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1.
J Environ Sci (China) ; 147: 630-641, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003078

RESUMEN

Cadmium (Cd) and arsenic (As) co-contamination has threatened rice production and food safety. It is challenging to mitigate Cd and As contamination in rice simultaneously due to their opposite geochemical behaviors. Mg-loaded biochar with outstanding adsorption capacity for As and Cd was used for the first time to remediate Cd/As contaminated paddy soils. In addition, the effect of zero-valent iron (ZVI) on grain As speciation accumulation in alkaline paddy soils was first investigated. The effect of rice straw biochar (SC), magnesium-loaded rice straw biochar (Mg/SC), and ZVI on concentrations of Cd and As speciation in soil porewater and their accumulation in rice tissues was investigated in a pot experiment. Addition of SC, Mg/SC and ZVI to soil reduced Cd concentrations in rice grain by 46.1%, 90.3% and 100%, and inorganic As (iAs) by 35.4%, 33.1% and 29.1%, respectively, and reduced Cd concentrations in porewater by 74.3%, 96.5% and 96.2%, respectively. Reductions of 51.6% and 87.7% in porewater iAs concentrations were observed with Mg/SC and ZVI amendments, but not with SC. Dimethylarsinic acid (DMA) concentrations in porewater and grain increased by a factor of 4.9 and 3.3, respectively, with ZVI amendment. The three amendments affected grain concentrations of iAs, DMA and Cd mainly by modulating their translocation within plant and the levels of As(III), silicon, dissolved organic carbon, iron or Cd in porewater. All three amendments (SC, Mg/SC and ZVI) have the potential to simultaneously mitigate Cd and iAs accumulation in rice grain, although the pathways are different.


Asunto(s)
Arsénico , Cadmio , Carbón Orgánico , Magnesio , Oryza , Contaminantes del Suelo , Suelo , Oryza/química , Cadmio/análisis , Cadmio/química , Carbón Orgánico/química , Contaminantes del Suelo/análisis , Arsénico/análisis , Suelo/química , Magnesio/química , Hierro/química , Restauración y Remediación Ambiental/métodos
2.
J Environ Sci (China) ; 147: 714-725, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003084

RESUMEN

In this study, an efficient stabilizer material for cadmium (Cd2+) treatment was successfully prepared by simply co-milling olivine with magnesite. Several analytical methods including XRD, TEM, SEM and FTIR, combined with theoretical calculations (DFT), were used to investigate mechanochemical interfacial reaction between two minerals, and the reaction mechanism of Cd removal, with ion exchange between Cd2+ and Mg2+ as the main pathway. A fixation capacity of Cd2+ as high as 270.61 mg/g, much higher than that of the pristine minerals and even the individual/physical mixture of milled olivine and magnesite, has been obtained at optimized conditions, with a neutral pH value of the solution after treatment to allow its direct discharge. The as-proposed Mg-based stabilizer with various advantages such as cost benefits, green feature etc., will boosts the utilization efficiency of natural minerals over the elaborately prepared adsorbents.


Asunto(s)
Cadmio , Compuestos de Hierro , Compuestos de Magnesio , Silicatos , Contaminantes Químicos del Agua , Cadmio/química , Contaminantes Químicos del Agua/química , Compuestos de Magnesio/química , Silicatos/química , Compuestos de Hierro/química , Adsorción , Modelos Químicos , Purificación del Agua/métodos
3.
J Environ Sci (China) ; 148: 375-386, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095172

RESUMEN

Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River-which is the longest river in China. As phytoplankton are sensitive indicators of trophic changes in water bodies, characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control. Here, we used direct microscopic count and environmental DNA (eDNA) metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin (Chengdu, Sichuan Province, China). The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis. Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling. At the phylum level, the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta, Chlorophyta, and Cyanophyta, in contrast with Chlorophyta, Dinophyceae, and Bacillariophyta identified by eDNA metabarcoding. In α-diversity analysis, eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method. Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios > 16:1 in all water samples. Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth. The results could be useful for implementing comprehensive management of the river basin environment. It is recommended to control the discharge of point- and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients (e.g., Jianyang-Ziyang). Algae monitoring techniques and removal strategies should be improved in 201 Hospital, Hongrihe Bridge and Colmar Town areas.


