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1.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 592-597, 2024 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-38825905

RESUMEN

Objective: To investigate the expression of DARS2 and its clinical significance in colorectal cancer. Methods: In this study, bioinformatics tools, especially gene expression profile interactive analysis 2 (GEPIA2), were used to conduct an in-depth analysis of DARS2 expression in colorectal cancer tissues. Immunohistochemical staining was carried out in 108 colorectal cancer specimens and 30 normal colorectal tissues obtained from the First Affiliated Hospital of Nanchang University, Nanchang, China. Colorectal cancer cell lines (HCT116 and SW480) were transfected with small interfering RNA (siRNA) and DARS2 overexpression plasmid to examine the effects of DARS2 knockdown and overexpression on cell function. To assess the effects on cell function, CCK8 and transwell migration assays were used to assess proliferation and cell motility, respectively. Additionally, protein immunoblotting was employed to scrutinize the expression of proteins associated with the epithelial-mesenchymal transition of colorectal cancer cells. Results: DARS2 exhibited a pronounced upregulation in expression within colorectal cancer tissues compared to their normal epithelial counterparts. Furthermore, DARS2 expression was higher in colorectal cancer of stage Ⅲ-Ⅳ than those of stage Ⅰ-Ⅱ, exhibiting a significant correlation with N staging, M staging, and pathological staging (P<0.05). Kaplan-Meier analyses showed a decreased overall survival rate in colorectal cancer with DARS2 expression compared to those without DARS2 expression (P<0.05). In the siRNA transfection group, there was a significant reduction in cell proliferation and migration (P<0.01 and P<0.05, respectively). Conversely, the transfection of DARS2 overexpression plasmids substantially increased both cell proliferation and migration (P<0.05). Additionally, immunoblotting revealed that DARS2 knockdown led to an upregulation of E-cadherin expression and a downregulation of N-cadherin and vimentin expression. In contrast, DARS2 overexpression resulted in increased N-cadherin and vimentin expression, coupled with reduction in E-cadherin expression. Conclusions: There is a strong association between DARS2 expression and colorectal cancer progression. Silencing DARS2 inhibits cell proliferation and migration, exerting a discernible influence on the epithelial-mesenchymal transition process.


Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , ARN Interferente Pequeño , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , ARN Interferente Pequeño/genética , Línea Celular Tumoral , Vimentina/metabolismo , Vimentina/genética , Cadherinas/metabolismo , Cadherinas/genética , Tasa de Supervivencia , Células HCT116 , Estadificación de Neoplasias , Regulación hacia Arriba , Regulación Neoplásica de la Expresión Génica , Relevancia Clínica
2.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(2): 215-218, 2024 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-38857969

RESUMEN

This case report summarizes the experience from diagnosis and treatment of a patient with repeated high fever, hepatosplenomegaly and pancytopenia. Following exclusion of bacterial, viral, fungal infections and hematological diseases, metagenomic next-generation sequencing of the patient's peripheral blood revealed Leishmania infantum infection, and rK39 rapid diagnostic test showed positive for anti-Leishmania antibody, while microscopic examination of bone marrow smears identified Leishmania amastigotes. Therefore, the case was definitively diagnosed as visceral leishmaniasis, and given anti-infective treatment with sodium antimony gluconate and hormone, hepatoprotection, elevation of white blood cell counts and personalized nursing. Then, the case was cured and discharged from hospital. Metagenomic next-generation sequencing is of great value in etiological detection of fever patients with unknown causes, which deserves widespread clinical applications.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Leishmaniasis Visceral , Humanos , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/parasitología , Masculino , Metagenómica/métodos , Adulto , Persona de Mediana Edad
3.
Sci Total Environ ; 934: 173139, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744394

