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1.
Mol Biol Evol ; 40(6): msad121, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37325551

RESUMO

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.


Assuntos
Carbonato de Cálcio , Juglandaceae , Cálcio , Especiação Genética , Genômica
2.
Mol Biol Evol ; 40(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37216901

RESUMO

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.


Assuntos
Carbonato de Cálcio , Juglandaceae , Ásia Oriental , Cálcio , Especiação Genética , Genômica , Juglandaceae/genética , Juglandaceae/fisiologia
3.
Allergy ; 79(4): 843-860, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38055191

RESUMO

Transcription therapy is an emerging approach that centers on identifying the factors associated with the malfunctioning gene transcription machinery that causes diseases and controlling them with designer agents. Until now, the primary research focus in therapeutic gene modulation has been on small-molecule drugs that target epigenetic enzymes and critical signaling pathways. However, nucleic acid-based small molecules have gained popularity in recent years for their amenability to be pre-designed and realize operative control over the dynamic transcription machinery that governs how the immune system responds to diseases. Pyrrole-imidazole polyamides (PIPs) are well-established DNA-based small-molecule gene regulators that overcome the limitations of their conventional counterparts owing to their sequence-targeted specificity, versatile regulatory efficiency, and biocompatibility. Here, we emphasize the rational design of PIPs, their functional mechanisms, and their potential as targeted transcription therapeutics for disease treatment by regulating the immune response. Furthermore, we also discuss the challenges and foresight of this approach in personalized immunotherapy in precision medicine.


Assuntos
Ácidos Nucleicos , Humanos , DNA , Imunidade
4.
J Nanobiotechnology ; 22(1): 189, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632615

RESUMO

Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Transcriptoma , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , DNA , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica
5.
Nucleic Acids Res ; 50(20): 11727-11737, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318259

RESUMO

CRISPR (clustered regularly interspaced short palindromic repeats) technology has achieved great breakthroughs in terms of convenience and sensitivity; it is becoming the most promising molecular tool. However, only two CRISPR activation modes (single and double stranded) are available, and they have specificity and universality bottlenecks that limit the application of CRISPR technology in high-precision molecular recognition. Herein, we proposed a novel CRISPR/Cas12a unrestricted activation mode to greatly improve its performance. The new mode totally eliminates the need for a protospacer adjacent motif and accurately activates Cas12a through toehold-mediated strand displacement and branch migration, which is highly universal and ultra-specific. With this mode, we discriminated all mismatch types and detected the EGFR T790M and L858R mutations in very low abundance. Taken together, our activation mode is deeply incorporated with DNA nanotechnology and extensively broadens the application boundaries of CRISPR technology in biomedical and molecular reaction networks.


Assuntos
Sistemas CRISPR-Cas , Neoplasias Pulmonares , Humanos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação
6.
Small ; : e2307421, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072808

RESUMO

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

7.
Phys Rev Lett ; 130(9): 096201, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930940

RESUMO

We report the manipulation of ultrafast quantum coherence of a two-level single hydrogen molecular system by employing static electric field from the sample bias in a femtosecond terahertz scanning tunneling microscope. A H_{2} molecule adsorbed on the polar Cu_{2}N surface develops an electric dipole and exhibits a giant Stark effect. An avoided crossing of the quantum state energy levels is derived from the resonant frequency of the single H_{2} two levels in a double-well potential. The dephasing time of the initial wave packet can also be changed by applying the electric field. The electrical manipulation for different tunneling gaps in three dimensions allows quantification of the surface electrostatic fields at the atomic scale. Our work demonstrated the potential application of molecules as controllable two-level molecular systems.

8.
Crit Rev Biotechnol ; 43(3): 415-432, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35156471

RESUMO

While the research field and industrial market of in vitro diagnosis (IVD) thrived during and post the COVID-19 pandemic, the development of isothermal nucleic acid amplification test (INAAT) based rapid diagnosis was engendered in a global wised large measure as a problem-solving exercise. This review systematically analyzed the recent advances of INAAT strategies with practical case for the real-world scenario virus detection applications. With the qualities that make INAAT systems useful for making diagnosis relevant decisions, the key performance indicators and the cost-effectiveness of enzyme-assisted methods and enzyme-free methods were compared. The modularity of nucleic acid amplification reactions that can lead to thresholding signal amplifications using INAAT reagents and their methodology design were examined, alongside the potential application with rapid test platform/device integration. Given that clinical practitioners are, by and large, unaware of many the isothermal nucleic acid test advances. This review could bridge the arcane research field of different INAAT systems and signal output modalities with end-users in clinic when choosing suitable test kits and/or methods for rapid virus detection.


