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4.
Nat Commun ; 15(1): 4347, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773146

RESUMO

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Astrócitos , Transtorno Depressivo Maior , Camundongos Knockout , Animais , Astrócitos/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Camundongos , Humanos , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/patologia , Masculino , Feminino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Estresse Psicológico/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Comportamento Animal , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Depressão/metabolismo , Depressão/genética , Adulto , Transmissão Sináptica , Pessoa de Meia-Idade
5.
Glob Med Genet ; 11(2): 142-149, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38606422

RESUMO

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

6.
ACS Nano ; 18(14): 10288-10301, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38556985

RESUMO

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.


Assuntos
Ferroptose , Neoplasias , Radioterapia Guiada por Imagem , Humanos , Espécies Reativas de Oxigênio , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Apoptose , Peróxido de Hidrogênio , Linhagem Celular Tumoral
7.
Endocr Pract ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657794

RESUMO

OBJECTIVE: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

8.
Bioconjug Chem ; 35(5): 665-673, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38598424

RESUMO

Enhancing the accumulation and retention of small-molecule probes in tumors is an important way to achieve accurate cancer diagnosis and therapy. Enzyme-stimulated macrocyclization of small molecules possesses great potential for enhanced positron emission tomography (PET) imaging of tumors. Herein, we reported an 18F-labeled radiotracer [18F]AlF-RSM for legumain detection in vivo. The tracer was prepared by a one-step aluminum-fluoride-restrained complexing agent ([18F]AlF-RESCA) method with high radiochemical yield (RCY) (88.35 ± 3.93%) and radiochemical purity (RCP) (>95%). More notably, the tracer can be transformed into a hydrophobic macrocyclic molecule under the joint action of legumain and reductant. Simultaneously, the tracer could target legumain-positive tumors and enhance accumulation and retention in tumors, resulting in the amplification of PET imaging signals. The enhancement of radioactivity enables PET imaging of legumain activity with high specificity. We envision that, by combining this highly efficient 18F-labeled strategy with our intramolecular macrocyclization reaction, a range of radiofluorinated tracers can be designed for tumor PET imaging and early cancer diagnosis in the future.


Assuntos
Cisteína Endopeptidases , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Flúor/química , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/análise , Animais , Ciclização , Camundongos , Humanos , Compostos Radiofarmacêuticos/química , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Fluoretos/química , Camundongos Nus
9.
Cureus ; 16(3): e55930, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601389

RESUMO

BACKGROUND: Persistent human papillomavirus (HPV) infection is the primary cause of cervical cancer. However, this can be prevented through vaccination and screening. This study aimed to clarify the relationship between behavior, knowledge, and attitude toward cervical cancer and regular screening and HPV infection among women in Lueyang County. METHODS: Women who underwent cervical cancer screening at the outpatient department of a maternal and child health center between September and December 2021 were invited to participate. In total, 2,303 women completed the questionnaire. Women who underwent regular or irregular screening were 1:1 matched for age. Differences in knowledge of HPV and attitudes toward HPV vaccination among different populations were assessed. Logistic regression analysis was performed to identify the factors influencing HPV infection. RESULTS:  In total, 417 pairs of women who underwent regular and irregular screening were successfully matched. Multivariate logistic regression results indicated that age is a risk factor for HPV infection (OR=1.056 95%CI: [1.031 1.082]), while regular screening acts as a protective factor against HPV infection (OR=0.174 95%CI: [0.117 0.259]). Additionally, regular screening was associated with a higher level of knowledge about HPV among women compared to those who did not undergo regular screening (p<0.001). CONCLUSIONS:  Women in Lueyang County have low levels of knowledge regarding HPV and cervical cancer. Regular screening is a protective factor against HPV infection. The regular screening group demonstrates a higher level of HPV knowledge compared with the irregular screening group. These findings highlight the importance of regular screening and the need to strengthen public health education.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38614212

