Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.220
Filtrar
1.
ACS Omega ; 9(25): 27093-27103, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947822

RESUMO

Talaromyces marneffei is the third most common infectious pathogen in AIDS patients and leads to the highest death rate in Guangxi, China. The lack of reliable biomarkers is one of the major obstacles in current clinical diagnosis, which largely contributes to this high mortality. Here, we present a study that aimed at identifying diagnostic biomarker candidates through genome-wide prediction and functional annotation of Talaromyces marneffei secreted proteins. A total of 584 secreted proteins then emerged, including 382 classical and 202 nonclassical ones. Among them, there were 87 newly obtained functional annotations in this study. The annotated proteins were further evaluated by combining RNA profiling and a homology comparison. Three proteins were ultimately highlighted as biomarker candidates with robust expression and remarkable specificity. The predicted phosphoinositide phospholipase C and the galactomannoprotein were suggested to play an interactive immune game through metabolism of arachidonic acid. Therefore, they hold promise in developing new tools for clinical diagnosis of Talaromyces marneffei and also possibly serve as molecular targets for future therapy.

2.
Nutrients ; 16(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999891

RESUMO

Hypertension remains a major global public health crisis due to various contributing factors, such as age and environmental exposures. This study delves into exploring the intricate association between biological aging, blood lead levels, and hypertension, along with examining the mediating role of blood lead levels in the relationship between biological aging and hypertension. We analyzed data from two cycles of the NHANES, encompassing 4473 individuals aged 18 years and older. Our findings indicate that biological aging potentially escalates the risk of hypertension and the incidences of systolic blood pressure (SBP) and diastolic blood pressure (DBP) abnormalities. Utilizing weighted quantile sum (WQS) and quantile g-computation (QGC) model analyses, we observed that exposure to heavy metal mixtures, particularly lead, may elevate the likelihood of hypertension, SBP, and DBP abnormalities. Further mediation analysis revealed that lead significantly mediated the relationship between biological aging and hypertension and between biological aging and SBP abnormalities, accounting for 64% (95% CI, 49% to 89%) and 64% (95% CI, 44% to 88%) of the effects, respectively. These outcomes emphasize the criticality of implementing environmental health measures.


Assuntos
Envelhecimento , Pressão Sanguínea , Hipertensão , Chumbo , Inquéritos Nutricionais , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/etiologia , Chumbo/sangue , Envelhecimento/sangue , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Exposição Ambiental/efeitos adversos , Idoso , Adulto Jovem , Adolescente , Estados Unidos/epidemiologia , Fatores de Risco , Bases de Dados Factuais
3.
Front Mol Biosci ; 11: 1301099, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993839

RESUMO

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

4.
World J Clin Cases ; 12(19): 3866-3872, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994274

RESUMO

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

5.
Nature ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987587

RESUMO

Exaggerated airway constriction triggered by repeated exposure to allergen, also called hyperreactivity, is a hallmark of asthma. Whereas vagal sensory neurons are known to function in allergen-induced hyperreactivity1-3, the identity of downstream nodes remains poorly understood. Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA sequencing, followed by RNAscope assay at baseline and allergen challenges, showed that a Dbh+ nTS population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+ nTS neurons project to the nucleus ambiguus (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.

6.
Acta Pharmacol Sin ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942954

RESUMO

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

7.
BMC Geriatr ; 24(1): 537, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907348

RESUMO

BACKGROUND: As older people have complex medical needs and still encounter challenges in accessing online health information, the relationship between Internet use and the choice of medical institution made by them is unclear, and we aimed to examine this relationship. METHODS: Data from the newly released 2020 China Family Panel Survey database were used. Furthermore, we used descriptive statistics to analyze the background characteristics of the sample and a logistic regression model to estimate the impact of Internet use on the choice of medical institution made by older adults. We conducted a stratified analysis to explore the influence of different characteristics on the relationship between Internet use and the choice of medical institution. RESULTS: Totally 4,948 older adults were included. Multivariate logistic regression showed that, compared to non-Internet users, Internet users were less likely to choose community health service centers over general hospitals (P < 0.001, OR = 0.667, 95CI%: 0.558-0.797). The subgroup analyses found that Internet use only had an impact on the choice of medical institution in older adults aged 65-69 years, those with partners, those with primary or secondary education, those residing in urban areas, those without medical insurance, those with a self-rated health status as average or healthy, those with unchanged or better health trend, and those without chronic disease. The effect of Internet use on the choice of medical institution did not differ by sex, satisfaction, or trust in doctors. CONCLUSION: Internet use may significantly affect older adults' tendency to choose general hospitals to meet their daily medical needs. The subgroup analyses indicated that different characteristics of older people affected this association.


