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Alterations in anion balance potential, along with the involvement of cation-chloride cotransporters, play pivotal roles in the development of hyperalgesia after peripheral nerve injury. Chloride voltage-gated channel seven (CLCN7) is the predominant member of the CLC protein family. Investigations on CLCN7 have focused primarily on its involvement in osteosclerosis and lysosomal storage disorders; nevertheless, its contribution to neuropathic pain has not been determined. In this investigation, we noted high expression of CLCN7 in neurons situated within the spinal dorsal horns and dorsal root ganglions (DRGs). Immunofluorescence analysis revealed that CLCN7 was predominantly distributed among IB4-positive and CGRP-positive neurons. Furthermore, the expression of CLCN7 was observed to be mainly reduced in neurons within the spinal dorsal horns and in small- and medium-sized neurons located in the DRGs of spared nerve injury mice. Knockdown of CLCN7 via siRNA in the DRGs resulted in increased mechanical and thermal hyperalgesia in naïve mice. Furthermore, the excitability of cultured DRG neurons in vitro was augmented upon treatment with CLCN7 siRNA. These findings suggested that CLCN7 downregulation following SNI was crucial for the manifestation of mechanical and thermal hyperalgesia, highlighting potential targeting strategies for treating neuropathic pain.
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Brevibacillus laterosporus is a strain of probiotic bacteria that has been widely used in pest control, cash crop, and other production areas. However, few studies have been conducted on its use as a feed additive in animals. Therefore, the probiotic potential of B. laterosporus PBC01 was evaluated by characterizing hydrophobicity, auto-aggregation activity, bile salt and simulated gastrointestinal fluid tolerance, bienzymatic, and antibacterial activity. Antibiotic susceptibility, hemolysis assays, and supplemental feeding of mice were also performed to evaluate safety features. Our results showed that B. laterosporus PBC01 had moderate hydrophobicity, high auto-agglutination ability. Meanwhile, B. laterosporus PBC01 had good tolerance to bile salt and simulated gastrointestinal fluid. It had the ability to secrete protease, cellulase, and to inhibit various pathogens. In addition, B. laterosporus PBC01 was sensitive to many antibiotics, and did not produce hemolysin. In the safety assessment of mice, it did not cause any deaths, nor did it affect the cell components of blood, antioxidant capacity, and reproductive health. The study indicated the great probiotic characteristics and safety of B. laterosporus PBC01. This may provide a theoretical basis for the clinical application and development of probiotic-based feed additives.
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Bacillus , Brevibacillus , Animales , Ratones , Antibacterianos/farmacología , Ácidos y Sales BiliaresRESUMEN
The anion of pyridine, C5H5N−, has been thought to be short lived in the gas phase and was only previously observed indirectly. In the condensed phase, C5H5N− is known to be stabilized by solvation with other molecules. We provide in this study striking results for the formation of isolated C5H5N− from microdroplets of water containing dissolved pyridine observed in the negative ion mass spectrum. The gas-phase lifetime of C5H5N− is estimated to be at least 50 ms, which is much longer than previously thought. The generated C5H5N− captured CO2 molecules to form a stable (Py-CO2)− complex, further confirming the existence of C5H5N−. We propose that the high electric field at the airwater interface of a microdroplet helps OH− to transfer an electron to pyridine to form C5H5N− and the hydroxyl radical â¢OH. Oxidation products of the Py reacting with â¢OH are also observed in the mass spectrum recorded in positive mode, which further supports this mechanism. The present study pushes the limits of the reducing and oxidizing power of water microdroplets to a new level, emphasizing how different the behavior of microdroplets can be from bulk water. We also note that the easy formation of C5H5N− in water microdroplets presents a green chemistry way to synthesize value-added chemicals.
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Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the application of machine learning (ML) to whole-genome sequences (WGSs) has facilitated pathogen identification. However, relying solely on genetic information to identify emerging or new pathogens is fundamentally constrained, especially if novel virulence factors exist. In addition, even WGSs with ML pipelines are unable to discern phenotypes associated with cryptic genetic loci linked to virulence. Here, we set out to determine if ML using phenotypic hallmarks of pathogenesis could assess potential pathogenic threat without using any sequence-based analysis. This approach successfully classified potential pathogenetic threat associated with previously machine-observed and unobserved bacteria with 99% and 85% accuracy, respectively. This work establishes a phenotype-based pipeline for potential pathogenic threat assessment, which we term PathEngine, and offers strategies for the identification of bacterial pathogens.
