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Cell metabolism generates numerous intermediate metabolites that could serve as feedback and feed-forward regulation substances for posttranslational modification. Lactate, a metabolic product of glycolysis, has recently been conceptualized to play a pleiotropic role in shaping cell identities through metabolic rewiring and epigenetic modifications. Lactate-derived carbons, sourced from glucose, mediate the crosstalk among glycolysis, lactate, and lactylation. Furthermore, the multiple metabolic fates of lactate make it an ideal substrate for metabolic imaging in clinical application. Several studies have identified the crucial role of protein lactylation in human diseases associated with cell fate determination, embryonic development, inflammation, neoplasm, and neuropsychiatric disorders. Herein, this review will focus on the metabolic fate of lactate-derived carbon to provide useful information for further research and therapeutic approaches in human diseases. We comprehensively discuss its role in reprogramming and modification during the regulation of glycolysis, the clinical translation prospects of the hyperpolarized lactate signal, lactyl modification in human diseases, and its application with other techniques and omics.
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Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day-old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry-induced sepsis. These mice featured persistent inflammatory responses and were effectively rescued by GC therapy. RNA sequencing analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine-induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients based on the status of RAI.
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Insuficiência Adrenal , Sepse , Humanos , Criança , Camundongos , Animais , Insuficiência Adrenal/etiologia , Citocinas , NF-kappa B , Ceco , Ligadura/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.
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Cannabidiol (CBD) has emerged as a phytocannabinoid with various beneficial effects for the skin, including anti-photoaging effects, but its mechanisms of action are not fully elucidated. The study assessed CBD's photoprotective effects against acute ultraviolet B (UVB)-induced damage in HaCaT human keratinocyte cells and murine skin tissue. CBD (8 µM) alleviated UVB-induced cytotoxicity, apoptosis, and G2/M cell cycle arrest in HaCaT cells. The contents of γH2AX and cyclobutane pyrimidine dimers were decreased after CBD treatment. CBD reduced the production of reactive oxygen species and modulated the expression of antioxidant-related proteins such as nuclear factor erythroid 2-related factor 2 in UVB-stimulated HaCaT cells. Furthermore, CBD mitigated the UVB-induced cytotoxicity by activating autophagy. In addition, a cream containing 5% CBD showed effectiveness against UVB-induced photodamage in a murine model. The CBD cream improved the skin's condition by lowering the photodamage scores, reducing abnormal skin proliferation, and decreasing expression of the inflammation-related protein cyclooxygenase-2 in UVB-irradiated skin tissue. These findings indicate that CBD might be beneficial in alleviating UVB-induced skin damage in humans. The photoprotective effects of CBD might be attributed to its modulatory effects on redox homeostasis and autophagy.
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Canabidiol , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Autofagia , Canabidiol/metabolismo , Canabidiol/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dano ao DNA , Humanos , Queratinócitos , Camundongos , Dímeros de Pirimidina , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
Frostbite in Southwestern China has been overlooked due to its low incidence, relatively mild temperature and lack of literature published before. However, it needs to be further studied for religious diversity and distinct geomorphology. In this article, we reported an 18-year-old Tibetan girl who suffered from blizzard attack during pilgrimage. Her feet and several fingers showed mummified gangrene upon physical examination with poor movement. She was diagnosed with 3rd to 4th degree of frostbite. The girl was given oral ibuprofen, debridement and other regular treatment daily, but she was eventually amputated due to insufficient thrombolytic management in primary hospital, delayed informing consent in the referral hospital and ethnic conflict between religion and guidelines. This case enriched the experience of managing complex frostbite in Tibetan population and alarms that efforts should be integrated to protect pilgrims and mountaineers in the Tibetan region.
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Amputação Cirúrgica , Congelamento das Extremidades , Adolescente , China , Feminino , Congelamento das Extremidades/etiologia , Congelamento das Extremidades/terapia , Humanos , Incidência , TibetRESUMO
Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.
