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1.
Taiwan J Obstet Gynecol ; 63(4): 506-512, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39004477

RESUMO

OBJECTIVE: Identification of heavy menstrual bleeding (HMB) cases in primary care settings is often done by using pictorial blood assessment charts (PBAC). The study aims to highlight the challenge of assessing blood loss, to develop a standardized method to efficiently customize a patient-reported pictorial chart, to validate the tool produced with our proposed method, and to demonstrate the feasibility of using PBACs in settings where resources are scarce. MATERIALS AND METHODS: Using blood samples and feedback from 21 women aged 30-51 years, we followed guidelines suggested in the literature, developed a method to produce PBACs for regular, long and night sizes, and had 9 participants testuse them. Linear regression analysis was performed to determine the correlation between participants' scores and menstrual blood weight. RESULTS: The study demonstrated the feasibility of customizing product-sensitive and size-specific pictorial charts by adopting essential steps including collecting menstrual blood with menstrual cups, employing fluid application techniques, and using sanitary pads as icons for easy identification. Linear regression analyses of score versus blood weight showed that the recorded blood weight was around 95% of the scored values (R2 = 0.9428, 0.947, and 0.9508, respectively; p < 0.001). CONCLUSION: Valid patient-reported PBACs created by the proposed method provides an innovative women's healthcare solution to assist HMB identification and reduce health expenditure by preventing risks for HMB related complications in varying economic and technological contexts. Women's participation in tracking menstrual abnormalities may improve health literacy.


Assuntos
Menorragia , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Estudos de Viabilidade , Menstruação , Modelos Lineares
2.
Int J Antimicrob Agents ; : 107262, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945178

RESUMO

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates. RESULTS: In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

3.
Health Aff Sch ; 2(6): qxae066, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855056

RESUMO

Despite a consensus that quality of care is critically deficient in low-income countries, few nationally representative studies provide comparable measures of quality of care across countries. To address this gap, we used nationally representative data from in-person administrations of clinical vignettes to measure the competence of 16 127 health care providers across 11 sub-Saharan African countries. Rather than large variations across countries, we found that 81% of the variation in competence is within countries and the characteristics of health care providers do not explain most of this variation. Professional qualifications-including cadre and education-are only weakly associated with competence: across our sample, one-third of nurses are more competent than the average doctor in the same country and one-quarter of doctors are less competent than the average nurse. Finally, while younger cohorts do tend to be more competent, perhaps reflecting improvements in medical education, it would take 25 decades of turnover to improve care by 10 percentage points, on average, if we were to rely on such improvements alone. These patterns necessitate a fundamentally different approach to health care human resource management, calling into question typical staffing policies based on qualifications and seniority rather than directly measured quality.

4.
Gerontology ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857585

RESUMO

INTRODUCTION: Existing evidence evaluating the impact of change in body mass index (BMI) on the risk of all-cause and cardiovascular disease (CVD)-related mortality in older people is limited and inconsistent. This population-based cohort study evaluated the association of changes in BMI over time with all-cause and CVD-related mortality in older adults. METHODS: We recruited 55,351 adults aged over 65 years between 2006-2011 from Taipei Elderly Health Examination Program who underwent repeated annual health examinations at 3.2 year-intervals and were followed-up for mortality over 5.5 years. Cox proportional hazard and Fine-Gray sub-distribution hazard models with death from non-CVD causes as the competing risk were used to determine the impact of changes in BMI status on the risk of all-cause or CVD-related mortality, respectively. RESULTS: Over 227,967 person-years of follow-up, 4,054 participants died, including 940 (23.2%) CVD-related deaths. After adjusting for other covariates, >10% decrease of BMI was significantly associated with a higher risk of all-cause (adjusted hazard ratio [AHR]= 1.93; 95% confidence interval [CI]: 1.74-2.13) and CVD-related mortality (AHR= 1.96; 95%CI: 1.60-2.40), compared with stable BMI. Sensitivity analysis showed that a >10% decrease in BMI was significantly associated with a high risk of all-cause and CVD-related mortality in participants with normal weight, underweight, overweight, or obesity at baseline. DISCUSSION/CONCLUSION: Older adults with >10% decrease in BMI are at high risk of all-cause and CVD-related mortality. Our findings suggest that older individuals experiencing a substantial reduction in BMI should undergo a thorough evaluation to minimize the risks associated with mortality.

