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1.
Sci Rep ; 14(1): 22959, 2024 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-39362976

RESUMEN

Gastric cancer (GC) is one of the most challenging malignant tumors worldwide, primarily because of its high incidence and mortality rates. Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been established as a pivotal factor for facilitating cell proliferation, invasion, and metastasis across multiple human tumors. Nevertheless, the precise role of P4HA3in GC has not been fully elucidated. In this study, we used data from The Cancer Genome Atlas (TCGA) to examine the role of P4HA3 as a potential biomarker for predicting immunotherapy response in patients with GC. Our comprehensive analysis of data from the TCGA, TIMER, and other databases revealed a significant association between elevated P4HA3 expression in GC and adverse prognostic outcomes. Furthermore, we confirmed that P4HA3 expression was strongly correlated with immune infiltrating cells, immune infiltration markers, the tumor mutational burden (TMB), microsatellite instability (MSI), the immune score, the stromal score, and immune checkpoints, thus highlighting P4HA3 as a crucial and dependable therapeutic target within the context of immune-based antitumor strategies. Our findings suggest that P4HA3 may function as an immune-related biomarker in the pathogenesis and treatment of GC, indicating that P4HA3 is a promising prognostic and therapeutic target for this malignancy.


Asunto(s)
Biomarcadores de Tumor , Inmunoterapia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Biomarcadores de Tumor/metabolismo , Pronóstico , Inmunoterapia/métodos , Regulación Neoplásica de la Expresión Génica , Procolágeno-Prolina Dioxigenasa/metabolismo , Procolágeno-Prolina Dioxigenasa/genética , Femenino , Inestabilidad de Microsatélites , Masculino , Mutación
2.
PLoS One ; 19(10): e0311625, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39365811

RESUMEN

Depression is accompanied by dyslipidemia, which may increase the risk of stroke and coronary heart disease. This study sought to quantitatively summarize the clinical data comparing peripheral blood triglyceride (TG) concentrations between patients with major depressive disorder (MDD) and healthy controls (HCs). Studies were searched in PubMed, EMBASE, PsycINFO, and Cochrane Databases up to March 2023. We also reviewed the reference lists of obtained articles. Mean (±SD) for TG concentrations were extracted, combined quantitatively using random-effects meta-analysis, and summarized as a standardized mean difference (SMD). Subgroup analysis and meta-regression was performed to explore the resource of heterogeneity. Thirty-eight studies measuring the concentrations of peripheral blood TG in 2604 patients with MDD and 3272 HCs were included. Meta-analysis results indicated that TG levels were significant higher in patients with MDD than in HCs (SMD = 0.31, 95% confidence interval [CI]: 0.16 to 0.46, Z46 = 4.05, p < 0.01). Heterogeneity was detected (χ2 = 269.97, p < 0.01, I2 = 85%). Subgroup analysis demonstrated significant differences in TG levels between patients with MDD and HCs depended on age, body mass index and drug use (p < 0.05), but no differences between groups. Meta-regression also found no significant variables. TG level was significantly elevated in depression, which may explain the increased risk of cardiovascular and cerebrovascular events in depression.


Asunto(s)
Trastorno Depresivo Mayor , Triglicéridos , Humanos , Triglicéridos/sangre , Trastorno Depresivo Mayor/sangre , Depresión/sangre
4.
Front Neurol ; 15: 1459678, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301473

RESUMEN

The hallmark pathological features of Alzheimer's disease (AD) consist of senile plaques, which are formed by extracellular ß-amyloid (Aß) deposition, and neurofibrillary tangles, which are formed by the hyperphosphorylation of intra-neuronal tau proteins. With the increase in clinical studies, the in vivo imbalance of iron homeostasis and the dysfunction of synaptic plasticity have been confirmed to be involved in AD pathogenesis. All of these mechanisms are constituted by the abnormal accumulation of misfolded or conformationally altered protein aggregates, which in turn drive AD progression. Proteostatic imbalance has emerged as a key mechanism in the pathogenesis of AD. Ubiquitination modification is a major pathway for maintaining protein homeostasis, and protein degradation is primarily carried out by the ubiquitin-proteasome system (UPS). In this review, we provide an overview of the ubiquitination modification processes and related protein ubiquitination degradation pathways in AD, focusing on the microtubule-associated protein Tau, amyloid precursor protein (APP), divalent metal transporter protein 1 (DMT1), and α-amino-3-hyroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. We also discuss recent advances in ubiquitination-based targeted therapy for AD, with the aim of contributing new ideas to the development of novel therapeutic interventions for AD.