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Canabidiol , Cannabis , Neoplasias , Humanos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Neoplasias/tratamento farmacológico , Apoptose , Transtornos de Ansiedade/tratamento farmacológico , Microambiente TumoralRESUMO
OBJECTIVE: Adrenal gland secretes stress-induced glucocorticoids (iGCs) to coping with stress. Previous study showed that SR-BI (scavenger receptor BI) null (SR-BI-/-) mice failed to generate iGC in stress conditions, suggesting that SR-BI-mediated cholesterol uptake from HDL (high-density lipoprotein) is a key regulator for iGC production. However, the LDL (low-density lipoprotein)/LDLr (LDL receptor) pathway can also provide cholesterol for iGC synthesis, but rodents have limited LDL levels in circulation. Here, we generated SR-BI-/-ApoBtg (apolipoprotein B transgenic) mice with normal LDL levels in circulation to determine the relative contribution of the HDL/SR-BI and LDL/LDLr pathways to iGC production in stress conditions. Approach and Results: To obtain mouse models with normal LDL levels, SR-BI-/- mice were bred to ApoBtg mice. Then, the F1 SR-BI±ApoBtg mice were backcrossed to SR-BI-/- to obtain SR-BI-/-ApoBtg, SR-BI-/-ApoBwt (apolipoprotein B wild type), and SR-BI+/+ApoBtg mice. We first examined the lipoprotein profile, which shows a 6.5-fold increase in LDL levels in SR-BI-/-ApoBtg mice compared with SR-BI-/-ApoBwt mice. Then, we induced stress with adrenocorticotropic hormone and cecal ligation and puncture. One hour after adrenocorticotropic hormone stimulation, SR-BI+/+ApoBtg control mice produced iGC (14.9-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg showed no iGC production (P<0.001). Three hours after cecal ligation and puncture treatment, SR-BI+/+ApoBtg control mice showed iGC production (6.4-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg mice showed no iGC production (P<0.001). CONCLUSIONS: SR-BI-/-ApoBtg mice fail to produce iGC in stress conditions even though with restored LDL levels in circulation. These findings clarify that the HDL/SR-BI, not LDL/LDLr, pathway is responsible for iGC production in stress conditions.
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Glucocorticoides/biossíntese , Receptores de LDL/fisiologia , Receptores Depuradores Classe B/fisiologia , Estresse Psicológico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Lipoproteínas LDL/sangue , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Cardiac hypertrophy (CH) is a major risk factor for heart failure accompanied by maladaptive cardiac remodeling. The role and potential mechanism of neuropeptide Y (NPY) in CH are still unclear. We will explore the role and the mechanism of NPY inactivation (NPY-I) in CH caused by pressure overload. Abdominal aortic constriction (AAC) was used to induce CH model in rats. NPY or angiotensin II (Ang II) was used to trigger CH model in vitro in neonatal rat ventricular myocytes (NRVMs). We found that NPY was increased in the heart and plasma of hypertrophic rats. However, Ang II did not increase NPY expression in cardiomyocytes. NPY-I attenuated CH as decreasing CH-related markers (ANP, BNP and ß-MHC mRNA) level, reducing cell surface area, and restoring cardiac function. NPY inactivation increased miR-216b and decreased FoxO4 expression in CH heart. Moreover, NPY decreased miR-216b and increased FoxO4 expression in NRVMs which were reversed by NPY type 1 receptor (NPY1R) antagonist BIBO3304. MiR-216b mimic and FoxO4 siRNA (small interfering RNA) inhibited NPY/Ang II-induced myocardial hypertrophy in vitro. Meanwhile, BIBO3304 reversed the pro-hypertrophy effect of NPY in vitro. Collectively, NPY deficiency attenuated CH by NPY1R-miR-216b-FoxO4 axis. These findings suggested that NPY would be a potential therapeutic target for the prevention and treatment of cardiac hypertrophy.
