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1.
Thorac Cancer ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984468

RESUMO

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.

2.
J Agric Food Chem ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38853533

RESUMO

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.

3.
Sheng Wu Gong Cheng Xue Bao ; 40(6): 1711-1727, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38914487

RESUMO

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.


Assuntos
Aminoácidos , Corynebacterium glutamicum , Escherichia coli , Engenharia Metabólica , Engenharia Metabólica/métodos , Aminoácidos/biossíntese , Aminoácidos/metabolismo , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Biologia Sintética , Microbiologia Industrial
4.
Front Genet ; 15: 1366453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694874

RESUMO

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.

5.
Materials (Basel) ; 17(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38793450

RESUMO

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.

7.
J Cachexia Sarcopenia Muscle ; 15(3): 1177-1186, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38644549

RESUMO

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.


Assuntos
Peso Corporal , Neoplasias , Humanos , Masculino , Feminino , Neoplasias/mortalidade , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos de Coortes , Adulto
8.
Int J Genomics ; 2024: 8846747, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567257

RESUMO

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.

9.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 164-168, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678607

RESUMO

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.


Assuntos
Apoptose , Inflamação , Degeneração do Disco Intervertebral , Sistema de Sinalização das MAP Quinases , MicroRNAs , Núcleo Pulposo , Ratos Sprague-Dawley , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Apoptose/genética , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Inflamação/genética , Inflamação/patologia , Sistema de Sinalização das MAP Quinases/genética , Masculino , Ratos , Receptor fas/genética , Receptor fas/metabolismo
10.
Environ Sci Pollut Res Int ; 31(16): 24139-24152, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38436855

RESUMO

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.


Assuntos
Poliestirenos , Poluentes Químicos da Água , Microplásticos , Plásticos , Ciprofloxacina , Adsorção , Água Doce , Poluentes Químicos da Água/análise
11.
Medicine (Baltimore) ; 103(9): e37394, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428865

RESUMO

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.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
12.
Int Immunopharmacol ; 131: 111815, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38492335

RESUMO

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.


Assuntos
Linfócitos T CD8-Positivos , Osteomielite , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Contagem de Células , Osteomielite/genética
13.
Front Public Health ; 12: 1346914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347929

RESUMO

Background: This study aimed to explore the relationship between air pollution and hospital admissions for asthma in older adults, and to further assess the health and economic burden of asthma admissions attributable to air pollution. Methods: We collected information on asthma cases in people over 65 years of age from nine cities in Sichuan province, as well as air pollution and meteorological data. The relationship between short-term air pollutant exposure and daily asthma hospitalizations was analyzed using the generalized additive model (GAM), and stratified by gender, age, and season. In addition, we assessed the economic burden of hospitalization for air pollution-related asthma in older adults using the cost of disease approach. Results: The single pollutant model showed that every 1 mg/m3 increase in CO was linked with an increase in daily hospitalizations for older adults with asthma, with relative risk values of 1.327 (95% CI: 1.116-1.577) at lag7. Each 10 µg/m3 increase in NO2, O3, PM10, PM2.5 and SO2, on asthma hospitalization, with relative risk values of 1.044 (95% CI: 1.011-1.078), 1.018 (95% CI: 1.002-1.034), 1.013 (95% CI: 1.004-1.022), 1.015 (95% CI: 1.003-1.028) and 1.13 (95% CI: 1.041-1.227), respectively. Stratified analysis shows that stronger associations between air pollution and asthma HAs among older adult in females, those aged 65-69 years, and in the warm season, although all of the differences between subgroups did not reach statistical significance. During the study period, the number of asthma hospitalizations attributable to PM2.5, PM10, and NO2 pollution was 764, 581 and 95, respectively, which resulted in a total economic cost of 6.222 million CNY, 4.73 million CNY and 0.776 million CNY, respectively. Conclusion: This study suggests that short-term exposure to air pollutants is positively associated with an increase in numbers of asthma of people over 65 years of age in Sichuan province, and short-term exposure to excessive PM and NO2 brings health and economic burden to individuals and society.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Feminino , Humanos , Idoso , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Cidades , Fatores de Tempo , Dióxido de Nitrogênio , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Asma/epidemiologia , Hospitalização , China/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Hospitais
15.
Cell Transplant ; 33: 9636897241228031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38353224

