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1.
Endocrine ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970759

RESUMO

PURPOSE: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness. METHODS: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews. RESULTS: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis. CONCLUSION: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.

2.
Biomed Pharmacother ; 177: 117065, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971010

RESUMO

Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.

3.
BMC Public Health ; 24(1): 1852, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992625

RESUMO

BACKGROUND: The growing prevalence of non-alcoholic fatty liver disease (NAFLD) in younger populations, particularly those of working age (15-64 years), has become a public health concern. Being diagnosed at a younger age implies a greater likelihood of accruing disability-adjusted life years (DALYs) later in life due to potential progression to conditions such as cirrhosis or hepatocellular carcinoma. This study aims to analyze NAFLD prevalence trends over three decades globally, regionally, and nationally, with a focus on age, period, and birth cohort associations. METHODS: Global, regional, and country time trends in the prevalence of NAFLD among working-age people from 1990 to 2019: Age-period-cohort analysis based on Global Burden of Disease Study 2019 estimates and 95% uncertainty interval (UI) of NAFLD prevalence in the working age population was extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. Age-period-cohort models were used to estimate the prevalence within each age group from 1990 to 2019 (local drift, % per year), fitted longitudinal age-specific rates adjusted for period bias (age effect), and period/cohort relative risk (period/cohort effect). RESULTS: The global age-standardized prevalence (ASPR) of NAFLD increased significantly from 1990 (14,477.6 per 100 000) to 2019 (19,837.6 per 100 000). In the Western Pacific, there were 42,903.8 NAFLD cases in 2019, 54.15% higher than in 1990. The ASPR also increased significantly in the region over the past three decades. At the national level, Palau had the highest ASPR while Brunei Darussalam had the lowest. Age-period-cohort analysis showed that in the Western Pacific, unlike globally, the risk of NAFLD declined after age 60-64 years. Relative to 1980-1989, incidence and DALY risks decreased but prevalence increased in subsequent birth cohorts. Future predictions indicate an upward trend in NAFLD burden, especially among women and medium (SDI) regions like China. CONCLUSION: Non-alcoholic fatty liver disease imparts an immense health burden that continues to grow globally and in the Asia Pacific region. Our work highlights working age adults as an at-risk group and calls attention to socioeconomic gradients within Western Pacific countries. Upward future projections demonstrate that NAFLD prevention is an urgent priority.


Assuntos
Carga Global da Doença , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pessoa de Meia-Idade , Adulto , Carga Global da Doença/tendências , Feminino , Masculino , Adulto Jovem , Adolescente , Prevalência , Estudos de Coortes , Fatores de Risco , Anos de Vida Ajustados por Deficiência
4.
J Inflamm Res ; 17: 4247-4256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38973998

RESUMO

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) increases the risk of cardiovascular disease and existing evidence indicates that MASLD affects the cardiovascular system through systemic inflammation. Our aim was to assess the association of hematological biomarkers of inflammation with the 10-year risk of major adverse cardiovascular events (MACE) and all-cause mortality in MASLD patients. Methods: A total of 1858 MASLD participants from the Atherosclerosis Risk in Communities cohort study at visit 2 (1990-1992) were included. A total of 1338 non-MASLD participants were also included in the comparison. At baseline, hematological biomarkers of inflammation such as leukocytes, neutrophils, lymphocytes, monocytes, and C-reactive protein (CRP) were measured. Participants were followed up for MACE and all-cause mortality for a period of 10 years. Multivariate adjusted Cox models were used to estimate hazard ratios (HR). Results: The 10-year MACE was higher in MASLD participants than in non-MASLD participants (20.8% vs 9.3%). Monocytes (HR 1.114, [95% CI, 1.022-1.216] per 1-SD, P=0.015) and CRP (HR 1.109 [95% CI, 1.032-1.190] per 1-SD, P=0.005) were associated with an increased 10-year risk of MACE, independent of other cardiovascular risk factors. This association was specific to the MASLD population. None of these hematological biomarkers demonstrated a significant association with 10-year all-cause mortality. Conclusion: Increased levels of monocytes and CRP were associated with an increased 10-year risk of MACE in the MASLD population. Hematological biomarkers of inflammation may help identify MASLD populations at higher risk for cardiovascular events.