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Cardiomegalia/genética , Fatores de Transcrição Forkhead/genética , MicroRNAs/metabolismo , Miocárdio/patologia , Neuropeptídeo Y/metabolismo , Angiotensina II/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Cardiomegalia/patologia , Células Cultivadas , Modelos Animais de Doenças , Humanos , Masculino , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Miocárdio/citologia , Miócitos Cardíacos/patologia , Cultura Primária de Células , Ratos , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/antagonistas & inibidores , Receptores de Neuropeptídeos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
A one-step solvothermal method for the preparation of carbon dots with red fluorescence (R-CDs) was put forward, in which sodium citrate and formamide were chosen as precursors, while formamide was adopted as the solvent. The fluorescence emission peak of the as-prepared R-CDs remained the same (600 nm) when the excitation wavelength increased from 490 nm to 560 nm, and the fluorescence quantum yield is 35.3%. Furthermore, the fluorescence intensity of the as-prepared R-CDs could be selectively quenched by copper ions, and the mechanism of Cu2+ quenching R-CDs is the combination of static and dynamic quenching. As a result, the R-CDs were applied for the construction of a fluorescent sensor without any modification for the quantitative and visual detection of copper ions, which is a typical contaminant in water. The limit of detection for the fluorescent sensor was as low as 5 nmol/L, and it can be used to fast and directly confirm whether the content of copper ions in drinking water meets the criteria of the United States Environmental Protection Agency and the World Health Organization.
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Carbono , Pontos Quânticos , Cobre , Íons , Espectrometria de FluorescênciaRESUMO
OBJECTIVE: To assess the efficacy of 595 nm pulsed dye laser (PDL) in the treatment of facial and neck port-wine stains (PWSs), and to explore the main factors affecting the efficacy. METHODS: A total of 259 PWS cases who were treated with 595 nm PDL were retrospectively enrolled and their clinical information was analyzed in the study. Before- and after-treatment comparison of individual patient was done by comparing patient photographs taken before and after PDL treatment of the PWSs in order to assess the treatment efficacy, using mild purpura as the endpoint of the PDL treatment. A total of 82 male and 177 female cases were included, with patient age ranging between 1 month and 63 years. Univariate analysis was done to select factors influencing the treatment efficacy. Then, ordered multivariate logistic regression analysis was performed to evaluate the main factors affecting the efficacy. Statistics of adverse reaction of patients were also collected. RESULTS: Of the 259 patients covered in the study, 57 (22%) had achieved complete clearing of PWS, 106 (40.9%) showed significant improvement, and 68 (26.3%) showed moderate improvement, amounting to a total of 231 effective treatment cases, indicating a 89.2% overall rate of effective treatment. There were 28 ineffective treatment cases (10.8%). Ordered multivariate logistic regression analysis showed that the color of PWS, the area of PWS, anatomical sites of PWS and the number of treatment sessions were the main factors affecting the therapeutic efficacy, while proliferation did not affect the therapeutic efficacy. Red-type PWS had better treatment efficacy than that of the purple-type PWS (odds ratio [ OR]=2.748, P<0.05). Patients with PWS≤10 cm 2 showed better treatment efficacy than those with PWS>10 cm 2 ( OR=2.094, P<0.05). Treatment efficacy of PWS located in the central section of the face was not as good as those located on the neck ( OR=0.190, P<0.05), and the treatment efficacy of PWS located in the central and lateral section of the face was not as good as those located on the neck ( OR=0.243, P<0.05). Patients who had more than 3 treatment sessions showed better efficacy than those who had 1-3 sessions of treatment ( OR=0.508, P<0.05). No patients incurred any serious adverse reactions. CONCLUSION: Patients with PWS located on the neck, red-type PWS and area ≤10 cm 2 are suitable for treatment with 595 nm PDL and there should be more than three sessions of treatment. Patient sex, age, or proliferation do not affect the treatment effect.
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Lasers de Corante , Mancha Vinho do Porto , Face , Feminino , Humanos , Lactente , Lasers de Corante/uso terapêutico , Masculino , Mancha Vinho do Porto/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.
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Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doença de Alzheimer/tratamento farmacológico , Mineração de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , PrescriçõesRESUMO
Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.
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Medicamentos de Ervas Chinesas , Orthomyxoviridae , Pneumonia , Pulsatilla , Animais , Camundongos , Farmacologia em Rede , Pneumonia/tratamento farmacológico , Pneumonia/genéticaRESUMO
BACKGROUND: The aim of this study was to investigate the association between telomerase reverse transcriptase (TERT) gene polymorphisms and acute myeloid leukemia (AML) susceptibility in a Chinese Han population. METHODS: A total of 102 AML patients and 108 healthy controls were enrolled in this case-control study. TERT gene rs2853669 and rs2736100 polymorphisms were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-square test was applied to compare polymorphism distributions between case and control groups. The strength of the association between TERT gene polymorphisms and AML susceptibility was evaluated utilizing odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: CC genotype and C allele of rs2736100 polymorphism were more frequent in AML patients (P < 0.05), and individuals carrying CC genotype showed higher risk of suffering from AML (OR = 2.632, 95% CI 1.129-6.133). But for rs2853669 polymorphism, no significant differences were detected in either genotype or allele distributions between groups (P > 0.05). CONCLUSIONS: This study suggested a positive association between TERT gene rs2736100 polymorphism and AML susceptibility in Chinese Han population.