Assuntos
Comportamento de Escolha , Uso da Internet , Humanos , Idoso , Masculino , Feminino , China/epidemiologia , Uso da Internet/estatística & dados numéricos , Uso da Internet/tendências , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Internet , População do Leste Asiático
8.
Heliyon ; 10(11): e32498, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912473

RESUMO

Dental follicle cells (DFCs) promote bone regeneration in vivo and in vitro. Circular RNAs (circRNAs) play crucial roles in bone development and regeneration. Our previous study demonstrated the upregulation of circFgfr2 expression during the osteogenic differentiation of DFCs. However, the molecular mechanisms and functional roles of circFgfr2 in DFCs osteogenesis remain unclear. In this study, we aimed to investigate the subcellular localization of circFgfr2 in DFCs using fluorescence in situ hybridization. In vitro investigations demonstrated that circFgfr2 overexpression promoted osteogenic differentiation, as evidenced by real-time quantitative polymerase chain reaction. By integrating the outcomes of bioinformatics analyses, dual luciferase reporter experiments, and chromatin isolation by RNA purification, we identified circFgfr2 as a sponge for miR-133a-3p, a key regulator of osteogenic differentiation. Moreover, miR-133a-3p suppressed osteogenic differentiation by targeting DLX3 and RUNX2 in DFCs. We validated that circFgfr2 promoted the osteogenic differentiation of DFCs through the miR-133a-3p/DLX3 axis. To further investigate the therapeutic potential of circFgfr2 in bone regeneration, we conducted in vivo experiments and histological analyses. Overall, these results confirmed the crucial role of circFgfr2 in promoting osteogenesis. In summary, our findings demonstrated that the circFgfr2/miR-133a-3p/DLX3 pathway acts as a cascade, thereby identifying circFgfr2 as a promising molecular target for bone tissue engineering.

9.
Acta Pharmacol Sin ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871923

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

10.
BMC Oral Health ; 24(1): 515, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698359

RESUMO

OBJECTIVE: Low impacted third molars are usually asymptomatic and are often found by X-ray examination. The removal of asymptomatic low impacted third molars is one of the most controversial clinical issues in oral and maxillofacial surgery. METHODS: In this study, 806 patients with low impacted mandibular third molars (LIMTMs) (full bony impaction) were analyzed to determine the prevalence and risk factors for cystic lesions and adjacent tooth root resorption throughout the patients' entire life cycle. RESULTS: The results showed that the prevalence of adjacent tooth root resorption and cystic lesions was age-related, exhibiting a trend of first increasing and then decreasing; prevalence peaked at the age of 41 to 45 years old, the prevalence rates were 12.50% and 11.11% respectively. And the lowest prevalence rate was 2.86% and 2.44% in ≥ 61 group and 56- to 60-year age group respectively. Age was an independent risk factor for adjacent tooth root resorption of LIMTMs, whereas age and impaction type (especially inverted impaction) were independent risk factors for cystic lesions. CONCLUSIONS: The full life cycle management strategy for LIMTMs may need to be individualized. Surgical removal is recommended for LIMTMs in patients younger than 41 to 45 years, especially for inverted, mesioangular, and horizontally impacted LIMTMs. LIMTMs in patients older than 41 to 45 years may be treated conservatively with regular follow-up, but surgical removal of inverted impacted LIMTMs is still recommended to avoid cyst formation.


Assuntos
Dente Serotino , Reabsorção da Raiz , Dente Impactado , Humanos , Dente Impactado/complicações , Dente Impactado/diagnóstico por imagem , Reabsorção da Raiz/etiologia , Feminino , Estudos Retrospectivos , Masculino , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Mandíbula , Prevalência , Adulto Jovem , Adolescente , Fatores Etários , Idoso
11.
J Matern Fetal Neonatal Med ; 37(1): 2357168, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38812361

