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1.
Plant Physiol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250752

RESUMEN

Colletotrichum brevisporum is an important fungal pathogen that causes anthracnose and has led to serious postharvest losses of papaya (Carica papaya L.) fruit in recent years. WRKY transcription factors play vital roles in regulating plant resistance to pathogens, but their functions in papaya anthracnose resistance need further exploration. In this study, we identified a WRKY transcription factor, CpWRKY50, which belongs to the WRKY IIc subfamily. During infection with C. brevisporum, expression of CpWRKY50 in anthracnose-resistant papaya cultivars was significantly higher than that in susceptible cultivars. CpWRKY50 was induced by methyl jasmonate, and CpWRKY50 localized in the nucleus. In yeast, full-length CpWRKY50 had transactivation activity, but CpWRKY50 variants truncated at the N or C termini did not. CpWRKY50 positively regulated papaya resistance to C. brevisporum, as demonstrated by transient overexpression of CpWRKY50 in papaya and heterologous expression of CpWRKY50 in tomato. Moreover, endogenous jasmonic acid (JA) and JA-isoleucine levels in the fruits of transgenic tomato OE lines were higher than in wild type both before and after inoculation with C. brevisporum, indicating that increased CpWRKY50 expression promotes JA accumulation. Furthermore, our results revealed CpWRKY50 directly binds to W-box motifs (TTGACC) in the promoters of two JA signaling-related genes, CpMYC2 and pathogenesis-related 4 CpPR4, thereby activating their expression. Our data support that CpWRKY50 positively regulates anthracnose resistance in papaya by promoting JA signaling. These results broaden our understanding of papaya disease resistance mechanisms and will facilitate the genetic improvement of papaya through molecular breeding.

2.
Front Public Health ; 12: 1442728, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224554

RESUMEN

Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , China/epidemiología , Estudios Retrospectivos , Hospitalización/estadística & datos numéricos , Teorema de Bayes , Política de Salud , Pandemias
3.
Cell Signal ; 124: 111398, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39265728

RESUMEN

Angiogenesis plays a pivotal role in the progression and metastasis of solid cancers, including prostate cancer (PCa). While small extracellular vesicles derived from PCa cell lines induce a proangiogenic phenotype in vascular endothelial cells, the contribution of plasma exosomes from patients with PCa to this process remains unclear. Here, we successfully extracted and characterized plasma exosomes. Notably, a ring of PKH67-labeled exosomes was observed around the HUVEC nucleus using fluorescence microscopy, indicating the uptake of exosomes by HUVEC. At the cellular level, PCa plasma exosomes enhanced angiogenesis, proliferation, invasion, and migration of HUVEC cells. Moreover, PCa plasma exosomes promoted angiogenesis and aortic sprouting. MicroRNAs are the most common genetic material in exosomes, and to identify miRNAs associated with the angiogenic response, we performed small RNA sequencing followed by RT-qPCR and bioinformatics analysis. These analyses revealed distinct miRNA profiles in plasma exosomes from patients with PCa compared to healthy individuals. Notably, hsa-miR-184 emerged as a potential regulator implicated in the proangiogenic effects of PCa plasma exosomes.

4.
Heliyon ; 10(17): e37090, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286198

RESUMEN

To explore the effect of interchange spacing on drivers' visual characteristics in the merging areas of interchange, a high-density group of five interchanges on the expressway of Chongqing, China, was selected as the test site. An naturalistic driving test was conducted with 47 participants, and the Tobii Glasses II portable eye tracker was used to collect gaze data during driving. The drivers' fixation field was divided into six areas by applying a K-means dynamic clustering algorithm combined with the actual scenario. Markov chains were used to calculate the drivers' gaze transition probability matrices under different driving conditions, and the analysis of gaze transition behaviors was directed at common spacing interchanges, small spacing interchanges, and composite interchanges. Under the ramp-mainline condition, drivers' fixations were primarily concentrated on the near ahead and the left side areas, with higher rates of repeated fixations on the left rearview mirror and left-side line areas. The average value of fixation duration, saccade distance, and saccade speed of small spacing interchange is higher than common spacing interchange. Additionally, under the mainline condition, the probability of one-step transition and repeated fixation rates significantly increased for the right-side lane areas, and the average values of fixation index and saccade index of small spacing interchange are lower than those of common spacing interchange. The results show that the highest probabilities of repeated fixation by drivers occurred in the near ahead and far ahead areas in the interchange merging areas. Insufficient spacing resulted in more frequent occurrences of zero values in one-step transition probability matrices. The research conclusions provide theoretical support for the optimal design and safe operation of the merging area of high-density interchange group of urban expressway.