RESUMO

The management of granulocytopenia-associated infections is challenging, and a high mortality rate is associated with traditional supportive therapies. Neutrophils-the primary defenders of the human immune system-have potent bactericidal capabilities. Here, we investigated the dynamic in vivo distribution of neutrophil transfusion and their impact on the treatment outcome of severe granulocytopenic infections. We transfused 89Zr-labeled neutrophils in the C57BL/6 mice and observed the dynamic neutrophil distribution in mice for 24 h using the micro-positron emission tomography (Micro-PET) technique. The labeled neutrophils were predominantly retained in the lungs and spleen up to 4 h after injection and then redistributed to other organs, such as the spleen, liver, and bone marrow. Neutrophil transfusion did not elicit marked inflammatory responses or organ damage in healthy host mice. Notably, allogeneic neutrophils showed rapid chemotaxis to the infected area of the host within 1 h. Tail vein infusion of approximately 107 neutrophils substantially bolstered host immunity, ameliorated the inflammatory state, and increased survival rates in neutrophil-depleted and infected mice. Overall, massive allogeneic neutrophil transfusion had a therapeutic effect in severe infections and can have extensive applications in the future.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neutrófilos , Camundongos , Humanos , Animais , Neutrófilos/fisiologia , Taxa de Sobrevida , Camundongos Endogâmicos C57BL , Medula Óssea
16.
Rapid Commun Mass Spectrom ; 38(6): e9703, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38356091

RESUMO

RATIONALE: Secondary hypertension is often caused by activation of complex multi-organ endocrine systems, while renin activity indicated by angiotensins (Angs), aldosterone (ALD) and cortisol (COR) in such systems are generally accepted as its diagnostic markers. As antibody-based methods cannot offer comparable quantification for these biomarkers, a liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based approach was developed to quantify them simultaneously and accurately. METHODS: Five different beads for magnetic solid-phase extraction (MSPE) were evaluated towards their enrichment efficiency for these biomarkers. An LC system with optimized elution gradient and a triple-quadrupole MS with tuned parameters were coupled to quantitatively monitor the extracted analytes. The method performance was further examined such as linearity, precision, stability, recovery rate and matrix effect. Based on the developed method, the abundance of Ang II, ALD and COR in plasma was measured and the quantification was compared with that derived from commercial ELISA kits. RESULTS: As compared with other MSPEs, Angs, ALD and COR were highly enriched by the HLB magnetic beads with satisfactory recoveries. These analytes were simultaneously quantified by LC/MS/MS and all the method parameters for quantification were well matched with the requirements of clinical testing. Comparison of the quantitative results derived from ELISA and LC/MS/MS exhibited that the two methods offered basically comparable values with Pearson r values at 0.896, 0.895 and 0.835, respectively. The stability test for plasma Angs at room temperature indicated that the abundance of Ang II was relatively stable within 3 h, whereas that of Ang I and Ang 1-7 was time-dependently changed. CONCLUSIONS: Coupling of HLB beads and LC/MS/MS thus enables simultaneous quantification of a set of biomarkers related to secondary hypertension.


Assuntos
Hipertensão , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , Extração em Fase Sólida/métodos , Biomarcadores , Fenômenos Magnéticos , Cromatografia Líquida de Alta Pressão
17.
J Drug Target ; 32(2): 128-147, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217526

RESUMO

Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and angina. Although traditional surgical and pharmacological interventions can effectively retard or slow down the progression of atherosclerosis, it is very difficult to prevent or even reverse this disease. In recent years, with the rapid development of nanotechnology, various nanoagents have been designed and applied to different diseases including atherosclerosis. The unique atherosclerotic microenvironment with signature biological components allows nanoplatforms to distinguish atherosclerotic lesions from normal tissue and to approach plaques specifically. Based on the process of atherosclerotic plaque formation, this review summarises the nanodrug delivery strategies for atherosclerotic therapy, trying to provide help for researchers to understand the existing atherosclerosis management approaches as well as challenges and to reasonably design anti-atherosclerotic nanoplatforms.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Sistemas de Liberação de Medicamentos , Nanotecnologia
18.
Burns ; 50(3): 653-665, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38185615