Asunto(s)
Monitoreo del Ambiente , Fitoplancton , Ríos , Ríos/química , China , Contaminantes Químicos del Agua/análisis , Fósforo/análisis
4.
Antiviral Res ; : 105974, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39089331

RESUMEN

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 µg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 µg and 20 µg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

5.
World J Stem Cells ; 16(7): 739-741, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39086559

RESUMEN

Recently, we read an article published by the Yang et al. The results of this study indicated that engineered exosomes loaded with microRNA-29a (miR-29a) alleviate knee inflammation and maintain extracellular matrix stability in Sprague Dawley rats. The study's results provide useful information for treating knee osteoarthritis (KOA). This letter, shares our perspectives on treating KOA using engineered exosomes for miR-29a.

7.
Cell ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39094568

RESUMEN

Innate immune responses to microbial pathogens are regulated by intracellular receptors known as nucleotide-binding leucine-rich repeat receptors (NLRs) in both the plant and animal kingdoms. Across plant innate immune systems, "helper" NLRs (hNLRs) work in coordination with "sensor" NLRs (sNLRs) to modulate disease resistance signaling pathways. Activation mechanisms of hNLRs based on structures are unknown. Our research reveals that the hNLR, known as NLR required for cell death 4 (NRC4), assembles into a hexameric resistosome upon activation by the sNLR Bs2 and the pathogenic effector AvrBs2. This conformational change triggers immune responses by facilitating the influx of calcium ions (Ca2+) into the cytosol. The activation mimic alleles of NRC2, NRC3, or NRC4 alone did not induce Ca2+ influx and cell death in animal cells, suggesting that unknown plant-specific factors regulate NRCs' activation in plants. These findings significantly advance our understanding of the regulatory mechanisms governing plant immune responses.

9.
Small ; : e2402674, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096071

RESUMEN

Hydrolytic enzymes are essential components in second-generation biofuel technology and food fermentation processes. Nanozymes show promise for large-scale industrial applications as replacements for natural enzymes due to their distinct advantages. However, there remains a research gap concerning glycosidase nanozymes. In this study, a Zn-based single-atom nanozyme (ZnN4-900) is developed for efficient glycosidic bond hydrolysis in an aqueous solution. The planar structure of the class-porphyrin N4 material approximatively mimicked the catalytic centers of natural enzymes, facilitating oxidase-like (OXD-like) activity and promoting glycosidic bond cleavage. Theoretical calculations show that the Zn site can act as Lewis acids, attacking the C─O bond in glycosidic bonds. Additionally, ZnN4-900 has the ability to degrade starch and produce reducing sugars that increased yeast cell biomass by 32.86% and ethanol production by 14.56%. This catalyst held promising potential for enhancing processes in ethanol brewing and starch degradation industries.

10.
BMC Mol Cell Biol ; 25(1): 19, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090552

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underlying mechanisms driving this phenomenon remain elusive. This study aims to shed light on this issue by examining alterations in paternally imprinted genes within sperm. METHODS: A cohort of 35 individuals with normal semen analysis, comprising 17 hepatitis B surface antigen (HBsAg)-positive and 18 negative individuals, was recruited. Based on the previous research and the Online Mendelian Inheritance in Man database (OMIM, https://www.omim.org/ ), targeted promoter methylation sequencing was employed to investigate 28 paternally imprinted genes associated with various diseases. RESULTS: Bioinformatic analyses revealed 42 differentially methylated sites across 29 CpG islands within 19 genes and four differentially methylated CpG islands within four genes. At the gene level, an increase in methylation of DNMT1 and a decrease in methylation of CUL7, PRKAG2, and TP53 were observed. DNA methylation haplotype analysis identified 51 differentially methylated haplotypes within 36 CpG islands across 22 genes. CONCLUSIONS: This is the first study to explore the effects of HBV infection on sperm DNA methylation and the potential underlying mechanisms of intergenerational influence of paternal HBV infection.


