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1.
Adv Sci (Weinh) ; : e2400049, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38952055

RESUMEN

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

2.
Front Oncol ; 14: 1388750, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993643

RESUMEN

Breast cancer stands as the most prevalent malignancy among women, with radiotherapy serving as a primary treatment modality. Despite radiotherapy, a subset of breast cancer patients experiences local recurrence, attributed to the intrinsic resistance of tumors to radiation. Therefore, there is a compelling need to explore novel approaches that can enhance cytotoxic effects through alternative mechanisms. Traditional Chinese Medicine (TCM) and its active constituents exhibit diverse pharmacological actions, including anti-tumor effects, offering extensive possibilities to identify effective components capable of overcoming radiotherapy resistance. This review delineates the mechanisms underlying radiotherapy resistance in breast cancer, along with potential candidate Chinese herbal medicines that may sensitize breast cancer cells to radiotherapy. The exploration of such herbal interventions holds promise for improving therapeutic outcomes in the context of breast cancer radiotherapy resistance.

4.
BMC Med ; 22(1): 285, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38972971

RESUMEN

BACKGROUND: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. METHODS: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. RESULTS: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50-26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15-28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25-35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. CONCLUSIONS: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.


Asunto(s)
Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/epidemiología , Humanos , Incidencia , Salud Global , Femenino , Masculino
5.
J Environ Manage ; 364: 121371, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38879965

RESUMEN

Rapid urbanization and high-intensity socio-economic activities in China have caused severe ecological problems. Implementing ecological restoration in China has become an inevitable way to restore the ecosystem. Ecosystem health is crucial for evaluating ecological conditions and trends, but comprehensive national studies that use quantitative ecosystem health assessments to guide specific ecological restoration are lacking. This study constructs the Vigor-Organization-Resilience-Services (VORS) model to evaluate the ecosystem health level of China during 2000-2020. Then, through the natural breakpoint and intelligent clustering correction, we carried out the ecological restoration zoning and proposed corresponding measures. The results show that China's overall ecosystem health declined from 2000 to 2020, and ecological restoration is imminent. The spatial pattern of ecosystem health is generally favorable in the south and usually poor in the north. China protects poor ecosystems' health well but needs more for better ones. To combat this degradation, we propose a zoning strategy that classifies the landscape into five categories: Ecosystem Conservation Areas (3.47%), focusing on biodiversity preservation; Ecosystem Enhancement Areas (10.53%), aiming at increasing ecological resilience; Ecosystem Buffer Zones (23.04%), intending to mitigate human impacts; Ecosystem Correction Zones (33.79%), targeting at restoring degraded ecosystems; and Ecosystem Reshaping Zones (29.17%), designing to revitalize ecological functions. The ecological restoration zoning in China proposed in this study, combined with appropriate and practical restoration tools, will help mitigate ecological problems and improve stability and ecosystem health.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , China , Biodiversidad , Urbanización , Ecología , Humanos
6.
SAGE Open Med Case Rep ; 12: 2050313X241260152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911175

RESUMEN

Valproate encephalopathy is one of the unusual and severe but treatable side effect. This research focuses on four female patients who had valproate medication for epilepsy and developed an increased frequency of seizures, exacerbated disruption of consciousness, gastrointestinal problems, cognitive dysfunction, ataxia, and psychobehavioral abnormalities. The patient's symptoms improved over time once sodium valproate was stopped. As a result, when using sodium valproate, one should be aware of the risk of sodium valproate encephalopathy and cease using the medication right once if any of the above symptoms of unknown etiology manifest clinically. We also go over the potential pathogenesis that lead to valproate encephalopathy and the heightened risk of encephalopathy from taking antiepileptic medications together. It was stressed how crucial it is to identify, diagnose, and treat sodium valproate encephalopathy as soon as possible.

7.
Front Immunol ; 15: 1392804, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38868762

RESUMEN

Rabies virus (RABV) causes a fatal neurological disease, consisting of unsegmented negative-strand RNA, which encodes five structural proteins (3'-N-P-M-G-L-5'). Apolipoprotein D (ApoD), a lipocalin, is upregulated in the nervous system after injury or pathological changes. Few studies have focused on the role of ApoD during virus infection so far. This study demonstrated that ApoD is upregulated in the mouse brain (in vivo) and C8-D1A cells (in vitro) after RABV infection. By upregulating ApoD expression in C8-D1A cells, we found that ApoD facilitated RABV replication. Additionally, Co-immunoprecipitation demonstrated that ApoD interacted with RABV glycoprotein (G protein). The interaction could promote RABV replication by upregulating the cholesterol level. These findings revealed a novel role of ApoD in promoting RABV replication and provided a potential therapeutic target for rabies.