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Bacterias , Genoma Bacteriano , Aprendizaje Automático , Factores de Virulencia , Secuenciación Completa del Genoma , Bacterias/genética , Bacterias/patogenicidad , Fenotipo , Virulencia/genética , Factores de Virulencia/genéticaRESUMEN
Fiber quality is a major breeding goal in cotton, but phenotypically direct selection is often hindered. In this study, we identified fiber quality and yield related loci using GWAS based on 2.97 million SNPs obtained from 10.65× resequencing data of 1081 accessions. The results showed that 585 novel fiber loci, including two novel stable SNP peaks associated with fiber length on chromosomes At12 and Dt05 and one novel genome regions linked with fiber strength on chromosome Dt12 were identified. Furthermore, by means of gene expression analysis, GhM_A12G0090, GhM_D05G1692, GhM_D12G3135 were identified and GhM_D11G2208 function was identified in Arabidopsis. Additionally, 14 consistent and stable superior haplotypes were identified, and 25 accessions were detected as possessing these 14 superior haplotype in breeding. This study providing fundamental insight relevant to identification of genes associated with fiber quality and yield will enhance future efforts toward improvement of upland cotton.
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Gossypium , Haplotipos , Fitomejoramiento , Polimorfismo de Nucleótido Simple , Gossypium/genética , Genoma de Planta , Fibra de Algodón , Estudio de Asociación del Genoma Completo , Sitios de Carácter CuantitativoRESUMEN
With the increasing incidence of oral cancer in the world, it has become a hotspot to explore the pathogenesis and prevention of oral cancer. It has been proved there is a strong link between periodontal pathogens and oral cancer. However, the specific molecular and cellular pathogenic mechanisms remain to be further elucidated. Emerging evidence suggests that periodontal pathogens-induced epithelial-mesenchymal transition (EMT) is closely related to the progression of oral cancer. Cells undergoing EMT showed increased motility, aggressiveness and stemness, which provide a pro-tumour environment and promote malignant metastasis of oral cancer. Plenty of studies proposed periodontal pathogens promote carcinogenesis via EMT. In the current review, we discussed the association between the development of oral cancer and periodontal pathogens, and summarized various mechanisms of EMT caused by periodontal pathogens, which are supposed to play an important role in oral cancer, to provide targets for future research in the fight against oral cancer.
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Neoplasias de la Boca , Porphyromonas gingivalis , Humanos , Neoplasias de la Boca/patología , Transición Epitelial-Mesenquimal , Carcinogénesis , Fusobacterium nucleatumRESUMEN
Sialylation catalysed by sialyltransferase 7A (SIAT7A) plays a role in the development of cardiac hypertrophy. However, the regulatory mechanisms upstream of SIAT7A in this context remain poorly elucidated. Previous study demonstrated that KLF4 activates the SIAT7A gene in ischemic myocardium by binding to its promoter region. Nevertheless, the potential involvement of KLF4 in regulating SIAT7A expression in Ang II-induced hypertrophic cardiomyocytes remains uncertain. This study seeks to deepen the underlying mechanisms of the KLF4 and SIAT7A interaction in the progression of Ang II-induced cardiac hypertrophy. The results showed a concurrent increase in SIAT7A and KLF4 levels in hypertrophic myocardium of essential hypertension patients and in hypertrophic cardiomyocytes stimulated by Ang II. In vitro experiments revealed that reducing KLF4 levels led to a decrease in both SIAT7A synthesis and Sialyl-Tn antigen expression, consequently inhibiting Ang II-induced cardiomyocyte hypertrophy. Intriguingly, reducing SIAT7A levels also resulted in decreased KLF4 expression and suppression cardiomyocyte hypertrophy. Consistent with this, elevating SIAT7A levels increased KLF4 expression and exacerbated cardiomyocyte hypertrophy in both in vivo and in vitro experiments. Additionally, a time-course analysis indicated that KLF4 expression preceded that of SIAT7A. Luciferase reporter assays further confirmed that modulating SIAT7A levels directly influenced the transcriptional activity of KLF4 in cardiomyocytes. In summary, KLF4 expression is upregulated in cardiomyocytes treated with Ang II, which subsequently induces the expression of SIAT7A. The elevated levels of SIAT7A, in turn, enhance the transcription of KLF4. These findings suggest a positive feedback loop between KLF4 and SIAT7A-Sialyl-Tn, ultimately promoting Ang II-induced cardiac hypertrophy.
