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1.
Opt Lett ; 49(11): 3142-3145, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824348

RESUMO

Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1 GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6 GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7 GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.

2.
Eur J Nutr ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847866

RESUMO

BACKGROUND: Antioxidant and pro-oxidant dietary patterns and lifestyle changes have been considered to play a crucial role in Helicobacter pylori (H. pylori) infection. We conducted this study to investigate the underlying association between oxidative balance score (OBS) and H. pylori infection in the US population. METHODS: This was a cross-sectional study according to data from the National Health and Nutrition Examination Survey (1999-2000), and included individuals with complete information about dietary intake and H. pylori serologic testing results. In the present study, we used multivariate logistic regression analysis, smoothed curve fitting, subgroup analyses, and Cox proportional hazards modeling based on demographic and clinical variables to examine the relationship between OBS and H. pylori infection. RESULTS: A total of 3413 individuals participated in our analysis with an average age of 32.31 years. The prevalence of H. pylori infection in the study population was 29.77%. By performing smooth curve fitting analysis, we observed an approximately linear relationship between OBS and H. pylori infection, indicating that lower OBS was associated with higher risk of H. pylori infection, especially in over 60 years of age and non-Hispanic white populations. All-cause mortality was also found lower in individuals with higher OBS levels. CONCLUSION: In the US population, increased levels of OBS were associated with a reduced risk of H. pylori infection and decreased all-cause mortality. More and further work is still needed to elucidate the precise mechanism of the association between OBS and H. pylori infection.

3.
Front Immunol ; 15: 1365604, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779684

RESUMO

Background: Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Methods: Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Results: Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE. Conclusion: Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.


Assuntos
Anticorpos Antibacterianos , Esofagite Eosinofílica , Infecções por Helicobacter , Helicobacter pylori , Análise da Randomização Mendeliana , Humanos , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/complicações , Esofagite Eosinofílica/imunologia , Esofagite Eosinofílica/genética , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/etiologia , Esofagite Eosinofílica/microbiologia , Helicobacter pylori/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Polimorfismo de Nucleotídeo Único , Citocinas , Predisposição Genética para Doença
4.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2047-2063, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812222

RESUMO

Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Animais , Rubiaceae/química , Controle de Qualidade
5.
Adv Healthc Mater ; : e2400752, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38794825

RESUMO

Atherosclerosis is a primary contributor to cardiovascular disease. Current studies have highlighted the association between the immune system, particularly immune cells, and atherosclerosis, although treatment options and clinical trials remain scarce. Immunotherapy for cardiovascular disease is still in its infancy. Bruton's tyrosine kinase (BTK), widely expressed in various immune cells, represents a promising therapeutic target for atherosclerosis by modulating the anti-inflammatory function of immune cells. This study introduces a polydopamine-based nanocarrier system to deliver the BTK inhibitor, ibrutinib, to atherosclerotic plaques with an active targeting property via an anti-CD47 antibody. Leveraging polydopamine's pH-sensitive reversible disassembly, the system offers responsive, controlled release within the pathologic microenvironment. This allows precise and efficient ibrutinib delivery, concurrently inhibiting the activation of the NF-κB pathway in B cells and the NLRP3 inflammasome in macrophages within the plaques. This treatment also modulates both the immune cell microenvironment and inflammatory conditions in atherosclerotic lesions, thereby conveying promising therapeutic effects for atherosclerosis in vivo. This strategy also provides a novel option for atherosclerosis treatment.

6.
Int Immunopharmacol ; 134: 112235, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761779

RESUMO

The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-ß1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-ß1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-ß1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-ß1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-ß1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-ß1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.