Asunto(s)
Apolipoproteínas D , Colesterol , Virus de la Rabia , Rabia , Replicación Viral , Animales , Femenino , Humanos , Masculino , Ratones , Apolipoproteínas D/metabolismo , Apolipoproteínas D/genética , Encéfalo/virología , Encéfalo/metabolismo , Línea Celular , Colesterol/metabolismo , Células HEK293 , Rabia/metabolismo , Rabia/virología , Virus de la Rabia/fisiología , Regulación hacia Arriba
8.
Discov Oncol ; 15(1): 237, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904918

RESUMEN

BACKGROUND: The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive (ER +), HER2-, advanced breast cancer (ABC). BOLERO-5 investigated this combination in a Chinese population (NCT03312738). METHODS: BOLERO-5 is a randomized, double-blind, multicenter, placebo controlled, phase II trial comparing EVE (10 mg/day) or placebo (PBO) in combination with EXE (25 mg/day). The primary endpoint was progression-free survival (PFS) per investigator assessment. Secondary endpoints included PFS per blinded independent review committee (BIRC), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), pharmacokinetics, and safety. RESULTS: A total of 159 patients were randomized to EVE + EXE (n = 80) or PBO + EXE (n = 79). By investigator assessment, treatment with EVE + EXE prolonged median PFS by 5.4 months (HR 0.52; 90% CI 0.38, 0.71), from 2.0 months (PBO + EXE; 90% CI 1.9, 3.6) to 7.4 months (EVE + EXE; 90% CI 5.5, 9.0). Similar results were observed following assessment by BIRC, with median PFS prolonged by 4.3 months. Treatment with EVE + EXE was also associated with improvements in ORR and CBR. No new safety signals were identified in BOLERO-5, with the incidence of adverse events in Chinese patients consistent with the safety profile of both drugs. CONCLUSION: The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER + , HER2- ABC. NCT03312738, registered 18 October 2017.

9.
Euro Surveill ; 29(24)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873796

RESUMEN

In 2003-2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19PAS, 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23, bla OXA-72, and/or bla NDM-5. Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Proteínas Bacterianas , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , beta-Lactamasas/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Humanos , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Proteínas Bacterianas/genética , Ucrania/epidemiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Filogenia , Farmacorresistencia Bacteriana Múltiple/genética , Georgia (República)/epidemiología , Tipificación de Secuencias Multilocus
11.
12.
JAC Antimicrob Resist ; 6(3): dlae090, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38872715

RESUMEN

Objectives: To better understand the source and potential transmission routes of antibiotic-resistant bacteria infecting injured service members in Ukraine. Methods: Phenotypic and genomic characterizations were performed on 11 Gram-negative pathogens cultured from war wounds at an intermediate evacuation hospital in Dnipro. Results: The analysis revealed both susceptible and extensively drug-resistant strains present in cultures, including high-risk global clones carrying carbapenemases. Conclusions: Globally distributed carbapenemase-producing lineages are being acquired early in the medical evacuation process.

13.
Front Cardiovasc Med ; 11: 1326897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742172

RESUMEN

Objective: Leucine-rich α-2 glycoprotein 1 (LRG1) promotes inflammation and myocardial injury, but its clinical role in ST-elevation myocardial infarction (STEMI) is rarely disclosed. Herein, this prospective study aimed to explore the value of plasma LRG1 at different time points to predict major adverse cardiovascular event (MACE) risk in patients with STEMI. Methods: In total, 209 patients with STEMI were enrolled for determining plasma LRG1 at admission and on day (D)1/D7/D30 after admission via enzyme-linked immunosorbent assay, as well as for determination of peripheral blood T helper 17 (Th17) cells and regulatory T (Treg) cells by flow cytometry. In addition, plasma LRG1 was obtained from 30 healthy controls at enrollment. Results: LRG1 was increased in patients with STEMI at admission compared with healthy controls (P < 0.001). In patients with STEMI, LRG1 varied at different time points (P < 0.001), which elevated from admission to D1, and gradually declined thereafter. LRG1 at admission was positively associated with Th17 cells (P = 0.001) and Th17/Treg ratio (P = 0.014). LRG1 at admission (P = 0.013), D1 (P = 0.034), D7 (P = 0.001), and D30 (P = 0.010) were increased in patients with MACE compared with those without. LRG1 at D7 exhibited good ability to estimate MACE risk (area under curve = 0.750, 95% confidence interval = 0.641-0.858). LRG1 at admission > 60 µg/ml (P = 0.031) and D7 > 60 µg/ml (P = 0.018) were linked with increased accumulating MACE. Importantly, LRG1 at D7 > 60 µg/ml was independently correlated with increased MACE risk (hazard ratio = 5.216, P = 0.033). Conclusion: Plasma LRG1 increases from admission to D1 and gradually declines until D30, which positively links with Th17 cells and MACE risk in patients with STEMI.