5.
Dalton Trans ; 53(37): 15608-15617, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39233653

RESUMEN

With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.

6.
Front Oncol ; 14: 1442237, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39324002

RESUMEN

Osimertinib, a third-generation inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, exhibits remarkable efficacy in prolonging the survival of patients with non-small cell lung cancer (NSCLC) carrying EGFR mutations, surpassing the efficacy of first- and second-generation EGFR tyrosine kinases. Nevertheless, the emergence of osimertinib resistance is inevitable, necessitating an investigation into the underlying mechanisms. Increasing evidence has revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, play a significant role in the development and progression of lung cancer. These ncRNAs regulate essential signaling pathways, offering a novel avenue for understanding the fundamental mechanisms of osimertinib resistance. Recent studies have reported the significant impact of ncRNAs on osimertinib resistance, achieved through various mechanisms that modulate treatment sensitivity. We provide a concise overview of the functions and underlying mechanisms of extensively researched ncRNAs in the development of osimertinib resistance and emphasize their potential clinical application in EGFR-mutated NSCLC resistant to osimertinib. Finally, we discuss the obstacles that must be addressed to effectively translate ncRNA-based approaches into clinical practice.

7.
Thorac Cancer ; 15(22): 1688-1704, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38984468

RESUMEN

BACKGROUND: Lung cancer (LC) is currently the number one malignancy death rate disease in China, and its disease burden is serious. The study aimed to analyze trends of LC and its risk factor attributable disease in China from 1990 to 2019 and predict the next 41 years. METHODS: The average annual percentage change (AAPC) was used to analyze the trend of LC and its risk factor attributable incidence, deaths, and disability-adjusted life years (DALYs) rate in China from 1990 to 2019, collected in the Global Burden of Disease 2019. Cochran-Armitage trends examine trends in lung cancer disease burden by sex, age, and attributable risk factor groups in China from 1990 to 2019. In addition, based on data on death and DALYs rate due to LC and its risk factors between 1990 and 2019, an autoregressive integrated moving average (ARIMA) model was developed to predict the change in the trend of burden of disease due to LC and its risk factors over the next 41 years, and the model was evaluated using the model parameters root mean square error, mean absolute error, and mean absolute percentage error. RESULTS: From 1990 to 2019, the incidence, mortality and DALYs of LC were all increased. Among the eight risk factors associated with lung cancer, the DALYs rate and mortality rate of lung cancer risk factors for Chinese residents increased from 1990 to 2019, except for household air pollution from solid fuels and diet low in fruit, which showed a decrease; among them, the DALYs rate and mortality rate due to ambient particulate matter pollution showed the greatest increase with AAPC values of 2.880 and 3.310, respectively, while DALYs and mortality rates due to household air pollution from solid fuels showed the largest decreases, with AAPC values of -4.755 and -4.348, respectively. The results of the ARIMA model predictions show that both the mortality rate and the rate of DALYs for lung cancer are increasing yearly, and it is predicted that the rate of DALYs for lung cancer by 2060 will reach 740.095/100 000 and the mortality rate will reach 35.151/100 000. It is expected that by 2060, the top four risk factors for lung cancer in China will be, in order of DALYs rate and mortality rate, smoking, ambient particulate matter pollution, high fasting plasma glucose (HFPG), and secondhand smoke, with HFPG showing the greatest increase. CONCLUSIONS: The LC burden increased from 1990 to 2019 in China, the LC burden that could be attributed to HFPG will continue to increase in the next 40 years, and will be the third most factor by 2060. Targeted interventions are warranted to facilitate the prevention of LC and improvement of health-related quality of life patients with LC.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , China/epidemiología , Factores de Riesgo , Masculino , Femenino , Persona de Mediana Edad , Incidencia , Anciano , Adulto , Costo de Enfermedad , Carga Global de Enfermedades/tendencias , Años de Vida Ajustados por Calidad de Vida
8.
Mol Genet Genomics ; 299(1): 71, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031208