5.
Chem Biodivers ; : e202401643, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230656

RESUMEN

Five previously undescribed guaialactone-type sesquiterpenes (1-5), called Lanicepsmines A-E, along with eleven know compounds (6-16), were isolated from the whole plant of Saussurea laniceps. NMR spectroscopic data analysis and MASS permitted the definition of their structures. The stereochemistry of the compounds was confirmed by ECD calculations. It is worth noting that compound 1 and 2 contain amino groups. Part of compounds were tested the anti-inflammasome activity, and compound 14 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC50 values of 0.698 µM.

6.
Clin Transl Oncol ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196498

RESUMEN

INTRODUCTION: This multi-center study aims to explore the roles of plasma exosomal microRNAs (miRNAs), ultrasound (US) radiomics, and total prostate-specific antigen (tPSA) levels in early prostate cancer detection. METHODS: We analyzed the publicly available dataset GSE112264 to identify the differentially expressed miRNAs associated with prostate cancer. Then, PyRadiomics was used to extract image features, and least absolute shrinkage and selection operator (LASSO) was used to screen the data. Subsequently, according to strict inclusion and exclusion criteria, the internal dataset (n = 199) was used to construct a diagnostic model, and the receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), and DeLong test were used to evaluate its diagnostic performance. Finally, we used an external dataset (n = 158) for further validation. RESULTS: The number of features extracted by PyRadiomics was 851, and the number of features screened by LASSO was 23. We combined the hsa-miR-320c, hsa-miR-944, radiomics, and tPSA features to construct a joint model. The area under the ROC curve of the combined model was 0.935. In the internal validation, the area under the curve (AUC) of the training set was 0.943, and the AUC of the test set was 0.946. The AUC of the external data set was 0.910. The calibration curve and decision curve were consistent with the performance of the combined model. There was a significant difference in the prediction ability between the combined prediction model and the single index prediction model, indicating the high credibility and accuracy of the combined model in predicting PCa. CONCLUSIONS: The combined prediction model, consisting of plasma exosomal miRNAs (hsa-miR-320c and hsa-miR-944), US radiomics, and clinical tPSA, can be utilized for the early diagnosis of prostate cancer.

7.
Sci Rep ; 14(1): 17962, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095448

RESUMEN

The intensities of the hydrogen Balmer lines of solar-like stars are investigated for stellar chromospheric activity by using the co-source spectral data of the LAMOST Low-Resolution Spectroscopic Survey (LRS) and Medium-Resolution Spectroscopic Survey (MRS). The Balmer H α , H ß , H γ , and H δ lines in the LRS data and the H α line in the MRS data are analyzed. The absolute flux indexes, defined as the ratios of the absolute fluxes at the centers of the Balmer lines to the stellar bolometric flux, are employed to indicate the intensity magnitudes of the Balmer lines in response to stellar activity. The H α indexes derived from the LRS data and the MRS data, respectively, are calibrated to be quantitatively consistent with each other. It is found that, as the H α index increases, the H ß , H γ , and H δ indexes first present trend of increasing and then decreasing, and finally increase synchronously with the H α index. The distributions of the Balmer line indexes also reveal the three distinct stages of stellar activity (normal stage, intense stage, and extremely intense stage), in which the extremely intense stage is characterized by the synchronous growth of the indexes of the four Balmer lines. The different behaviors of the H ß , H γ , and H δ lines from that of the H α line can be interpreted by the different mechanisms by which the line-core intensities are formed, and the three distinct activity stages imply the very different magnetic field environments and physical conditions of solar-like stars.

9.
Pharmacol Res ; 206: 107293, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38971271

RESUMEN

Colorectal cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated cholesterol levels that subsequently hindered cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression.


Asunto(s)
Neoplasias Colorrectales , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Hidroximetilglutaril-CoA Reductasas , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Hidroximetilglutaril-CoA Reductasas/genética , Hidroximetilglutaril-CoA Reductasas/metabolismo , Animales , Masculino , Proliferación Celular , Línea Celular Tumoral , Colesterol/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Ratones , Apoptosis , Persona de Mediana Edad , Ratones Endogámicos BALB C
11.
Chemphyschem ; 25(16): e202400143, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-38726743

RESUMEN

Electrocatalytic nitrogen reduction reaction (NRR) is a green and highly efficient way to replace the industrial Haber-Bosch process. Herein, clusters consisting of three transition metal atoms loaded on C2N as NRR electrocatalysts are investigated using density functional theory (DFT). Meanwhile, Ca was introduced as a promoter and the role of Ca in NRR was investigated. It was found that Ca anchored to the catalyst can act as an electron donor and effectively promote the activation of N2 on M3. In both M3@C2N and M3Ca@C2N (M=Fe, Co, Ni), the limiting potential (UL) is less negative than that of the Ru(0001) surface and has the ability to suppress the competitive hydrogen evolution reaction (HER). Among them, Fe3@C2N is suggested to be the most promising candidate for NRR with high thermal stability, strong N2 adsorption ability, low limiting potential, and good NRR selectivity. The concepts of trimetallic sites and alkaline earth metal promoters in this work provide theoretical guidance for the rational design of atomically active sites in electrocatalytic NRR.