5.
J Formos Med Assoc ; 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38740535

RESUMO

BACKGROUND/PURPOSE: Vaccination is the most important preventive measure to protect people from coronavirus disease 2019 (COVID-19). Governments worldwide have prioritized their vaccination policy against COVID-19. However, there is a lack of relevant research on Taiwanese attitudes and considerations toward COVID-19 vaccination. This study aimed to investigate the cognition, preventive behaviors, and attitudes toward COVID-19 vaccines that influence people's willingness to get vaccinated in Taiwan. METHODS: From October 1 to 31, 2021, a computer-assisted telephone interview system was used to randomly select Taiwanese people to investigate their COVID-19 preventive behaviors, knowledge, and willingness to be vaccinated. RESULTS: We included 2000 participants of whom 96.45% showed vaccination willingness. The overall mean age and knowledge scores were 48.6 years and 5.78, respectively. All of the participants chose to wear masks, and 80% chose to be vaccinated to prevent COVID-19. Compared with the non-willing vaccination participants, those with younger ages, higher incomes, and higher knowledge scores regarding masks and vaccination were more likely to be vaccinated. Furthermore, apprehensions about vaccine side effects and negative news about COVID-19 vaccines were the major reasons for vaccination hesitancy. CONCLUSION: To improve people's willingness to get vaccinated, the government should strive to deliver correct knowledge and refute inappropriate negative information about COVID-19 vaccination. Moreover, recommendation by physicians was an important factor for older individuals to decide on receiving the COVID-19 vaccine, and policies could be implemented from this aspect.

6.
Surg Endosc ; 38(7): 3520-3530, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38816620

RESUMO

BACKGROUND: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND. METHODS: We performed a systemic literature review of PubMed, Embase, and Web of Science databases. Perioperative parameters were extracted and pooled for analysis. This meta-analysis provided an analysis of heterogeneity and prediction intervals. RESULTS: Five studies were included: 567 patients divided between 266 robotic and 301 LPLND. Overall operation time was longer in the robotic group than laparoscopic group (difference in means = 67.11, 95% CI [30.80, 103.42], p < 0.001) but the difference in the pelvic lateral lymph dissection time was not statistically significant (difference in means = - 1.212, 95% CI [ - 11.594, 9.171], p = 0.819). There were fewer overall complications in the robotic than in the laparoscopic group (OR = 1.589, 95% CI [1.009, 2.503], p = 0.046), especially with respect to urinary retention (OR = 2.23, 95% CI [1.277, 3.894], p = 0.005). More pelvic lateral lymph nodes were harvested by robotic surgery than by laparoscopy (differences in means = - 1.992, 95% CI [ - 2.421, 1.563], p < 0.001). CONCLUSIONS: In this meta-analysis, robotic pelvic lateral lymph node dissection was associated with more pelvic lateral lymph nodes harvested and lower overall complications, especially urinary retention when compared to LPLND. Further studies are needed to reinforce these findings.


Assuntos
Laparoscopia , Excisão de Linfonodo , Pelve , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Excisão de Linfonodo/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
7.
Adv Mater ; : e2400658, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782446

RESUMO

Ion migration is a major factor affecting the long term stability of perovskite light-emitting diodes (LEDs), which limits their commercialization potential. The accumulation of excess halide ions at the grain boundaries of perovskite films is a primary cause of ion migration in these devices. Here, it is demonstrated that the channels of ion migrations can be effectively impeded by elevating the hole transport layer between the perovskite grain boundaries, resulting in highly stable perovskite LEDs. The unique structure is achieved by reducing the wettability of the perovskites, which prevents infiltration of the upper hole-transporting layer into the spaces of perovskite grain boundaries. Consequently, nanosized gaps are formed between the excess halide ions and the hole transport layer, effectively suppressing ion migration. With this structure, perovskite LEDs with operational half-lifetimes of 256 and 1774 h under current densities of 100 and 20 mA cm-2 respectively are achieved. These lifetimes surpass those of organic LEDs at high brightness. It is further found that this approach can be extended to various perovskite LEDs, showing great promise for promoting perovskite LEDs toward commercial applications.

