Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.044
Filtrar
1.
J Environ Sci (China) ; 148: 46-56, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095180

RESUMEN

Thermodynamic modeling is still the most widely used method to characterize aerosol acidity, a critical physicochemical property of atmospheric aerosols. However, it remains unclear whether gas-aerosol partitioning should be incorporated when thermodynamic models are employed to estimate the acidity of coarse particles. In this work, field measurements were conducted at a coastal city in northern China across three seasons, and covered wide ranges of temperature, relative humidity and NH3 concentrations. We examined the performance of different modes of ISORROPIA-II (a widely used aerosol thermodynamic model) in estimating aerosol acidity of coarse and fine particles. The M0 mode, which incorporates gas-phase data and runs the model in the forward mode, provided reasonable estimation of aerosol acidity for coarse and fine particles. Compared to M0, the M1 mode, which runs the model in the forward mode but does not include gas-phase data, may capture the general trend of aerosol acidity but underestimates pH for both coarse and fine particles; M2, which runs the model in the reverse mode, results in large errors in estimated aerosol pH for both coarse and fine particles and should not be used for aerosol acidity calculations. However, M1 significantly underestimates liquid water contents for both fine and coarse particles, while M2 provides reliable estimation of liquid water contents. In summary, our work highlights the importance of incorporating gas-aerosol partitioning when estimating coarse particle acidity, and thus may help improve our understanding of acidity of coarse particles.


Asunto(s)
Aerosoles , Contaminantes Atmosféricos , Modelos Químicos , Termodinámica , Aerosoles/análisis , Aerosoles/química , Contaminantes Atmosféricos/química , Contaminantes Atmosféricos/análisis , China , Monitoreo del Ambiente/métodos , Material Particulado/química , Material Particulado/análisis , Concentración de Iones de Hidrógeno , Tamaño de la Partícula
2.
Heliyon ; 10(14): e34722, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39130420

RESUMEN

Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1ß and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38973529

RESUMEN

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

4.
Int J Mol Sci ; 25(14)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39062962

RESUMEN

Postharvest fibrosis and greening of Toona sinensis buds significantly affect their quality during storage. This study aimed to clarify the effects of low-temperature storage on postharvest red TSB quality harvested in different seasons. Red TSB samples were collected from Guizhou province, China, 21 days after the beginning of spring (Lichun), summer (Lixia), and autumn (Liqiu), and stored at 4 °C in dark conditions. We compared and analyzed the appearance, microstructure, chlorophyll and cellulose content, and expression levels of related genes across different seasons. The results indicated that TSB harvested in spring had a bright, purple-red color, whereas those harvested in summer and autumn were green. All samples lost water and darkened after 1 day of storage. Severe greening occurred in spring-harvested TSB within 3 days, a phenomenon not observed in summer and autumn samples. Microstructural analysis revealed that the cells in the palisade and spongy tissues of spring and autumn TSB settled closely during storage, while summer TSB cells remained loosely aligned. Xylem cells were smallest in spring-harvested TSB and largest in autumn. Prolonged storage led to thickening of the secondary cell walls and pith cell autolysis in the petioles, enlarging the cavity area. Chlorophyll content was higher in leaves than in petioles, while cellulose content was lower in petioles across all seasons. Both chlorophyll and cellulose content increased with storage time. Gene expression analysis showed season-dependent variations and significant increases in the expression of over half of the chlorophyll-related and cellulose-related genes during refrigeration, correlating with the observed changes in chlorophyll and cellulose content. This research provides valuable insights for improving postharvest storage and freshness preservation strategies for red TSB across different seasons.


Asunto(s)
Celulosa , Clorofila , Frío , Estaciones del Año , Clorofila/metabolismo , Celulosa/metabolismo , Regulación de la Expresión Génica de las Plantas , China
5.
Materials (Basel) ; 17(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39063788

RESUMEN

Chemodynamic therapy (CDT) alone cannot achieve sufficient therapeutic effects due to the excessive glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Developing a novel strategy to improve efficiency is urgently needed. Herein, we prepared a copper silicate nanoplatform (CSNP) derived from colloidal silica. The Cu(II) in CSNP can be reduced to Cu(I), which cascades to induce a subsequent CDT process. Additionally, benefiting from GSH depletion and oxygen (O2) generation under 660 nm laser irradiation, CSNP exhibits both Fenton-like and hypoxia-alleviating activities, contributing to the effective generation of superoxide anion radical (•O2-) and hydroxyl radical (•OH) in the TME. Furthermore, given the suitable band-gap characteristic and excellent photochemical properties, CSNP can also serve as an efficient type-I photosensitizer for photodynamic therapy (PDT). The synergistic CDT/PDT activity of CSNP presents an efficient antitumor effect and biosecurity in both in vitro and in vivo experiments. The development of an all-in-one nanoplatform that integrates Fenton-like and photosensing properties could improve ROS production within tumors. This study highlights the potential of silicate nanomaterials in cancer treatment.

