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1.
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
2.
Angew Chem Int Ed Engl ; : e202401451, 2024 Apr 02.
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.

3.
J Anim Sci Technol ; 66(1): 178-203, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38618031

RESUMO

Constipation, which refers to difficulties in defecation and infrequent bowel movement in emptying the gastrointestinal system that ultimately produces hardened fecal matters, is a health concern in livestock and aging animals. The present study aimed to evaluate the potential effects of dairy-isolated lactic acid bacteria (LAB) strains to alleviate constipation as an alternative therapeutic intervention for constipation treatment in the aging model. Rats were aged via daily subcutaneous injection of D-galactose (600 mg/body weight [kg]), prior to induction of constipation via oral administration of loperamide hydrochloride (5 mg/body weight [kg]). LAB strains (L. fermentum USM 4189 or L. plantarum USM 4187) were administered daily via oral gavage (1 × 10 Log CFU/day) while the control group received sterile saline. Aged rats as shown with shorter telomere lengths exhibited increased fecal bulk and soften fecal upon administration of LAB strains amid constipation as observed using the Bristol Stool Chart, accompanied by a higher fecal moisture content as compared to the control (p < 0.05). Fecal water-soluble metabolite profiles showed a reduced concentration of threonine upon administration of LAB strains compared to the control (p < 0.05). Histopathological analysis also showed that the administration of LAB strains contributed to a higher colonic goblet cell count as compared to the control (p < 0.05). The present study illustrates the potential of dairy-sourced LAB strains as probiotics to ameliorate the adverse effect of constipation amid aging, and as a potential dietary intervention strategy for dairy foods including yogurt and cheese.

4.
Br J Psychiatry ; : 1-10, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38660761

RESUMO

BACKGROUND: Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time. AIMS: To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10-24 years. METHOD: Our research focused on young people (aged 10-24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019. RESULTS: The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20-24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males. CONCLUSIONS: Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.

5.
BMJ Open ; 14(4): e080612, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589255

RESUMO

OBJECTIVE: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019. RESULTS: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend. CONCLUSIONS: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment.


Assuntos
Asma , Dermatite Atópica , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de Vida , Prevalência , Incidência , Asma/epidemiologia , Dermatite Atópica/epidemiologia , Saúde Global , Fatores de Risco
6.
World J Gastrointest Oncol ; 16(3): 945-967, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577477

RESUMO

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

7.
Anal Methods ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682943

RESUMO

NH3 gas sensors operating at room temperature, consisting of Ag nanoparticles decorated ß-AgVO3 nanorods (Ag/ß-AgVO3 NRs), were fabricated via a facile hydrothermal method without the need for a template. The surface characteristics and compositions of Ag/ß-AgVO3 NRs were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Ag nanoparticles, ranging in diameter from approximately 20 to 40 nm, were dispersed on the surface of monoclinic ß-AgVO3 NRs with diameters ranging from 50 to 105 nm and lengths from 0.3 to 1.3 µm. The NH3 gas sensing properties of Ag/ß-AgVO3 NRs were studied under both dry air and humid conditions at room temperature. Comparative analysis demonstrated that the Ag/ß-AgVO3 NRs exhibited a strong response to NH3 gas under 70% relative humidity (RH) at room temperature compared to α-AgVO3 NRs. Specifically, the response of the Ag/ß-AgVO3 NRs to 5 ppm NH3 increased by 2.25 times as the RH varied from 20% to 80% at room temperature. This enhanced response was attributed to the effects of formation of nanoheterojunctions, nano-metallic Ag activity and the conductivity of NH4+ and OH- ions induced by the presence of humidity. The room temperature NH3 gas sensors based on Ag/ß-AgVO3 NRs demonstrated strong responses to low NH3 concentrations, high selectivity, good reproducibility, and long-term stability, and show promise for the development of low-power and cost-effective NH3 gas sensors for practical applications even under high humidity.

8.
Sleep Med ; 119: 155-163, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38678759

RESUMO

OBJECTIVES: Sleep is associated with cognitive function in older adults. In the current study, we examined this relationship from subjective and objective perspectives, and determined the robustness and dimensional specificity of the associations using a comprehensive modelling approach. METHODS: Multiple dimensions of subjective (sleep quality and daytime sleepiness) and objective sleep (sleep stages, sleep parameters, sleep spindles, and slow oscillations), as well as subjectively reported and objectively measured cognitive function were collected from 55 older adults. Specification curve analysis was used to examine the robustness of correlations for the effects of sleep on cognitive function. RESULTS: Robust associations were found between sleep and objectively measured cognitive function, but not with subjective cognitive complaints. In addition, subjective sleep showed robust and consistent associations with global cognitive function, whereas objective sleep showed a more domain-specific association with episodic memory. Specifically, subjective sleep quality and daytime sleepiness correlated with global cognitive function, and objective sleep parameters correlated with episodic memory. CONCLUSIONS: Overall, associations between sleep and cognitive function in older adults depend on how they are measured and which specific dimensions of sleep and domains of cognitive function are considered. It highlights the importance of focusing on specific associations to ameliorate the detrimental effects of sleep disturbance on cognitive function in later life.