RESUMO

OBJECTIVE: Limited evidence exists regarding the efficacy of preoperative exercise in reducing short-term complications after minimally invasive surgery in patients with non-small cell lung cancer. This study aims to investigate the impact of preoperative exercise on short-term complications after minimally invasive lung resection. METHODS: In this prospective, open-label, randomized (1:1) controlled trial at Xiangya Hospital, China (September 2020 to February 2022), patients were randomly assigned to a preoperative exercise group with 16-day alternate supervised exercise or a control group. The primary outcome assessed was short-term postoperative complications, with a follow-up period of 30 days postsurgery. RESULTS: A total of 124 patients were recruited (preoperative exercise group n = 62; control n = 62). Finally, 101 patients (preoperative exercise group; n = 51 and control; n = 50) with a median age of 56 years (interquartile range, 50-62 years) completed the study. Compared with the control group, the preoperative exercise group showed fewer postoperative complications (preoperative exercise 3/51 vs control 10/50; odds ratio, 0.17; 95% CI, 0.04-0.86; P = .03) and shorter hospital stays (mean difference, -2; 95% CI, -3 to -1; P = .01). Preoperative exercise significantly improved depression, stress, functional capacity, and quality of life (all P < .05) before surgery. Furthermore, preoperative exercise demonstrated a significantly lower minimum blood pressure during surgery and lower increases in body temperature on day 2 after surgery, neutrophil-to-lymphocyte ratio, and neutrophil count after surgery (all P < .05). Exploratory research on lung tissue RNA sequencing (5 in each group) showed downregulation of the tumor necrosis factor signaling pathway in the preoperative exercise group compared with the control group. CONCLUSIONS: Preoperative exercise training decreased short-term postoperative complications in patients with non-small cell lung cancer.

11.
Cureus ; 16(4): e58081, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38616979

RESUMO

Purpose This study delves into the epidemiology of high-risk human papillomavirus (HR-HPV) infection and its link to precancerous lesions among perimenopausal (40-59 years) and elderly (60-65 years) women in a Chinese county with a notably high incidence of cervical cancer. By uniquely focusing on these age groups in underdeveloped regions, the research aims to offer novel strategies for the management and prevention of cervical cancer. It seeks to inform targeted interventions and public health policies that could significantly benefit women at heightened risk for HPV, addressing a critical gap in current prevention efforts in economically disadvantaged communities. Methods This observational study was conducted at the Maternal and Child Health and Family Planning Service Centre in Lueyang County, from September 2021 to January 2022. It assessed 2008 women aged 40-65 for HPV screening, with 342 undergoing further cytological examination. The study evaluated the prevalence of HPV infection across different age groups and risk categories. It utilized a questionnaire to collect participants' basic information, health behaviors, and other relevant data to analyze factors influencing HR-HPV infection. Statistical analyses comprised chi-square tests, trend analysis, logistic regression, and multiple imputation techniques to address missing data. Results The prevalence of HR-HPV infection among women aged 40-65 years in Lueyang County was 18.43%. Older women exhibited a higher incidence of HPV infection, abnormal ThinPrep Cytology Test (TCT) results (Shaanxi Fu'an Biotechnology Co. Ltd., Baoji City, China), and low/high-grade squamous intraepithelial lesions (LSIL/HSIL) (P<0.05). The most prevalent HR-HPV genotypes in the overall, perimenopausal, and elderly groups were HPV-52, -53, and -58; HPV-52, -53, and -16; and HPV-58, -52, and -53, respectively. The prevalent HR-HPV genotypes in the abnormal The Bethesda System (TBS) results were HPV-16, -52, -33, -58; -16, -52, -58; and-16, -33, and -52. HPV-16, -18, -33 prevalence increased with increasing lesion severity (P<0.05). In this study, factors affecting HR-HPV in the three age groups were found to be mainly related to sexual behavior and education level, including history of lower genital tract diseases, multiple pregnancies, contraceptive methods without tubal ligation, age at first marriage greater than 18 years, never washing the vulva after sex, abstinence from sex, education level of junior high school or above, and spouse's education level of high school or above. Conclusions These findings suggest that the elevated rate of abnormal TBS in the older age group may be attributed to the higher prevalence of persistent infection-prone HR-HPV genotypes (HPV-58, -52, and-53), multiple infections, and potent oncogenic HR-HPV genotypes (HPV-16 and -33). Additionally, the higher HR-HPV prevalence in older patients may be related to lower education attainment, reduced screening rate, and limited condom usage. Therefore, strategies targeting perimenopausal and older women should prioritize enhancing health awareness, increasing screening rates, and encouraging condom utilization.