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Angiotensina II , Cardiomegalia , Factor 4 Similar a Kruppel , Miocitos Cardíacos , Sialiltransferasas , Angiotensina II/farmacología , Cardiomegalia/metabolismo , Cardiomegalia/inducido químicamente , Cardiomegalia/genética , Cardiomegalia/patología , Animales , Sialiltransferasas/metabolismo , Sialiltransferasas/genética , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/efectos de los fármacos , Masculino , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Ratones , Ratas , Regulación de la Expresión GénicaRESUMEN
Rechargeable aluminum batteries (RABs) are an emerging energy storage device owing to the vast Al resources, low cost, and high safety. However, the poor cyclability and inferior reversible capacity of cathode materials have limited the enhancement of RABs performance. Herein, a high configurational entropy strategy is presented to improve the electrochemical properties of RABs for the first time. The high-entropy (Fe, Mn, Ni, Zn, Mg)3 O4 cathode exhibits an ultra-stable cycling ability (109 mAh g-1 after 3000 cycles), high specific capacity (268 mAh g-1 at 0.5 A g-1 ), and rapid ion diffusion. Ex situ characterizations indicate that the operational mechanism of (Fe, Mn, Ni, Zn, Mg)3 O4 cathode is mainly based on the redox process of Fe, Mn, and Ni. Theoretical calculations demonstrate that the oxygen vacancies make a positive contribution to adjusting the distribution of electronic states, which is crucial for enhancing the reaction kinetics at the electrolyte and cathode interface. These findings not only propose a promising cathode material for RABs, but also provide the first elucidation of the operational mechanism and intrinsic information of high-entropy electrodes in multivalent ion batteries.
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Gummosis is 1 of the most common and destructive diseases threatening global peach (Prunus persica) production. Our previous studies have revealed that ethylene and methyl jasmonate enhance peach susceptibility to Lasiodiplodia theobromae, a virulent pathogen inducing gummosis; however, the underlying molecular mechanisms remain obscure. Here, 2 ethylene response factors (ERFs), PpERF98 and PpERF1, were identified as negative regulators in peach response to L. theobromae infection. Expression of 2 putative paralogs, PpERF98-1/2, was dramatically induced by ethylene and L. theobromae treatments and accumulated highly in the gummosis-sensitive cultivar. Silencing of PpERF98-1/2 increased salicylic acid (SA) content and pathogenesis-related genes PpPR1 and PpPR2 transcripts, conferring peach resistance to L. theobromae, whereas peach and tomato (Solanum lycopersicum) plants overexpressing either of PpERF98-1/2 showed opposite changes. Also, jasmonic acid markedly accumulated in PpERF98-1/2-silenced plants, but reduction in PpPR3, PpPR4, and PpCHI (Chitinase) transcripts indicated a blocked signaling pathway. PpERF98-1 and 2 were further demonstrated to directly bind the promoters of 2 putative paralogous PpERF1 genes and to activate the ERF branch of the jasmonate/ethylene signaling pathway, thus attenuating SA-dependent defenses. The lesion phenotypes of peach seedlings overexpressing PpERF1-1/2 and PpERF98-1/2 were similar. Furthermore, PpERF98-1/2 formed homodimers/heterodimers and interacted with the 2 PpERF1 proteins to amplify the jasmonate/ethylene signaling pathway, as larger lesions were observed in peach plants cooverexpressing PpERF98 with PpERF1 relative to individual PpERF98 overexpression. Overall, our work deciphers an important regulatory network of ethylene-mediated peach susceptibility to L. theobromae based on a PpERF98-PpERF1 transcriptional cascade, which could be utilized as a potential target for genetic engineering to augment protection against L. theobromae-mediated diseases in crops and trees.