RESUMEN

BACKGROUND: DNA methylation is an important epigenetic modification that plays a crucial role in the development and progression of various tumors. However, the association between methylation­driven genes and diagnosis, prognosis, and immune characteristics of head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: We obtained transcriptome, methylation, and clinical data from HNSCC patients in TCGA database, and used MethylMix algorithm to identify methylation-driven genes. A methylation driven gene-related risk model was constructed using Lasso regression analysis, and validated using data from GEO database. Immune infiltration and immune function analysis of the expression profiles were conducted using ssGSEA. Differences in immune checkpoint-related genes were analyzed, and the efficacy of immunotherapy was evaluated using TCIA database. Finally, a series of cell functional experiments were conducted to validate the results. RESULTS: Five methylation-driven genes were identified and utilized to construct a prognostic risk model. Based on the median risk score, all patients were categorized into high-risk and low-risk groups. The K-M analysis revealed that patients in the high-risk group have a worse prognosis. Additionally, the risk model demonstrated better prognostic predictive value as indicated by ROC analysis. GSEA enrichment analysis indicated that gene sets in the high and low-risk groups were primarily enriched in pathways associated with tumor immunity and metabolism. Our subsequent investigations showed that high-risk patients exhibited more immunosuppressive phenotypes, while low-risk patients were more likely to respond positively to immunotherapy. CONCLUSION: These findings of our research have the potential to improve patient stratification, guide treatment decisions, and advance the development of personalized therapies for HNSCC.


Asunto(s)
Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Transcriptoma , Humanos , Metilación de ADN/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Pronóstico , Transcriptoma/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/diagnóstico , Biomarcadores de Tumor/genética , Masculino , Femenino , Inmunoterapia , Perfilación de la Expresión Génica , Epigénesis Genética , Bases de Datos Genéticas
9.
Micromachines (Basel) ; 15(7)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39064420

RESUMEN

To explore the size, morphology, and distribution patterns of internal pore defects in WE43 magnesium alloy formed by laser powder bed fusion (LPBF), as well as their impact on its mechanical properties, computer tomography (CT), metallographic microscopy, and scanning electron microscopy were used to observe the material's microstructure and the morphology of tensile test fractures. The study revealed that a large number of randomly distributed non-circular pore defects exist internally in the LPBF-formed WE43 magnesium alloy, with a defect volume fraction of 0.16%. Approximately 80% of the defects had equivalent diameters concentrated in the range of 10∼40 µm, and 56.2% of the defects had sphericity values between 0.65∼0.7 µm, with the maximum defect equivalent diameter being 122 µm. There were a few spherical pores around 20 µm in diameter in the specimens, and unfused powder particles were found in pore defects near the edges of the parts. Under the test conditions, the fusion pool structure of LPBF-formed WE43 magnesium alloy resembled a semi-elliptical shape with a height of around 66 µm, capable of fusion three layers of powder material in a single pass. Columnar grains formed at the edge of individual fusion pools, while the central area exhibited equiaxed grains. The "scale-like pattern" formed by overlapping fusion pool structures resulted in the microstructure of LPBF-formed WE43 magnesium alloy mainly consisting of fine equiaxed grains with a size of 2.5 µm and columnar grains distributed in a band-like manner.