Assuntos
Antineoplásicos , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Serina-Treonina Quinases TOR , Fator de Crescimento Transformador beta1 , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Feminino , Humanos , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/imunologia , Transdução de Sinais/efeitos dos fármacos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Interferon gama/metabolismo , Camundongos Nus , Camundongos Endogâmicos BALB C , Peptídeos e Proteínas de Sinalização Intracelular
7.
Front Public Health ; 12: 1385628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716244

RESUMO

Background: During the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are metabolized and excreted in urine, they may have carcinogenic effects on the bladder urinary tract epithelium. This meta-analysis aimed to compare bladder cancer carcinogens in the urine of tobacco users and e-cigarette users using a large number of samples. Methods: A systematic meta-analysis was performed using data obtained from several scientific databases (up to November 2023). This cumulative analysis was performed following the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) and Assessing the Methodological Quality of Systematic Evaluations (AMSTAR) guidelines, according to a protocol registered with PROSPERO. This study was registered on PROSPERO and obtained the unique number: CRD42023455600. Results: The analysis included 10 high-quality studies that considered polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs). Statistical indicators show that there is a difference between the tobacco user group and the e-cigarette user group in terms of 1-Hydroxynaphthalene (1-NAP) [weighted mean difference (WMD)10.14, 95% confidence interval (CI) (8.41 to 11.88), p < 0.05], 1-Hydroxyphenanthrene (1-PHE) [WMD 0.08, 95% CI (-0.14 to 0.31), p > 0.05], 1-Hydroxypyrene (1-PYR) [WMD 0.16, 95% CI (0.12 to 0.20), p < 0.05], 2-Hydroxyfluorene (2-FLU) [WMD 0.69, 95% CI (0.58 to 0.80), p < 0.05], 2-Hydroxynaphthalene (2-NAP) [WMD 7.48, 95% CI (4.15 to 10.80), p < 0.05], 3-Hydroxyfluorene (3-FLU) [WMD 0.57, 95% CI (0.48 to 0.66), p < 0.05], 2-Carbamoylethylmercapturic acid (AAMA) [WMD 66.47, 95% CI (27.49 to 105.46), p < 0.05], 4-Hydroxy-2-buten-1-yl-mercapturic acid (MHBMA) [WMD 287.79, 95% CI (-54.47 to 630.04), p > 0.05], 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) [WMD 189.37, 95% CI (78.45 to 300.29), p < 0.05], or N0-nitrosonornicotine (NNN) [WMD 11.66, 95% CI (7.32 to 16.00), p < 0.05]. Conclusion: Urinary bladder cancer markers were significantly higher in traditional tobacco users than in e-cigarette users.Systematic review registration: PROSPERO (CRD42023455600: https://www.crd.york.ac.uk/PROSPERO/).


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/urina , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Carcinógenos/análise , Compostos Orgânicos Voláteis/urina , Carcinogênese , Hidrocarbonetos Policíclicos Aromáticos/urina , Biomarcadores/urina , Nitrosaminas/urina , Produtos do Tabaco
8.
Sci Total Environ ; 935: 173329, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772482

RESUMO

The remediation of high-concentration thallium (Tl+) contaminated wastewater is a critical environmental concern. Current research emphasizes the effectiveness of adsorption and oxidation methods for Tl+ treatment, yet challenges persist in enhancing their performance. This study explores the feasibility of emergency Tl+ wastewater treatment and elucidates the mechanisms of Tl+ incorporation into mineral structures, with a focus on the struvite mineral as a framework for Tl+ integration via NH4+ ion exchange. To assess the efficacy and mechanisms of Tl+ immobilization, we utilized comprehensive analytical techniques, including X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (SEM-EDS), Thermogravimetric Analysis (TG), and Density Functional Theory (DFT) calculations. The findings reveal that struvite adsorbs Tl+ onto its surface, followed by an ion exchange process between monovalent cations (NH4+/K+) within the structure and Tl+. Ultimately, Tl+ is incorporated in the form of a (NH4,Tl)MgPO4 solid solution within the structure, achieving a remarkable maximum incorporation capacity of 320.56 mg/g, which significantly surpasses the capacity of typical adsorbents. The findings demonstrate significant Tl+ incorporation, validating the approach for emergency wastewater treatment and suggesting the potential of mineralogy in environmental remediation. This research contributes to advancing heavy metal wastewater treatment strategies, offering a foundation for further investigation.