RESUMO

OBJECTIVE: Epidural-related maternal fever in women is a common clinical phenomenon that leads to adverse consequences for mothers and neonates. The meta-analysis aimed to quantify the risk for intrapartum maternal fever after epidural analgesia (EA) stratified according to parity. The secondary objective was to investigate the association between EA and maternal outcomes. METHODS: An electronic literature search of the Medline/PubMed, Embase, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure databases was performed to identify studies reporting the occurrence of intrapartum fever in parturients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and meta-analysis was performed using Review Manager version 5.3. RESULTS: Seventeen randomized controlled trials (RCTs) (5959 parturients) were included. Odds ratios for maternal fever in the analysis were 4.17 (95% confidence interval (CI) 2.93-5.94) and 5.83 (95% CI 4.96-6.87), respectively. Results of subgroup analysis according to parity were consistent. EA significantly prolonged the length of the first stage of labor (MD 34.52 [95% CI 12.13-56.91]) and the second stage of labor (MD 9.10 [95% CI 4.51-13.68]). Parturients who received EA were more likely to undergo instrumental delivery (OR 2.03 [95% CI 1.44-2.86]) and oxytocin augmentation (OR 1.45 [95% CI 1.12-1.88]). There were no differences in cesarean delivery rates between the EA and non-EA groups. CONCLUSIONS: Parturients who received EA exhibited a higher incidence of intrapartum fever. Credibility of the subgroup analyses was low because the mixed group did not effectively represent multiparas.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Febre , Humanos , Analgesia Epidural/efeitos adversos , Analgesia Epidural/estatística & dados numéricos , Feminino , Gravidez , Febre/epidemiologia , Analgesia Obstétrica/métodos , Analgesia Obstétrica/efeitos adversos , Analgesia Obstétrica/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
BMC Public Health ; 24(1): 1333, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760740

RESUMO

BACKGROUND: Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. METHOD: Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. RESULTS: A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507-0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116-1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425-0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135-0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322-0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells < 200 cells/µL subgroup, temperature, precipitation, and PM10 had a significant hysteretic effect on TB incidence, while temperature and precipitation had a significant cumulative lag effect. However, these effects were not observed in the CD4(+) T cells ≥ 200 cells/µL subgroup. CONCLUSION: For PLWHA in subtropical Guangxi, temperature and precipitation had a significant cumulative effect on TB incidence among PLWHA, while air pollutants had little effect. Moreover, the influence of meteorological factors on the incidence of TB also depends on the immune status of PLWHA.


Assuntos
Poluentes Atmosféricos , Infecções por HIV , Conceitos Meteorológicos , Tuberculose , Humanos , China/epidemiologia , Incidência , Tuberculose/epidemiologia , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Infecções por HIV/epidemiologia , Feminino , Masculino , Adulto , Síndrome da Imunodeficiência Adquirida/epidemiologia , Pessoa de Meia-Idade
13.
World J Clin Cases ; 12(15): 2655-2663, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38817237

RESUMO

BACKGROUND: High-grade B-cell lymphoma (HGBL) is an unusual malignancy that includes myelocytomatosis viral oncogene (MYC), B-cell lymphoma-2 (BCL-2), and/or BCL-6 rearrangements, termed double-hit or triple-hit lymphomas, and HGBL-not otherwise specific (HGBL-NOS), which are morphologically characteristic of HGBL but lack MYC, BCL-2, or BCL-6 rearrangements. HGBL is partially transformed by follicular lymphoma and other indolent lymphoma, with few cases of marginal zone lymphoma (MZL) transformation. HGBL often has a poor prognosis and intensive therapy is currently mainly advocated, but there is no good treatment for these patients who cannot tolerate chemotherapy. CASE SUMMARY: We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression. Gene analysis revealed the gene expression profile was identical in the pre- and post-transformed tissues, suggesting that the two diseases are homologous, not secondary tumors. The chemotherapy was ineffective and the side effect was severe, so we tried combination therapy including venetoclax and obinutuzumab. The patient tolerated treatment well, and reached partial response. The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure. He survived for 12 months after diagnosis. CONCLUSION: Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients, who are unsuitable for chemotherapy.