10.
Sheng Wu Gong Cheng Xue Bao ; 40(6): 1711-1727, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38914487

RESUMEN

Amino acids as the building blocks of proteins are widely applied in food, medicine, feed, and chemical industries. Amino acid production by microbial cell factories from renewable resources is praised for the environmental friendliness, mild reaction conditions, and high product purity, which helps to achieve the goal of carbon neutrality. Researchers have employed the methods of metabolic engineering and synthetic biology to engineer Escherichia coli and Corynebacterium glutamicum and optimized the culture conditions to construct the microbial cell factories with high performance for producing branched chain amino acids, amino acids of the aspartic acid and glutamic acid families, and aromatic amino acids. We review the engineering process of microbial cell factories for high production of amino acids, in the hope of providing a reference for the creation of high-performance microbial cell factories.


Asunto(s)
Aminoácidos , Corynebacterium glutamicum , Escherichia coli , Ingeniería Metabólica , Ingeniería Metabólica/métodos , Aminoácidos/biosíntesis , Aminoácidos/metabolismo , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Biología Sintética , Microbiología Industrial
11.
J Agric Food Chem ; 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853533

RESUMEN

Microglia phagocytose synapses have an important effect on the pathogenesis of neurological disorders. Here, we investigated the neuroprotective effects of the walnut-derived peptide, TWLPLPR(TW-7), against LPS-induced cognitive deficits in mice and explored the underlying C1q-mediated microglia phagocytose synapses mechanisms in LPS-treated HT22 cells. The MWM showed that TW-7 improved the learning and memory capacity of the LPS-injured mice. Both transmission electron microscopy and immunofluorescence analysis illustrated that synaptic density and morphology were increased while associated with the decreased colocalized synapses with C1q. Immunohistochemistry and immunofluorescence demonstrated that TW-7 effectively reduced the microglia phagocytosis of synapses. Subsequently, overexpression of C1q gene plasmid was used to verify the contribution of the TW-7 via the classical complement pathway-regulated mitochondrial function-mediated microglia phagocytose synapses in LPS-treated HT22 cells. These data suggested that TW-7 improved the learning and memory capability of LPS-induced cognitively impaired mice through a mechanism associated with the classical complement pathway-mediated microglia phagocytose synapse.

13.
Front Genet ; 15: 1366453, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694874

RESUMEN

Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis. Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes' relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement. Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response's significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model. Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment.

14.
Materials (Basel) ; 17(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38793450

RESUMEN

In this study, crumpled graphene oxide balls (CGBs) were prepared via capillary compression using a rapidly evaporating aerosol droplet method. The CGBs were observed using scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and Raman spectroscopy. The size distributions of crumpled particles were obtained using a laser nanometer particle size analyzer (DLS). The dispersibility of the water and the ionic liquid (IL) was tested by ultrasonic dispersion. The tribological properties of water or ionic liquids containing crumpled graphene oxide ball additives (W/IL-CGB) were tested by a reciprocating friction tester and compared with water/ionic liquids with graphene oxide. The morphology of the wear scar was observed by a three-dimensional optical microscope and its lubrication mechanism was analyzed. The results show that the CGBs were successfully prepared by rapid evaporation of aerosol droplets, and the obtained CGBs were crumpled paper spheres. The CGBs had good water dispersion and ionic liquid dispersion, and IL-CGB has excellent anti-friction and anti-wear effects on steel-steel friction pairs. During the friction process, the CGB was adsorbed at the interface of the steel-steel friction pair to form a protective layer, which avoids the direct contact of the friction pair, thereby reducing friction and wear.