9.
Eur J Pain ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563383

RESUMO

BACKGROUND AND OBJECTIVE: The relationship between chronic daily headache (CDH), depression symptoms, and brain volume remains unclear. METHODS: To investigate the effects of CDH on brain volume and the impact of depressive symptoms (DSs) as well as the effects of demography and medication overuse, PubMed, Embase, and Web of Science databases were systematically searched using appropriate keyword strings to retrieve observational studies from inception to May 2023. RESULTS: Two distinct comparisons were made in CDH patients: (1) those with DSs versus their pain-free counterparts and (2) those without DSs versus pain-free controls. The first comprised nine studies enrolling 225 CDH patients with DSs and 234 controls. Beck depression inventory, Hamilton depression scale, and Hospital anxiety/depression scale were used to assess DSs, revealing significantly more DSs in CDH patients with DSs compared to their controls (all p < 0.05). Besides, the second analysed four studies involving 117 CDH patients without DSs and 155 comparators. Compared to CDH patients without DSs, those with DSs had a smaller brain volume than controls (p = 0.03). Furthermore, CDH patients with DSs who did not overuse medications showed a smaller right cerebral cortical volume than overusers (p = 0.003). A significant inverse correlation between female prevalence and brain volume (p = 0.02) was revealed using regression analysis. CONCLUSIONS: Pain-induced persistent depressive symptoms not only incur structural alterations but also encompass affective-motivational changes, involving medication use and gender-specific health concerns. SIGNIFICANCE: This study highlighted the importance of an integrated CDH treatment, emphasizing psychological interventions for the affective-motivational component alongside pain management.

11.
Psychiatry Res ; 336: 115889, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38621309

RESUMO

BACKGROUND: Depression is a highly prevalent and disabling mental health condition among adolescents. The epidemiology of depression in adolescents has been changing over time, reflecting changes in risk factors as well as disease concepts and diagnosis. However, few studies have characterized the longitudinal epidemiology of depression in adolescents. Understanding trends of disease burden provides key insights to improve resource allocation and design targeted interventions for this vulnerable population. The Western Pacific Region (WPR) is home to over 1.3 billion people with tremendous diversity in culture and socioeconomic development. The epidemiology of adolescent depression in WPR remains largely unknown. In this study, we aimed to estimate trends of disease burden attributable to depressive disorders among adolescents aged 10-24 years in WPR countries between 1990 and 2019, and to investigate period and cohort effects using the Global Burden of Disease (GBD) study database. METHODS: The study utilized data from the Global Burden of Disease, Injuries, and Risk Factors Study 2019, concentrating on adolescents aged 10 to 24 years with depression. We conducted an in-depth analysis of depression, including its age-standardized prevalence, incidence, and Disability-Adjusted Life Years (DALYs), across diverse demographics such as regions, ages, genders, and socio-demographic indexes, spanning from 1990 to 2019. RESULTS: The analysis found decreasing trends in the prevalence, incidence, and DALYs of adolescent depression in the WPR between 1990-2019, although some countries like Australia and Malaysia showed increases. Specifically, the prevalence of adolescent depression in the region decreased from 9,347,861.6 cases in 1990 to 5,551,341.1 cases in 2019. The incidence rate declined from 2,508.6 per 100,000 adolescents in 1990 to 1,947.9 per 100,000 in 2019. DALYs decreased from 371.9 per 100,000 in 1990 to ASR 299.7 per 100,000 in 2019. CONCLUSION: This study found an overall decreasing trend in adolescent depression burden in the Western Pacific Region between 1990 and 2019, with heterogeneity across countries. For 30 years, the 20-24 age group accounted for the majority of depression among adolescents Widening inequality in depression burden requires policy attention. Further analysis of risk factors contributing to epidemiological trends is warranted to inform prevention strategies targeting adolescent mental health in the region.


Assuntos
Carga Global da Doença , Humanos , Adolescente , Masculino , Feminino , Criança , Adulto Jovem , Prevalência , Carga Global da Doença/tendências , Incidência , Transtorno Depressivo/epidemiologia , Depressão/epidemiologia , Estudos de Coortes , Anos de Vida Ajustados por Deficiência/tendências , Fatores de Risco
12.
World J Gastroenterol ; 30(13): 1926-1933, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38659487

RESUMO

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.