RESUMEN

The global surge in pharmaceutical consumption, driven by increasing population and the demand for animal proteins, leads to the discharge of diverse pollutants, including antibiotic residues, into water bodies. Sulfonamides, being water-soluble compounds, can readily enter surface run-off, posing potential risks to non-target species despite their low environmental concentrations. Latin America has implemented intensive production systems highly dependent on antimicrobials for productivity and animal health, yet there is a paucity of information regarding their concentration in the region. The objective of this study was to evaluate the presence of sulfonamides in water and sediment samples and assess their potential ecological risks through an environmental risk assessment. The Río de la Plata basin collects the waters of the Paraguay, Paraná, and Uruguay rivers, together with their tributaries and various wetlands, passing through the provinces in Argentina known for their significant animal husbandry production. Two sampling campaigns were carried out for sediment, while only one campaign was conducted for surface waters. The samples were analyzed by high performance liquid chromatography tandem mass-spectrometry (HPLC-MS/MS). None of the examined sulfonamide antibiotics were detected in the sediment samples from both sampling campaigns. In contrast, sulfadiazine (95 %), sulfamethoxazole (91 %), and sulfathiazole (73 %) were detected in the water samples. Sulfadiazine was found in the concentration range of 8 to 128 ng/L, while sulfamethoxazole and sulfathiazole were observed at concentrations ranging from 3.0 to 32.5 ng/L and 2.9 to 8.1 ng/L, respectively. Based on the environmental risk assessment conducted using the sulfonamide concentrations, most samples indicated a medium risk for aquatic biota, with only one sample surpassing the high-risk threshold. This study represents the first report presenting data on the presence of sulfonamide antibiotics in the aquatic environment of Argentina.


Asunto(s)
Monitoreo del Ambiente , Sulfonamidas , Contaminantes Químicos del Agua , Argentina , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Sulfonamidas/análisis , Antibacterianos/análisis , Ríos/química , Sedimentos Geológicos/química , Espectrometría de Masas en Tándem
4.
J Hosp Infect ; 149: 144-154, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705475

RESUMEN

INTRODUCTION: The prevention and control of hospital-acquired infections remain a significant challenge worldwide, as textiles used in hospital wards are highly involved in transmission processes. This paper reports a new antibacterial medical fabric used to prepare hospital pillowcases, bottom sheets and quilt covers for controlling and reducing hospital-acquired infections. METHOD: The medical fabric was composed of blended yarns of staple polyester (PET) and degradable poly(3-hydroxybutyrate co-3-hydroxyvalerate) (PHBV)/polylactic acid (PLA) fibres, which were coated with polylactide oligomers (PLAO), which are environmentally friendly and safe antimicrobial agents with excellent thermal stability in high-temperature laundry. A clinical trial was conducted, with emphasis on the bacterial species that were closely related to the infection cases in the study hospital. RESULT: After 7 days of use, 94% of PET/PHBV/PLA-PLAO fabric retained <20 colony-forming units/100 cm2 of the total bacterial amount, meeting hygiene and cleanliness standards. CONCLUSION: This study demonstrates the potential of fabrics containing polyhydroxyalkanoate oligomers as highly effective, safe and long-lasting antimicrobial medical textiles that can effectively reduce the incidence of hospital-acquired infections.

5.
Public Health ; 232: 201-207, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38815542

RESUMEN

OBJECTIVES: Rehabilitation is crucial to improve the health status of people with disabilities. Previous studies mainly analysed the impact of health insurance on utilisation of general health services; the relationship between health insurances and rehabilitation services utilisation among Chinese people with disabilities has been long neglected. This study aimed to analyse the association between health insurance programs and rehabilitation services utilisation among disabled people. STUDY DESIGN: This was a cross-sectional study. METHODS: The data used in this study were derived from 2021 National Household Income Survey of Disabled People and National Basic Database of People with Disabilities conducted by China Disabled Persons' Federation. Logistic regression model was used to analyse the relationship between health insurance and rehabilitation services utilisation, and the propensity score matching method was used to check the robustness of the results. RESULTS: (1) Disabled people insured by the Basic Medical Insurance System for Urban Employees (BMISUE) and the Basic Medical Insurance System for Urban and Rural Residents (BMISURR) were positively associated with rehabilitation service utilisation (odds ratio [OR] = 1.852, 95% confidence interval [CI]:1.268, 2.707; OR = 1.375, 95% CI: 0.962, 1.966). (2) The utilisation level of rehabilitation service among disabled people insured by BMISUE was significantly higher than those insured by BMISURR (OR = 1.355, 95% CI: 1.161, 1.581). (3) The supply of rehabilitation services at the community level was positively correlated with the utilisation by people with disabilities. CONCLUSION: Health insurance can improve the financial accessibility of using rehabilitation services, and the utilisation level will increase as the benefits level of health insurance increase.