14.
J Med Virol ; 96(5): e29521, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38727013

RESUMEN

Methylation panels, tools for investigating epigenetic changes associated with diseases like cancer, can identify DNA methylation patterns indicative of disease, providing diagnostic or prognostic insights. However, the application of methylation panels focusing on the sex-determining region Y-box 1 (SOX1) and paired box gene 1 (PAX1) genes for diagnosing cervical lesions is under-researched. This study aims to examine the diagnostic performance of PAX1/SOX1 gene methylation as a marker for cervical precancerous lesions and its potential application in triage diagnosis. From September 2022 to April 2023, 181 patients with abnormal HPV-DNA tests or cytological exam results requiring colposcopy were studied at Hubei Maternal and Child Health Hospital, China. Data were collected from colposcopy, cytology, HPV-DNA tests, and PAX1/SOX1 methylation detection. Patients were categorized as control, cervical intraepithelial neoplasia Grade 1 (CIN1), Grade 2 (CIN2), Grade 3 (CIN3), and cervical cancer (CC) groups based on histopathology. We performed HPV testing, liquid-based cytology, and PAX1/SOX1 gene methylation testing. We evaluated the diagnostic value of methylation detection in cervical cancer using DNA methylation positivity rate, sensitivity, specificity, and area under the curve (AUC), and explored its potential for triage diagnosis. PAX1/SOX1 methylation positivity rates were: control 17.1%, CIN1 22.5%, CIN2 100.0%, CIN3 90.0%, and CC 100.0%. The AUC values for PAX1 gene methylation detection in diagnosing CIN1+, CIN2+, and CIN3+ were 0.52 (95% confidence interval [CI]: 0.43-0.62), 0.88 (95% CI: 0.80-0.97), and 0.88 (95% CI: 0.75-1.00), respectively. Corresponding AUC values for SOX1 gene methylation detection were 0.47 (95% CI: 0.40-0.58), 0.80 (95% CI: 0.68-0.93), and 0.92 (95% CI: 0.811-1.00), respectively. In HPV16/18-negative patients, methylation detection showed sensitivity of 32.4% and specificity of 83.7% for CIN1+. For CIN2+ and CIN3+, sensitivity was all 100%, with specificities of 83.0% and 81.1%. Among the patients who underwent colposcopy examination, 166 cases had cytological examination results ≤ASCUS, of which 37 cases were positive for methylation, and the colposcopy referral rate was 22.29%. PAX1/SOX1 gene methylation detection exhibits strong diagnostic efficacy for cervical precancerous lesions and holds significant value in triage diagnosis.


Asunto(s)
Metilación de ADN , Factores de Transcripción Paired Box , Infecciones por Papillomavirus , Factores de Transcripción SOXB1 , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Biomarcadores de Tumor/genética , China , Colposcopía , Detección Precoz del Cáncer/métodos , Factores de Transcripción Paired Box/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Sensibilidad y Especificidad , Factores de Transcripción SOXB1/genética , Triaje/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética
15.
Angew Chem Int Ed Engl ; : e202407748, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818639

RESUMEN

Selective producing ethanol from CO2 electroreduction is highly demanded, yet the competing ethylene generation route is commonly more thermodynamically preferred. Herein, we reported an efficient CO2-to-ethanol conversion (53.5 % faradaic efficiency at -0.75 V versus reversible hydrogen electrode (vs. RHE)) over an oxide-derived nanocubic catalyst featured with abundant "embossment-like" structured grain-boundaries. The catalyst also attains a 23.2 % energy efficiency to ethanol within a flow cell reactor. In situ spectroscopy and electrochemical analysis identified that these dualphase Cu(I) and Cu(0) sites stabilized by grain-boundaries are very robust over the operating potential window, which maintains a high concentration of co-adsorbed *CO and hydroxyl (*OH) species. Theoretical calculations revealed that the presence of *OHad not only promote the easier dimerization of *CO to form *OCCO (ΔG~0.20 eV) at low overpotentials but also preferentially favor the key *CHCOH intermediate hydrogenation to *CHCHOH (ethanol pathway) while suppressing its dehydration to *CCH (ethylene pathway), which is believed to determine the remarkable ethanol selectivity. Such imperative intermediates associated with the bifurcation pathway were directly distinguished by isotope labelling in situ infrared spectroscopy. Our work promotes the understanding of bifurcating mechanism of CO2ER-to-hydrocarbons more deeply, providing a feasible strategy for the design of efficient ethanol-targeted catalysts.