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Prunus persica , Prunus persica/genética , Prunus persica/metabolismo , Etilenos/metabolismo , PlantasRESUMEN
Caffeine is one of the most popular consumed psychostimulants that mitigates several neurodegenerative diseases. Nevertheless, the roles and molecular mechanisms of caffeine in HIV-associated neurocognitive disorders (HAND) remain largely unclear. Transactivator of transcription (Tat) is a major contributor to the neuropathogenesis of HAND in the central nervous system. In the present study, we determined that caffeine (100 µM) treatment significantly ameliorated Tat-induced decreased astrocytic viability, oxidative stress, inflammatory response and excessive glutamate and ATP release, thereby protecting neurons from apoptosis. Subsequently, SIRT3 was demonstrated to display neuroprotective effects against Tat during caffeine treatment. In addition, Tat downregulated SIRT3 expression via activation of EGR1 signaling, which was reversed by caffeine treatment in astrocytes. Overexpression of EGR1 entirely abolished the neuroprotective effects of caffeine against Tat. Furthermore, counteracting Tat or caffeine-induced differential expression of SIRT3 abrogated the neuroprotection of caffeine against Tat-triggered astrocytic dysfunction and neuronal apoptosis. Taken together, our study establishes that caffeine ameliorates astrocytes-mediated Tat neurotoxicity by targeting EGR1/SIRT3 signaling pathway. Our findings highlight the beneficial effects of caffeine on Tat-induced astrocytic dysfunction and neuronal death and propose that caffeine might be a novel therapeutic drug for relief of HAND.
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Apoptosis , Astrocitos , Cafeína , Proteína 1 de la Respuesta de Crecimiento Precoz , VIH-1 , Neuronas , Transducción de Señal , Sirtuina 3 , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/virología , Astrocitos/patología , Sirtuina 3/genética , Sirtuina 3/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Transducción de Señal/efectos de los fármacos , Cafeína/farmacología , Humanos , Apoptosis/efectos de los fármacos , VIH-1/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Neuronas/virología , Regulación hacia Arriba/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Complejo SIDA Demencia/tratamiento farmacológico , Complejo SIDA Demencia/genética , Complejo SIDA Demencia/metabolismo , Complejo SIDA Demencia/patología , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/toxicidadRESUMEN
The unique two-dimensional layered structure of BiOCl makes it highly promising for energy storage applications. In this study, we successfully synthesized BiOCl nanoparticles encapsulated in N-doped carbon nanonecklaces (BiOCl NPs/N-CNNs) using well-established electrospinning and solvothermal substitution. As an anode material for lithium-ion batteries, BiOCl NPs/N-CNNs exhibited enhanced rate performance, delivering a capacity of 220.2 mA h g-1 at 8 A g-1. Furthermore, it demonstrated remarkable long cycle stability, retaining a capacity of 200.5 mA h g-1 after 9000 cycles with a discharge rate of 8.0 A g-1. The superior electrochemical performance can be attributed to the stacked layered structure of BiOCl, facilitated by van der Waals force, as well as the ingenious nanonecklace structures. These structures not only provide fast ion diffusion pathways but also enhance electrolyte penetration and offer more active sites for Li+ insertion and extraction. Additionally, the nanonecklace structure prevents the aggregation of nanopolyhedra, promoting the complete reaction of BiOCl with Li+. Moreover, the unique nanopolyhedron structure alleviates the stress caused by the volume expansion of Bi nanoparticles during cycling and reduces the internal resistance of the electrode.
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Metal-organic frameworks (MOFs) are increasingly becoming an important choice for developing robust and efficient electrocatalysts; therefore, exploring the relationship between the structure, catalytic activity, and stability of MOFs is of great significance. MOFs 1-3 with different spatial configurations are designed and synthesized based on linear pyridine ligands, tetragonal carboxylic acid ligands, and triangular carboxylic acid ligands, while MOF 4 displays a three-dimensional (3D) supramolecule assembled through a mixed-ligand strategy. Compared with MOFs 1-3, MOF 4 has the lowest overpotential of 106 mV (at 10 mA·cm-2) and a Tafel slope of 80.9 mV·dec-1, as well as sturdy long-term stability in the process of oxygen evolution reaction (OER). The presence of dense metal clusters and µ3-O promotes the optimal catalytic performance of MOF 4. Density functional theory (DFT) calculations of MOF 4 demonstrate that the process from O* to OOH* is the rate-determining step. This investigation further reveals the relationship between MOF structural composition and electrocatalytic OER performance and provides an effective strategy for the assembly of MOF-based electrocatalysts.
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Converting CO2 to valuable chemicals and fuels is a viable method to establish a carbon-neutral energy cycle in the environment. Metal-organic frameworks (MOFs), characterized by dispersed active sites, high porosity, etc., have displayed a great application prospect in the electrochemical/chemical CO2 reduction reaction (CO2RR) process. Herein, we proposed a one-step production to establish a series of pillar-layered porous MOFs, [Co2(L)(bimb)]n (MOF 1) and [Co4(L)2(bidpe)2]n (MOF 2) [H4L = 5'-(4-carboxyphenyl)-(1,1':2',1â³-terphenyl)-4,4',4â³-tricarboxylic, bimb = 1,4-bis(imidazol-1-yl)-butane, bidpe = 4'-bis(imidazolyl) diphenyl ether], for preferential conversion of CO2 via ligand adjustment and increase of active sites' density. According to single-crystal X-ray diffraction studies, [Co2(L)(bimb)]n exhibits pillar-layered binuclear 3D frameworks with a 2,4,6-linked 3-nodes new topology structure, while [Co4(L)2(bidpe)2]n displays pillar-layered tetranuclear interspersed networks with a 4,6-linked 2-nodes fsc topology structure through a ligand adjustment strategy. Meanwhile, the pillar-layered structure of the MOFs with abundant active sites is conducive to mass diffusion and benefits the conversion of CO2. MOFs 1-2 exhibit good electrocatalytic activity for CO2RR in 0.5 M KHCO3 solution. Especially, the current density of MOF 2 generated at -0.90 V (vs. RHE) reaches -81.6 mA·cm-2, which is 3.1 times higher than that under an Ar atmosphere. In addition, MOFs 1-2 can be used as a heterogeneous catalyst for chemical conversion of CO2. The results are expected to provide inspiration for rational design to develop stable and high-efficiency MOF-based electrocatalysts for CO2RR.
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Extracellular vesicles (EVs) represent a diverse class of nanoscale membrane vesicles actively released by cells. These EVs can be further subdivided into categories like exosomes and microvesicles, based on their origins, sizes, and physical attributes. Significantly, disease-derived EVs have been detected in virtually all types of body fluids, providing a comprehensive molecular profile of their cellular origins. As a result, EVs are emerging as a valuable addition to liquid biopsy techniques. In this collective statement, the authors share their current perspectives on EV-related research and product development, with a shared commitment to translating this newfound knowledge into clinical applications for cancer and other diseases, particularly as disease biomarkers. The consensus within this document revolves around the overarching recognition of the merits, unresolved questions, and existing challenges surrounding EVs. This consensus manuscript is a collaborative effort led by the Committee of Exosomes, Society of Tumor Markers, Chinese anti-Cancer Association, aimed at expediting the cultivation of robust scientific and clinically applicable breakthroughs and propelling the field forward with greater swiftness and efficacy.
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Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.
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Senescencia Celular , Cilostazol , Inflamación , Proteínas de la Membrana , Ratones Endogámicos C57BL , Mitocondrias , Animales , Proteínas de la Membrana/metabolismo , Cilostazol/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Humanos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Senescencia Celular/efectos de los fármacos , Ratones , Envejecimiento/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Citosol/metabolismo , ADN/metabolismo , Masculino , Células Endoteliales de la Vena Umbilical Humana , Fenotipo Secretor Asociado a la Senescencia , Células CultivadasRESUMEN
BACKGROUND: The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. METHODS: A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. RESULTS: Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. CONCLUSIONS: APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.
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Apolipoproteína E4 , Disfunción Cognitiva , Humanos , Anciano , Masculino , Femenino , Disfunción Cognitiva/genética , Disfunción Cognitiva/inducido químicamente , Apolipoproteína E4/genética , China/epidemiología , Persona de Mediana Edad , Alelos , Anciano de 80 o más Años , Estudios de Cohortes , Contaminantes Ambientales/sangre , Contaminantes Ambientales/toxicidad , Metales Pesados/toxicidad , Metales Pesados/sangreRESUMEN
BACKGROUND: TNF-α processing inhibitor-1 (TAPI-1) is a known metalloproteinase inhibitor with potential anti-inflammatory effects. However, its anti-cancer effects on esophageal squamous cell carcinoma (ESCC) have not been uncovered. AIM: In the present study, the effects of TAPI-1 on ESCC cell viability, migration, invasion, and cisplatin resistance and the underlying molecular mechanisms were investigated in TE-1 and Eca109 cells. METHODS: To this end, TE-1 and Eca109 cells were exposed to TAPI-1 for indicated time intervals. Cell viability was assessed using cell counting kit-8 assay and apoptosis was evaluated using flow cytometry assay. Migration and invasion were assessed using Transwell assays. Gene expressions were analyzed using quantitative reverse transcription polymerase chain reaction. The activation of NF-κB signaling pathway was elucidated via Western blot and chromatin immunoprecipitation assay. RESULTS: We observed that higher doses (10, 20 µM) of TAPI-1 inhibited ESCC cell viability, while a lower dose (5 µM) of TAPI-1 inhibited ESCC cell migration and invasion and enhanced the chemosensitivity of ESCC cells to cisplatin. Moreover, TAPI-1 suppressed the activation of NF-κB signaling and the target genes expression in the stage of transcription initiation. Furthermore, blocking NF-κB signaling in advance could abolish all the effects of TAPI-1 on ESCC cells. CONCLUSION: Overall, these results indicated that TAPI-1 impairs ESCC cell viability, migration, and invasion and facilitates cisplatin-induced apoptosis via suppression of NF-κB signaling pathway. TAPI-1 may serve as a potential adjuvant agent with cisplatin for ESCC therapy.
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Carcinoma de Células Escamosas , Dipéptidos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Ácidos Hidroxámicos , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Cisplatino/farmacología , Cisplatino/uso terapéutico , Línea Celular Tumoral , Transducción de Señal , Proliferación Celular , Movimiento CelularRESUMEN
BACKGROUND: Occupational carcinogens, smoking, and obesity are believed to be the main causing agents of kidney cancer. China is undergoing rapid industrialization, and hence the people's lifestyles have witnessed tremendous changes. However, the trend of kidney cancer incidence during the late 20th and early 21st centuries remains unexplored in China. MATERIALS AND METHODS: Data from the Global Burden of Diseases (GBD; 2019) was retrieved for the incidence of kidney cancer from 1990 to 2019. The rates of disease average annual percentage changes (AAPC) were assessed using joinpoint regression analysis. Age-period-cohort (APC) model was used to assess age, period, and cohort effects on the incidence of the disease simultaneously. RESULTS: An increase in age-standardized incidence rates (ASIR) of kidney cancer was observed from 1990 to 2019 in total residents (1.33 - 4.24), men (1.56 - 6.15), and women (1.11 - 2.31) per 100,000 population suggesting a more obvious increase in males than in females. A consistent increase in age effects was observed in all age groups, especially in males. On the other hand, the 70 - 74 age group in females showed greater age effects. In addition, the period effects analysis showed that the incidence of kidney cancer increased with time. Moreover, the analysis of cohort effects showed a decrease in the disease in birth cohorts, especially before 1940. CONCLUSION: The incidence of kidney cancer is increasing rapidly in China. The kidney cancer burden will rise in the next decades due to population aging, environmental pollution, occupation, food safety, and so on. Results of this study suggest that more etiological studies should be performed to identify the driving factors for kidney cancer trends, and appropriate preventive measures should be implemented for the age-, period-, and cohort-related factors in the population.
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Neoplasias Renales , Fumar , Masculino , Humanos , Femenino , Incidencia , Estudios de Cohortes , China/epidemiología , Neoplasias Renales/epidemiologíaRESUMEN
BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.
Asunto(s)
Depresión , Obesidad , Humanos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Obesidad/epidemiología , Depresión/epidemiología , Depresión/sangre , Anciano , Estudios Longitudinales , Factores de Riesgo , Índice de Masa Corporal , Lípidos/sangre , Circunferencia de la Cintura , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. OBJECTIVES: Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. METHODS: Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. RESULTS: Social support was negatively associated with emotional exhaustion (ß = - 0.088, P = 0.020), personality disintegration (ß = - 0.235, P < 0.001), and reduced sense of achievement (ß = - 0.075, P = 0.040). Moreover, psychological capital was negatively associated with emotional exhaustion (ß = - 0.079, P = 0.030), personality disintegration (ß = - 0.156, P < 0.001), and reduced sense of achievement (ß = - 0.432, P < 0.001). All three dimensions of job burnout positively affected turnover intention (emotional exhaustion: ß = 0.246, P < 0.001; personality disintegration: ß = 0.076, P = 0.040; reduced sense of achievement: ß = 0.119, P = 0.001). CONCLUSIONS: The results highlight the importance of social support and psychological capital for diminishing the three dimensions of job burnout for primary medical staff and, in turn, lowering their turnover intention. Accordingly, to alleviate job burnout and improve staff retention, material and psychological supports from leaders, colleagues, family, relatives, and friends are essential, as are measures to improve the psychological energy of primary medical staff.