6.
ACS Pharmacol Transl Sci ; 7(7): 2196-2203, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39022367

RESUMEN

Histone deacetylase 6 (HDAC6) enzyme plays a crucial role in a variety of cellular processes related to cancer, and inhibition of HDAC6 is emerging as an effective strategy for cancer treatment. Although several hydroxamate-based HDAC6 inhibitors showed promising anticancer activities, the intrinsic defects such as poor selectivity, stability, and pharmacokinetics limited their application. In this study, a potent selenocyanide-bearing HDAC6 inhibitor, 5-phenylcarbamoylpentyl selenocyanide (SelSA), was evaluated for its antihepatocellular carcinoma (HCC) activity and further explored for its antitumor mechanisms. In vitro studies demonstrated that SelSA exhibited excellent antiproliferative activity against three HCC cells HepG2 (2.3 ± 0.29 µM), Huh7 (0.83 ± 0.48 µM), and LM3 (2.6 ± 0.24 µM). Further studies indicated that SelSA could downregulate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, inhibit the growth, invasion, and migration of Huh7 cells, and promote their apoptosis. Moreover, SelSA significantly suppressed tumor growth in Huh7 xenograft mouse models. Our findings suggest that SelSA could be a potential therapeutic agent for HCC.

7.
Mol Immunol ; 173: 40-52, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39053388

RESUMEN

HIV-1 chronically infects host CD4+ T lymphocytes and further affects a variety of immune cells, including CD8+ T cells. In our previous study, by analyzing unbiased high-dimensional single-cell RNA-seq data (scRNA-seq), we found that the frequency of GZMK+CD8+ T cells expressing granzyme K (GZMK) was increased in people living with HIV-1 (PLWHs). However, the phenotypic and functional characteristics of these cells in chronic HIV-1 infection and their correlation with disease are not well understood. In this study, we conducted a comprehensive analysis of scRNA-seq and matched T-cell receptor repertoire (TCR) sequencing data to delve into the characterizations of GZMK+CD8+ T cells, which was further validated by flow cytometry. We observed heterogeneity within the GZMK+CD8+ T cells, which could be further subdivided into a GZMK+GZMB- subset and a GZMK+GZMB+ subset, with the latter being significantly enriched in PLWHs. The GZMK+GZMB+ cells are a unique subset within CD8+ T cells, characterized by high proliferation, activation, inflammatory response, clone transition, etc., and are one of the differentiation endpoints by pseudotemporal analysis of CD8+αß T cells. Despite being predominantly composed of effector memory T cells (Tem), similar to the GZMK+GZMB- subset, the GZMK+GZMB+ subset exhibits differentiation at a later stage than the GZMK+GZMB- subset. We also observed that the frequency/count of GZMK+GZMB+CD8+ T cells was negatively correlated with CD4/CD8 ratio, and positively correlated with HIV DNA, IP-10, and MIG levels in PLWHs. In vitro experiments demonstrate that GZMK can potentiate the stimulatory effects of lipopolysaccharide (LPS) on THP-1 macrophages via the TLR-4 pathway, significantly enhancing the secretion of IP-10, MIG, and MCP-1, as well as increasing the proportion of TNF-α+ cells. In conclusion, in PLWHs, GZMK+GZMB+CD8+ T cells are a highly reactive and inflammatory-inducing subset that may be associated with systemic inflammation.

8.
J Pediatr Urol ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39054235

RESUMEN

Laparoscopic ureteral reimplantation has gained increasing popularity in treating pediatric primary vesicoureteral reflux (VUR) and obstructive megaureter (OM). However, it is technically challenging with a relatively low success rate compared to open surgery. Here we designed a hybrid technique which incorporates laparoscopic surgery and pneumovesical ureteral reimplantation. From 2023 February to 2024 February, five boys and four girls underwent the hybrid reimplantation smoothly. There were seven children with VUR and two with OM. Patient age ranged from eight months to ten years. The mean time was 201.5 min (range 155-240 min) for unilateral operation and 260 min for bilateral operation. Follow-up ranged from 6.4 to 18.7 months. All patients remained asymptomatic, with voiding cystourethrogram showing cure or urinary ultrasonography showing significant improvement. In conclusion, the hybrid laparoscopic ureteral reimplantation appeared to be a simple and effective minimally invasive surgery for treating primary VUR and OM in children.