13.
Molecules ; 29(7)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38611765

RESUMEN

The color of the pericarp is a crucial characteristic that influences the marketability of papaya fruit. Prior to ripening, normal papaya exhibits a green pericarp, whereas the cultivar 'Zihui' displays purple ring spots on the fruit tip, which significantly affects the fruit's visual appeal. To understand the mechanism behind the formation of purple pericarp, this study performed a thorough examination of the transcriptome, plant hormone, and metabolome. Based on the UPLC-ESI-MS/MS system, a total of 35 anthocyanins and 11 plant hormones were identified, with 27 anthocyanins and two plant hormones exhibiting higher levels of abundance in the purple pericarp. In the purple pericarp, 14 anthocyanin synthesis genes were up-regulated, including CHS, CHI, F3H, F3'5'H, F3'H, ANS, OMT, and CYP73A. Additionally, through co-expression network analysis, three MYBs were identified as potential key regulators of anthocyanin synthesis by controlling genes encoding anthocyanin biosynthesis. As a result, we have identified numerous key genes involved in anthocyanin synthesis and developed new insights into how the purple pericarp of papaya is formed.


Asunto(s)
Carica , Carica/genética , Antocianinas , Reguladores del Crecimiento de las Plantas , Transcriptoma , Espectrometría de Masas en Tándem , Metaboloma , Verduras
14.
Ying Yong Sheng Tai Xue Bao ; 35(1): 255-267, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38511463

RESUMEN

The optimization of production-living-ecology (PLE) space is an important basis for promoting regional high-quality development. Taking the Dongting Lake Eco-economic Zone as an example, from the perspective of improving the comprehensive benefits of the development and protection of the PLE space, we coupled the GMOP-FLUS model, and proposed an optimization method combining the scenario configuration and the bottom line protection of the PLE space. We compared the three optimization scenarios (economic optimization scenario, ecological optimization scenario, and multi-objective optimization scenario), and coordinated the conflict areas of two lines to clarify the comprehensive optimization scheme of the PLE space in the Dongting Lake Eco-economic Zone. The results showed the characteristics of increasing production space and living space and decreasing ecological space from 2010 to 2020, resulting in the partial loss of land ecological and environmental benefits. Under the economic optimization scenario, the ecological optimization scenario promoted the rapid growth of regional economy but damaged regional ecological security. The ecological optimization scenario inhibited regional economic development. The multi-objective optimization scenario led to improvement of economic and ecological benefits of the PLE space, which increased by 2.0% and 1.3%, respectively. The multi-objective optimization scenario was the best optimization scenario among the three scenarios. By superimposing the best scenario and the two-line conflict regional coordination results, we obtained the comprehensive optimization scheme for 2030. The production space, living space, and ecological space areas of the scheme were 25777.18, 2062.94, and 32552.68 km2, respectively. Based on the natural and social conditions, combining the comprehensive optimization scheme, we put forward different control suggestions for each type of PLE space. Our results could provide reference for the rational formulation of territorial spatial planning and the formulation of policies for the coordinated development of ecological environment and social economy in the Dongting Lake Eco-economic Zone.


Asunto(s)
Conservación de los Recursos Naturales , Ecología , Conservación de los Recursos Naturales/métodos , Lagos , Desarrollo Económico , China , Ecosistema
15.
Cancer Med ; 13(4): e7074, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38457215