14.
J Pharm Biomed Anal ; 245: 116191, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38728950

RESUMO

A method involving chitosan-assisted magnetic-stirring-enhanced mechanical amorphous dispersion extraction was developed and utilized to extract hydrophobic anthraquinones from Rhei Radix et Rhizoma prior to ultrahigh performance liquid chromatography analysis. Incorporating natural chitosan as a dispersant facilitated the extraction of hydrophobic anthraquinones using purified water, considerably enhancing the eco-friendliness of the extraction methodology. To optimize extraction efficiency, an extensive evaluation of the crucial parameters influencing rhubarb yield was conducted. Furthermore, a response surface methodology was applied to optimize the extraction conditions. Under these optimized conditions, the method exhibited linearity ranges of 0.1-100 µg/mL, with correlation coefficients between 0.9990 and 0.9998. The method's intraday (n = 6) and interday (n = 6) precision levels were maintained at ≤3.58%, which was considered to be within acceptable limits. The computed detection and quantification limits were 16.54-24.60 and 54.91-82.04 ng/mL, respectively. Consequently, this optimized method was effectively employed to extract five specific compounds (aloe-emodin, emodin, rhein, chrysophanol, and physcion) from Rhei Radix et Rhizoma, achieving recoveries ranging from 86.43% to 102.75%.


Assuntos
Antraquinonas , Interações Hidrofóbicas e Hidrofílicas , Plantas Medicinais , Rheum , Antraquinonas/química , Antraquinonas/análise , Cromatografia Líquida de Alta Pressão/métodos , Rheum/química , Plantas Medicinais/química , Quitosana/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/isolamento & purificação , Água/química , Emodina/análogos & derivados , Emodina/química , Emodina/análise , Limite de Detecção , Extratos Vegetais/química
15.
Mol Breed ; 44(6): 39, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38766512

RESUMO

Grain shape is one of the most important factors that affects rice yield. Cloning novel grain shape genes and analyzing their genetic mechanisms are crucial for high yield breeding. In this study, a slender grain CSSL-Z485 with 3-segments substitution in the genetic background of Nipponbare was constructed in rice. Cytological analysis showed that the longer grain length of Z485 was related to the increase in glume cell numbers, while the narrower grain width was associated with the decrease in cell width. Three grain shape-related quantitative trait locus (QTLs), including qGL12, qGW12, and qRLW12, were identified through the F2 population constructed from a cross between Nipponbare and Z485. Furthermore, four single segment substitution lines (SSSLs, S1-S4) carrying the target QTLs were dissected from Z485 by MAS. Finally, three candidate genes of qGL12 for grain length and qGW12 for grain width located in S3 were confirmed by DNA sequencing, RT-qPCR, and protein structure prediction. Specifically, candidate gene 1 encodes a ubiquitin family protein, while candidate genes 2 and 3 encode zinc finger proteins. The results provide valuable germplasm resources for cloning novel grain shape genes and molecular breeding by design. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-024-01480-x.

16.
Transl Lung Cancer Res ; 13(3): 623-634, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38601435

RESUMO

Background and Objective: Traditional cell line models are the commonly used preclinical models for lung cancer research. However, cell lines cannot recapitulate the complex tumor heterogeneity and cannot mimic the microenvironment of human cancer. Recently, 3D multicellular in vitro self-assembled models called "organoids" have been developed at a fast pace in the field of research, which can mimic the actual primary tumor. At present, several studies have reported on protocols of lung cancer organoids (LCOs) generation, and using LCOs can provide novel insight into the basic and translational research of lung cancer. However, the establishment of the LCO models remains challenging due to the complexity of lung cancer and the immaturity of organoid technology, so it is necessary to understand the influences of different methodologies on LCO generation and review the applications and limitations of LCO models. Methods: In this review, we searched the literature in the recent ten years in the field of LCOs. Key Content and Findings: We summarized the methodology, the problems, and the solutions in the LCOs generation, its application and limitations, as well as proposing future challenges and perspectives. Conclusions: Currently, LCOs are successfully generated via exploring the methodology by the researchers. Though there are still challenges in clinical application, LCOs are applied in some cancer studies including investigation of anti-cancer treatment response in vitro, modeling tumor immune microenvironment, and construction of organ chips, which are forging a promising path towards precision medicine.

17.
Sci Adv ; 10(16): eadi1782, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38630819

RESUMO

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.


Assuntos
Glutaratos , Leucemia Mieloide Aguda , Lisina , Humanos , Necroptose , Leucemia Mieloide Aguda/tratamento farmacológico , Apoptose , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
18.
Sci Transl Med ; 16(743): eadk5395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630847

RESUMO

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.


Assuntos
Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Pessoa de Meia-Idade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Lesões Pré-Cancerosas/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...