8.
Mol Cell ; 84(9): 1711-1726.e11, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569554

RESUMO

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.


Assuntos
Adenosina , Adenosina/análogos & derivados , RNA Helicases DEAD-box , Exorribonucleases , Instabilidade Genômica , Metiltransferases , Estruturas R-Loop , RNA Polimerase II , Terminação da Transcrição Genética , Humanos , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Adenosina/metabolismo , Adenosina/genética , Exorribonucleases/metabolismo , Exorribonucleases/genética , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Células HEK293 , Cromatina/metabolismo , Cromatina/genética , Dano ao DNA , Células HeLa , RNA/metabolismo , RNA/genética , Transcrição Gênica , Metilação de RNA
9.
Diagn Microbiol Infect Dis ; 109(2): 116264, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493510

RESUMO

This study was performed to investigate the frequency of angiogenic T cells (CD4+ Tang cells) among CD4+ T cells in patients with hepatitis B-induced liver cirrhosis (HBV-LC) and to evaluate the predictive role of these cells in the clinical outcome. In total, 185 patients with HBV-LC were recruited to measure the frequency of CD4+ Tang cells and chemokine levels using flow cytometry. RESULTS: There was 11.4% of death after 3-momth follow-up. The AUC for the ability of the frequency of CD4+ Tang cell to predict death was 0.724 (higher than those for the MELD score, FIB-4 score, and Child-Pugh classification). Cox regression analysis revealed an association between the frequency of CD4+ Tang cells and a 3-month survival chance. CONCLUSIONS: The lower frequency of CD4+ T ang cells was correlated with the severity of HBV-LC and may serve as a prognostic predictor.


Assuntos
Linfócitos T CD4-Positivos , Cirrose Hepática , Humanos , Masculino , Feminino , Cirrose Hepática/virologia , Prognóstico , Pessoa de Meia-Idade , Linfócitos T CD4-Positivos/imunologia , Adulto , Hepatite B/complicações , Citometria de Fluxo , Quimiocinas/sangue , Hepatite B Crônica/complicações , Idoso
10.
World J Stem Cells ; 16(2): 137-150, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38455095

RESUMO

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.

11.
Sci Rep ; 14(1): 6161, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485750

RESUMO

The present study aimed to elucidate the prognostic mutation signature (PMS) associated with long-term survival in a diffuse large B-cell lymphoma (DLBCL) cohort. All data including derivation and validation cohorts were retrospectively retrieved from The Cancer Genome Atlas (TCGA) database and whole-exome sequencing (WES) data. The Lasso Cox regression analysis was used to construct the PMS based on WES data, and the PMS was determined using the area under the receiver operating curve (AUC). The predictive performance of eligible PMS was analyzed by time-dependent receiver operating curve (ROC) analyses. After the initial evaluation, a PMS composed of 94 PFS-related genes was constructed. Notably, this constructed PMS accurately predicted the 12-, 36-, and 60-month PFS, with AUC values of 0.982, 0.983, and 0.987, respectively. A higher level of PMS was closely linked to a significantly worse PFS, regardless of the molecular subtype. Further evaluation by forest plot revealed incorporation of international prognostic index or tumor mutational burden into PMS increased the prediction capability for PFS. The drug-gene interaction and pathway exploration revealed the PFS-related genes were associated with DNA damage, TP53, apoptosis, and immune cell functions. In conclusion, this study utilizing a high throughput genetic approach demonstrated that the PMS could serve as a prognostic predictor in DLBCL patients. Furthermore, the identification of the key signaling pathways for disease progression also provides information for further investigation to gain more insight into novel drug-resistant mechanisms.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Estudos Retrospectivos , Mutação , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Dano ao DNA
12.
J Microbiol Immunol Infect ; 57(3): 365-374, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503632