Asunto(s)
Personas con Discapacidad , Seguro de Salud , Humanos , China , Masculino , Femenino , Estudios Transversales , Personas con Discapacidad/estadística & datos numéricos , Personas con Discapacidad/rehabilitación , Adulto , Persona de Mediana Edad , Seguro de Salud/estadística & datos numéricos , Adolescente , Adulto Joven , Anciano , Niño , Aceptación de la Atención de Salud/estadística & datos numéricos
6.
Clin Radiol ; 79(7): 501-514, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38670918

RESUMEN

AIM: The objective of this study is to explore the diagnostic value of machine learning (ML) in borderline ovarian tumors through meta-analysis. METHODS: Pubmed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved from database inception untill February 16, 2023. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was adopted to evaluate the risk of bias in the original studies. Sub-group analyses of ML were conducted according to clinical features and radiomics features. We separately discussed the discriminative value of ML for borderline vs benign and borderline vs malignant tumors. RESULTS: Eighteen studies involving 12,778 subjects were included in our analysis. The modeling variables mainly consisted of radiomics features (n=13) and a small number of clinical features (n=5). When distinguishing between borderline and benign tumors, the ML model based on radiomic features achieved a c-index of 0.782 (95% CI: 0.732-0.831), sensitivity of 0.75 (95% CI: 0.67-0.82), and specificity of 0.75 (95% CI: 0.67-0.81) in the validation set. When distinguishing between borderline and malignant tumors, the ML model based on radiomic features achieved a c-index of 0.916 (95% CI: 0.891-0.940), sensitivity of 0.86 (95% CI: 0.78-0.91), and specificity of 0.88 (95% CI: 0.82-0.92) in the validation set. In addition, we analyzed the discriminatory ability of radiologists and found that their sensitivity was 0.26 (95% CI: 0.12-0.46) and specificity was 0.94 (95% CI: 0.90-0.97). CONCLUSIONS: ML has tremendous potential in the preoperative diagnosis and differentiation of borderline ovarian tumors and may be more accurate than radiologists in diagnosing and differentiating borderline ovarian tumors.


Asunto(s)
Aprendizaje Automático , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/diagnóstico por imagen , Sensibilidad y Especificidad , Ovario/diagnóstico por imagen , Diagnóstico Diferencial , Reproducibilidad de los Resultados
7.
J Frailty Aging ; 13(2): 125-130, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616368

RESUMEN

BACKGROUND: Physical resilience is an emerging concept that describes an individual's capacity to recover from stressors. However, few instruments are currently available for assessing physical resilience. OBJECTIVE: To develop a scale to assess physical resilience in older adults. DESIGN: Development of a clinical scale. SETTING AND PARTICIPANTS: A total of 172 hospitalized older adults were recruited. MEASUREMENTS: This study comprised two stages. First, a pool of physical resilience scale items was created through a literature review, and the Delphi method was used to establish an initial scale. Second, the initial physical resilience scale was tested on hospitalized older adults. RESULTS: Five primary and 19 secondary items were identified after reviewing the literature. After two rounds of expert consultations, three primary and 16 secondary items were determined. The overall Cronbach's alpha for the scale was 0.760. Except for items N2, N4, N5, N8, and N14, Pearson's correlation between the scores of the remaining items and the total score ranged from 0.407 to 0.672. Except for items N2, N4, and N5, the corrected item-total correlation results ranged from 0.301 to 0.580, indicating good consistency between each item and the overall scale. Factor analysis showed that except for N7, the factor loadings of the remaining items were between 0.584 and 0.844. After expert discussions, items N2, N4, N7, and N14 were included in the scale, and items N5 and N8 were removed. CONCLUSION: A 14-item physical resilience scale, CHEES, was developed to assess physical resilience levels in older adults.