Asunto(s)
Islas de CpG , Metilación de ADN , Impresión Genómica , Virus de la Hepatitis B , Hepatitis B , Regiones Promotoras Genéticas , Espermatozoides , Humanos , Masculino , Metilación de ADN/genética , Regiones Promotoras Genéticas/genética , Espermatozoides/metabolismo , Islas de CpG/genética , Impresión Genómica/genética , Hepatitis B/genética , Hepatitis B/virología , Adulto , Virus de la Hepatitis B/genética , Haplotipos/genética , Persona de Mediana Edad
11.
J Am Chem Soc ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052434

RESUMEN

As the most promising hydrogen evolution reaction (HER) electrocatalysts, platinum (Pt)-based catalysts still struggle with sluggish kinetics and expensive costs in alkaline media. Herein, we accelerate the alkaline hydrogen evolution kinetics by optimizing the local environment of Pt species and metal oxide heterointerfaces. The well-dispersed PtRu bimetallic clusters with adjacent MO2-x (M = Sn and Ce) on carbon nanotubes (PtRu/CNT@MO2-x) are demonstrated to be a potential electrocatalyst for alkaline HER, exhibiting an overpotential of only 75 mV at 100 mA cm-2 in 1 M KOH. The excellent mass activity of 12.3 mA µg-1Pt+Ru and specific activity of 32.0 mA cm-2ECSA at an overpotential of 70 mV are 56 and 64 times higher than those of commercial Pt/C. Experimental and theoretical investigations reveal that the heterointerfaces between Pt clusters and MO2-x can simultaneously promote H2O adsorption and activation, while the modification with Ru further optimizes H adsorption and H2O dissociation energy barriers. Then, the matching kinetics between the accelerated elementary steps achieved superb hydrogen generation in alkaline media. This work provides new insight into catalytic local environment design to simultaneously optimize the elementary steps for obtaining ideal alkaline HER performance.

12.
Nano Lett ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052908

RESUMEN

Multimodal luminescent materials hold great promise in a diversity of frontier applications. However, achieving the multimodal responsive luminescence at the single nanoparticle level, especially besides light stimuli, has remained a challenge. Here, we report a conceptual model to realize multimodal luminescence by constructing both mechanoluminescence and photoluminescence in a single nanoparticle. We show that the lanthanide-doped fluoride nanoparticles are able to produce excellent mechanoluminescence through X-ray irradiation, and color-tunable mechanoluminescence becomes available by selecting suitable lanthanide emitters in a core-shell-shell structure. Furthermore, the design of a multilayer core-shell nanostructure enables multimodal emissions including radioluminescence, persistent luminescence, mechanoluminescence, upconversion, downshifting, and thermal-stimulated luminescence simultaneously in a single nanoparticle under multichannel excitation and stimuli. These results provide new insights into the mechanism of X-ray induced mechanoluminescence in nanocrystals and contribute to the development of smart luminescent materials toward X-ray imaging encryption, stress sensing, and anticounterfeiting.