9.
Sci Rep ; 14(1): 8758, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627582

RESUMO

Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.


Assuntos
Geriatria , Insuficiência Renal Crônica , Idoso , Humanos , Estudos Transversais , Atividades Cotidianas , Avaliação Geriátrica/métodos , Insuficiência Renal Crônica/diagnóstico
10.
Sci Total Environ ; 927: 172381, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604374

RESUMO

BACKGROUND: In fisheries, hypoxia stress is one of the most common environmental stresses that often lead to the death of large numbers of fish and cause significant economic losses. The pituitary, an important endocrine gland, lies below the hypothalamus region of the brain. It plays a crucial part in controlling vital physiological functions in fish, such as growth, reproduction, and responses to stress. However, the detailed mechanisms of how hypoxia affects these physiological processes via the pituitary remain largely unknown. METHODS: Fat greenlings (Hexagrammous otakii) were exposed to different dissolved oxygen (DO = 7. 6 mg/L and DO = 2 mg/L) for 24 h. miRNA-mRNA association analysis of H. otakii pituitary after hypoxia stress. Detecting apoptosis in H. otakii pituitary using Tunel and qPCR. Subsequent detection of hormones in H. otakii liver, gonads and serum by ELISA. RESULTS: In this study, hypoxia causes immune system disorders and inflammatory responses through the combined analysis of miRNAs and mRNAs. Subsequent verification indicated a significant accumulation of reactive oxygen species (ROS) subsequent to hypoxia treatment. The overproduction of ROS cause oxidative stress and apoptosis in the pituitary, ultimately causing pituitary damage and reduced growth hormone and luteinising hormone release. CONCLUSIONS: According to the association study of miRNA-mRNA, apoptosis problems caused by hypoxia stress result in H. otakii pituitary damage. In the meantime, this work clarifies the possible impact of hypoxia-stress on the pituitary cells, as well as on the gonadal development and growth of H. otakii.


Assuntos
Hipófise , Animais , Hipófise/metabolismo , Hipóxia , Apoptose , Espécies Reativas de Oxigênio/metabolismo
11.
Anal Methods ; 16(16): 2606-2613, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38618990

RESUMO

2,6-Pyridinedicarboxylic acid (DPA) is a significant biomarker of anthrax, which is a deadly infectious disease for human beings. However, the development of a convenient anthrax detection method is still a challenge. Herein, we report a novel europium metal-organic framework (Eu-MOF) with an enhanced peroxidase-like activity and fluorescence property for DPA detection. The Eu-MOF was one-step synthesized using Eu3+ ions and 2-methylimidazole. In the presence of DPA, the intrinsic fluorescence of Eu3+ ions is sensitized, the fluorescence intensity linearly increases with an increase in DPA concentration, and the fluorescence color changes from blue to purple. Simultaneously, the peroxide-like activity of the Eu-MOF is enhanced by DPA, which can promote the oxidation of TMB to oxTMB. The absorbance values increase linearly with DPA concentrations, and the colorimetric images change from colorless to blue. The dual-mode detection of DPA has good sensitivity with a colorimetric detection limit of 0.67 µM and a fluorescent detection limit of 16.67 nM. Moreover, a simple detection method for DPA was developed using a smartphone with the RGB analysis system. A portable kit with standard color cards was developed using paper test strips. The proposed methods have good practicability for DPA detection in real samples. In conclusion, the developed Eu-MOF biosensor offers a valuable and general platform for anthrax diagnosis.