Assuntos
COVID-19 , Ácidos Nucleicos , Vírus , Humanos , Pandemias , Técnicas de Amplificação de Ácido Nucleico/métodos , Tecnologia
9.
Surg Endosc ; 37(7): 5265-5273, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36971816

RESUMO

BACKGROUND: Anastomosis-related complications such as bleeding, leakage, and strictures, continue to be serious complications of gastric cancer surgery. Presently, these complications have yet to be reliably prevented. Here we design a comprehensive leak testing procedure which combines gastroscopy, air, and methylene blue (GAM) leak testing. We aimed to evaluated the efficacy and safety of the GAM procedure in patients with gastric cancer. METHODS: Patients aged 18-85 years without an unresectable factor as confirmed via CT were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital and were randomly assigned to two groups: intraoperative leak testing group (IOLT) and no intraoperative leak testing group (NIOLT). The primary endpoint was the incidence of postoperative anastomosis-related complications in the two groups. RESULTS: 148 patients were initially randomly assigned to the IOLT group (n = 74) and to the NIOLT group (n = 74) between September 2018 and September 2022. After exclusions, 70 remained in the IOLT group and 68 in the NIOLT group. In the IOLT group, 5 patients (7.1%) were found to have anastomotic defects intraoperatively, which included anastomotic discontinuity, bleeding, and strictures. The NIOLT group had a higher incidence of postoperative anastomotic leakage compared to the IOLT group: 4 patients (5.8%) vs 0 patients (0%), respectively. No GAM-related complications were observed. CONCLUSION: The GAM procedure is an intraoperative leak test that can be performed safely and efficiently after a laparoscopic total gastrectomy. GAM anastomotic leak testing may effectively prevent technical defect-related anastomotic complications in patients with gastric cancer who undergo a gastrectomy. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT04292496.


Assuntos
Anastomose Cirúrgica , Fístula Anastomótica , Neoplasias Gástricas , Humanos , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Constrição Patológica/cirurgia , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações
10.
BMC Ophthalmol ; 23(1): 240, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248486

RESUMO

PURPOSE: To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). METHODS: We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated. RESULTS: Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab. CONCLUSION: Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.


Assuntos
Anticorpos Monoclonais , Uveíte , Humanos , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anticorpos Monoclonais Humanizados , Fator de Necrose Tumoral alfa , Uveíte/tratamento farmacológico , Inflamação/tratamento farmacológico
11.
Sheng Li Xue Bao ; 75(2): 291-302, 2023 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-37089103

RESUMO

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and ß-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. ß-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Aminoácidos de Cadeia Ramificada/metabolismo , Resistência à Insulina/fisiologia , Insulina/farmacologia , Cetoácidos/metabolismo
12.
Nutr Cancer ; 74(8): 2769-2778, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35876250

RESUMO

To evaluate the effectiveness of Helicobacter pylori (Hp) related gastric cancer screening (Hp-GCS) and cost-effectiveness of protocol candidates in a hospital-based cross-sectional study. A total of 163 gastric cancer patients in West China Hospital were retrospectively collected according to ICD-10 code and histologic proof between April 1, 2013 and March 31, 2014, and 15,599 cancer-free controls were simultaneously collected from the health checkup registry. Hp infection was examined by urea breath test (UBT). The prevalence of Hp infection was compared between patients and controls. The diagnostic performance of UBT-based predictive index was tested in both training and validation settings. Cost-effectiveness analysis was conducted to assess candidates of Hp-GCS protocols. The prevalence of Hp infection was 55.8% and 41.2% in gastric cancers and controls, respectively (p < 0.001). UBT-based model showed moderate diagnostic strength in Hp-GCS (AUC = 0.78, 95% CI 0.74-0.82), better than UBT alone (p < 0.001). The sensitivity and specificity of UBT-based index were 80.2% and 61.9% at optimal cutoff in training setting, comparable in validation setting, which sensitivity and specificity were 76.9% and 59.6%. Number needed to screen was decreased along with older age, as well as stronger positivity of UBT. The optimal cost-effective Hp-GCS protocol with detection rate (DR = 77.9%) was endoscopic screening in age 40-59 years and positive UBT, or age ≥60 years without UBT. Incremental analysis suggested a preferable protocol as endoscopic screening in age ≥40 years without UBT (DR = 93.3%). UBT had moderate diagnostic strength in massive gastric cancer screening, and might be cost-effective in middle-aged population (40-59 years). More robust Hp-GCS protocol needs further investigate in test methods and individual biologic features.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Análise Custo-Benefício , Estudos Transversais , Detecção Precoce de Câncer , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Hospitais , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Ureia
13.
Sheng Li Xue Bao ; 74(5): 805-815, 2022 Oct 25.
Artigo em Zh | MEDLINE | ID: mdl-36319103