RESUMO

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Infecções por Citomegalovirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Taiwan/epidemiologia , Fatores de Risco , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Incidência , Adulto Jovem , Citomegalovirus/isolamento & purificação , Doença Enxerto-Hospedeiro/epidemiologia , Adolescente , Idoso , Transplante Homólogo/efeitos adversos , Criança , Pré-Escolar , Sistema de Registros
13.
Oncol Lett ; 27(5): 206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38516683

RESUMO

Glioblastoma (GBM) is characterized by significant heterogeneity, leading to poor survival outcomes for patients, despite the implementation of comprehensive treatment strategies. The roles of cyclin A2 (CCNA2) and NIMA related kinase 2 (NEK2) have been extensively studied in numerous cancers, but their specific functions in GBM remain to be elucidated. The present study aimed to investigate the potential molecular mechanisms of CCNA2 and NEK2 in GBM. CCNA2 and NEK2 expression and prognosis in glioma were evaluated by bioinformatics methods. In addition, the distribution of CCNA2 and NEK2 expression in GBM subsets was determined using pseudo-time analysis and tricycle position of single-cell sequencing. Gene Expression Omnibus and Kyoto Encyclopedia of Genes and Genome databases were employed and enrichment analyses were conducted to investigate potential signaling pathways in GBM subsets and a nomogram was established to predict 1-, 2- and 3-year overall survival probability in GBM. CCNA2 and NEK2 expression levels were further validated by western blot analysis and immunohistochemical staining in GBM samples. High expression of CCNA2 and NEK2 in glioma indicates poor clinical outcomes. Single-cell sequencing of GBM revealed that these genes were upregulated in a subset of positive neural progenitor cells (P-NPCs), which showed significant proliferation and progression properties and may activate G2M checkpoint pathways. A comprehensive nomogram predicts 1-, 2- and 3-year overall survival probability in GBM by considering P-NPCs, age, chemotherapy and radiotherapy scores. CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle, thus indicating the potential of novel therapy directed to CCNA2 and NEK2 in GBM.

14.
Integr Med Res ; 13(1): 101022, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38434793

RESUMO

This article - Recommendations and Guidelines of Integrative Medicine (IM) for COVID-19 Care - was one of the outcomes from an Asia-Pacific Economic Cooperation (APEC) Project (Integrative Medicine (IM) and COVID -19 Care) during the time between May 2022 and March 2023. With the efforts from care providers, researchers, health policy makers and healthcare administrative leaders among APEC economies, the purpose of this file was to provide comprehensive IM systems for COVID-19 care as recommendations and suggestive guidelines including care methods, tools, procedures, symptom conditions and targets selections, and points need to be considered during care applications. All cited COVID-19 care practices have confirmed their efficacy and usefulness either used alone or combined with conventional medicine. This article provides current useful medical information on IM for COVID-19 care which could benefit APEC economies and world health communities on their healthcare system.