Asunto(s)
Resiliencia Psicológica , Humanos , Anciano , Derivación y Consulta , China
8.
Zhonghua Gan Zang Bing Za Zhi ; 32(3): 257-261, 2024 Mar 20.
Artículo en Chino | MEDLINE | ID: mdl-38584111

RESUMEN

Systemic treatment, including molecular targeted therapy, immunotherapy, and chemotherapy, is an important means of achieving long-term survival in patients with intermediate-and advanced-stage liver cancer. However, some patients are insensitive to treatment and even develop drug resistance. Mitochondria are the center of cellular energy metabolism and, at the same time, are the priority targets for systemic therapy. Mitochondrial homeostasis plays an important role in the treatment of liver cancer. The relationship between the two advances is elucidated so as to provide better ideas for the clinical treatment of liver cancer.


Asunto(s)
Neoplasias Hepáticas , Mitocondrias , Humanos , Inmunoterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Homeostasis
10.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(5): 496-501, 2024 May 09.
Artículo en Chino | MEDLINE | ID: mdl-38637004

RESUMEN

Regenerating tissues similar to dental structure with normal function are putatively to be the aim in tooth regeneration filed. Currently, researchers preliminarily achieved tooth regeneration by applying dental pulp stem cells (DPSC) and stem cells from human exfoliated deciduous teeth (SHED). However, the regeneration efficiency remains unstable and needs further investigation. The development of single-cell RNA sequencing and organoid culture system provide potential of precise, targeted and controllable functional regeneration. This article reviews the current state of DPSC/SHED on tooth regeneration, and analyzes characteristics and hotspots of them, aiming to shed light on clinical translational application of stable and efficient tooth regeneration.


Asunto(s)
Pulpa Dental , Regeneración , Células Madre , Diente Primario , Pulpa Dental/citología , Humanos , Células Madre/citología , Diente Primario/citología , Ingeniería de Tejidos/métodos , Organoides/citología , Diferenciación Celular
11.
J Dairy Sci ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38554823

RESUMEN

The study investigated the effects of dietary protein level and the inclusion of hydroponic barley sprouts (HB) on lactation performance, blood biochemistry and N use efficiency in mid-lactation dairy cows. Treatments were arranged in a 2 × 2 factorial design with 2 crude protein (CP) levels [16.8% and 15.5% of dry matter (DM)], with HB (4.8% of DM, replacing 4.3% of alfalfa hay and 0.5% of distillers dried grains with solubles (DDGS)) or without HB. Forty-eight multiparous Holstein dairy cows (146 ± 15 d in milk, 40 ± 5 kg/d of milk) were randomly allocated to 1 of 4 diets: high protein diet (16.8% CP, HP), HP with HB (HP+HB), low protein diet (15.5% CP, LP), or LP with HB (LP+HB). An interaction between CP × HB on dry matter intake (DMI) was detected, with DMI being unaffected by HB inclusion in cows fed the high CP diets, but was lower in cows fed HB when the low CP diet was fed. A CP × HB interaction was also observed on milk and milk protein yield, which was higher in cows fed HB with HP, but not LP. Inclusion of HB also tended to reduce milk fat content, and feeding HP resulted in a higher milk protein and milk urea N content, but lower milk lactose content. Feed efficiency was increased by feeding HP or HB diets, whereas N efficiency was higher for cows fed LP or HB diets. There was an interaction on the apparent total-tract digestibility of DM and CP, which was higher when HB was fed along with HP, but reduced when fed with LP, whereas the digestibility of ADF was increased by feeding low protein diets. In conclusion, feeding a low protein diet had no adverse effect on cow performance, while feeding HB improved milk and milk component yield, and N efficiency when fed with a high CP diet, but compromised cow performance with a low CP diet.

13.
Zootaxa ; 5403(4): 447-458, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38480425

RESUMEN

The taxonomy of the genus Telostholus (Hymenoptera: Pompilidae: Pompilinae) from China is studied and one species is newly described and illustrated: T. venarectus Song & Ma, sp. nov. Additionally, two species, T. lao and T. malayensis are newly reported from China. A key to the world species of Telostholus is provided.