Assuntos
Neoplasias Hepáticas , Neoplasias de Células Epitelioides Perivasculares , Humanos , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico , Hepatectomia , Cuidados Pré-Operatórios/métodos , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Fígado/patologia , Fígado/cirurgia , Fígado/diagnóstico por imagem
13.
J Clin Hypertens (Greenwich) ; 26(5): 491-499, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38501750

RESUMO

Postexercise blood pressure (BP) may be a better predictor of cardiovascular risk than office BP, but there is a lack of data supporting this claim. We hypothesized that postexercise BP may be an important prognostic marker. Our aim was to evaluate the association of postexercise BP with major adverse cardiovascular events (MACE) and all-cause mortality. A total of 2581 participants (median age, 46 years; 55.9% women) from the Coronary Artery Risk Development in Young Adults study at year 20 (2005-2006) who underwent a graded exercise treadmill test using a modified Balke graded protocol were included. Postexercise BP was measured at baseline. Cox models were used to estimate the associations of postexercise BP with MACE and all-cause mortality. Participants were followed up until December 31, 2021. In the entire population, postexercise systolic BP showed no significant association with MACE or all-cause mortality, while postexercise diastolic BP was associated with MACE (hazard ratios [HR], 1.27 [95% CI, 1.06-1.52], per 10 mmHg increase) and all-cause mortality (HR, 1.26 [95% CI, 1.05-1.51], per 10 mmHg increase). In the normal BP group, postexercise systolic BP was not significantly associated with MACE or all-cause mortality, and postexercise diastolic BP was strongly associated with MACE (HR, 1.57 [95% CI, 1.18-2.09], per 10 mmHg increase). In this population-based cohort study, postexercise diastolic BP was significantly associated with the risk of MACE and all-cause mortality. Among individuals with normal BP, postexercise diastolic BP could identify those at a higher risk of cardiovascular events.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares , Teste de Esforço , Exercício Físico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea/fisiologia , Adulto , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Exercício Físico/fisiologia , Teste de Esforço/métodos , Fatores de Risco , Hipertensão/epidemiologia , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Modelos de Riscos Proporcionais , Prognóstico , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Fatores de Risco de Doenças Cardíacas
14.
Neuroscience ; 545: 185-195, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38522660

RESUMO

Post-stroke cognitive impairment is a significant challenge with limited treatment options. Electroacupuncture (EA) has shown promise in improving cognitive function after stroke. Our study explores the underlying mechanism of EA in alleviating cognitive impairment through the inhibition of autophagy. We utilized a rat model of stroke induced by middle cerebral artery occlusion (MCAO) to evaluate the efficacy of EA. Treatment with EA was observed to markedly improve cognitive function and reduce inflammation in MCAO rats, as evidenced by decreased neurological deficit scores, shorter latencies in the water maze test, and diminished infarct volumes. EA also attenuated tissue damage in the hippocampus and lowered the levels of pro-inflammatory cytokines and oxidative stress markers. Although autophagy was upregulated in MCAO rats, EA treatment suppressed this process, indicated by a reduction in autophagosome formation and alteration of autophagy-related protein expression. The protective effects of EA were reversed by the autophagy activator rapamycin. EA treatment elevated the levels of microRNA (miR)-135a-5p expression, and suppression of this elevation attenuated the remedial efficacy of EA in addressing cognitive impairment and inflammation. MiR-135a-5p targeted mammalian target of rapamycin (mTOR)/NOD-like receptor protein 3 (NLRP3) signaling to repress autophagy. EA treatment inhibits autophagy and alleviates cognitive impairment in post-stroke rats. It exerts its beneficial effects by upregulating miR-135a-5p and targeting the mTOR/NLRP3 axis.


Assuntos
Autofagia , Disfunção Cognitiva , Eletroacupuntura , MicroRNAs , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Acidente Vascular Cerebral , Serina-Treonina Quinases TOR , Animais , Eletroacupuntura/métodos , MicroRNAs/metabolismo , Autofagia/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Masculino , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Ratos , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/metabolismo , Transdução de Sinais/fisiologia , Hipocampo/metabolismo , Modelos Animais de Doenças
15.
Heliyon ; 10(6): e28066, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524612

RESUMO

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

16.
Nat Commun ; 15(1): 2484, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509096

RESUMO

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.


Assuntos
Carcinoma de Células Escamosas , Interferon gama , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Imunidade , Interferon gama/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
17.
Mol Biol Rep ; 51(1): 386, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441676

RESUMO

BACKGROUND: There was significant difference in muscle development between fat-type and lean-type pig breeds. METHODS AND RESULTS: In current study, transcriptome analysis and bioinformatics analysis were used to compare the difference in longissimus dorsi (LD) muscle at three time-points (38 days post coitus (dpc), 58 dpc, and 78 dpc ) between Huainan (HN) and Large white (LW) pig breeds. A total of 24500 transcripts were obtained in 18 samples, and 2319, 2799, and 3713 differently expressed genes (DEGs) were identified between these two breeds at 38 dpc, 58 dpc, and 78 dpc, respectively. And the number and foldchange of DEGs were increased, the alternative splice also increased. The cluster analysis of DEGs indicated the embryonic development progress of LD muscle between these two breeds was different. There were 539 shared DEGs between HN and LW at three stages, and the top-shared DEGs were associated with muscle development and lipid deposition, such as KLF4, NR4A1, HSP70, ZBTB16 and so on. CONCLUSIONS: The results showed DEGs between Huainan (HN) and Large white (LW) pig breeds, and contributed to the understanding the muscle development difference between HN and LW, and provided basic materials for improvement of meat quality.