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Copy number variations (CNVs) have been identified as another important structural variation of genome. In recent years, a large amount of CNVRs have been identified in humans and animals. However, association and dosage effects studies of CNVs are very limited. Apolipoprotein L3 (APOL3) gene plays a central role in modulating gene transcription and is located within a CNVR that encompasses quantitative trait locis (QTLs) for economic traits like meat quality. Herein, we analyzed the CNV polymorphism of APOL3 in 421 individuals from five distinct cattle breeds, and then correlated their genotypes with growth traits. Association analysis revealed that the APOL3 CNV was significantly associated with hip height and cannon circumference of Xianan (XN) cattle (P < .01), and visibly associated with body slanting length and hucklebone width of Pinan (PN) cattle (P < .05). Overall, the data provide evidence for the functional role of APOL3 CNV and a basis for future applications in cattle breeding.
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Apolipoproteínas L/genética , Tamanho Corporal/genética , Bovinos/genética , Variações do Número de Cópias de DNA/genética , Animais , Cruzamento , Bovinos/crescimento & desenvolvimento , Locos de Características QuantitativasRESUMO
Phosphorylated histone H2AX, termed 'γH2AX', mediates the chromatin response to DNA double strand breaks (DSBs) in mammalian cells. H2AX deficiency increases the numbers of unrepaired DSBs and translocations, which are partly associated with defects in non-homologous end joining (NHEJ) and contributing to genomic instability in cancer. However, the role of γH2AX in NHEJ of general DSBs has yet to be clearly defined. Here, we showed that despite little effect on overall NHEJ efficiency, H2AX deficiency causes a surprising bias towards accurate NHEJ and shorter deletions in NHEJ products. By analyzing CRISPR/Cas9-induced NHEJ and by using a new reporter for mutagenic NHEJ, we found that γH2AX, along with its interacting protein MDC1, is required for efficient classical NHEJ (C-NHEJ) but with short deletions and insertions. Epistasis analysis revealed that ataxia telangiectasia mutated (ATM) and the chromatin remodeling complex Tip60/TRRAP/P400 are essential for this H2AX function. Taken together, these data suggest that a subset of DSBs may require γH2AX-mediated short-range nucleosome repositioning around the breaks to facilitate C-NHEJ with loss of a few extra nucleotides at NHEJ junctions. This may prevent outcomes such as non-repair and translocations, which are generally more destabilizing to genomes than short deletions and insertions from local NHEJ.
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Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Histonas/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas Mutadas de Ataxia Telangiectasia/fisiologia , Sequência de Bases , Sistemas CRISPR-Cas , Proteínas de Ciclo Celular , Linhagem Celular , Proteína Quinase Ativada por DNA/fisiologia , Proteínas de Ligação a DNA/fisiologia , Histonas/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Nucleotídeos/análise , Deleção de SequênciaRESUMO
As a treasure of traditional Chinese medicine culture,Dao-di herbs are famous for their high quality and good effect.However,traditional characteristics of Dao-di herbs and their producing areas are mostly confined to qualitative description,lacking objective evaluation indicators. Numerical taxonomy,which uses mathematical methods to improve the research of taxonomy from qualitative description to quantitative comprehensive analysis,is objective and accurate,so is widely used in the field of biology and medicine.This paper reviews the concept and main research fields of numerical taxonomy,and summarizes its application status and development prospects in the study of Dao-di herbs and characteristics of production areas,in order to lay the foundation for the objectification and standardization of Dao-di herbs.
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Medicamentos de Ervas Chinesas/classificação , Plantas Medicinais/classificação , Medicamentos de Ervas Chinesas/normas , Medicina Tradicional ChinesaRESUMO
Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-ß-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.