13.
Mol Cell Neurosci ; 130: 103954, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39032719

RESUMEN

BACKGROUND: Tau post-translational modifications (PTMs) result in the gradual build-up of abnormal tau and neuronal degeneration in tauopathies, encompassing variants of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Tau proteolytically cleaved by active caspases, including caspase-6, may be neurotoxic and prone to self-aggregation. Also, our recent findings show that caspase-6 truncated tau represents a frequent and understudied aspect of tau pathology in AD in addition to phospho-tau pathology. In AD and Pick's disease, a large percentage of caspase-6 associated cleaved-tau positive neurons lack phospho-tau, suggesting that many vulnerable neurons to tau pathology go undetected when using conventional phospho-tau antibodies and possibly will not respond to phospho-tau based therapies. Therefore, therapeutic strategies against caspase cleaved-tau pathology could be necessary to modulate the extent of tau abnormalities in AD and other tauopathies. METHODS: To understand the timing and progression of caspase activation, tau cleavage, and neuronal death, we created two mAbs targeting caspase-6 tau cleavage sites and probed postmortem brain tissue from an individual with FTLD due to the V337M MAPT mutation. We then assessed tau cleavage and apoptotic stress response in cortical neurons derived from induced pluripotent stem cells (iPSCs) carrying the FTD-related V337M MAPT mutation. Finally, we evaluated the neuroprotective effects of caspase inhibitors in these iPSC-derived neurons. RESULTS: FTLD V337M MAPT postmortem brain showed positivity for both cleaved tau mAbs and active caspase-6. Relative to isogenic wild-type MAPT controls, V337M MAPT neurons cultured for 3 months post-differentiation showed a time-dependent increase in pathogenic tau in the form of caspase-cleaved tau, phospho-tau, and higher levels of tau oligomers. Accumulation of toxic tau species in V337M MAPT neurons was correlated with increased vulnerability to pro-apoptotic stress. Notably, this mutation-associated cell death was pharmacologically rescued by the inhibition of effector caspases. CONCLUSIONS: Our results suggest an upstream, time-dependent accumulation of caspase-6 cleaved tau in V337M MAPT neurons promoting neurotoxicity. These processes can be reversed by caspase inhibition. These results underscore the potential of developing caspase-6 inhibitors as therapeutic agents for FTLD and other tauopathies. Additionally, they highlight the promise of using caspase-cleaved tau as biomarkers for these conditions.

14.
BMC Neurol ; 24(1): 254, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048961

RESUMEN

OBJECTIVE: The primary objective of this study was to explore the clinical characteristics of apoplectic intratumoral hemorrhage in gliomas and offer insights for improving the diagnosis and treatment of this disease. METHODS: We analyzed the clinical data of 35 patients with glioma and hemorrhage. There were eight cases of multiple cerebral lobe involvement, and 22 cases involved a single lobe. Twenty-one patients had a preoperative Glasgow Coma Scale (GCS) score of ≥ 9 and had a craniotomy with tumor resection and hematoma evacuation after undergoing preoperative preparation. A total of 14 patients with GCS < 9, including one with thalamic hemorrhage breaking into the ventricles and acute obstructive hydrocephalus, underwent craniotomy for tumor resection after external ventricular drainage (EVD). One patient had combined thrombocytopenia, which was surgically treated after platelet levels were normalized through transfusion. The remaining 12 patients received immediate intervention in the form of craniotomy hematoma evacuation and tumor resection. RESULTS: We performed subtotal resection on three tumors of thalamic origin and two tumors of corpus callosum origin, but we were able to successfully resect all the tumors in other locations that were gross total resection Pathology results showed that 71.43% of cases accounted for WHO-grade 4 tumors. Among the 21 patients with a GCS score of ≥ 9, two died perioperatively. Fourteen patients had a GCS score < 9, of which eight patients died perioperatively. CONCLUSIONS: Patients with a preoperative GCS score ≥ 9 who underwent subemergency surgery and received aggressive treatment showed a reasonable prognosis. We found their long-term outcomes to be correlated with the pathology findings. On the other hand, patients with a preoperative GCS score < 9 required emergency treatment and had a high perioperative mortality rate.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Glioma/complicaciones , Glioma/cirugía , Masculino , Femenino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/complicaciones , Persona de Mediana Edad , Adulto , Anciano , Adulto Joven , Adolescente , Hemorragia Cerebral/cirugía , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/complicaciones , Niño , Craneotomía/métodos , Escala de Coma de Glasgow , Estudios Retrospectivos , Resultado del Tratamiento
15.
J Orthop Surg Res ; 19(1): 429, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054551

RESUMEN

BACKGROUND: The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. METHODS: Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136-1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p < 0.05, OR > 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. CONCLUSIONS: This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.