5.
Brain Res Bull ; 215: 111023, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964662

RESUMO

BACKGROUND: Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. OBJECTIVE: This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). METHODS: Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. RESULTS: The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P<0.0001, AUC=1.000), and furthermore could effectively distinguish MCS from UWS (P=0.037, AUC=0.821, sensitivity: 85.7 %, specificity: 75.0 %). Particularly in the subgroup of DOC patients survived global hypoxic-ischemic brain injury, DOCRP expression exhibited even better discriminatory power between MCS and UWS (P=0.046, AUC=1.000). CONCLUSIONS: DOCRP might serve as an objective biomarker in distinguishing between UWS and MCS, especially in patients survived global hypoxic-ischemic brain injury. TRIAL REGISTRATION NUMBER: ChiCTR2300073717 (Chinese clinical trial registry site, http://www.chictr.org).

6.
Free Radic Res ; 58(5): 311-322, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38946540

RESUMO

It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.


Assuntos
Fatores de Transcrição ARNTL , Antioxidantes , Camundongos Endogâmicos C57BL , Músculo Esquelético , Condicionamento Físico Animal , Animais , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Músculo Esquelético/metabolismo , Camundongos , Antioxidantes/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo
7.
Sci Rep ; 14(1): 16635, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025906

RESUMO

The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/ß-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.


Assuntos
Vesículas Extracelulares , Fígado , Camundongos Knockout , MicroRNAs , Hipófise , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Vesículas Extracelulares/metabolismo , Hipófise/metabolismo , Camundongos , Fígado/metabolismo , Proliferação de Células , Hepatócitos/metabolismo , Via de Sinalização Wnt , Masculino , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/genética , Regeneração Hepática/genética , Tetracloreto de Carbono/toxicidade
8.
Crit Rev Immunol ; 44(6): 99-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848297

RESUMO

Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Electroacupuncture (EA) has been shown to exert a neuroprotective effect in IS. However, its specific anti-IS mechanisms remain to be fully elucidated. By constructing a rat IS (middle cerebral artery occlusion, or MCAO) model and performing EA treatment, neurological deficit score, brain water content, and cerebral infarction were evaluated. ELISA was used to measure the levels of oxidative stress-related molecules (MDA, SOD, GSH, and CAT). Ferroptosis-related proteins (GPX4, SLC7A11, TfR1, L-ferritin, and hepcidin), neurological damage-related proteins (GFAP, Iba-1, and Nestin), α7nAChR, and mTOR pathway-related proteins (mTOR, p-mTOR, and SREBP1) in the rat brain penumbra were assessed by western blotting. Following EA treatment, neurological deficit scores, brain water content, cerebral infarction area, and GFAP, Iba-1, and Nestin expression were reduced. Additionally, EA treatment decreased MDA and increased SOD, GSH, and CAT. Moreover, the rats showed elevated GPX4 and SLC7A11 and lowered TfR1, L-ferritin, and hepcidin. In contrast, a7nAChR, mTOR, p-mTOR, and SREBP1 expression were upregulated. EA treatment inhibited OS and ferroptosis to exert a neuroprotective effect in IS, which might be realized via the activation of mTOR/SREBP1 signaling.


Assuntos
Eletroacupuntura , Ferroptose , AVC Isquêmico , Estresse Oxidativo , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Ratos , Serina-Treonina Quinases TOR/metabolismo , AVC Isquêmico/metabolismo , AVC Isquêmico/terapia , Modelos Animais de Doenças , Masculino , Humanos , Ratos Sprague-Dawley
9.
J Neuroeng Rehabil ; 21(1): 100, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867287