RESUMO

BACKGROUND: The pathophysiology of severe burn injuries in the early stages involves complex emergency responses, inflammatory reactions, immune system activation, and a significant increase in vascular permeability. Neutrophils, crucial innate immune cells, undergo rapid mobilization and intricate pathophysiological changes during this period. However, the dynamic alterations and detailed mechanisms governing their biological behavior remain unclear. Stomatin protein, an essential component of the cell membrane, stabilizes and regulates the membrane and participates in cell signal transduction. Additionally, it exhibits elevated expression in various inflammatory diseases. While Stomatin expression has been observed in the cell and granule membranes of neutrophils, its potential involvement in post-activation functional regulation requires further investigation. METHODS: Neutrophils were isolated from human peripheral blood, mouse peripheral blood, and mouse bone marrow using the magnetic bead separation method. Flow cytometry was used to assess neutrophil membrane surface markers, ROS levels, and phagocytic activity. The expression of the Stomatin gene and protein was examined using quantitative real-time polymerase chain reaction and western blotting methods, respectively. Furthermore, the enzyme-linked immunosorbent assay was used to evaluate the expression of neutrophil-derived inflammatory mediators (myeloperoxidase (MPO), neutrophil elastase (NE), and matrix metalloproteinase 9 (MMP9)) in the plasma. Images and videos of vascular leakage in mice were captured using in vivo laser confocal imaging technology, whereas in vitro confocal microscopy was used to study the localization and levels of the cytoskeleton, CD63, and Stomatin protein in neutrophils. RESULTS: This study made the following key findings: (1) Early after severe burn, neutrophil dysfunction is present in the peripheral blood characterized by significant bone marrow mobilization, excessive degranulation, and impaired release and chemotaxis of inflammatory mediators (MPO, NE, and MMP9). (2) After burn injury, expression of both the stomatin gene and protein in neutrophils was upregulated. (3) Knockout (KO) of the stomatin gene in mice partially inhibited neutrophil excessive degranulation, potentially achieved via reduced production of primary granules and weakened binding of primary granules to the cell skeleton protein F-actin. (4) In severely burned mice, injury led to notable early-stage vascular leakage and lung damage, whereas Stomatin gene KO significantly ameliorated lung injury and vascular leakage. CONCLUSIONS: Stomatin promotes neutrophil degranulation in the early stage of severe burn injury via increasing the production of primary granules and enhancing their binding to the cell skeleton protein F-actin in neutrophils. Consequently, this excessive degranulation results in aggravated vascular leakage and lung injury.


Assuntos
Queimaduras , Lesão Pulmonar , Animais , Humanos , Camundongos , Actinas/metabolismo , Queimaduras/metabolismo , Mediadores da Inflamação/análise , Mediadores da Inflamação/metabolismo , Lesão Pulmonar/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Knockout , Neutrófilos
19.
World J Gastrointest Oncol ; 16(1): 244-250, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38292849

RESUMO

BACKGROUND: Schwannomas are uncommon tumors originating from Schwann cells, forming the neural sheath. They account for approximately 2%-6% of all mesenchymal tumors and are most commonly identified in peripheral nerve trunks, with rarity in the gastrointestinal tract. Among gastrointestinal locations, the stomach harbors the majority of nerve sheath tumors, while such occurrences in the sigmoid colon are exceptionally infrequent. CASE SUMMARY: This study presented a clinical case involving a 60-year-old female patient who, during colonoscopy, was diagnosed with a submucosal lesion that was later identified as a nerve sheath tumor. The patient underwent surgical resection, and the diagnosis was confirmed through immunohistochemistry. This study highlighted an exceptionally uncommon occurrence of a nerve sheath tumor in the sigmoid colon, which was effectively managed within our department. Additionally, a comprehensive review of relevant studies was conducted. CONCLUSION: The preoperative diagnosis of nerve sheath tumors poses challenges, as the definitive diagnosis still relies on pathology and immunohistochemistry. Although categorized as benign, these tumors have the potential to demonstrate malignant behavior. Consequently, the optimal treatment approach entails the complete surgical excision of the tumor, ensuring the absence of residual lesions at the margins.

20.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101697, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37890588

RESUMO

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.


Assuntos
Eletroquimioterapia , Hiperpigmentação , Polietilenoglicóis , Malformações Vasculares , Humanos , Polidocanol/efeitos adversos , Soluções Esclerosantes , Bleomicina/efeitos adversos , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Eletroquimioterapia/efeitos adversos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/terapia , Malformações Vasculares/complicações , Resultado do Tratamento , Dor/etiologia , Estudos Retrospectivos , Hiperpigmentação/etiologia
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