9.
MedComm (2020) ; 5(8): e627, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39015557

RESUMEN

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38995342

RESUMEN

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

11.
Nat Commun ; 15(1): 5997, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39013885

RESUMEN

Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Redes Reguladoras de Genes , Leucemia Mieloide Aguda , Redes Neurales de la Computación , Humanos , Leucemia Mieloide Aguda/genética , Neoplasias de la Mama/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Neurregulina-1/genética , Neurregulina-1/metabolismo
12.
Viruses ; 16(7)2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-39066169

RESUMEN

BACKGROUND: T-cell responses can be protective or detrimental during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the underlying mechanism is poorly understood. METHODS: In this study, we screened 144 15-mer peptides spanning the SARS-CoV-2 spike, nucleocapsid (NP), M, ORF8, ORF10, and ORF3a proteins and 39 reported SARS-CoV-1 peptides in peripheral blood mononuclear cells (PBMCs) from nine laboratory-confirmed coronavirus disease 2019 (COVID-19) patients (five moderate and four severe cases) and nine healthy donors (HDs) collected before the COVID-19 pandemic. T-cell responses were monitored by IFN-γ and IL-17A production using ELISA, and the positive samples were sequenced for the T cell receptor (TCR) ß chain. The positive T-cell responses to individual SARS-CoV-2 peptides were validated by flow cytometry. RESULTS: COVID-19 patients with moderate disease produced more IFN-γ than HDs and patients with severe disease (moderate vs. HDs, p < 0.0001; moderate vs. severe, p < 0.0001) but less IL-17A than those with severe disease (p < 0.0001). A positive correlation was observed between IFN-γ production and T-cell clonal expansion in patients with moderate COVID-19 (r = 0.3370, p = 0.0214) but not in those with severe COVID-19 (r = -0.1700, p = 0.2480). Using flow cytometry, we identified that a conserved peptide of the M protein (Peptide-120, P120) was a dominant epitope recognized by CD8+ T cells in patients with moderate disease. CONCLUSION: Coordinated IFN-γ production and clonal expansion of SARS-CoV-2-specific T cells are associated with disease resolution in COVID-19. Our findings contribute to a better understanding of T-cell-mediated immunity in COVID-19 and may inform future strategies for managing and preventing severe outcomes of SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Mapeo Epitopo , Epítopos de Linfocito T , Interferón gamma , SARS-CoV-2 , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , COVID-19/inmunología , COVID-19/virología , Epítopos de Linfocito T/inmunología , SARS-CoV-2/inmunología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Interleucina-17/inmunología , Interleucina-17/metabolismo , Anciano , Linfocitos T/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T CD8-positivos/inmunología
13.
World J Clin Oncol ; 15(7): 936-944, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39071465

RESUMEN

BACKGROUND: Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis. Adenocarcinoma is the most common pathological type of cholangiocarcinomas, but rare squamous, adenosquamous, and mucinous variants have been reported without adequate clinical data. CASE SUMMARY: This report describes a rare case of primary squamous cell carcinoma (SCC) of the intrahepatic bile duct. The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms. Examination revealed hepatitis B surface antigen positivity, a slight increase in alfa-fetoprotein to 16.34 ng/mL, and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe, which was initially thought to be hepatocellular carcinoma. Laparoscopic resection was performed, and the final pathology suggested a rare primary SCC of the intrahepatic bile duct. Immunohistochemistry indicated positivity for villin, partial positivity for p63, and negativity for hepatocyte, CK7, CK8, CK19, and CK20. The Ki-67 index was approximately 60%. The patient received six cycles of Tegio chemotherapy. A new lesion was detected in the liver after 15 months. The surgery was performed, and the patient was followed-up at a local hospital. To date, no new lesions have been observed. CONCLUSION: Surgery is the first choice for resectable lesions, and combined chemotherapy based on pathology is essential for increasing overall survival.