Assuntos
Biologia Computacional , Perfilação da Expressão Gênica , Feminino , Gravidez , Suínos/genética , Animais , Análise por Conglomerados , Desenvolvimento Embrionário , Obesidade , Vitaminas
18.
Commun Biol ; 7(1): 332, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491167

RESUMO

Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we find myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential (ΔΨm) permanently impairs mitochondria-endoplasmic reticulum (ER) contacts and abolish Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restores cytosolic Ca2+ homeostasis, remotivates myogenic spontaneous vasomotion, achieves optimal reperfusion, and ameliorates neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow.


Assuntos
Isquemia , Músculo Liso Vascular , Animais , Camundongos , Arteríolas , Miócitos de Músculo Liso
19.
Chin J Dent Res ; 27(1): 17-28, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546516

RESUMO

The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II). These three disorders may have similar molecular mechanisms involved in bridging the DSPP mutations and the resulting abnormal dentine mineralisation. The DSPP encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) are positive regulators of dentine formation and perform a function during dentinogenesis. The present review focused on the recent findings and viewpoints regarding the relationship between DSPP and dentinogenesis as well as mineralisation from multiple perspectives, involving studies relating to spatial structure and tissue localisation of DSPP, DSP and DPP, the biochemical characteristics and biological function of these molecules, and the causative role of the proteins in phenotypes of the knockout mouse model and in hereditary dentine defects.


Assuntos
Calcinose , Dentinogênese Imperfeita , Fosfoproteínas , Sialoglicoproteínas , Animais , Camundongos , Calcificação Fisiológica , Dentina , Dentinogênese Imperfeita/genética , Modelos Animais de Doenças , Camundongos Knockout , Humanos , Sialoglicoproteínas/genética , Fosfoproteínas/genética
20.
JMIR Public Health Surveill ; 10: e55327, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483459

RESUMO

BACKGROUND: Asthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. OBJECTIVE: This study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged <20 years by leveraging the latest data from the Global Burden of Disease Study 2019. Findings from this study can help inform priority areas for intervention to alleviate the rising burden of childhood asthma globally. METHODS: The study used data from the Global Burden of Disease Study 2019, concentrating on children aged 0 to 14 years with asthma. We conducted an in-depth analysis of asthma, including its age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs), across diverse demographics, such as region, age, sex, and sociodemographic index, spanning 1990 to 2019. We also projected the future burden of the disease. RESULTS: Overall, in the Western Pacific Region, the age-standardized prevalence rate of asthma among children increased slightly, from 3898.4 cases per 100,000 people in 1990 to 3924 per 100,000 in 2019. The age-standardized incidence rate of asthma also increased slightly, from 979.2 to 994.9 per 100,000. In contrast, the age-standardized death rate of asthma decreased from 0.9 to 0.4 per 100,000 and the age-standardized DALY rate decreased from 234.9 to 189.7 per 100,000. At the country level, Japan experienced a considerable decrease in the age-standardized prevalence rate of asthma among children, from 6669.1 per 100,000 in 1990 to 5071.5 per 100,000 in 2019. Regarding DALYs, Japan exhibited a notable reduction, from 300.6 to 207.6 per 100,000. Malaysia also experienced a DALY rate reduction, from 188.4 to 163.3 per 100,000 between 1990 and 2019. We project that the burden of disease in countries other than Japan and the Philippines will remain relatively stable up to 2045. CONCLUSIONS: The study indicates an increase in the prevalence and incidence of pediatric asthma, coupled with a decrease in mortality and DALYs in the Western Pacific Region between 1990 and 2019. These intricate phenomena appear to result from a combination of lifestyle shifts, environmental influences, and barriers to health care access. The findings highlight that nations such as Japan have achieved notable success in managing asthma. Overall, the study identified areas of improvement in view of persistent disease burden, underscoring the need for comprehensive collaborative efforts to mitigate the impact of pediatric asthma throughout the region.


Assuntos
Asma , Epidemias , Criança , Humanos , Asma/epidemiologia , Efeitos Psicossociais da Doença , Acessibilidade aos Serviços de Saúde , Japão , Lactente , Pré-Escolar , Adolescente
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