Assuntos
Colorimetria , Európio , Estruturas Metalorgânicas , Ácidos Picolínicos , Európio/química , Estruturas Metalorgânicas/química , Colorimetria/métodos , Ácidos Picolínicos/análise , Ácidos Picolínicos/química , Limite de Detecção , Humanos , Fluorescência , Antraz/diagnóstico , Smartphone , Espectrometria de Fluorescência/métodos , Peroxidase/química , Peroxidase/metabolismo
12.
Transl Oncol ; 44: 101890, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579527

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of colon cancer (CC). This study aimed to examine the role of a new circRNA circ_0101050 in CC. METHODS: Dual-luciferase reporter and RNA immunoprecipitation analyses were performed to validate the target relationships among maternal embryonic leucine zipper kinase (MELK), microRNA (miR)-140-3 p, and circ_0101050. Expression levels were calculated using western blotting and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blotting was performed to evaluate the relative expression of Bcl-2 and Bax proteins to determine cell death. Cell Counting Kit-8 (CCK-8) and colony formation assays were performed to determine the proliferative potential of CC cells. The migration rate of CC cells was evaluated using wound healing assays. Tumor formation tests were performed to determine the effect of circ_0101050 on tumor development in vivo. RESULTS: Elevated levels of circ_0101050 and MELK were observed in CC. By inhibiting circ 0,101,050 or MELK, CC cell proliferation and migration were inhibited, but CC cell apoptosis was promoted. Silencing circ_0101050 also inhibited CC growth in vivo. We also found that miR-140-3 p was downregulated, which alleviated the repressive effects of circ_0101050 knockdown on proliferating and migrating CC cells, as well as the stimulating effect on apoptosis. In addition, the absence of MELK alleviated the effects of miR-140-3 p downregulation, which enhanced CC cell malignancy. CONCLUSIONS: Circ_0101050 exacerbates malignant phenotypes in CC by targeting the miR-140-3 p/MELK axis. These findings suggested that the circ_0101050/miR-140-3 p/MELK network may be a prospective target for CC treatment.

13.
Curr Pharm Des ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38571356

RESUMO

BACKGROUND: A classic Chinese medicine decoction, Pinellia ternata (Thunb.) Breit-Zingiber officinale Roscoe (Ban-Xia and Sheng-Jiang in Chinese) decoction (PZD), has shown significant therapeutic effects on lung cancer. OBJECTIVE: This study aimed to explore and elucidate the mechanism of action of PZD on lung cancer using network pharmacology methods. METHODS: Active compounds were selected according to the ADME parameters recorded in the TCMSP database. Potential pathways related to genes were identified through GO and KEGG analysis. The compound target network was constructed by using Cytoscape 3.7.1 software, and the core common targets were obtained by protein-protein interaction (PPI) network analysis. Batch molecular docking of small molecule compounds and target proteins was carried out by using the AutoDock Vina program. Different concentrations of PZD water extracts (10, 20, 40, 80, and 160 µg/mL) were used on lung cancer cells. Moreover, MTT and Transwell experiments were conducted to validate the prominent therapeutic effects of PZD on lung cancer cell H1299. RESULTS: A total of 381 components in PZD were screened, of which 16 were selected as bioactive compounds. The compound-target network consisting of 16 compounds and 79 common core targets was constructed. MTT experiment showed that the PZD extract could inhibit the cell proliferation of NCI-H1299 cells, and the IC50 was calculated as 97.34 ± 6.14 µg/mL. Transwell and wound-healing experiments showed that the PZD could significantly decrease cell migration and invasion at concentrations of 80 and 160 µg/mL, respectively. The in vitro experiments confirmed that PZD had significant therapeutic effects on lung cancer cells, mainly through the PI3K/AKT signaling pathway. CONCLUSION: PZD could inhibit the cell proliferation, migration, and invasion of NCI-H1299 cells partially through the PI3K/AKT signaling pathway. These findings suggested that PZD might be a potential treatment strategy for lung cancer patients.

14.
Cell Biochem Funct ; 42(3): e4017, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38603595

RESUMO

Chromosomal instability (CIN), caused by errors in the segregation of chromosomes during mitosis, is a hallmark of many types of cancer. The fidelity of chromosome segregation is governed by a sophisticated cellular signaling network, one crucial orchestrator of which is Heterochromatin protein 1 (HP1). HP1 dynamically localizes to distinct sites at various stages of mitosis, where it regulates key mitotic events ranging from chromosome-microtubule attachment to sister chromatid cohesion to cytokinesis. Our evolving comprehension of HP1's multifaceted role has positioned it as a central protein in the orchestration of mitotic processes.


