels of GPX4, SLC7A11 and FTH1,and increasing the levels of LIP and lipid ROS. Our findings indicate that Met eases HS-induced ferroptosis in MAC-T through the Nrf2 pathway, revealing that Met produces a marked effect on easing HS-induced bovine mammary gland injury in dairy cows.


Asunto(s)
Ferroptosis , Femenino , Bovinos , Animales , Especies Reactivas de Oxígeno/metabolismo , Metionina/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Peróxido de Hidrógeno/metabolismo , Antioxidantes/metabolismo , Células Epiteliales , Racemetionina/metabolismo , Racemetionina/farmacología , Respuesta al Choque Térmico , Hierro/metabolismo , Lípidos
17.
J Microbiol Biotechnol ; 33(6): 831-839, 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-36994618

RESUMEN

Tylosin is a potent veterinary macrolide antibiotic produced by the fermentation of Streptomyces fradiae; however, it is necessary to modify S. fradiae strains to improve tylosin production. In this study, we established a high-throughput, 24-well plate screening method for identifying S. fradiae strains that produce increased yields of tylosin. Additionally, we constructed mutant libraries of S. fradiae via ultraviolet (UV) irradiation and/or sodium nitrite mutagenesis. A primary screening of the libraries in 24-well plates and UV spectrophotometry identified S. fradiae mutants producing increased yields of tylosin. Mutants with tylosin yield 10% higher than the wild-type strain were inoculated into shake flasks, and the tylosin concentrations produced were determined by high-performance liquid chromatography (HPLC). Joint (UV irradiation and sodium nitrite) mutagenesis resulted in higher yields of mutants with enhanced tylosin production. Finally, 10 mutants showing higher tylosin yield were re-screened in shake flasks. The yield of tylosin A by strains UN-C183 (6767.64 ± 82.43 µg/ml) and UN-C137 (6889.72 ± 70.25 µg/ml) was significantly higher than that of the wild-type strain (6617.99 ± 22.67 µg/ml). These mutant strains will form the basis for further strain breeding in tylosin production.


Asunto(s)
Nitrito de Sodio , Tilosina , Mutagénesis , Antibacterianos
18.
Curr Med Sci ; 43(2): 324-328, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36892787

RESUMEN

OBJECTIVE: This study aimed to investigate the effect of penile selective dorsal neurectomy (SDN) on erectile function in rats. METHODS: Twelve adult male Sprague-Dawley rats (15 weeks old) were divided into three groups (n=4 per group): in control group, rats received no treatment; in sham group, rats underwent a sham operation; in SDN group, rats underwent SDN with half of the dorsal penile nerve severed. The mating test was performed, and the intracavernous pressure (ICP) assessed six weeks after the surgical treatment. RESULTS: At postoperative six weeks, the mating test revealed no significant difference in mounting latency and mounting frequency among the three groups (P>0.05), while the ejaculation latency (EL) was significantly longer and ejaculation frequency (EF) lower in the SDN group than in the control and sham groups (P<0.05). There were no significant differences in preoperative and postoperative ICP and ICP/mean arterial blood pressure (MAP) among the three groups (P>0.05). CONCLUSION: SDN does not adversely affect the erectile function and sexual desire of rats, and at the same time it can reduce EL and EF, providing an application basis for SDN in the clinical treatment of premature ejaculation.


Asunto(s)
Disfunción Eréctil , Humanos , Ratas , Masculino , Animales , Disfunción Eréctil/etiología , Disfunción Eréctil/cirugía , Disfunción Eréctil/tratamiento farmacológico , Ratas Sprague-Dawley , Erección Peniana/fisiología , Pene/cirugía , Pene/inervación , Desnervación
19.
Food Chem Toxicol ; 174: 113683, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36809826

RESUMEN

Inflammation is an important part of the development of various organ diseases. The inflammasome, as an innate immune receptor, plays an important role in the formation of inflammation. Among various inflammasomes, the NLRP3 inflammasome is the most well studied. The NLRP3 inflammasome is composed of skeletal protein NLRP3, apoptosis-associated speck-like protein (ASC) and pro-caspase-1. There are three types of activation pathways: (1) "classical" activation pathway; (2) "non-canonical" activation pathway; (3) "alternative" activation pathway. The activation of NLRP3 inflammasome is involved in many inflammatory diseases. A variety of factors (such as genetic factors, environmental factors, chemical factors, viral infection, etc.) have been proved to activate NLRP3 inflammasome and promote the inflammatory response of the lung, heart, liver, kidney and other organs in the body. Especially, the mechanism of NLRP3 inflammation and its related molecules in its associated diseases remains not to be summarized, namely they may promote or delay inflammatory diseases in different cells and tissues. This article reviews the structure and function of the NLRP3 inflammasome and its role in various inflammations, including inflammations caused by chemically toxic substances.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Inflamasomas/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamación , Apoptosis , Caspasa 1/genética , Interleucina-1beta/metabolismo
20.
HLA ; 101(5): 525-527, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36479606

RESUMEN

HLA-A*24:02:160 differs from HLA-A*24:02:01:01 by one nucleotide in exon 3.


Asunto(s)
Pueblos del Este de Asia , Nucleótidos , Humanos , Alelos , Análisis de Secuencia de ADN
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