RESUMO

Skeletal muscle is the largest organ of human body, which completes 80%-90% of glucose intake stimulated by insulin, and is closely related to the occurrence and development of insulin resistance (IR). Skeletal muscle is one of the main places of lipid metabolism, and lipid metabolites participate in skeletal muscle metabolism as signal molecules. Fatty acids regulate skeletal muscle insulin sensitivity through insulin signaling pathway, inflammatory response and mitochondrial function. Saturated fatty acids (SFAs) induce insulin resistance by impairing insulin signal transduction, inducing mitochondrial dysfunction and inflammatory response, while unsaturated fatty acids reverse the adverse effects of SFAs and ameliorate IR by enhancing insulin signal transduction and anti-inflammatory effect. In addition, disorders of lipid metabolism in skeletal muscle cause accumulation of harmful metabolic intermediates, such as diacylglycerol, ceramide and long-chain acyl-coenzyme A, and induce IR by directly or indirectly damaging insulin signaling pathway. This article reviews the research progress of lipid metabolic intermediates regulating insulin sensitivity in skeletal muscle, which will help to better understand the pathogenesis of diabetes.


Assuntos
Resistência à Insulina , Humanos , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo
14.
Wei Sheng Yan Jiu ; 51(4): 550-555, 2022 Jul.
Artigo em Zh | MEDLINE | ID: mdl-36047257

RESUMO

OBJECTIVE: To examine the association between fruit intake and blood glucose metabolism. METHODS: Healthy singleton pregnant women with 6-14 weeks of gestation were selected in a maternal-and-child health care institution in Chengdu from February to July 2017. Dietary information was obtained by 3-day 24-hour dietary recall during each trimester, and the average daily total fruit intake per person were calculated. According to the Dietary guidelines for Chinese pregnant women(2016), insufficient rates of fruits were calculated, and the participants were divided into insufficient intake group, suitable intake group and higher intake group. Multiple linear regression was used to analyze the association between fruit intake during pregnancy and fasting blood glucose, 1-h plasma glucose and 2-h plasma glucose. Log-binomial regression model was used to analyze the association between fruit intake during pregnancy and the risk of gestational diabetes mellitus(GDM). RESULTS: Valid samples of 1453 cases in early pregnancy, 1049 cases in middle pregnancy were included, the age was(28.5±4.0)years old. The average fruit intake during the early and middle pregnancy(M(P25, P75)) were 279.7(180.8, 415.2) g/d and 232.0(100.0, 390.0) g/d, respectively. The insufficient rates were 18.8% and 43.2%, respectively. After adjusting for age, pre-pregnancy BMI, education level, family income, family history of diabetes, parity, physical activity, energy, vegetables, grains, red meat, and beverages, multiple linear regression result showed that compared with the insufficient fruit intake group, in the suitable fruit intake group, the fasting blood glucose level was decreased(ß=-0.071, 95%CI-0.111--0.003). Results of log binomial regression analysis showed that when compared with the fruit suitable intake group during the second trimester, the insufficient intake group may increase the risk of GDM(RR=1.13, 95% CI 1.11-1.58); no association between fruit intake during the early pregnancy and blood glucose metabolism was observed. CONCLUSION: Fruit intake during pregnancy is associated with blood glucose metabolism. The appropriate amount of fruit intake may improve fasting blood glucose and insufficient intake of fruits during the second trimester may increase the risk of GDM.


Assuntos
Glicemia , Diabetes Gestacional , Adulto , Glicemia/análise , Dieta , Feminino , Frutas/química , Humanos , Gravidez , Segundo Trimestre da Gravidez , Adulto Jovem
15.
BMC Genomics ; 22(1): 762, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702184