Assuntos
Homólogo 5 da Proteína Cromobox , Mitose
15.
Adv Sci (Weinh) ; 11(21): e2306486, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38588050

RESUMO

Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis-Specific Protein, Y-Encoded-Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFß causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFß signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial-mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFß signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFß to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter-balancing role of TSPYL1 and TSPYL2 in regulating TGFß signaling is also unraveled.


Assuntos
Receptor do Fator de Crescimento Transformador beta Tipo I , Transdução de Sinais , Fator de Crescimento Transformador beta , Humanos , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral
16.
Front Endocrinol (Lausanne) ; 15: 1354528, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544686

RESUMO

Background: Previous observational researchers have found an inverse bidirectional link between Alzheimer's disease (AD) and prostate cancer (PCa); yet, the causative nature of this link remains unclear. To investigate the causal interactions between AD and PCa, a bidirectional Mendelian randomization (MR) analysis was conducted. Methods: This study comprised two Genome-Wide Association Study (GWAS) summary statistics for AD (17,008 cases and 37,154 controls) and PCa (79,148 cases and 61,106 controls) in individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as the primary approach, while MR-Egger, weighted median, weighted mode, and simple mode served as supplementary methods for estimating the causal effect. To assess pleiotropy, the MR-PRESSO global test and MR-Egger regression were used. Cochran's Q test was adopted to check heterogeneity, MR Steiger test and the leave-one-out analysis was performed to confirm the robustness and reliability of the results. Results: The causal association genetically inferred of AD on PCa was found using IVW (OR = 0.974, 95% CI = 0.958-0.991, p = 0.003) in forward MR analysis and the causal association genetically inferred of PCa on AD was not found using IVW (OR = 1.000, 95% CI: 0.954-1.049, P = 0.988) in reverse MR analysis. The sensitivity analysis showed that no pleiotropy and heterogeneity was observed. The leave-one-out analysis showed that the findings were not inordinately affected by any instrumental variables. Conclusion: The results of this study demonstrated an absence of bidirectional causality between AD and PCa among the European population, suggested that a genetically predicted possibility of decreased PCa risk in AD patients, and no significant genetically predicted causal effect of PCa on AD.


Assuntos
Doença de Alzheimer , Neoplasias da Próstata , Masculino , Humanos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 188-193, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38436318

RESUMO

OBJECTIVES: To study the in vitro expression of three phenylalanine hydroxylase (PAH) mutants (p.R243Q, p.R241C, and p.Y356X) and determine their pathogenicity. METHODS: Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein. Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells. Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants, and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay. RESULTS: Bioinformatics analysis predicted that all three mutants were pathogenic. The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control (P>0.05), while the mRNA expression level of the p.Y356X mutant significantly decreased (P<0.05). The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control (P<0.05). The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control (P<0.05), while there was no significant difference between the p.R243Q mutant and the wild type control (P>0.05). CONCLUSIONS: p.R243Q, p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells, with p.R241C and p.Y356X mutants also affecting the function of PAH protein. These three PAH mutants are to be pathogenic.


Assuntos
Fenilalanina Hidroxilase , Humanos , Células HEK293 , Fenilalanina Hidroxilase/genética , Western Blotting , Biologia Computacional , RNA Mensageiro
18.
Appl Radiat Isot ; 207: 111247, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432032

RESUMO

Recently, a novel radiohybrid tracer [18F]Lu-LuFL targeting the fibroblast activation protein (FAP) has been developed for PET imaging of solid tumors. This tracer has shown promising results, prompting us to conduct a first-in-human study to evaluate its efficacy for PET imaging of FAP in human body. In order to facilitate the routine production and clinical application of [18F]Lu-LuFL, a straightforward and efficient automated synthesis is described. The optimum labeling parameters were determined at laboratory scale, and subsequently incorporated into an automated production process. Further studies have demonstrated that clinical doses of [18F]Lu-LuFL can be prepared within 19 min, with excellent radio chemical purity (>99%) and activity yield (23.58% ± 2.20%, non-decay corrected), coupled with solid phase extraction (SPE) purification method. All the quality control results satisfy the required criteria for release. In conclusion, we have successfully synthesized [18F]Lu-LuFL with sufficient radioactivity and superior quality, thereby establishing its potential for further clinical application.