14.
Artículo en Inglés | MEDLINE | ID: mdl-39052528

RESUMEN

Background: Necrotizing soft-tissue infection (NSTI) is a rare and serious disease with high morbidity and mortality. Standard therapeutic concepts have included urgent surgical intervention, broad-spectrum antibiotic treatment, and intensive care. Hyperbaric oxygen therapy (HBOT) is used as adjuvant therapy in some centers, but its benefits remain controversial. Methods: A retrospective analysis was conducted in which 98 patients with a clinical diagnosis of NSTI were treated with standard treatments plus HBOT. The clinical outcomes were wound healing, performance status, hospital length, complication rate, recurrence rate, morbidity (amputation rate), and mortality. Primary or secondary outcomes were compared between the time interval of HBOT and the clinical outcomes. Results: The average times from diagnosis of NSTI to initial HBO treatment and from initial surgery to initial HBO treatment were both significantly longer in dead patients than in surviving patients (P = 0.031; P = 0.020). These two time intervals were both significantly longer in amputated patients than in preserved patients (P = 0.031; P = 0.037). Conclusions: Using combined treatment with early surgical debridement combined with HBOT, it is possible to reduce hospital stay, intensive care unit stay, number of debridements, improve complete wound healing rate, and lower amputation and mortality rates among patients with NSTI. The early onset of HBOT soon after diagnosis, especially during critical conditions, is proved to be associated with higher survival and preservation rates.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38987064

RESUMEN

Herpes zoster (HZ) is a painful, vesicular, cutaneous eruption from reactivation of varicella zoster virus (VZV), which can lead to potentially debilitating complications. The lifetime risk of HZ is estimated to be 20%-30% in the general population, with an increased risk in the elderly and immunocompromised populations. The most effective strategy to prevent HZ and its complications is by vaccination. Two types of HZ vaccines, zoster vaccine live and recombinant zoster vaccine, have been approved for use. This guidance offers recommendations and suggestions for HZ vaccination in adults, aiming to reduce the disease burden of HZ and its complications. It is intended as a guide to first-line healthcare providers, but does not supersede clinical judgement when assessing risk and providing recommendations to individuals. The Working Group on Adult Immunization Practice was appointed by the Infectious Diseases Society of Taiwan (IDST) and recommendations were drafted after a full literature review, using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. The recommendations were reviewed and revised by expert review panels during a series of consensus meetings and endorsed by the IDST, Taiwan Association of Family Medicine, the Taiwanese Dermatological Association, the Taiwan Oncology Society, the Taiwan Society of Blood and Marrow Transplantation, the Transplantation Society of Taiwan, the Taiwan AIDS Society, and the Taiwan College of Rheumatology. This guidance describes the epidemiology of HZ and provides recommendations for HZ vaccination in adults with varying levels of risk, differing history of previous VZV infection and past varicella or zoster vaccinations.

16.
J Pept Sci ; : e3628, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950972

RESUMEN

Cell-penetrating peptides (CPPs) with better biomolecule delivery properties will expand their clinical applications. Using the MLCPP2.0 machine algorithm, we screened multiple candidate sequences with potential cellular uptake ability from the nuclear localization signal/nuclear export signal database and verified them through cell-penetrating fluorescent tracing experiments. A peptide (NCR) derived from the Rev protein of the caprine arthritis-encephalitis virus exhibited efficient cell-penetrating activity, delivering over four times more EGFP than the classical CPP TAT, allowing it to accumulate in lysosomes. Structural and property analysis revealed that a high hydrophobic moment and an appropriate hydrophobic region contribute to the high delivery activity of NCR. Trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, could improve its anti-tumor activity by enhancing targeted delivery efficiency and increasing lysosomal drug delivery. This study designed a new NCR vector to non-covalently bind T-DM1 by fusing domain Z, which can specifically bind to the Fc region of immunoglobulin G and effectively deliver T-DM1 to lysosomes. MTT results showed that the domain Z-NCR vector significantly enhanced the cytotoxicity of T-DM1 against HER2-positive tumor cells while maintaining drug specificity. Our results make a useful attempt to explore the potential application of CPP as a lysosome-targeted delivery tool.

17.
Pak J Med Sci ; 40(6): 1087-1092, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952500

RESUMEN

Objective: To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus. Methods: This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared. Results: At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05). Conclusion: Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus.