12.
Quant Imaging Med Surg ; 14(2): 1971-1984, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415120

RESUMO

Background: The solid component of subsolid nodules (SSNs) is closely associated with the invasiveness of lung adenocarcinoma, and its accurate assessment is crucial for selecting treatment method. Therefore, this study aimed to evaluate the accuracy of solid component size within SSNs measured on multiplanar volume rendering (MPVR) and compare it with the dimensions of invasive components on pathology. Methods: A pilot study was conducted using a chest phantom to determine the optimal MPVR threshold for the solid component within SSN, and then clinical validation was carried out by retrospective inclusion of patients with pathologically confirmed solitary SSN from October 2020 to October 2021. The radiological tumor size on MPVR and solid component size on MPVR (RSSm) and on lung window (RSSl) were measured. The size of the tumor and invasion were measured on the pathological section, and the invasion, fibrosis, and inflammation within SSNs were also recorded. The measurement difference between computed tomography (CT) and pathology, inter-observer and inter-measurement agreement were analyzed. Receiver operating characteristic (ROC) analysis and Bland-Altman plot were performed to evaluate the diagnostic efficiency of MPVR. Results: A total of 142 patients (mean age, 54±11 years, 39 men) were retrospectively enrolled in the clinical study, with 26 adenocarcinomas in situ, 92 minimally invasive adenocarcinomas (MIAs), and 24 invasive adenocarcinomas (IAs). The RSSl was significantly smaller than pathological invasion size with fair inter-measurement agreement [intraclass correlation coefficient (ICC) =0.562, P<0.001] and moderate interobserver agreement (ICC =0.761, P<0.001). The RSSm was significantly larger than pathological invasion size with the excellent inter-measurement agreement (ICC =0.829, P<0.001) and excellent (ICC =0.952, P<0.001) interobserver agreement. ROC analysis showed that the cutoff value of RSSm for differentiating adenocarcinoma in situ from MIA and MIA from IA was 1.85 and 6.45 mm (sensitivity: 93.8% and 95.5%, specificity: 85.7% and 88.2%, 95% confidence internal: 0.914-0.993 and 0.900-0.983), respectively. The positive predictive value-and negative predictive value of MPVR in predicting invasiveness were 92.8% and 100%, respectively. Conclusions: Using MPVR to predict the invasive degree of SSN had high accuracy and good inter-observer agreement, which is superior to lung window measurements and helpful for clinical decision-making.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38319321

RESUMO

PURPOSE: Neuropilin-1 (NRP-1) is a multifunctional protein involved in a variety of biological processes such as angiogenesis, tumorigenesis and immunomodulation. It was usually overexpressed in many cancer cell lines and correlated with poor prognosis of breast cancer. Positron emission tomography (PET) is an advanced imaging technique for detecting the function and metabolism of tumor-associated molecules in real time, dynamically, quantitatively and noninvasively. To improve the level of early diagnosis and evaluate the prognosis of breast cancer, an NRP-1 targeting peptide-based tracer [68 Ga]Ga-NOTA-PEG4-CK2 was designed to sensitively and specifically detect the NRP-1 expression in vivo via PET imaging. METHODS: In silico modeling and microscale thermophoresis (MST) assay were carried out to design the NRP-1 targeting peptide NOTA-PEG4-CK2, and it was further radiolabeled with 68 Ga to prepare the tracer [68 Ga]Ga-NOTA-PEG4-CK2. The radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), lipid-water partition coefficient (Log P) and stability of [68 Ga]Ga-NOTA-PEG4-CK2 were assessed. The targeting specificity of the tracer for NRP-1 was investigated by in vitro cellular uptake assay and in vivo PET imaging as well as blocking studies. The sensitivity of the tracer in monitoring the dynamic changes of NRP-1 expression induced by chemical drug was also investigated in vitro and in vivo. Ex vivo biodistribution, autoradiography, western blot, and immunofluorescence staining were also performed to study the specificity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1. RESULTS: [68 Ga]Ga-NOTA-PEG4-CK2 was designed and synthesized with high RCY (> 98%), high stability (RCP > 95%) and high affinity to NRP-1 (KD = 25.39 ± 1.65 nM). In vitro cellular uptake assay showed that the tracer [68 Ga]Ga-NOTA-PEG4-CK2 can specifically bind to NRP-1 positive cancer cells MDA-MB-231 (1.04 ± 0.04% at 2 h) rather than NRP-1 negative cancer cells NCI-H1299 (0.43 ± 0.05%). In vivo PET imaging showed the maximum tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 in MDA-MB-231 xenografts (4.16 ± 0.67%ID/mL) was significantly higher than that in NCI-H1299 xenografts (1.03 ± 0.19%ID/mL) at 10 min post injection, and the former exhibited higher tumor-to-muscle uptake ratio (5.22 ± 0.18) than the latter (1.07 ± 0.27) at 60 min post injection. MDA-MB-231 xenografts pretreated with nonradioactive precursor NOTA-PEG4-CK2 showed little tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 (1.67 ± 0.38%ID/mL at 10 min post injection). Both cellular uptake assay and PET imaging revealed that NRP-1 expression in breast cancer MDA-MB-231 could be effectively suppressed by SB-203580 treatment and can be sensitively detected by [68 Ga]Ga-NOTA-PEG4-CK2. Ex vivo analysis also proved the high specificity and sensitivity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1 expression in MDA-MB-231 xenografts. CONCLUSION: A promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was successfully prepared. It showed remarkable specificity and sensitivity in monitoring the dynamic changes of NRP-1 expression. Hence, it could provide valuable information for early diagnosis of NRP-1 relevant cancers and evaluating the prognosis of cancer patients.