Asunto(s)
Hipertiroidismo , Análisis de la Aleatorización Mendeliana , Osteoartritis , Análisis de Secuencia de ARN , Triyodotironina , Análisis de la Aleatorización Mendeliana/métodos , Osteoartritis/genética , Humanos , Hipertiroidismo/genética , Hipertiroidismo/complicaciones , Triyodotironina/sangre , Análisis de Secuencia de ARN/métodos , Condrocitos/metabolismo , Diferenciación Celular/genética , Progresión de la Enfermedad
16.
Biomimetics (Basel) ; 9(7)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-39056847

RESUMEN

The present investigations on tandem wing configurations primarily revolve around the effects of the spacing L and the phase difference φ between the forewing and the hindwing on aerodynamic performance. However, in nature, organisms employing biplane flight, such as dragonflies, demonstrate the ability to achieve superior aerodynamic performance by flexibly adjusting their flapping trajectories. Therefore, this study focuses on the effects of φ, as well as the trajectory of the hindwing, on aerodynamic performance. By summarizing four patterns of wake-wing interaction processes, it is indicated that φ=-90∘ and 0∘ enhances the thrust of the hindwing, while φ=90∘ and 180∘ result in reductions. Furthermore, the wake-wing interactions and shedding modes are summarized corresponding to three kinds of trajectories, including elliptical trajectories, figure-eight trajectories, and double figure-eight trajectories. The results show that the aerodynamic performance of the elliptical trajectory is similar to that of the straight trajectory, while the figure-eight trajectory with positive surging motion significantly enhances the aerodynamic performance of the hindwing. Conversely, the double-figure-eight trajectory degrades the aerodynamic performance of the hindwing.

17.
Nat Commun ; 15(1): 6123, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033143

RESUMEN

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.


Asunto(s)
Antibacterianos , Biopelículas , Farmacorresistencia Bacteriana Múltiple , Genoma Bacteriano , Filogenia , Salmonella typhimurium , Secuenciación Completa del Genoma , Salmonella typhimurium/genética , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , China , Genoma Bacteriano/genética , Plásmidos/genética , Pruebas de Sensibilidad Microbiana , Humanos , Infecciones por Salmonella/microbiología
18.
Obes Res Clin Pract ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054194

RESUMEN

OBJECTIVE: This study aimed to define the calf proportion index (CPI) and investigate its association with malnutrition and survival in overweight and obese patients with cancer. METHODS: This multicenter observational cohort study included 3499 patients diagnosed with cancer, including 3145 overweight and 354 obese individuals. The CPI was defined as the ratio of the cross-sectional area of the calf circumference (CC) to the body surface area (BSA). A CPI calculator that automatically calculated the CPI and survival probability based on the patient's sex, height, weight, and CC was developed. RESULTS: During a median follow-up of 44.1 months, 935 deaths were recorded. Receiver operating characteristic curves revealed that the CPI was better than CC and BSA as a predictor of survival, with AUCs for the 3-year mortality rate were 0.574, 0.553 and 0.529, respectively. In overweight and obese patients with cancer, the optimal CPI cut-off value was 0.65 % for men and 0.57 % for women. The Kaplan-Meier curve revealed that patients with a low CPI had lower survival. After adjusting confounding factors, a low CPI was an independent risk factor for overweight (hazard ratio [HR]: 1.29, 95 % confidence interval [CI]: 1.11-1.51, P < 0.001) and obesity (HR: 1.92, 95 % CI: 1.20-3.09, P = 0.007) in patients with cancer. The CPI exhibited significant prognostic value in patients with lung and digestive system cancers. The risk of malnutrition was significantly higher in patients with a low CPI (HR: 1.25, 95 % CI: 1.04-1.50, P = 0.019). CONCLUSIONS: The CPI is a useful prognostic indicator in overweight and obese patients with cancer, especially in obese patients.