15.
Int J Genomics ; 2024: 8846747, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567257

RESUMEN

The MC4-2 bacterium strain was isolated and purified from the Periplaneta americana intestine as a biocontrol agent with good antagonistic effect against the pathogens of a soil-borne disease called tobacco black shank. The MC4-2 strain was found to have good broad-spectrum inhibition by plate stand-off test. Based on 16S rRNA and gyrB genes, ANI analysis, and other comparative genomics methods, it was determined that the MC4-2 strain was Bacillus subtilis. The complete genome sequence showed that the genome size was 4,076,630 bp, the average GC content was 43.78%, and the total number of CDSs was 4,207. Genomic prediction analysis revealed that a total of 145 genes were annotated by the CAZy, containing mainly GH and CE enzymes that break down carbohydrates such as glucose, chitin, starch, and alginate, and a large number of enzymes involved in glycosylation were present. A total of ten secondary metabolite clusters were predicted, six clusters of which were annotated as surfactin, bacillaene, fengycin, bacillibactin, subtilosin A, and bacilysin. The present investigation found the biological control mechanism of B. subtilis MC4-2, which provides a strong theoretical basis for the best use of this strain in biological control methods and provides a reference for the subsequent development of agents of this bacterium.

16.
J Cachexia Sarcopenia Muscle ; 15(3): 1177-1186, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38644549

RESUMEN

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.


Asunto(s)
Peso Corporal , Neoplasias , Humanos , Masculino , Femenino , Neoplasias/mortalidad , Persona de Mediana Edad , Pronóstico , Anciano , Estudios de Cohortes , Adulto
17.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 164-168, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38678607

RESUMEN

This study aimed to explore the effects of miR-129-5p on inflammation and nucleus pulposus (NP) cell apoptosis in rats with intervertebral disc degeneration (IVDD) through the c-Jun N-terminal kinase (JNK) signaling pathway. A total of 20 rats were randomly divided into control group (n=10) or IVDD group (n=10). The mRNA expressions of miR-129-5p and apoptosis index Fas in IVDD tissues were determined using RT-PCR. NP cell apoptosis rate was detected via TUNEL assay. NP cells were extracted from IVDD tissues for primary culture. Subsequently, the cells were transfected with miR-129-5p inhibitor or mimic to inhibit or overexpress miR-129-5p, respectively. Furthermore, the changes in the JNK pathway indexes and apoptosis indexes were detected using Western blotting. In IVDD group, the expression of miR-129-5p was significantly down-regulated, while the transcriptional level of Fas was up-regulated compared with those in control group. Pearson correlation analysis revealed a negative correlation between the expressions of miR-129-5p and Fas mRNA (r=-0.75, P<0.05). IVDD group exhibited significantly higher levels of serum TNF-α, IL-6 and IL-1 than control group. Subsequent TUNEL assay indicated that the apoptosis rate was evidently higher in IVDD group (60.6%) than control group (2.5%). The results of Western blotting showed that the protein expressions of JNK1, JNK2 and Fas remarkably rose in IVDD group compared with those in control group. However, they declined remarkably in miR-129-5p mimic group compared with those in control group. Furthermore, such trends were significantly reversed in miR-129-5p inhibitor group. MiR-129-5p was significantly down-regulated in IVDD, whose overexpression has anti-inflammatory and anti-apoptotic effects.


Asunto(s)
Apoptosis , Inflamación , Degeneración del Disco Intervertebral , Sistema de Señalización de MAP Quinasas , MicroARNs , Núcleo Pulposo , Ratas Sprague-Dawley , Animales , MicroARNs/genética , MicroARNs/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/metabolismo , Apoptosis/genética , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Inflamación/genética , Inflamación/patología , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratas , Receptor fas/genética , Receptor fas/metabolismo
18.
Medicine (Baltimore) ; 103(9): e37394, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38428865

RESUMEN

Therapeutic resistance in cancer remains a dilemma that scientists and oncologists are eager to solve. Despite several preclinical and clinical studies dedicated to overcoming therapeutic resistance, they often do not yield the expected outcomes. This is primarily due to the multifactorial phenomenon of therapeutic resistance. Norcantharidin (NCTD) is an artificial compound derived from cantharidin that has significant anticancer efficacy without incurring serious side effects. Intriguingly, extensive research suggests that NCTD is essential for boosting anticancer efficacy and reversing treatment resistance. This review article presents a full description of how NCTD can effectively overcome cancer resistance to standard treatments such as chemotherapy, radiation, hormone therapy, and targeted therapy. We also discuss the potential prospects and challenges associated with using NCTD as a therapeutic strategy for reversing resistance to cancer therapy. We anticipate that our review will serve as a valuable reference for researchers and clinicians.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Apoptosis , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico
19.
Int Immunopharmacol ; 131: 111815, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38492335