14.
Mol Pharm ; 21(3): 1382-1389, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38372213

RESUMO

Cathepsin B, a lysosomal protease, is considered as a crucial biomarker for tumor diagnosis and treatment as it is overexpressed in numerous cancers. A stimulus-responsive SF scaffold has been reported to detect the activity of a variety of tumor-associated enzymes. In this work, a small-molecule PET tracer ([68Ga]NOTA-SF-CV) was developed by combining an SF scaffold with a cathepsin B-specific recognition substrate Cit-Val. Upon activation by cathepsin B, [68Ga]NOTA-SF-CV could form the cyclization product in a reduction environment, resulting in reduced hydrophilicity. This unique property could effectively prevent exocytosis of the tracer in cathepsin B-overexpressing tumor cells, leading to prolonged retention and amplified PET imaging signal. Moreover, [68Ga]NOTA-SF-CV had great targeting specificity to cathepsin B. In vivo microPET imaging results showed that [68Ga]NOTA-SF-CV was able to effectively visualize the expression level of cathepsin B in various tumors. Hence, [68Ga]NOTA-SF-CV may be served as a potential tracer for diagnosing cathepsin B-related diseases.


Assuntos
Radioisótopos de Gálio , Neoplasias , Humanos , Radioisótopos de Gálio/química , Catepsina B , Tomografia por Emissão de Pósitrons/métodos , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos/química , Linhagem Celular Tumoral
15.
Biochem Biophys Res Commun ; 703: 149646, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38350212

RESUMO

Legumain is overexpressed in diverse tumors, serving as a significant tumor biomarker. Our study aimed to develop a new positron emission tomography (PET) probe [68Ga]Ga-NOTA-SF-AANM for imaging the expression level of legumain in vivo. The radio-labeling of [68Ga]Ga-NOTA-SF-AANM was accomplished within 15 min. The probe has good stability in vitro. NOTA-SF-AANM exhibited rapid response to recombinant human legumain enzyme, enabling intramolecular condensation cyclization. Cellular uptake and lysosomal co-localization experiments demonstrated that the probe was able to differentiate specifically between MDA-MB-468 and PC-3 cancer cells with varying degrees of legumain expression. PET imaging displayed a significant and persistent signal (3.59 ± 0.30 %ID/mL at 60 min) in MDA-MB-468 tumors, while PC-3 tumors exhibited lower radioactivity (1.08 ± 0.35 %ID/mL at 60 min), further validating the specific targeting of [68Ga]Ga-NOTA-SF-AANM towards legumain. [68Ga]Ga-NOTA-SF-AANM is a promising tool for precise diagnosis of legumain-related diseases due to its advantages in radio-labeling and accurate monitoring of legumain expression levels.


Assuntos
Cisteína Endopeptidases , Radioisótopos de Gálio , Neoplasias , Humanos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias/diagnóstico por imagem , Lisossomos , Linhagem Celular Tumoral
16.
Acta Diabetol ; 61(6): 705-714, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38400938

RESUMO

AIMS: Several studies have reported dietary microorganisms' beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018. METHODS: According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups. In patients with T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin to creatinine ratio ≥ 30 mg/g), or both. Weighted univariate and multivariate logistic regression and subgroup analyses were conducted to investigate the independent association between dietary live microbe and DKD. RESULTS: The study included 3836 participants, of whom 1467 (38.24%) had DKD for the diagnosis. Our study demonstrated that participants in the high dietary live microbe group were more likely to be older, female, non-Hispanic White, have higher education levels, have a lower prevalence of smoking, have a high poverty-income ratio, have higher energy intake, lower haemoglobin (HbA1c) and serum creatinine levels, and lower risk of progression. After adjustment for covariates, patients in the high dietary live microbe group had a low prevalence of DKD, whereas no significant association with DKD was found between the medium and low dietary live microbe groups. No statistically significant interaction was observed in all subgroup analyses except for HbA1c (p for interaction < 0.05). CONCLUSIONS: Our results indicate that high dietary live microbe intake was associated with a low DKD prevalence.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inquéritos Nutricionais , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Idoso , Adulto , Dieta/estatística & dados numéricos , Estados Unidos/epidemiologia , Taxa de Filtração Glomerular
17.
Clin Chim Acta ; 553: 117749, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169194