RESUMO

BACKGROUND: In-home rehabilitation systems are a promising, potential alternative to conventional therapy for stroke survivors. Unfortunately, physiological differences between participants and sensor displacement in wearable sensors pose a significant challenge to classifier performance, particularly for people with stroke who may encounter difficulties repeatedly performing trials. This makes it challenging to create reliable in-home rehabilitation systems that can accurately classify gestures. METHODS: Twenty individuals who suffered a stroke performed seven different gestures (mass flexion, mass extension, wrist volar flexion, wrist dorsiflexion, forearm pronation, forearm supination, and rest) related to activities of daily living. They performed these gestures while wearing EMG sensors on the forearm, as well as FMG sensors and an IMU on the wrist. We developed a model based on prototypical networks for one-shot transfer learning, K-Best feature selection, and increased window size to improve model accuracy. Our model was evaluated against conventional transfer learning with neural networks, as well as subject-dependent and subject-independent classifiers: neural networks, LGBM, LDA, and SVM. RESULTS: Our proposed model achieved 82.2% hand-gesture classification accuracy, which was better (P<0.05) than one-shot transfer learning with neural networks (63.17%), neural networks (59.72%), LGBM (65.09%), LDA (63.35%), and SVM (54.5%). In addition, our model performed similarly to subject-dependent classifiers, slightly lower than SVM (83.84%) but higher than neural networks (81.62%), LGBM (80.79%), and LDA (74.89%). Using K-Best features improved the accuracy in 3 of the 6 classifiers used for evaluation, while not affecting the accuracy in the other classifiers. Increasing the window size improved the accuracy of all the classifiers by an average of 4.28%. CONCLUSION: Our proposed model showed significant improvements in hand-gesture recognition accuracy in individuals who have had a stroke as compared with conventional transfer learning, neural networks and traditional machine learning approaches. In addition, K-Best feature selection and increased window size can further improve the accuracy. This approach could help to alleviate the impact of physiological differences and create a subject-independent model for stroke survivors that improves the classification accuracy of wearable sensors. TRIAL REGISTRATION NUMBER: The study was registered in Chinese Clinical Trial Registry with registration number CHiCTR1800017568 in 2018/08/04.


Assuntos
Gestos , Mãos , Redes Neurais de Computação , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/instrumentação , Mãos/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Idoso , Aprendizado de Máquina , Transferência de Experiência/fisiologia , Adulto , Eletromiografia , Dispositivos Eletrônicos Vestíveis
10.
Stroke ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38920043

RESUMO

BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.

11.
Appl Microbiol Biotechnol ; 108(1): 359, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836885

RESUMO

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.


Assuntos
Doença de Newcastle , Vírus da Doença de Newcastle , Temperatura , Vacinas Virais , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/química , Projetos Piloto , Doença de Newcastle/prevenção & controle , Doença de Newcastle/virologia , Vacinas Virais/química , Vacinas Virais/imunologia , Vácuo , Animais , Galinhas , Dessecação , China , Estabilidade de Medicamentos , Carga Viral
12.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1221-1228, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856440

RESUMO

Twisted partially coherent light, characterized by its unique twist factor, offers novel control over the statistical properties of random light. However, the recognition of the twist factor remains a challenge due to the low coherence and the stochastic nature of the optical beam. This paper introduces a method for the recognition of twisted partially coherent beams by utilizing a circular aperture at the source plane. This aperture produces a characteristic hollow intensity structure due to the twist phase. A deep learning model is then trained to identify the twist factor of these beams based on this signature. The model, while simple in structure, effectively eliminates the need for complex optimization layers, streamlining the recognition process. This approach offers a promising solution for enhancing the detection of twisted light and paves the way for future research in this field.

13.
Diabetes Obes Metab ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934214

RESUMO

AIM: The association of overweight/obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) in young adulthood with subclinical atherosclerosis [coronary artery calcification (CAC) and abdominal aortic calcification (AAC)] by middle age is unknown. METHOD: In total, 2274 participants aged 28-39 years from the coronary artery risk development in young adults study at year 10 (1995-1996) who were re-examined 15 years later were included. CAC and AAC were measured at year 25 using computed tomography. We examined the utility of three young adult phenotypes (lean group; overweight/obese group; overweight/obese MASLD group) at year 10 in predicting CAC or AAC by middle age. Modified Poisson regression was used to estimate the association between groups and CAC, and AAC. Independent determinates of CAC and AAC were determined with linear regression models. RESULTS: Compared with individuals categorized as lean in young adulthood, the relative risk for CAC by middle age was 1.09 (95% confidence interval: 0.93-1.28) for those with overweight/obesity and 1.32 (95% confidence interval: 1.08-1.61) for those with overweight/obesity-related MASLD. For AAC, no difference was observed between these three groups. Group, systolic blood pressure and group × systolic blood pressure interaction were all the independent determinates for CAC. CONCLUSION: In this study, young adults with overweight/obesity-related MASLD have a higher risk of developing CAC by middle age. These abnormalities are only partially explained by traditional cardiovascular risk factors, and overweight/obesity-related MASLD has an independent impact on CAC. Our study provides evidence for identifying young adults at higher risk of developing subclinical atherosclerosis.