Asunto(s)
Himenópteros , Avispas , Animales , China
14.
Phys Rev Lett ; 132(7): 072502, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38427897

RESUMEN

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

15.
Eur Rev Med Pharmacol Sci ; 28(2): 556-570, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38305600

RESUMEN

OBJECTIVE: The aim of this study was to investigate the causes, diagnostic markers, and treatment methods for recurrent pregnancy loss (RPL) using bioinformatics approaches. MATERIALS AND METHODS: Bioinformatics methods were utilized to analyze gene expression databases to identify key genes and modules associated with RPL. Weighted gene co-expression network analysis (WGCNA) was employed to identify gene sets related to maternal-fetal immunity. Gene set variation analysis (GSVA) and protein-protein interaction networks were used to explore signaling pathways and molecular interactions in RPL. Immune cell infiltration was assessed using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Thirteen genes were identified as potential diagnostic markers, some of which were involved in placental amino acid transport, glucose absorption, and reactive oxygen species production. Several gene sets related to protein transport, steroid synthesis, and glycosaminoglycan degradation were found to be associated with RPL. Immune cell infiltration analysis found that CD56bright NK cells and monocytes showed significantly increased infiltration in RPL and were associated with key hub genes. The validation of hub genes, including PCSK5, CCND2, SLC5A3, RASAL1, MYZAP, MFAP4, and P2RY14, as potential diagnostic markers, showed promising value. CONCLUSIONS: This study contributes to a better understanding of the etiology of RPL and potential diagnostic markers. The identified immune-related gene sets, signaling pathways, and immune cell infiltrations provide valuable insights for future research and therapeutic advancements in RPL.


Asunto(s)
Aborto Habitual , Placenta , Embarazo , Femenino , Humanos , Transporte Biológico , Biomarcadores , Biología Computacional , Aborto Habitual/genética , Proteínas Portadoras , Glicoproteínas , Proteínas de la Matriz Extracelular
16.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(2): 132-136, 2024 Feb 12.
Artículo en Chino | MEDLINE | ID: mdl-38309962

RESUMEN

Objective: To analyze the diagnostic efficacy of urinary lipoarabinomannan (LAM) antigen detection method in tuberculosis patients, and to provide an experimental basis for the clinical application of urinary LAM kit in China. Methods: From March to May 2023, 228 patients with lung diseases [134 male, 94 female, age 20-82 (44.8±16.7) years] were prospectively collected in Beijing Chest Hospital, Capital Medical University, including 143 pulmonary tuberculosis patients and 85 non-tuberculosis patients. Urine and sputum samples from patients were collected for traditional etiological detection and urinary LAM antigen detection. The screening results of each positive detection combination were analyzed, and the difference analysis and regression analysis were performed. Results: The detection sensitivity and specificity of the urinary LAM kit were 46.2% (95%CI: 37.9%-54.7%) and 96.5% (95%CI: 89.3%-99.1%), respectively, with an overall coincidence rate of 64.9%. The detection rate of LAM antigen detection and GeneXpert MTB/RIF (Xpert) combined (60.8%, 87/143) was significantly higher than that of Xpert alone (49.7%, 71/143), and the difference was statistically significant (P<0.05). The results of risk factor analysis showed that the risk of negative urinary LAM antigen test results increased significantly as the bacterial load decreased. Conclusions: Urine LAM antigen detection method has a high specificity and can be combined with traditional methods to effectively improve the detection rate. Urinary LAM antigen detection method still has limitations, such as the influence of bacterial load and the inability to distinguish nontuberculosis mycobacteria samples, which needs further experimental verification.


Asunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Lipopolisacáridos , Sensibilidad y Especificidad , Esputo/microbiología
17.
J Endocrinol Invest ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38285310

RESUMEN

PURPOSE: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). METHODS: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 µM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. RESULTS: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p­AKT (Ser473), p­AKT (Thr308), p­mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. CONCLUSIONS: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

18.
J Dairy Sci ; 107(2): 1286-1298, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37776998

RESUMEN

Oxidative stress is the imbalanced redox status between oxidant production and their scavengers leading to intestinal physiological dysfunction. However, the role of systemic and local oxidative status during neonatal calf diarrhea is not known. This study assessed systemic (serum) and local (fecal) oxidative status when calves either naturally developed diarrhea or naturally recovered. Healthy calves were enrolled in the study at d 18 of age, and their health status was monitored from the enrollment. Based on their enteric health status on d 21 and 28, calves were grouped as continuous diarrhea from d 21 to 28 (n = 14), diarrhea at d 21 but recovered at d 28 (DH group, n = 19), healthy at d 21 but developed diarrhea at d 28 (HD group, n = 15), and healthy throughout the study (HH group, n = 16). Serum and fecal samples were collected at d 21 and 28 from all calves in the morning 2 h after feeding. Dynamics of oxidative stress indicators including reactive oxygen species (ROS), malondialdehyde (MDA), H2O2, 8-hydroxy-2'-deoxyguanosine (8-OHDG), glutathione peroxidase, superoxide dismutase, catalase (CAT), and total antioxidant capacity and inflammatory indicators TNF-α, IL-1ß, IL-4, IL-6, IL-10, and IFN-γ were evaluated using serum samples. In addition, fecal oxidative stress indicators ROS and MDA were measured. Serum ROS, MDA, 8-OHDG, as well as fecal ROS and MDA, were higher, whereas serum CAT and H2O2 were lower in diarrheic calves than those of healthy calves. Serum ROS, MDA, and 8OHDG and fecal ROS and MDA increased in the HD group from d 21 to 28 as they developed diarrhea. In contrast, all these oxidative stress markers decreased in the DH group from d 21 to 28 as they recovered. However, serum H2O2 had an opposite changing trend, which became lower in the HD group and higher in the DH group at d 28. In conclusion, both systemic and local oxidative stress markers and cytokine profiles altered as calves moved from being healthy to having diarrhea or vice versa. Serum ROS, MDA, and 8-OHDG can be used to develop biomarkers to screen calves prone to enteric infections during the preweaning period.


Asunto(s)
Peróxido de Hidrógeno , Estrés Oxidativo , Animales , Bovinos , Especies Reactivas de Oxígeno , Diarrea/veterinaria , Inmunidad
19.
Ann Oncol ; 35(2): 190-199, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37872020

RESUMEN

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Sunitinib/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
20.
Plant Biol (Stuttg) ; 26(1): 117-125, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38014496

RESUMEN

Both NO and GAs are essential for regulating various physiological processes and stress responses in plants. However, the interaction between these two molecules remains unclear. We investigated the distinct response patterns of Arabidopsis thaliana Col-0 and GA synthesis functional deficiency mutants to NO by measuring root length. To investigate underlying mechanisms, we detected bioactive GA content using UHPLC-ESI-MS/MS, assessed the accumulation of ROS by chemical staining Arabidopsis roots. We also conducted RNA-seq analysis and compared results between Col-0 and ga3ox1, with and without SNP (as NO donor) treatment. Phenotypic results revealed that the inhibitory effect of NO on primary roots of Arabidopsis was primarily mediated by GA3-oxidase, rather than GA20-oxidase or GA2-oxidase. The content of GA3 decreased in Col-0 treated with SNP, whereas this decrease was not observed in ga3ox1. The deficiency of GA3-oxidase alleviated the buildup of H2 O2 in roots when treated with SNP. We identified 222 DEGs. GO annotation of these DEGs revealed that all top 20 GO terms were related to stress responses. Moreover, three DEGs were annotated to GA-related processes (DDF1, DDF2, EXPA1), and seven DEGs were associated with root development (RAV1, RGF2, ERF71, ZAT6, MYB77, XT1, and DTX50). In summary, NO inhibits primary root growth partially by repressing GA3-oxidase catalysed GA3 synthesis in Arabidopsis. ROS, Ca2+ , DDF1, DDF2, EXPA1 and seven root development-related genes may be involved in crosstalk between NO and GAs.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Óxido Nítrico , Oxidorreductasas/genética , Espectrometría de Masas en Tándem , Especies Reactivas de Oxígeno , Giberelinas/farmacología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas
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