19.
Nat Nanotechnol ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054386

RESUMEN

Gamma-delta (γδ) T cell-based cancer immunotherapies represent a promising avenue for cancer treatment. However, their development is challenged by the limited expansion and differentiation of the cells ex vivo. Here we induced the endogenous expansion and activation of γδ T cells through oral administration of garlic-derived nanoparticles (GNPs). We found that GNPs could significantly promote the proliferation and activation of endogenous γδ T cells in the intestine, leading to generation of large amount of interferon-γ (IFNγ). Moreover GNP-treated mice showed increased levels of chemokine CXCR3 in intestinal γδ T cells, which can drive their migration from the gut to the tumour environment. The translocation of γδ T cells and IFNγ from the intestine to extraintestinal subcutaneous tumours remodels the tumour immune microenvironment and synergizes with anti-PD-L1, inducing robust antitumour immunity. Our study delineates mechanistic insight into the complex gut-tumour interactome and provides an alternative approach for γδ T cell-based immunotherapy.

20.
Discov Med ; 36(186): 1430-1440, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39054714

RESUMEN

BACKGROUND: Keloid, a fibroproliferative disorder, significantly impacts patients' quality of life, yet effective therapies remain elusive. This study explored the role of silent information regulator 6 (SIRT6) in modulating the proliferation, invasion, and collagen synthesis of keloid fibroblasts. METHODS: Keloid and normal skin specimens were collected, and fibroblasts were isolated from the keloid tissue. SIRT6 recombinant adenovirus (Ad) was constructed to infect keloid fibroblasts to overexpress SIRT6. This study entails three groups: Control group, adenovirus-Negative Control (Ad-NC) group, and Ad-SIRT6 group. SIRT6 protein and mRNA levels were measured via Western blotting and Quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Cell viability was determined using 5-ethynyl-2'-deoxyuridine (EdU) assay. Flow cytometry was exploited to measure cell apoptosis. To investigate cell migration, wound healing assay and Transwell assay were employed. Western blotting was also utilized to study the expression levels of apoptotic proteins, collagen deposition-related proteins, and Mitogen-Activated Protein Kinases (MAPK)/extracellular regulated protein kinases (ERK) pathway-related proteins. RESULTS: Compared to the control and Ad-NC groups, the Ad-SIRT6 group exhibited significantly elevated SIRT6 level; diminished cell proliferation, migration and invasion; reduced protein levels of α-smooth muscle actin (α-SMA), collagen I, collagen III, phospho SMAD Family Member 3 (p-Smad3), transforming growth factor-ß 1 (TGF-ß1), and MAPK/ERK pathway proteins (phospho extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phospho MAP kinase-ERK kinase (p-MEK) and phospho-c-Raf (p-c-Raf)). Treatment with epidermal growth factor (EGF), an MAPK/ERK pathway agonists, reversed the inhibitory effect of SIRT6 on cell activity and inhibited apoptosis in keloid fibroblasts. CONCLUSION: SIRT6 overexpression in keloid fibroblasts attenuates proliferation, invasion, and collagen synthesis, while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity. This suggests a potential therapeutic target for keloid treatment.


Asunto(s)
Proliferación Celular , Colágeno , Fibroblastos , Queloide , Sistema de Señalización de MAP Quinasas , Sirtuinas , Humanos , Sirtuinas/metabolismo , Sirtuinas/genética , Queloide/patología , Queloide/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Colágeno/biosíntesis , Colágeno/metabolismo , Apoptosis/genética , Movimiento Celular , Masculino , Femenino , Células Cultivadas , Adulto
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