14.
Mol Med Rep ; 30(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38818834

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell migration assay data shown in Fig. 4D on p. 4876 were strikingly similar to data that had already been published in different form in another article written by different authors at a different research institute. In addition, a pair of the data panels in Fig. 4D were overlapping, indicating that data derived from the same original source had been used to represent what were intended to be the results obtained from differently performed experiments.  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 4872­4878, 2016; DOI: 10.3892/mmr.2016.5127].

15.
Bioorg Chem ; 149: 107492, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38820939

RESUMO

As a member of glycosyltransferases, fucosyltransferase 8 (FUT8) is essential to core fucosylation and has been considered as a potential therapeutic target for malignant tumors, including colorectal cancer (CRC). Based on the identification of key binding residues and probable conformation of FUT8, an integrated strategy that combines virtual screening and chemical optimization was carried out and compound 15 was identified as a potent FUT8 inhibitor with novel chemical structure and in vitro antitumor activity. Moreover, chemical pulldown experiments and binding assays confirmed that compound 15 selectively bound to FUT8. In vivo, compound 15 showed promising anti-CRC effects in SW480 xenografts. These data support that compound 15 is a potential FUT8 inhibitor for CRC treatment and deserve further optimization studies.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Descoberta de Drogas , Inibidores Enzimáticos , Fucosiltransferases , Fucosiltransferases/antagonistas & inibidores , Fucosiltransferases/metabolismo , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Relação Estrutura-Atividade , Camundongos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo , Simulação de Acoplamento Molecular
16.
BMC Public Health ; 24(1): 1224, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702746

RESUMO

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.


Assuntos
Inquéritos Nutricionais , Antígeno Prostático Específico , Neoplasias da Próstata , Riboflavina , Humanos , Masculino , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Riboflavina/administração & dosagem , Adulto
17.
J Cereb Blood Flow Metab ; : 271678X241258576, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38820436

RESUMO

Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca2+ dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca2+ and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca2+ activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.

18.
Front Pediatr ; 12: 1409046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774298

RESUMO

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

19.
J Hazard Mater ; 472: 134499, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38759282

RESUMO

Cl- activated peroxymonosulfate (PMS) oxidation technology can effectively degrade pollutants, but the generation of chlorinated disinfection byproducts (DBPs) limits the application of this technology in water treatment. In this study, a method of nanobubbles (NBs) synergistic Cl-/PMS system was designed to try to improve this technology. The results showed the synergistic effects of NBs/Cl-/PMS were significant and universal while its upgrade rate was from 12.89% to 34.97%. Moreover, the synergistic effects can be further improved by increasing the concentration and Zeta potential of NBs. The main synergistic effects of NBs/Cl-/PMS system were due to the electrostatic attraction of negatively charged NBs to Na+ from NaCl, K+ from PMS, and H+ from phenol, which acted as a "bridge" between Cl- and HSO5- as well as phenol and Cl-/HSO5-, increasing active substance concentration. In addition, the addition of NBs completely changed the oxidation system of Cl-/PMS from one that increases environmental toxicity to one that reduces it. The reason was that the electrostatic attraction of NBs changed the active sites and degradation pathway of phenol, greatly reducing the production of highly toxic DBPs. This study developed a novel environmentally friendly oxidation technology, which provides an effective strategy to reduce the generation of DBPs in the Cl-/PMS system.

20.
Angew Chem Int Ed Engl ; 63(23): e202401451, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38563752

RESUMO

The diversified synthesis of chiral fluorinated cyclobutane derivatives has remained a difficult task in synthetic chemistry. Herein, we present an approach for asymmetric hydroboration and formal hydrodefluorination of gem-difluorinated cyclobutenes through rhodium catalysis, providing chiral gem-difluorinated α-boryl cyclobutanes and monofluorinated cyclobutenes with excellent regio- and enantioselectivity, respectively. The key to the success of the two transformations relies on an efficient, mild and highly selective rhodium-catalyzed asymmetric hydroboration with HBPin (pinacolborane), in which the subsequent addition of a base, and a catalytic amount of palladium in some cases, results in the formation of formal hydrodefluorination products with the four-membered ring retained. The obtained chiral gem-difluorinated α-boryl cyclobutanes are versatile building blocks that provide a platform for the synthesis of enantioenriched fluorinated cyclobutane derivatives to a great diversity.

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