RESUMO

BACKGROUND: Alternative splicing (AS) is an important mechanism of posttranscriptional modification and dynamically regulates multiple physiological processes in plants, including fruit ripening. However, little is known about alternative splicing during fruit development in fleshy fruits. RESULTS: We studied the alternative splicing at the immature and ripe stages during fruit development in cucumber, melon, papaya and peach. We found that 14.96-17.48% of multiexon genes exhibited alternative splicing. Intron retention was not always the most frequent event, indicating that the alternative splicing pattern during different developmental process differs. Alternative splicing was significantly more prevalent at the ripe stage than at the immature stage in cucumber and melon, while the opposite trend was shown in papaya and peach, implying that developmental stages adopt different alternative splicing strategies for their specific functions. Some genes involved in fruit ripening underwent stage-specific alternative splicing, indicating that alternative splicing regulates fruits ripening. Conserved alternative splicing events did not appear to be stage-specific. Clustering fruit developmental stages across the four species based on alternative splicing profiles resulted in species-specific clustering, suggesting that diversification of alternative splicing contributes to lineage-specific evolution in fleshy fruits. CONCLUSIONS: We obtained high quality transcriptomes and alternative splicing events during fruit development across the four species. Dynamics and nonconserved alternative splicing were discovered. The candidate stage-specific AS genes involved in fruit ripening will provide valuable insight into the roles of alternative splicing during the developmental processes of fleshy fruits.


Assuntos
Frutas , Prunus persica , Processamento Alternativo , Frutas/genética , Regulação da Expressão Gênica de Plantas , Plantas , Transcriptoma
16.
Cancer Sci ; 112(6): 2126-2139, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33735492

RESUMO

The tumor microenvironment, comprised of tumor cells and tumor-infiltrating immune cells, is closely associated with the clinical outcome of clear cell renal cell carcinoma (ccRCC) patients. However, the landscape of immune infiltration in ccRCC has not been fully elucidated. Herein, we applied multiple computational methods and various datasets to reveal the immune infiltrative landscape of ccRCC patients. The tumor immune infiltration (TII) levels of 525 ccRCC patients using a single-sample gene were examined and further categorized into immune infiltration subgroups. The TII score was characterized by distinct clinical traits and showed a significant divergence based on gender, grade, and stage. A high TII score was associated with the ERBB signaling pathway, the TGF-ß signaling pathway, and the MTOR signaling pathway, as well as a better prognosis. Furthermore, patients with high TII scores exhibited greater sensitivity to pazopanib. The low TII score was characterized by a high immune infiltration level of CD8+ T cells, T follicular helper cells, and regulatory T cells (Tregs). Moreover, the immune check point genes, including CTLA-4, LAG3, PD-1, and IDO1, presented a high expression level in the low TII score group. Patients in the high TII score group demonstrated significant therapeutic advantages and clinical benefits. The findings in this study have the potential to assist in the strategic design of immunotherapeutic treatments for ccRCC.


Assuntos
Carcinoma de Células Renais/imunologia , Imunoterapia , Neoplasias Renais/imunologia , Microambiente Tumoral/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Checkpoint Imunológico/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Linfócitos do Interstício Tumoral/imunologia , Prognóstico , Transdução de Sinais/imunologia , Análise de Sobrevida , Subpopulações de Linfócitos T/imunologia
17.
Br J Nutr ; 126(12): 1872-1880, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-33597060

RESUMO

We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.


Assuntos
Diabetes Gestacional , Animais , Carboidratos , China/epidemiologia , Diabetes Gestacional/epidemiologia , Dieta com Restrição de Carboidratos/efeitos adversos , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Fatores de Risco
18.
Anal Bioanal Chem ; 413(28): 6929-6939, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34523014

RESUMO

Glycosylated PD-L1 is a more reliable biomarker for immune checkpoint therapy and plays important roles in tumor immunity. Glycosylation of PD-L1 hinders antibody-based detection, which is partially responsible for the inconsistency between PD-L1 immunohistochemical results and therapeutic treatment response. Herein, we present a proximity ligation assay mediated rolling circle amplification (PLA-RCA) strategy for amplified imaging of glycosylated PD-L1 in situ. The strategy relies on a pair of DNA probes: an aptamer probe to specifically recognize cellular surface protein PD-L1 and a glycan conversion (GC) probe for metabolic glycan labeling. Upon proximity ligation of sequence binding to the two probes, the proximity ligation-triggered RCA occurs. The feasibility of the as-proposed strategy has been validated as it realized the visualization of PD-L1 glycosylation in different cancer cells and the monitoring of the variation of PD-L1 glycosylation during drug treatment. Thus, we envision the present work offers a useful alternative to track protein-specific glycosylation and potentially advances the investigation of the dynamic glycan state associated with the disease process.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Eletroforese em Gel de Ágar , Glicosilação , Humanos
19.
Public Health Nutr ; 24(13): 4054-4063, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33947494