16.
BMJ Open ; 14(5): e083888, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821572

RESUMEN

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.


Asunto(s)
Trastornos de la Conciencia , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Humanos , Estimulación del Nervio Vago/métodos , Trastornos de la Conciencia/terapia , Trastornos de la Conciencia/fisiopatología , China , Estimulación Eléctrica Transcutánea del Nervio/métodos , Estado de Conciencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Estudios Multicéntricos como Asunto , Recuperación de la Función , Femenino , Resultado del Tratamiento , Masculino
17.
Clin Nutr ; 43(6): 1475-1487, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723301

RESUMEN

BACKGROUND & AIMS: The past few decades have witnessed a rapid growth in the prevalence of nonalcoholic fatty liver disease (NAFLD). While the ketogenic diet (KD) is considered for managing NAFLD, the safety and efficacy of the KD on NAFLD has been a controversial topic. Here, we aimed to investigate the effect of KD of different durations on metabolic endpoints in mice with NAFLD and explore the underlying mechanisms. METHODS: NAFLD mice were fed with KD for 1, 2, 4 and 6 weeks, respectively. The blood biochemical indexes (blood lipids, AST, ALT and etc.) and liver fat were measured. The LC-MS/MS based proteomic analysis was performed on liver tissues. Metallothionein-2 (MT2) was knocked down with adeno-associated virus (AAV) or small interfering RNA (siRNA) in NAFLD mice and AML-12 cells, respectively. H&E, BODIPY and ROS staining were performed to examine lipid deposition and oxidative stress. Furthermore, MT2 protein levels, nucleus/cytoplasm distribution and DNA binding activity of peroxisome proliferators-activated receptors α (PPARα) were evaluated. RESULTS: KD feeding for 2 weeks showed the best improvement on NAFLD phenotype. Proteomic analysis revealed that MT2 was a key candidate for different metabolic endpoints of NAFLD affected by different durations of KD feeding. MT2 knockdown in NAFLD mice blocked the effects of 2 weeks of KD feeding on HFD-induced steatosis. In mouse primary hepatocytes and AML-12 cells, MT2 protein levels were induced by ß-hydroxybutyric acid (ß-OHB). MT2 Knockdown blunted the effects of ß-OHB on alleviating PA-induced lipid deposition. Mechanistically, 2 weeks of KD or ß-OHB treatment reduced oxidative stress and upregulated the protein levels of MT2 in nucleus, which subsequently increased its DNA binding activity and PPARα protein expression. CONCLUSIONS: Collectively, these findings indicated that KD feeding prevented NAFLD in a time dependent manner and MT2 is a potential target contributing to KD improvement on steatosis.


Asunto(s)
Dieta Cetogénica , Metalotioneína , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Regulación hacia Arriba , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/genética , Metalotioneína/genética , Metalotioneína/metabolismo , Dieta Cetogénica/métodos , Ratones , Masculino , Hígado/metabolismo , Antioxidantes/metabolismo , PPAR alfa/metabolismo , PPAR alfa/genética , Modelos Animales de Enfermedad , Metabolismo de los Lípidos , Factores de Tiempo
18.
Nanoscale ; 16(23): 11126-11137, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38787697

RESUMEN

Natural killer T (NKT) cell-mediated immunotherapy shows great promise in hepatocellular carcinoma featuring an inherent immunosuppressive microenvironment. However, targeted delivery of NKT cell agonists remains challenging. Here, we developed a hyaluronic acid (HA) modified metal organic framework (zeolitic imidazolate framework-8, ZIF-8) to encapsulate α-galactosylceramide (α-Galcer), a classic NKT cell agonist, and doxorubicin (DOX) for eliminating liver cancer, denoted as α-Galcer/DOX@ZIF-8@HA. In the tumor microenvironment (TME), these pH-responsive nano-frameworks can gradually collapse to release α-Galcer for activating NKT cells and further boosting other immune cells in order to initiate an antitumor immune cascade. Along with DOX, the released α-Galcer enabled efficient NKT cell activation in TME for synergistic immunotherapy and tumor elimination, leading to evident tumor suppression and prolonged animal survival in both subcutaneous and orthotopic liver tumor models. Manipulating NKT cell agonists into functional nano-frameworks in TME may be matched with other advanced managements applied in a wider range of cancer therapies.