18.
Hepatol Int ; 18(4): 1122-1134, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38829576

RESUMEN

BACKGROUND: The role of neutrophils in hepatitis B virus (HBV) infection has been a subject of debate due to their involvement in antiviral responses and immune regulation. This study aimed to elucidate the neutrophil characteristics in patients with chronic hepatitis B (CHB). METHODS: Through flow cytometry and ribonucleic acid-sequencing analysis, the phenotypes and counts of neutrophils were analyzed in patients with CHB. Moreover, the effects of HBeAg on neutrophils and the corresponding pattern recognition receptors were identified. Simultaneously, the cross-talk between neutrophils and natural killer (NK) cells was investigated. RESULTS: Neutrophils were activated in patients with CHB, characterized by higher expression levels of programmed death-ligand 1 (PD-L1), cluster of differentiation 86, and interleukin-8, and lower levels of CXC motif chemokine receptor (CXCR) 1 and CXCR2. Hepatitis B e antigen (HBeAg) partially induces neutrophil activation through the Toll-like receptor 2 (TLR2). A consistent upregulation of the TLR2 and HBeAg expression was observed in patients with CHB. Notably, the genes encoding molecules pivotal for NK-cell function upon NK receptor engagement enriched in neutrophils after HBeAg activation. The HBeAg-activated neutrophils demonstrated the ability to decrease the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in NK cells, while the PD-1 and PD-L1 pathways partially mediated the immunosuppression. CONCLUSIONS: The immunosuppression of neutrophils induced by HBeAg suggests a novel pathogenic mechanism contributing to immune tolerance in patients with CHB.


Asunto(s)
Antígenos e de la Hepatitis B , Hepatitis B Crónica , Células Asesinas Naturales , Activación Neutrófila , Neutrófilos , Humanos , Hepatitis B Crónica/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Antígenos e de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/sangre , Masculino , Femenino , Adulto , Neutrófilos/inmunología , Neutrófilos/metabolismo , Persona de Mediana Edad , Antígeno B7-H1/metabolismo , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Interferón gamma/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
19.
J Dent ; 147: 105133, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38880468

RESUMEN

OBJECTIVES: The objective of this study was to analyze the occlusal contact characteristics of the food-impacted teeth using a new digital technique. METHODS: A 3D occlusal analysis method was developed for studying the occlusal contact characteristics of teeth affected by food impaction. In this self-controlled study, food-impacted molars from 20 participants constituted the experimental group. The corresponding healthy teeth on the opposite side served as the control group. Variables such as occlusal force (OF), occlusal contact area (OCA), and the number and distribution of occlusal contact points (OCN) in the mesio-distal directions were measured and compared between the two groups. RESULTS: There was no statistical significant difference in the values of OF, OCA and OCN between the food-impacted molars and the healthy control molars (P > 0.05). However, paired T-tests indicated significant difference in the proportion of mesial OF, OCA, and OCN in the second molars of the experimental group (0.22, 0.28 and 0.28, respectively) and the control group (0.66, 0.63, and 0.63 respectively) (P < 0.001). CONCLUSIONS: The abnormal distribution of occlusal contacts in the second molar, primarily characterized by excessive occlusal contact in the distal direction may contribute to the occurrence of food impaction. CLINICAL SIGNIFICANCE: The present study identified variations in the distribution of occlusal contacts and occlusal component force in food-impacted teeth. These findings can assist dentists in making more targeted occlusal adjustments, or applying other treatment modalities, to effectively address food impaction.


Asunto(s)
Fuerza de la Mordida , Alimentos , Diente Molar , Diente Impactado , Humanos , Femenino , Masculino , Adulto Joven , Adulto , Diente Impactado/diagnóstico por imagen , Oclusión Dental , Imagenología Tridimensional/métodos
20.
ACS Synth Biol ; 13(7): 2008-2018, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38900848

RESUMEN

Cannabis sativa L. is a multipurpose crop with high value for food, textiles, and other industries. Its secondary metabolites, including cannabidiol (CBD), have potential for broad application in medicine. With the CBD market expanding, traditional production may not be sufficient. Here we review the potential for the production of CBD using biotechnology. We describe the chemical and biological synthesis of cannabinoids, the associated enzymes, and the application of metabolic engineering, synthetic biology, and heterologous expression to increasing production of CBD.


Asunto(s)
Cannabidiol , Cannabis , Ingeniería Metabólica , Cannabidiol/metabolismo , Cannabis/metabolismo , Ingeniería Metabólica/métodos , Biología Sintética/métodos , Biotecnología/métodos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA