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Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.
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Neoplasias Primárias Desconhecidas , Medicina de Precisão , Humanos , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/terapia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/diagnóstico , Medicina de Precisão/métodos , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Aprendizado de Máquina , Prognóstico , Genômica/métodos , Biópsia Líquida/métodosRESUMO
The Bi0.5 Sb1.5 Te3 (BST) thin film shows great promise in harvesting low-grade heat energy due to its excellent thermoelectric performance at room temperature. In order to further enhance its thermoelectric performance, specifically the power factor and output power, new approaches are highly desirable beyond the common "composition-structure-performance" paradigm. This study introduces ferroelectric polarization engineering as a novel strategy to achieve these goals. A Pb(Zr0.52 Ti0.48 )O3 /Bi0.5 Sb1.5 Te3 (PZT/BST) hybrid film is fabricated via magnetron sputtering. Density functional theory calculations demonstrate PZT polarization's influence on charge redistribution and interlayer charge transfer at the PZT/BST interface, facilitating adjustable carrier transport behavior and power factor of the BST film. As a result, a 26.7% enhancement of the power factor, from unpolarized 12.0 to 15.2 µW cm-1 K-2 , is reached by 2 kV out-of-plane downward polarization of PZT. Furthermore, a five-leg generator constructed using this PZT/BST hybrid film exhibits a maximum output power density of 13.06 W m-2 at ΔT = 39 K, which is 20.8% higher than that of the unpolarized one (10.81 W m-2 ). The research presents a new approach to enhance thermoelectric thin films' power factor and output performance by introducing ferroelectric polarization engineering.
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Gastric cancer (GC) remains one of the world's most common and fatal malignant tumors. With a refined understanding of molecular typing in recent years, microsatellite instability (MSI) has become a major molecular typing approach for gastric cancer. MSI is well recognized for its important role during the immunotherapy of advanced GC. However, its value remains unclear in resectable gastric cancer. The reported incidence of microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) in resectable gastric cancer varies widely, with no consensus reached on the value of postoperative adjuvant therapy in patients with MSI-H/dMMR resectable GC. It has been established that MSI-H/dMMR tumor cells can elicit an endogenous immune antitumor response and ubiquitously express immune checkpoint ligands such as PD-1 or PD-L1. On the basis of these considerations, MSI-H/dMMR resectable GCs are responsive to adjuvant immunotherapy, although limited research has hitherto been conducted. In this review, we comprehensively describe the differences in geographic distribution and pathological stages in patients with MSI-H/dMMR with resectable gastric cancer and explore the value of adjuvant chemotherapy and immunotherapy on MSI-H/dMMR to provide a foothold for the individualized treatment of this patient population.
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Neoplasias Colorretais , Neoplasias Gástricas , Humanos , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Imunoterapia , Adjuvantes ImunológicosRESUMO
OBJECTIVE: Often, alternative splicing is used by cancer cells to produce or increase proteins that promote growth and survival through alternative splicing. Although RNA-binding proteins are known to regulate alternative splicing events associated with tumorigenesis, their role in oesophageal cancer (EC) has rarely been explored. METHODS: We analysed the expression pattern of several relatively well characterized splicing regulators on 183 samples from TCGA cohort of oesophageal cancer; the effectiveness of the knockdown of SRSF2 was subsequently verified by immunoblotting; we measured the ability of cells treated with lenti-sh-SRSF2/lenti-sh2-SRSF2 to invade through an extracellular matrix coating by transwell invasion assay; using RNA-seq data to identify its potential target genes; we performed qRT-PCR to detect the changes of exon 2 usage in lenti-sh-SRSF2 transduced KYSE30 cells to determine the possible effect of SRSF2 on splicing regulation of IRF3; RNA Electrophoretic mobility shift assay (RNA-EMSA) was performed by the incubation of purified SRSF2 protein and biotinylated RNA probes; we performed luciferase assay to confirm the effect of SRSF2 on IFN1 promoter activity. RESULTS: We found upregulation of SRSF2 is correlated with the development of EC; Knock-down of SRSF2 inhibits EC cell proliferation, migration, and invasion; SRSF2 regulates the splicing pattern of IRF3 in EC cells; SRSF2 interacts with exon 2 of IRF3 to regulate its exclusion; SRSF2 inhibits the transcription of IFN1 in EC cells. CONCLUSION: This study identified a novel regulatory axis involved in EC from the various aspects of splicing regulation.
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Processamento Alternativo , Neoplasias Esofágicas , Humanos , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Arginina/metabolismo , Fator Regulador 3 de Interferon/genética , Splicing de RNA , RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias Esofágicas/genéticaRESUMO
Zika virus (ZIKV), a flavivirus associated with neurological disorders, constitutes a global health threat. During pregnancy, ZIKV traverses the placenta and causes congenital disease such as microcephaly and Guillain-Barré syndrome in newborns. To develop a specific antiviral therapy against ZIKV-induced microcephaly that could cross placental and blood-brain barriers, we designed targeted small extracellular vesicles (sEVs) encapsulating antiviral siRNA (small interfering RNA) to inhibit ZIKV. The neuro-specific targeting was achieved by engineering EVs membrane protein lamp2b fused with a neuron-specific rabies virus glycoprotein derived peptide (RVG). Intravenous administration of the RVG-engineered sEVs loaded with siRNA (ZIKV-specific siRNA) protected pregnant AG6 mice against vertical transmission of ZIKV. Particularly, sEVsRVG-siRNA traversed placental and blood-brain barriers and suppressed ZIKV infection in fetal brains. Moreover, sEVsRVG-siRNA alleviated the neuroinflammation and neurological damage caused by ZIKV in the fetal mouse model. In general, we developed a sEVs-based targeted system of antiviral therapy for brain and fetal brain infections.
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Vesículas Extracelulares , Microcefalia , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Encéfalo , Modelos Animais de Doenças , Feminino , Feto , Camundongos , Microcefalia/complicações , Microcefalia/genética , Microcefalia/terapia , Placenta , Gravidez , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Zika virus/genética , Infecção por Zika virus/tratamento farmacológicoRESUMO
Wound healing involves multi-stages of physiological responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Satisfying all demands throughout different stages remains a rarely addressed challenge. Here we introduce an innovative all-aqueous microfluidic printing technique for fabricating multifunctional bioactive microfibers, effectively contributing to all four phases of the healing process. The distinctive feature of the developed microfibers lies in their capacity to be printed in a free-form manner in the aqueous-two phase system (ATPS). This is achieved through interfacial coacervation between alkyl-chitosan and alginate, with enhanced structural integrity facilitated by simultaneous crosslinking with calcium ions and alginate. The all-aqueous printed microfibers exhibit exceptional performance in terms of cell recruitment, blood cell coagulation, and hemostasis. The inclusion of a dodecyl carbon chain and amino groups in alkyl-chitosan imparts remarkable antimicrobial properties by anchoring to bacteria, complemented by potent antibacterial effects of encapsulated silver nanoparticles. Moreover, microfibers can load bioactive drugs like epidermal growth factor (EGF), preserving their activity and enhancing therapeutic effects during cell proliferation and tissue remodeling. With these sequential functions to guide the whole-stage wound healing, this work offers a versatile and robust paradigm for comprehensive wound treatment, holding great potential for optimal healing outcomes.
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Quitosana , Nanopartículas Metálicas , Microfluídica , Quitosana/farmacologia , Prata/farmacologia , Cicatrização , Antibacterianos/farmacologia , Alginatos/farmacologia , Alginatos/química , Impressão Tridimensional , Hidrogéis/farmacologiaRESUMO
Bi2Te3-based thin films are gaining recognition for their remarkable room temperature thermoelectric performance. Beyond the conventional "process-composition-performance" paradigm, it is highly desirable to explore new methods to enhance their performance further. Here, we designed a sandwich-structured Ag/PZT/PVDF/Bi0.5Sb1.5Te3(BST) thin film device and effectively regulated the performance of the BST film by controlling the polarization state of the PZT/PVDF layers. Results indicate that polarization induces interlayer charge redistribution and charge transfer between PZT/PVDF and BST, thereby achieving the continuous modulation of the electrical transport characteristics of BST films. Finally, following polarization at a saturation voltage of 3 kV, the power factor of the BST film increased by 13% compared to the unpolarized condition, reaching 20.8 µW cm-1 K-2. Furthermore, a device with 7 pairs of P-N legs was fabricated, achieving a cooling temperature difference of 11.0 K and a net cooling temperature difference of 2.4 K at a current of 10 mA after the saturation polarization of the PZT/PVDF layer. This work reveals the critical effect of introducing ferroelectric layer polarization to achieve excellent thermoelectric performance of the BST film.
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To explore the mediating role of resilience in the relationship between general self-efficacy and professional identity of nurses during the COVID-19 pandemic. A cross-sectional design was employed. A total of 982 nurses from four Grade III, class A hospitals in Shandong Province were investigated using general information questionnaire, nurses' professional identity rating scale, general self-efficacy scale (GSES), and Connor-Davidson flexibility scale (CD-RISC). SPSS22.0 and Amos21.0 were used for data analysis and structural equation modeling. p % counseling The nurses had a score of ï¼27.038±5.933ï¼ for general self-efficacy score, 38.290±6.234 for psychological resilience, and ï¼114.99±16.209ï¼ for professional identity. A positive correlation between general self-efficacy, professional identity, and psychological resilience (<0.01) was found. The SEM analysis shows that psychological resilience plays a mediating role between general self-efficacy and professional identity. The ratio of the effect is 75.155. During the COVID-19 pandemic, the levels of general self-efficacy and professional identity of nurses was medium, while psychological resilience was high. Nurses' general self-efficacy can affect their professional identity through psychological resilience. During the pandemic, the psychological status of nurses should not be ignored. Nursing managers should fully utilize of group and cognitive therapy based on mindfulness to improve nurses' psychological resilience and general self-efficacy, and to promote nurses' professional identity, so as to ensure the lower turnover rate.
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Polysaccharide-based hydrogel adsorbents become popular because of their high adsorption capacity and fast adsorption rate, but their low removal rate and poor pH resistance have always been fatal shortcomings. Herein, a feasible strategy was proposed to strengthen the ability of hydrogel adsorbent to remove organic pollutants (i.e., dye) by incorporating natural rectorite (REC) into chitosan-g-poly (2-acrylamido-2-methyl-propane-sulfonic-acid) hydrogel network to form a rectorite-in-polymer network structure. The introduction of less dosage of REC (1.2 wt%) into the hydrogel facilitates to improve its adsorption capacities toward methylene blue (MB) in deionized water, tap water, seawater, Yangtze River water, and Yellow River water (1083.39-1303.49 mg/g); while incorporating higher content of REC (15.8 wt% REC) helps to improve the removal rate (99.6% for MB in real waters), which are greatly superior to commercial activated carbons. The adsorbent keeps high adsorption efficiency in a broad pH range (2-11), and can be reused for >4 times.
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Quitosana , Poluentes Químicos da Água , Hidrogéis/química , Quitosana/química , Água , Concentração de Íons de Hidrogênio , Adsorção , Poluentes Químicos da Água/química , Azul de Metileno/química , CinéticaRESUMO
Autophagy is an evolutionarily conserved catabolic process that can degrade cytoplasmic materials and recycle energy to maintain metabolite homeostasis in cells. Autophagy is closely related to various physiological or pathological processes. Macromolecular materials are widely used in drug delivery systems and disease treatments due to their intrinsic effects, such as altered pharmacokinetics and biodistribution. Interaction of autophagic flux or the signal pathway with macromolecules may cause autophagy inhibition or autophagy cell death. This review covers autophagy regulation pathways and macromolecular materials (including functional micelles, biodegradable and pH-sensitive polymers, biomacromolecules, dendrimers, coordination polymers, and hybrid nanoparticles) mediated autophagy modulation.
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Injury and poisoning, common public health problems, currently rank fifth among the causes of death in China. In this study, we aimed to analyze the trends and influencing factors of injury and poisoning mortality in urban and rural China using an age-period-cohort model. Crude mortality data for injury and poisoning by sex, age group, and region were obtained from the China Health Statistical Yearbook (2006-2020). Age-standardized mortality rates for injury and poisoning in urban and rural areas were estimated using the Seventh Census of China 2020 population. The trends of injury and poisoning mortality were assessed using Joinpoint analysis. Age-period-cohort models were used to explore the age, period, and birth cohort effects affecting mortality risk. Over a 15-year period, age-standardized mortality rates decreased from 28.81/100,000 in 2006 to 24.78/100,000 in 2020 in urban areas and from 45.49/100,000 to 44.39/100,000 in rural areas. In the male population, the annual change in mortality was -0.4% (95% CI = -1.8%, 1.0%) in urban areas and -1.0% (95% CI = -1.9%, 0.0%) in rural areas. In the female population, the annual change in mortality was -1.2% (95% CI = -2.3%, -0.1%) in urban areas compared with -1.6% (95% CI = -3.1%, -0.1%) in rural areas. The age-period-cohort model showed a significant increase in urban and rural mortality rates starting at ages 49 and 39 years. Both showed a decline followed by an increase in the period. The cohort from 1929 to 2013 showed an overall trend of increasing and then decreasing. From 2006 to 2020, the overall injury and poisoning mortality rates in China showed a decreasing trend, and the mortality rates decreased faster in women than in men and in rural areas than in urban areas. Age effects were the most important risk factors for changes in injury and poisoning mortality. The results of this study will help researchers explore the possible causes of mortality changes in urban and rural areas and provide a scientific basis for injury and poisoning prevention and control priorities and policy formulation in China.
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Homens , População Rural , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Mortalidade , Fatores de Risco , População UrbanaRESUMO
Wound healing is a complex physiological process involving four coordinated stages, including hemostasis, anti-inflammatory, repair, and epithelial formation. Herein, multifunctional core-shell alkylated chitosan/calcium alginate microfibers are fabricated as a novel strategy for promoting wound healing by contributing to each four stages in the entire healing process. Taking advantages of the microfluidic technology, the core-shell microfibers can be generated in a continuous and convenient manner through the interfacial assembly between alkylated chitosan and Na-alginate, as well as the simultaneous crosslink between calcium and the alginate. Generated microfibers possess unique internal structure which can effectively promote the absorption of blood and exudate produced during trauma. Moreover, the dodecyl carbon chain and abundant amino groups of alkylated chitosan provide microfibers with excellent hemostatic and antibacterial properties, which can repair acute hemorrhage and destroy bacteria rapidly. Further, the chronic wound healing process of a skin injury model can be significantly promoted by applying the fabricated microfibers. With these sequential functions to guide the whole-stage wound healing, the presented multifunctional core-shell microfibers create a versatile and robust paradigm for comprehensive wound treatment.
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Background: "Pneumonia Prevention No.1" belongs to 'traditional Chinese medicine prescription for prevention of viral pneumonia and influenza' was urgently formulated by Notice on Printing the Novel Coronavirus Diagnosis and Treatment Scheme for COVID-19 (Trial Version 3) and Traditional Chinese Medicine Prevention and Treatment Scheme for COVID-19 in Hubei Province (Trial). Because the prescription drug has the bidirectional regulation function of human immune function, moderate improvement of immune function can effectively resist virus invasion, while excessive immune function will produce immune overresponse. Excessive immune response will aggravate the condition of patients with COVID-19, resulting in the death of severe patients. Methods: Twenty medical workers aged 20-60 years old, who had no immune disease, no current disease and healthy physical examination, were selected as participants. The participants took Hubei "Pneumonia Prevention No.1" decoction, one dosage each day, twice a day, for 7 consecutive days. With the before-after control method, blood samples were collected from the median cubital veins before and after medication. Immunoglobulin IgA, IgG and IgM were measured by immunoturbidimetry, and T lymphocyte subsets CD3, CD4, CD8 and CD4/CD8 were measured by flow cytometry. The changes of indexes before and after medication were compared with SPPS 13.0 statistical software. The data were expressed by (mean ± standard deviation). T-test was adopted, and P < 0.05 was considered statistically significant (P < 0.05). Results: The results of this study show that in healthy participants, the immunoglobulin and T lymphocyte subsets did not differ significantly before and after drug administration (P > 0.05). Conclusion: Under normal drug administration circumstances, "Pneumonia Prevention No. 1" had no significant regulating effect on the immune system in a healthy population and did not increase the immune system capacity beyond a reasonable range. It is safe to be used as a prophylactic measure in healthy populations.
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Herpes simplex virus 1 (HSV-1) infects eye corneal tissues leading to herpetic stromal keratitis (HSK), which is one of the leading causes of blindness. Here in our study, we found that 6-thioguanine (6-TG), a once clinically approved medication for child acute myelogenous leukemia, inhibited multiple strains of HSV-1 infection in vitro and in vivo. 6-TG is more potent than acyclovir (ACV) and ganciclovir (GCV), with the 50% inhibitory concentration (IC50) of 6-TG at 0.104 µM with high stimulation index (SI) (SI = 6,475.48) compared to the IC50 of ACV at 1.253 µM and the IC50 of GCV at 1.257 µM. In addition, 6-TG at 500 µM topically applied to the eyes with HSV-1 infection significantly inhibits HSV-1 replication, alleviates virus-induced HSK pathogenesis, and improves eye conditions. More importantly, 6-TG is effective against ACV-resistant HSV-1 strains, including HSV-1/153 and HSV-1/blue. Knockdown of Rac1 with small interfering RNA (siRNA) negatively affected HSV-1 replication, suggesting that Rac1 facilitated HSV-1 replication. Following HSV-1 infection of human corneal epithelial cells (HCECs), endogenous Rac1 activity was upregulated by glutathione S-transferase (GST) pulldown assay. We further found that Rac1 was highly expressed in the corneal tissue of HSK patients compared to normal individuals. Mechanistic study showed that 6-TG inhibited HSV-1 replication by targeting Rac1 activity in HSV-1 infected cells, and the Rac1 is critical in the pathogenesis of HSK. Our results indicated that 6-TG is a promising therapeutic molecule for the treatment of HSK. IMPORTANCE We reported the discovery of 6-TG inhibition of HSV-1 infection and its inhibitory roles in HSK both in vitro and in vivo. 6-TG was shown to possess at least 10× more potent inhibitory activity against HSV-1 than ACV and GCV and, more importantly, inhibit ACV/GCV-resistant mutant viruses. Animal model studies showed that gel-formulated 6-TG topically applied to eyes locally infected with HSV-1 could significantly inhibit HSV-1 replication, alleviate virus-induced HSK pathogenesis, and improve eye conditions. Further study showed that HSV-1 infection upregulated Rac1 expression, and knockdown of Rac1 using siRNA markedly restricted HSV-1 replication, suggesting that Rac1 is required for HSV-1 replication. In addition, we also documented that Rac1 is highly expressed in corneal tissues from HSK patients, indicating that Rac1 is associated with HSK pathogenesis. In view of the high potency of 6-TG, low cytotoxicity, targeting a distinct therapeutic target, we suggest that 6-TG is a potential candidate for development as a therapeutic agent for HSK therapy.
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Antivirais/administração & dosagem , Herpesvirus Humano 1/efeitos dos fármacos , Ceratite Herpética/tratamento farmacológico , Tioguanina/administração & dosagem , Animais , Antivirais/química , Ganciclovir/farmacologia , Herpes Simples , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/fisiologia , Humanos , Ceratite Herpética/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tioguanina/química , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Most countries in the world, including China, are experiencing serious aging problems. The decline of cognitive function seriously affects the quality of life of the elderly in their later years and brings an inevitable heavy burden to the family and society. Therefore, in order to achieve successful aging, the purpose of this study is to test the serial multiple mediation effect of anxiety and loneliness between leisure activity and cognitive function in Chinese elderly population. METHODS: Using 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, we finally selected 6,525 Chinese elderly people over 65 years old after screening. Firstly, we described the basic social demographic information of the sample population. Secondly, Spearman correlation analysis was used to determine whether there is a correlation between leisure activity, anxiety, loneliness and cognitive function in Chinese elderly. Finally, the serial multiple mediation analysis was completed using the SPSS macro PROCESS program. RESULTS: Leisure activity, anxiety, loneliness and cognitive function were significantly correlated (p<0.01). Leisure activity can not only have a direct positive impact on the cognitive function of the elderly (effect=0.2231; SE=0.0122; 95%CI: LL=0.1992, UL=0.2470), but also have an indirect impact on the cognitive function through three paths: the independent mediating role of anxiety (effect=0.0028; SE=0.0015; 95%CI: LL=0.0001, UL=0.0059), the independent mediating role of loneliness (effect=0.0032; SE=0.0016; 95%CI: LL=0.0002, UL=0.0065), and the chain mediating role of anxiety and loneliness (effect=0.0008; SE=0.0004; 95%CI: LL=0.0001, UL=0.0017). LIMITATIONS: All items were self-reported and some results may have biased. In the future, it may be more instructive to explore the impact of specific leisure activity on the cognitive function of the elderly. CONCLUSIONS: The study suggests that leisure activity can improve cognitive function through decreasing anxiety and loneliness among the Chinese elderly. Diversified interventions aimed at increasing leisure activity participation in older adults would be beneficial for their mental health and cognitive function.
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Solidão , Qualidade de Vida , Idoso , Ansiedade/epidemiologia , China , Cognição , Humanos , Atividades de LazerRESUMO
Glioma is a type of common primary intracranial tumor, which is difficult to treat. It has been confirmed by research that corilagin (the primary active constituent of the matsumura leafflower herb) has significant antitumor effect. In particular, our previous research demonstrated that corilagin effectively promotes apoptosis of glioma U251 cells and has a synergistic effect when used with temozolomide. However, the mechanism by which corilagin causes apoptosis in U251 cells has yet to be investigated. Proteasomes are catalytic centers of the ubiquitinproteasome system, which is the major protein degradation pathway in eukaryotic cells; they are primarily responsible for the degradation of signal molecules, tumor suppressors, cyclins and apoptosis inhibitors and serve an important role in tumor cell proliferation and apoptosis. The present study investigated the proapoptotic effect of corilagin on glioma U251 cells and confirmed that decreased proteasome activity and expression levels serve an important role in corilagininduced U251 cell apoptosis.
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Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Glioblastoma/imunologia , Glioblastoma/patologia , Glucosídeos/uso terapêutico , Humanos , Taninos Hidrolisáveis/uso terapêutico , Inibidores de Proteassoma/uso terapêutico , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: At present, most Chinese adults are under great psychological pressure, which seriously affects the improvement of life satisfaction. The purpose of this study was to shed light on the associations between individual social capital and life satisfaction among mainland Chinese adults. METHODS: We used a nationally representative dataset called 2016 China Family Panel Studies, and a total of 26,009 people suited our study requirements. Chi-squared test and binary regression analysis were used to determine the relationship between individual social capital and life satisfaction among mainland Chinese adults. RESULTS: The results indicated that cognitive social capital had significant effects on life satisfaction (p < 0.05), but the impact of structural social capital on life satisfaction became less significant when combined with sociodemographic variables and socioeconomic status (SES) (p > 0.05). Moreover, we also found that life satisfaction was better in married/cohabited (p < 0.05) and in over 65 age group people (p < 0.05). Self-rated income level, self-rated social status, and self-rated health all had positive effects on life satisfaction (p < 0.001). CONCLUSIONS: Given the stabilizing effect of cognitive social capital at the individual level on life satisfaction, the government should attach great importance to this aspect when trying to improve adults' life satisfaction.
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Capital Social , Adulto , China , Nível de Saúde , Humanos , Satisfação Pessoal , Classe Social , Apoio Social , Fatores SocioeconômicosRESUMO
Inflammation has been proven to be one of the key factors in the pathogenesis of moyamoya disease (MMD). Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are cheap and reliable biomarkers of inflammation. Nevertheless, evidence regarding the relationship among PLR and NLR in patients with MMD is limited. The focus of this subject was to explore the relationship between PLR and NLR in patients with newly diagnosed MMD. Patients and methods: A cross-sectional study was performed including 261 patients with diagnosed MMD for the first time who were enrolled from our hospital, from 24 March 2013 to 24 December 2018. The clinical characteristics were collected for each patient. Univariate analysis, smooth curve fitting and multivariate piecewise linear regression were showed. Results: The mean levels or median values (interquartile range) of PLR and NLR were 146.979 ± 51.203 and 2.241 (1.589-2.984), respectively. A significant positive correlation between PLR and NLR levels (P < 0.001) was showed by the univariate analysis. Furthermore, a non-linear relationship was detected between PLR and NLR by smooth curve fitting after adjusting for potential confounders. A multivariate piecewise linear regression model revealed a significant positive correlation between PLR and NLR when the PLR level was lower than 219.82 (ß 0.012, 95% CI 0.005, 0.019; P = 0.001). PLR was also significantly positively associated with NLR when PLR concentrations were >219.82 (ß 0.098, 95% CI 0.069, 0.128; P < 0.001). Conclusion: There seemed to be a positive association between PLR and NLR in patients with MMD. This may help to further explain the role of inflammation in the occurrence and progress of MMD.
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Corilagin, extracted from the Euphorbiaceae and Phyllanthus plants, inhibits the growth of a number of types of tumors. Compared with temozolomide, the traditional chemotherapy drug, corilagin has demonstrated stronger antitumor activity. However, the pharmaceutical mechanism of corilagin in glioma remains unclear. Nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2) is positively associated with several types of tumor including glioma. In the present study, NRF2 expression was higher in glioma tissues compared with nonglioma specimens. Therefore, it was hypothesized that corilagin targets NRF2 regulation of U251 cell apoptosis. The present study used Hoechst 33258 staining to demonstrate that corilagin induced glioma cell apoptosis and observed that the expression of the apoptosisrelated gene Bcl2 was reduced. In addition, corilagin induced autophagy and promoted the conversion of light chain 3 (LC3) protein from LC3â to LC3II. NRF2 expression was downregulated by corilagin stimulation. Furthermore, the gene expression pattern following knockdown of NRF2 in U251 cells using siRNA was consistent with corilagin stimulation. Therefore, it was preliminarily concluded that corilagin induces apoptosis and autophagy by reducing NRF2 expression.
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Autofagia/efeitos dos fármacos , Glioma/tratamento farmacológico , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Fator 2 Relacionado a NF-E2/genética , Adulto , Idoso , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Temozolomida/farmacologiaRESUMO
Chemokine-induced chemotaxis of leukocytes is an important part of the innate immunity and has been shown to mediate inflammation in all groups of jawed vertebrates. For jawless vertebrates, hagfish leukocytes are known to show chemotaxis toward mammalian complement anaphylotoxin and Gram-negative bacteria lipopolysaccharide. However, whether chemokines mediate chemotaxis of leukocytes in jawless vertebrates has not been conclusively examined. Here, we show C-X-C motif chemokine ligand 8 (CXCL8, also named interleukin 8) of the Northeast Chinese lamprey (Lethenteron morii) (designated as LmCXCL8) induces chemotaxis in its leukocytes. We identified LmCXCL8 and found it possesses the characteristic N-terminal cysteine residues and GGR (Gly-Gly-Arg) motif. The Lmcxcl8 gene was found to be expressed in all examined tissues, and its expression was inducible in the lamprey challenged by an infectious bacterium, Pseudomonas aeruginosa. A recombinant LmCXCL8 protein elicited concentration-dependent chemotaxis in peripheral blood leukocytes isolated from the Northeast Chinese lamprey. Based on these results, we conclude that LmCXCL8 is a constitutive and inducible acute-phase cytokine that mediates immune defense and trace the chemotactic function of chemokine to basal vertebrates.