Assuntos
Neoplasias , Tomografia por Emissão de Pósitrons , Humanos , Ligantes , Tomografia por Emissão de Pósitrons/métodos , Neoplasias/diagnóstico por imagem , Automação
19.
Eur J Surg Oncol ; 50(4): 108052, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447320

RESUMO

OBJECTIVE: Develop a method for selecting esophageal cancer patients achieving pathological complete response with pre-neoadjuvant therapy chest-enhanced CT scans. METHODS: Two hundred and one patients from center 1 were enrolled, split into training and testing sets (7:3 ratio), with an external validation set of 30 patients from center 2. Radiomics features from intra-tumoral and peritumoral images were extracted and dimensionally reduced using Student's t-test and least absolute shrinkage and selection operator. Four machine learning classifiers were employed to build models, with the best-performing models selected based on accuracy and stability. ROC curves were utilized to determine the top prediction model, and its generalizability was evaluated on the external validation set. RESULTS: Among 16 models, the integrated-XGBoost and integrated-random forest models performed the best, with average ROC AUCs of 0.906 and 0.918, respectively, and RSDs of 6.26 and 6.89 in the training set. In the testing set, AUCs were 0.845 and 0.871, showing no significant difference in ROC curves. External validation set AUCs for integrated-XGBoost and integrated-random forest models were 0.650 and 0.749. CONCLUSION: Incorporating peritumoral radiomics features into the analysis enhances predictive performance for esophageal cancer patients undergoing neoadjuvant chemoradiotherapy, paving the way for improved treatment outcomes.


Assuntos
Neoplasias Esofágicas , Terapia Neoadjuvante , Humanos , Radiômica , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Área Sob a Curva , Tomografia Computadorizada por Raios X , Estudos Retrospectivos
20.
Ann Surg Oncol ; 31(6): 3887-3893, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38472675

RESUMO

BACKGROUND: The rise of artificial intelligence (AI) in medicine has revealed the potential of ChatGPT as a pivotal tool in medical diagnosis and treatment. This study assesses the efficacy of ChatGPT versions 3.5 and 4.0 in addressing renal cell carcinoma (RCC) clinical inquiries. Notably, fine-tuning and iterative optimization of the model corrected ChatGPT's limitations in this area. METHODS: In our study, 80 RCC-related clinical questions from urology experts were posed three times to both ChatGPT 3.5 and ChatGPT 4.0, seeking binary (yes/no) responses. We then statistically analyzed the answers. Finally, we fine-tuned the GPT-3.5 Turbo model using these questions, and assessed its training outcomes. RESULTS: We found that the average accuracy rates of answers provided by ChatGPT versions 3.5 and 4.0 were 67.08% and 77.50%, respectively. ChatGPT 4.0 outperformed ChatGPT 3.5, with a higher accuracy rate in responses (p < 0.05). By counting the number of correct responses to the 80 questions, we then found that although ChatGPT 4.0 performed better (p < 0.05), both versions were subject to instability in answering. Finally, by fine-tuning the GPT-3.5 Turbo model, we found that the correct rate of responses to these questions could be stabilized at 93.75%. Iterative optimization of the model can result in 100% response accuracy. CONCLUSION: We compared ChatGPT versions 3.5 and 4.0 in addressing clinical RCC questions, identifying their limitations. By applying the GPT-3.5 Turbo fine-tuned model iterative training method, we enhanced AI strategies in renal oncology. This approach is set to enhance ChatGPT's database and clinical guidance capabilities, optimizing AI in this field.


Assuntos
Inteligência Artificial , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Neoplasias Renais/patologia , Carcinoma de Células Renais/patologia , Prognóstico
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