RESUMEN

BACKGROUND: The post-remission therapy (PRT) choices for adult t(8;21) acute myeloid leukemia (AML) in first complete remission (CR1) need to be further explored. AIMS: We aimed to investigate the impact of measurable residual disease (MRD) combined with CD19 on PRT choices for adult t(8;21) AML in CR1. METHODS: A total of 150 t(8;21) AML patients were enrolled, including 67 underwent chemotherapy (CMT) and 83 allogeneic hematopoietic stem cell transplantation (allo-SCT) as PRT in CR1. Subgroup analyses were performed according to MRD level after three cycles of chemotherapy combined with CD19 expression. RESULTS: Multivariate analysis indicated MRDhigh after three courses of treatment (HR, 0.14 [95% CI, 0.03-0.66]; p = 0.013) and CD19 negativity (HR, 0.14 [95% CI, 0.02-0.96]; p = 0.045) were risk factors for relapse, while allo-SCT was protective factor for relapse (HR, 0.34 [95% CI, 0.15-0.75]; p = 0.008). Grouped by MRD after three courses of chemotherapy, allo-SCT had lower CIR (p < 0.001) and better OS (p = 0.003) than CMT for MRDhigh patients, CMT showed a higher CIR (35.99% vs. 15.34%, p = 0.100) but comparable OS (p = 0.588) than allo-SCT for MRDlow patients. Grouped by CD19 expression, allo-SCT demonstrated lower CIR (p < 0.001) and better OS (p = 0.002) than CMT for CD19- patients. CMT had a higher CIR (41.37% vs. 10.48%, p = 0.007) but comparable OS (p = 0.147) than allo-SCT for CD19+ patients. Grouped by MRD combined with CD19, MRDhigh /CD19+ subsets were identified out of CD19+ patients benefiting from allo-SCT with lower CIR (p = 0.002) and superior OS (p = 0.020) than CMT. CMT preserved comparable CIR (p = 0.939) and OS (p = 0.658) with allo-SCT for MRDlow /CD19+ patients. MRDlow /CD19- subsets were also identified from MRDlow patients requiring allo-SCT with lower CIR (p < 0.001) and superior OS (p = 0.008) than CMT. Allo-SCT maintained lower CIR (p < 0.001) and superior OS (p = 0.008) than CMT for MRDhigh /CD19- patients. CONCLUSIONS: MRD combined with CD19 might optimize PRT choices for adult t(8;21) AML patients in CR1.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Trasplante Homólogo , Trasplante de Células Madre , Recurrencia , Respuesta Patológica Completa , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/metabolismo , Neoplasia Residual , Estudios Retrospectivos , Pronóstico
16.
JNCI Cancer Spectr ; 8(2)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38457606

RESUMEN

BACKGROUND: Opioid safety initiatives may secondarily impact opioid prescribing and pain outcomes for cancer care. METHODS: We reviewed electronic health record data at a tertiary Veterans Affairs system (VA Palo Alto) for all patients from 2015 to 2021. We collected outpatient Schedule II opioid prescriptions data and calculated morphine milligram equivalents (MMEs) using Centers for Disease Control and Prevention conversion formulas. To determine the clinical impact of changes in opioid prescription, we used the highest level of pain reported by each patient on the 0-to-10 Numeric Rating Scale in each year, categorized into mild (0-3), moderate (4-6), and severe (7 and above). RESULTS: Among 89 569 patients, 9073 had a cancer diagnosis. Cancer patients were almost twice as likely to have an opioid prescription compared with noncancer patients (69.0% vs 36.7%, respectively). The proportion of patients who received an opioid prescription decreased from 27.1% to 18.1% (trend P < .01) in cancer patients and from 17.0% to 10.2% in noncancer patients (trend P < .01). Cancer and noncancer patients had similar declines of MMEs per year between 2015 and 2019, but the decline was more rapid for cancer patients (1462.5 to 946.4, 35.3%) compared with noncancer patients (1315.6 to 927.7, 29.5%) from 2019 to 2021. During the study period, the proportion of noncancer patients who experienced severe pain was almost unchanged, whereas it increased among cancer patients, reaching a significantly higher rate than among noncancer patients in 2021 (31.9% vs 27.4%, P < .01). CONCLUSIONS: Our findings suggest potential unintended consequences for cancer care because of efforts to manage opioid-related risks.


Asunto(s)
Neoplasias , Veteranos , Humanos , Analgésicos Opioides/uso terapéutico , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/tratamiento farmacológico , Dolor/tratamiento farmacológico , Pautas de la Práctica en Medicina
17.
Biomed Pharmacother ; 173: 116318, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38401522

RESUMEN

Retinal ischemia is a significant factor in various vision-threatening diseases, but effective treatments are currently lacking. This study explores the potential of stem cell factor (SCF) in regulating the neurovascular unit as a therapeutic intervention for retinal ischemic diseases. A chronic retinal ischemia model was established in Brown Norway rats using bilateral common carotid artery occlusion (BCCAO). Subsequent SCF treatment resulted in a remarkable recovery of retinal function, as indicated by electroretinogram, light/dark transition test, and optokinetic head tracking test results. Histological examination demonstrated a significant increase in the number of retinal neurons and an overall thickening of the retina. Immunofluorescence confirmed these findings and further demonstrated that SCF treatment regulated retinal remodeling. Notably, SCF treatment ameliorated the disrupted expression of synaptic markers in the control group's BCCAO rats and suppressed the activation of Müller cells and microglia. Retinal whole-mount analysis revealed a significant improvement in the abnormalities in retinal vasculature following SCF treatment. Transcriptome sequencing analysis revealed that SCF-induced transcriptome changes were closely linked to the Wnt7 pathway. Key members of the Wnt7 pathway, exhibited significant upregulation following SCF treatment. These results underscore the protective role of SCF in the neurovascular unit of retinal ischemia rats by modulating the Wnt7 pathway. SCF administration emerges as a promising therapeutic strategy for retinal ischemia-related diseases, offering potential avenues for future clinical interventions.