Asunto(s)
Carcinoma Hepatocelular , Doxorrubicina , Galactosilceramidas , Ácido Hialurónico , Inmunoterapia , Neoplasias Hepáticas , Células T Asesinas Naturales , Microambiente Tumoral , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Animales , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Ratones , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Galactosilceramidas/química , Galactosilceramidas/farmacología , Humanos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Línea Celular Tumoral , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Nanopartículas/química , Nanopartículas/uso terapéutico
19.
J Environ Manage ; 360: 121020, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38763116

RESUMEN

Reducing soil erosion (SE) is crucial for achieving harmony between human society and the ecological environment. The cultivated land fragmentation (CLF), directly or indirectly, alters soil structure, diminishes its water-holding capacity, and escalates the risk of SE. Scientific assessment of the effect of CLF on SE can provide new insights into controlling of SE across watersheds in China. However, few studies have quantified the effect of CLF on SE. Therefore, we utilized land use change data in the Yangtze River basin from 2000 to 2020, measuring the levels of CLF and SE using Fragstats and InVEST models. The bivariate spatial autocorrelation model was employed to reveal the spatial relationship between CLF and SE. Additionally, we constructed a spatial Durbin model and introduced the geographically and temporally weighted regression model to analyze the role of CLF on SE. The south bank of the upper and middle reaches of the Yangtze River basin exhibited high CLF and SE. The bivariate spatial autocorrelation results showed a significant positive spatial correlation between CLF and SE. The spatial Durbin model results showed that CLF had a spatial spillover effect and time lag on SE, and the effect of CLF on SE had an inverted "N" curve. The study also confirmed that last SE and neighboring SE areas influenced local SE. Currently, CLF had a negative effect on SE in the Sichuan Basin, Yunnan-Guizhou Plateau, and the middle and lower Yangtze River Plain, and positively in Qinghai, Hunan, and Jiangxi provinces. These findings suggest that the government should enhance cross-regional and cross-sectoral cooperation and monitoring of cultivated land changes to prevent and control SE effectively.


Asunto(s)
Ríos , Erosión del Suelo , Suelo , China , Suelo/química , Conservación de los Recursos Naturales , Agricultura , Monitoreo del Ambiente
20.
BMC Public Health ; 24(1): 1212, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693488

RESUMEN

BACKGROUND: Combining smoking with poor eating habits significantly elevates the risk of chronic illnesses and early death. Understanding of how dietary quality shifts post-smoking cessation remains limited. The objective of this study is to examine dietary quality - using Healthy Eating Index (HEI - 2020) and its 13 components, among current, former, and never smokers, and particularly the impact of quitting and the duration of cessation on dietary habits. METHODS: A cross-sectional analysis of 31,569 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 was conducted. Dietary quality was assessed using HEI-2020 scores, which were determined by NIH developed - simple HEI scoring algorithm per person. Smoking status was categorized into current, former, and never smokers, with further subdivisions for current (heavy/light smokers) and former smokers (duration post-cessation). Descriptive analysis and multiple regression models weighted to represent the US population were performed. RESULTS: The current smoking rate was 19.4%, with a higher prevalence in males (22.5%) than females (17.5%). Current smokers reported statistically significantly lower HEI total score than both former and never smokers. Former smokers exhibited HEI scores similar to those of never smokers. The adjusted HEI total scores for current, former, and never smokers were 49.2, 54.0, and 53.3, respectively, with a statistically significant difference (p < 0.001). Moreover, light smokers had better total HEI score than heavy smokers (46.8 vs. 50.8, p < 0.001, respectively), but former and never smokers scored even higher. Quitting smoking immediately improved dietary quality, with former smokers reaching the dietary levels of never smokers within 5-10 years (53.8 vs. 53.3, p > 0.05, respectively). Compared to current smokers, former smokers tended to consume more beneficial foods (e.g., fruits, vegetables, greens and beans, whole grains, proteins, and fatty acids), while also consuming more sodium and less added sugar. CONCLUSIONS: Current smokers, particularly heavy smokers, exhibit poorer dietary habits than former and never smokers. The dietary quality of former smokers aligns with never smokers over time, highlighting the positive impact of smoking cessation on diet. This has implications for reducing chronic disease risks associated with poor diet and smoking.


Asunto(s)
Dieta Saludable , Encuestas Nutricionales , Fumar , Humanos , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Dieta Saludable/estadística & datos numéricos , Estados Unidos/epidemiología , Fumar/epidemiología , Adulto Joven , Cese del Hábito de Fumar/estadística & datos numéricos , Anciano , Conducta Alimentaria
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