RESUMO

OBJECTIVES: Fruit intake may influence gestational diabetes mellitus (GDM) risk. However, prospective evidence remains controversial and limited. The current study aimed to investigate whether total fruit and specific fruit intake influence GDM risk. DESIGN: A prospective cohort study was conducted. Dietary information was collected by a 3-d 24-h dietary recall. All participants underwent a standard 75-g oral glucose tolerance test at 24-28 gestational weeks. Log-binomial models were used to estimate the association between fruit intake and GDM risk, and the results are presented as relative risks (RR) and 95 % CI. SETTING: Southwest China. PARTICIPANTS: Totally, 1453 healthy pregnant women in 2017. RESULTS: Total fruit intake was not associated with lower GDM risk (RR of 1·03 (95 % CI 0·83, 1·27) (Ptrend = 0·789)). The RR of GDM risk was 0·73 for the highest anthocyanin-rich fruit intake quartile compared with the lowest quartile (95 % CI 0·56, 0·93; Ptrend = 0·015). A higher grape intake had a linear inverse association with GDM risk (Q4 v. Q1: RR = 0·65; 95 % CI 0·43, 0·98; Ptrend = 0·044), and after further adjustment for anthocyanin intake, the inverse association tended to be non-linear (Q4 v. Q1: RR = 0·65; 95 % CI 0·44, 0·98; Ptrend = 0·079). However, we did not find an association between glycaemic index-grouped fruit, glycaemic load-grouped fruit or other fruit subtype intake and GDM risk. CONCLUSIONS: In conclusion, specific fruit intake (particularly anthocyanin-rich fruit and grapes) but not total fruit intake was inversely associated with GDM risk.


Assuntos
Diabetes Gestacional , Carga Glicêmica , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/etiologia , Frutas , Teste de Tolerância a Glucose , Humanos , Gravidez , Estudos Prospectivos , Fatores de Risco
20.
Am J Perinatol ; 38(8): 834-840, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-31891957

RESUMO

OBJECTIVE: To investigate whether plasma lipid profiles are independently associated with pregnancy complications including gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), and intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: A prospective study was conducted among 1,704 pregnant women at three medical institutions in Chengdu, China. The concentrations of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at gestational weeks 12 ± 1, 24 ± 1, and 34 ± 1. Logistic regression models were used to estimate the association between lipid profiles and pregnancy complications. Receiver operating characteristic analysis was performed to determine the value of lipid profiles to predict GDM and HDCP. RESULTS: After adjusting for potential confounders, TG, TC, and LDL-C in the first trimester were independently associated with GDM (TG: odds ratio [OR] =2.00, 95% confidence interval [CI]: 1.57-2.56; TC: OR = 1.38, 95% CI: 1.16-1.64; LDL-C: OR = 1.43, 95% CI: 1.14-1.79) and HDCP (TG: OR = 2.42, 95% CI: 1.56-3.78, TC: OR = 1.64, 95% CI: 1.04-2.57; LDL-C: OR = 1.87, 95% CI: 1.07-3.25). The TC concentration during the whole pregnancy (first trimester: OR = 1.53, 95% CI: 1.13-2.08; second trimester: OR = 1.31, 95% CI: 1.06-1.61; third trimester: OR = 1.39, 95% CI: 1.17-2.04) and LDL-C in the last two trimesters (second trimester: OR = 1.62, 95% CI: 1.30-2.04; third trimester: OR = 1.56, 95% CI: 1.29-1.88) were positively associated with ICP. HDL-C in the third trimester was negatively associated with the risk of ICP (OR = 0.46, 95% CI: 0.22-0.98). Combining lipid profiles in the first trimester with the other common predictors to predict GDM or HDCP owned stronger predictive power with the largest area under the curve (GDM: 0.643 [95% CI: 0.613-0.673], HDCP: 0.707 [95% CI: 0.610-0.804]) than either indicator alone. CONCLUSION: Maternal lipid profiles during the whole pregnancy are significantly associated with GDM, HDCP, and ICP. Combining lipid profiles in the first trimester with the other common predictors could effectively improve the power of predicting GDM and HDCP.


Assuntos
Colesterol/sangue , Diabetes Gestacional/sangue , Hipertensão Induzida pela Gravidez/sangue , Complicações na Gravidez/sangue , Gravidez/sangue , Triglicerídeos/sangue , Adulto , Glicemia/análise , Colestase Intra-Hepática/sangue , Feminino , Humanos , Modelos Logísticos , Estudos Prospectivos
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