Asunto(s)
Arteriopatías Oclusivas , Enfermedades de las Arterias Carótidas , Enfermedades de la Retina , Ratas , Animales , Factor de Células Madre , Isquemia/metabolismo , Enfermedades de la Retina/prevención & control , Enfermedades de la Retina/patología , Retina , Vasos Retinianos/metabolismo , Arteriopatías Oclusivas/patología
18.
Nutr Cancer ; 76(2): 175-186, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38166549

RESUMEN

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.


Asunto(s)
Neoplasias de la Mama , Neoplasias Endometriales , Neoplasias de la Próstata , Masculino , Humanos , Apolipoproteína A-I , Leptina , Adiponectina , Análisis de la Aleatorización Mendeliana , Lípidos , Colesterol , Triglicéridos , LDL-Colesterol/genética , HDL-Colesterol , Lipoproteína(a) , Neoplasias Endometriales/etiología , Neoplasias Endometriales/genética , Neoplasias de la Próstata/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo
19.
Stem Cells Transl Med ; 13(1): 83-99, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-37935630

RESUMEN

Cone cell death is a characteristic shared by various retinal degenerative disorders, such as cone-rod dystrophy, Stargardt disease, achromatopsia, and retinitis pigmentosa. This leads to conditions like color blindness and permanently impaired visual acuity. Stem cell therapy focused on photoreceptor replacement holds promise for addressing these conditions. However, identifying surface markers that aid in enriching retinal progenitor cells (RPCs) capable of differentiating into cones remains a complex task. In this study, we employed single-cell RNA sequencing to scrutinize the transcriptome of developing retinas in C57BL/6J mice. This revealed the distinctive expression of somatostatin receptor 2 (Sstr2), a surface protein, in late-stage RPCs exhibiting the potential for photoreceptor differentiation. In vivo lineage tracing experiments verified that Sstr2+ cells within the late embryonic retina gave rise to cones, amacrine and horizontal cells during the developmental process. Furthermore, Sstr2+ cells that were isolated from the late embryonic mouse retina displayed RPC markers and exhibited the capability to differentiate into cones in vitro. Upon subretinal transplantation into both wild-type and retinal degeneration 10 (rd10) mice, Sstr2+ cells survived and expressed cone-specific markers. This study underscores the ability of Sstr2 to enrich late-stage RPCs primed for cone differentiation to a large extent. It proposes the utility of Sstr2 as a biomarker for RPCs capable of generating cones for transplantation purposes.


Asunto(s)
Receptores de Somatostatina , Retina , Degeneración Retiniana , Animales , Ratones , Ratones Endogámicos C57BL , Retina/metabolismo , Células Fotorreceptoras Retinianas Conos/metabolismo , Degeneración Retiniana/terapia , Degeneración Retiniana/metabolismo , Células Madre
20.
Expert Rev Anticancer Ther ; : 1-8, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38044867

RESUMEN

BACKGROUND: Dickkopf-1 (DKK1) exhibits abnormal expression in various cancers and correlates with poor prognosis. This study investigates DKK1's prognostic relevance in head and neck squamous cell carcinoma (HNSC). METHODS: We conducted a comprehensive search across literature and sequencing databases to gather eligible studies and HNSC datasets. We calculated pooled standardized mean differences (SMD) and 95% confidence intervals (CI) for clinical characteristics, as well as hazard ratios (HR) with 95% CIs for overall survival (OS) and progression-free/disease-free survival (PFS/DFS). Sensitivity analysis gauged result stability, and Egger's test assessed publication bias. RESULTS: Pooled results indicated that HNSC patients with higher T-stage exhibited elevated DKK1 expression levels, and this elevated expression was associated with shorter OS and PFS/DFS. While sensitivity analysis identified some studies significantly affecting pooled results, most were unaffected, and no publication bias was detected. CONCLUSION: DKK1 holds promise as a potential biomarker for predicting poor prognosis in HNSC patients, but further research is needed for confirmation.

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