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Antineoplásicos/farmacologia , Docetaxel/farmacologia , Neoplasias Pulmonares/patologia , Nanopartículas , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Micelas , Tamanho da Partícula , TaxoidesRESUMO
BACKGROUND The objective of this study was to detect the association between ERCC excision repair 2, TFIIH core complex helicase subunit (ERCC2) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) susceptibility. MATERIAL AND METHODS This study used a case-control design. ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) both in DLBCL patients and healthy controls. The association between ERCC2 gene polymorphisms and DLBCL risk was assessed by χ² test. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to address the association strength. Subgroup analyses were also performed to investigate the genetic effects of ERCC2 polymorphisms on clinical characteristics of DLBCL patients. RESULTS A significant association was discovered between the rs1799793 A allele and increased DLBCL risk (P=0.031, OR=1.928, 95% CI=1.052-3.534). The C allele of rs13181 was obviously associated with elevated DLBCL susceptibility (P=0.047, OR=1.820, 95% CI=1.002-3.305). The subgroup analysis demonstrated that rs1799793 and rs13181 polymorphisms had no relationship with serum lactate dehydrogenase level, nidus number, B-symptoms, Ann Arbor stages, or immunological types in DLBCL cases (P>0.05 for all). CONCLUSIONS Minor allele carriers of ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms had higher susceptibility to DLBCL.
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Linfoma Difuso de Grandes Células B/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , China , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Proteína Grupo D do Xeroderma Pigmentoso/fisiologiaRESUMO
Objective To evaluate the correlation of the positron emission tomography/magnetic resonance imaging (PET/MR) parameters with the pathological differentiation of head and neck squamous cell carcinoma(HNSCC) and the diagnostic efficiencies of PET/MR parameters. Methods Patients with clinical suspicion of HNSCC were included and underwent PET/MR scan. HNSCC was pathologically confirmed in all these patients. The PET/MR examination included PET and MR sequences of diffusion-weighted imaging (DWI) and T2-and T1-weighted imaging. The multiple parameters of PET/MR included the mean values of apparent diffusion coefficient(ADCmean) and the maximum and mean values of standardized uptake value (SUVmax and SUVmean) were measured and estimated. The correlations of all the parameters and distribution between the different tumor differentiation groups were analyzed. Logistic regression was utilized to build the model as the PET/MR combined parameter for predicting the differentiation by multiple parameters of PET/MR. The receiver operating characteristic curve was calculated for each parameter and the combination. Results Totally 23 patients were included in this study:9 patients (9 males and 0 female) had well-differentiated tumor,with an average age of (61.0±6.8)years;14 cases had moderately-differentiated (n=10) or poorly-differentiated tumors (n=4),with an average age of (62.0±9.1) years. All the patients were males. There was statistical correlation between SUVmean and SUVmax (P<0.001);however,ADCmean showed no statistical correlation with SUVmax and with SUVmean (P=0.42,P=0.13). ADCmean and SUVmean showed significant difference between well-differentiated group and moderately-poorly-differentiated group (P=0.005,P=0.007). Compared with the individual parameters,the combination of PET/MR parameters with SUVmean and ADCmean had higher efficacy in predicting tumor differentiation,with an area under curve of 0.84. Conclusions The distributions of ADCmean,SUVmax and SUVmean differ among HNSCC with different pathological differentiation. Compared with the individual parameters,the combination of the PET/MR parameters has higher efficiency in predicting tumor differentiation.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To assess the reliability and validity of a simplified version of acne-specific quality of life (Acne-Qol-19) instrument in Han populations in Sichuan province. METHODS: Acne-Qol-19 was administered to 264 acne patients. Internal consistency, split-half reliability, content validity, criterion validity and construct validity (factor analysis) of Acne-Qol-19 were assessed. RESULTS: The Acne-Qol-19 obtained a Cronbach's α of 0.953 and split-half reliability of 0.902 (Spearman-Brown). Its content validity was well confirmed by dermatologists. The Acne-Qol-19 result was strongly associated (r =#-0.745) with Cardiff acne disabled index (CADI) (P <0.001). Confirmatory factor analysis yielded standardized loading of 0.853-0.944 on self-perception, 0.865-0.945 on role-social dimension, 0.383-0.898 on role-emotional dimension, and 0.612-0.867 on acne symptoms (P <0.01). CONCLUSION: Acne-Qol-19 has good validity and reliability in Han populations in Sichuan.