RESUMO

The measurement of steroid hormones in blood and urine, which reflects steroid biosynthesis and metabolism, has been recognized as a valuable tool for identifying and distinguishing steroidogenic disorders. The application of mass spectrometry enables the reliable and simultaneous analysis of large panels of steroids, ushering in a new era for diagnosing adrenal diseases. However, the interpretation of complex hormone results necessitates the expertise and experience of skilled clinicians. In this scenario, machine learning techniques are gaining worldwide attention within healthcare fields. The clinical values of combining mass spectrometry-based steroid profiles analysis with machine learning models, also known as steroid metabolomics, have been investigated for identifying and discriminating adrenal disorders such as adrenocortical carcinomas, adrenocortical adenomas, and congenital adrenal hyperplasia. This promising approach is expected to lead to enhanced clinical decision-making in the field of adrenal diseases. This review will focus on the clinical performances of steroid profiling, which is measured using mass spectrometry and analyzed by machine learning techniques, in the realm of decision-making for adrenal diseases.


Assuntos
Neoplasias do Córtex Suprarrenal , Doenças das Glândulas Suprarrenais , Adenoma Adrenocortical , Carcinoma Adrenocortical , Humanos , Doenças das Glândulas Suprarrenais/diagnóstico , Doenças das Glândulas Suprarrenais/metabolismo , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/diagnóstico , Esteroides/metabolismo , Neoplasias do Córtex Suprarrenal/diagnóstico
18.
BMC Oral Health ; 24(1): 32, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184544

RESUMO

BACKGROUND: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. METHODS: Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. RESULTS: A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites. CONCLUSION: This large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Esvaziamento Cervical , Neoplasias Bucais/cirurgia , Estudos de Coortes , Estudos Retrospectivos
19.
Anal Chem ; 96(4): 1707-1716, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38241523

RESUMO

Improving the retention of small-molecule-based therapeutic agents in tumors is crucial to achieve precise diagnosis and effective therapy of cancer. Herein, we propose a ß-galactosidase (ß-Gal)-activated and red light-induced RNA modification (GALIRM) strategy for prolonged tumor imaging. A ß-Gal-activatable near-infrared (NIR) fluorescence (FL) and positron emission tomography (PET) bimodal probe 68Ga-NOTA-FCG consists of a triaaza triacetic acid chelator NOTA for 68Ga-labeling, a ß-Gal-activated photosensitizer CyGal, and a singlet oxygen (1O2)-susceptible furan group for RNA modification. Studies have demonstrated that the probe emits an activated NIR FL signal upon cleavage by endogenous ß-Gal overexpressed in the lysosomes, which is combined with the PET imaging signal of 68Ga allowing for highly sensitive imaging of ovarian cancer. Moreover, the capability of 68Ga-NOTA-FCG generating 1O2 under 690 nm illumination could be simultaneously unlocked, which can trigger the covalent cross-linking between furan and nucleotides of cytoplasmic RNAs. The formation of the probe-RNA conjugate can effectively prevent exocytosis and prolong retention of the probe in tumors. We thus believe that this GALIRM strategy may provide entirely new insights into long-term tumor imaging and efficient tumor treatment.


Assuntos
Neoplasias Ovarianas , Luz Vermelha , Feminino , Humanos , Fluorescência , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons/métodos , beta-Galactosidase , Furanos
20.
Rev Esp Enferm Dig ; 116(1): 55-56, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37073689

RESUMO

Brunner's gland adenoma (BGA), also known as Brunneroma or polypoid hamartoma, is a rare benign duodenal tumor that proliferates from Brunner's glands of the duodenum. They are usually asymptomatic and discovered by chance during endoscopy. Some giant lesions can sometimes present with chronic abdominal pain, nausea, vomiting, and anemia, including gastrointestinal bleeding and obstructive symptoms, and need to be resected by surgery or endoscopy. Here we report a giant BGA that was easily and safely removed by Endoloop pre-ligation assisted resection.


Assuntos
Adenoma , Glândulas Duodenais , Neoplasias Duodenais , Humanos , Neoplasias Duodenais/diagnóstico por imagem , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/patologia , Glândulas Duodenais/diagnóstico por imagem , Glândulas Duodenais/cirurgia , Glândulas Duodenais/patologia , Duodeno/patologia , Endoscopia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/patologia
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