RESUMEN

BACKGROUND: Osteomyelitis is considered as a deleterious inflammatory condition affecting the bone, primarily attributed to pathogenic infection. However, the underlying factors predisposing individuals to osteomyelitis remain incompletely elucidated. The immune system plays a multifaceted role in the progression of this condition, yet previous observational studies and randomized controlled trials investigating the association between circulating immune cell counts and osteomyelitis have been constrained. In order to address this knowledge gap, we conducted a Mendelian randomization (MR) analysis to evaluate the impact of diverse immune cell counts on the risk of developing osteomyelitis. METHODS: In our study, we utilized single nucleotide polymorphisms (SNPs) that have been strongly linked to circulating immune cells or specific lymphocyte subtypes, as identified in large-scale genome-wide association studies (GWAS). These SNPs served as instrumental variables (IVs) for our MR analysis. We employed a more relaxed clumping threshold to conduct MR analysis on several related lymphocyte subtypes. To estimate causal effects, we utilized the Wald ratio, as well as the random-effects inverse variance weighted (IVW) and weighted median (WM) methods. To enhance the credibility of our results, we performed F-statistic calculations and a series of sensitivity analyses. RESULTS: Our findings revealed a significant correlation between the absolute count of circulating lymphocytes and the risk of osteomyelitis [odds ratio(OR) 1.20;95 % confidence interval (CI), 1.08-1.32;P = 0.0005]. Furthermore, we identified a causal relationship between the absolute count of CD8+ T cells and susceptibility to osteomyelitis (OR 1.16; 95 % CI, 1.04-1.30; P = 0.0098). Importantly, these findings remained robust across a wide range of sensitivity analyses. CONCLUSION: Through our MR analysis, we have provided evidence supporting a causal relationship between genetic predisposition to higher circulating immune cell counts and an increased risk of osteomyelitis. Specifically, our findings highlight the association between elevated CD8+ T cell counts and a heightened susceptibility to osteomyelitis. These results offer valuable insights for the future exploration of immunotherapy approaches in the management of osteomyelitis.


Asunto(s)
Linfocitos T CD8-positivos , Osteomielitis , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Recuento de Células , Osteomielitis/genética
20.
Environ Sci Pollut Res Int ; 31(16): 24139-24152, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38436855

RESUMEN

In order to reveal the adsorption mechanism of microplastics (MPs) on antibiotics, polystyrene (PS) was chosen as a typical microplastic, Fenton and high-temperature aging methods were used to obtain aged MPs particles. The adsorption behavior and mechanism of ciprofloxacin hydrochloride (CIP) on PS before and after aging were studied by batch adsorption experiments, and other influencing environmental conditions were evaluated concurrently. The results showed that the adsorption of CIP on PS was an exothermic reaction, the pseudo-second-order model and Freundlich isothermal models could fit the adsorption of CIP on PS. Aging treatment enhanced the adsorption capacity of PS to CIP, and Fenton aging for 7 days had the best effect. The highest adsorption was observed when the solution pH was 6. The adsorption capacity of microplastics gradually decreased with increasing ionic strength and the concentration of fulvic acid, while the aging microplastics changed little with the concentration of fulvic acid. The presence of both Cu (II) and CIP inhibits the adsorption of each other on microplastics. Based on the above findings, the adsorption of CIP on PS is dominated by physical adsorption, and electrostatic interactions and hydrogen bonding interactions are also important mechanisms for the adsorption of CIP on microplastics.


Asunto(s)
Poliestirenos , Contaminantes Químicos del Agua , Microplásticos , Plásticos , Ciprofloxacina , Adsorción , Agua Dulce , Contaminantes Químicos del Agua/análisis
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