15.
BMC Public Health ; 24(1): 549, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383321

RESUMO

BACKGROUND: The temporality of household income level with overweight/obesity in children has not been extensively studied. Little research has been conducted to determine the impact of household income on the risk of childhood overweight/obesity over time. This population-based cohort study aimed to investigate the impact of household income on the risk of overweight/obesity over time among preschool-aged children in Taiwan. METHODS: From 2009 to 2018, we recruited 1,482 preschool-aged children ( ≦ 7 y of age) from low-income households and selected age- and sex-matched controls from non-low-income households for comparison; All participants were selected from those who consistently participated in the Taipei Child Development Screening Program and were monitored for overweight/obesity using body mass index (BMI) until December 31, 2018. Low-income households were defined as those with an average monthly disposable income < 60% of the minimum standard of living expense in Taiwan. The primary outcome was childhood overweight or obesity in study participants, defined as BMI (kg/m2) ≥ 85th percentile or ≥ 95th percentile, respectively. The generalized estimating equations (GEE) model was used to determine the impact of low-income households on the risk of overweight/obesity in study participants. RESULTS: Over 21,450 person-years of follow-up, 1,782 participants developed overweight /obesity, including 452 (30.5%) and 1,330 (22.4%) children from low- and non-low-income households, respectively. The GEE model showed that the first group had a significantly higher risk of becoming overweight/obese than the other during the follow-up period (adjusted odds ratio [aOR] = 1.44, 95% CI: 1.29-1.60). Moreover, children of foreign mothers had a higher risk of becoming overweight/obese than those of Taiwanese mothers during the follow-up period (aOR = 1.51, 95% CI: 1.24-1.8). The subgroup analysis revealed a significant association between low-income households and an increased risk of overweight/obesity in children aged 2-7 years (P =.01). However, this association was not observed in children aged 0-1 years (P >.999). CONCLUSIONS: During the follow-up period, there was a notable correlation between low-income households and an increased risk of preschool-aged children developing overweight or obesity. Implementing health promotion initiatives aimed at reducing overweight and obesity in this demographic is crucial.


Assuntos
Sobrepeso , Obesidade Infantil , Criança , Feminino , Pré-Escolar , Humanos , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Estudos de Coortes , Índice de Massa Corporal , Mães , Renda
17.
Prostate ; 84(6): 605-619, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38375594

RESUMO

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti-CRPC strategy. METHODS: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay and anchorage-dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell-cycle progression. Cell-based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis. RESULTS: A total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC50, 3.5 nM in enzyme assay; IC50, 1.0 µM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC50, 5.4 µM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α-tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl-2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin-induced cell death through impairment of cisplatin-evoked DNA damage response and DNA repair in both ATR-Chk1 and ATM-Chk2 pathways. CONCLUSION: The data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin-induced cell apoptosis through impeding DNA damage repair pathways.


Assuntos
Cisplatino , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Cisplatino/farmacologia , Neoplasias de Próstata Resistentes à Castração/patologia , Tubulina (Proteína)/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Microtúbulos/metabolismo , Microtúbulos/patologia , Desacetilase 6 de Histona/metabolismo
18.
Heliyon ; 10(1): e23686, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38259960

RESUMO

Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.

19.
Nat Commun ; 15(1): 670, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253630

RESUMO

The endeavor to enhance utility of organic molecular cages involves the evolution of them into higher-level chiral superstructures with self-similar, presenting a meaningful yet challenging. In this work, 2D tri-bladed propeller-shaped triphenylbenzene serves as building blocks to synthesize a racemic 3D tri-bladed propeller-shaped helical molecular cage. This cage, in turn, acts as a building block for a pair of higher-level 3D tri-bladed chiral helical molecular cages, featuring multilayer sandwich structures and displaying elegant characteristics with self-similarity in discrete superstructures at different levels. The evolutionary procession of higher-level cages reveals intramolecular self-shielding effects and exclusive chiral narcissistic self-sorting behaviors. Enantiomers higher-level cages can be interconverted by introducing an excess of corresponding chiral cyclohexanediamine. In the solid state, higher-level cages self-assemble into supramolecular architectures of L-helical or D-helical nanofibers, achieving the scale transformation of chiral characteristics from chiral atoms to microscopic and then to mesoscopic levels.

20.
Int J Rheum Dis ; 27(1): e14986, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38014453

RESUMO

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.


Assuntos
Gota , Hiperuricemia , Adulto , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/tratamento farmacológico , Ácido Úrico , Medicina Tradicional Chinesa , Gota/diagnóstico , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Resultado do Tratamento
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