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1.
Lasers Med Sci ; 39(1): 170, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958779

RESUMO

PURPOSE: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. METHODS: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. RESULTS: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. CONCLUSION: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.


Assuntos
Automonitorização da Glicemia , Glicemia , Hemorragia , Lasers , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Automonitorização da Glicemia/instrumentação , Glicemia/análise , Hemorragia/etiologia , Hemoglobinas Glicadas/análise , Coleta de Amostras Sanguíneas/instrumentação , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/efeitos adversos , Diabetes Mellitus/sangue , Trombocitopenia/sangue , Trombocitopenia/etiologia , Capilares , Inibidores da Agregação Plaquetária/uso terapêutico
2.
ACS Omega ; 9(27): 29870-29883, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005763

RESUMO

Idiopathic pulmonary fibrosis (IPF) affects an estimated global population of around 3 million individuals. IPF is a medical condition with an unknown cause characterized by the formation of scar tissue in the lungs, leading to progressive respiratory disease. Currently, there are only two FDA-approved small molecule drugs specifically for the treatment of IPF and this has created a demand for the rapid development of drugs for IPF treatment. Moreover, denovo drug development is time and cost-intensive with less than a 10% success rate. Drug repurposing currently is the most feasible option for rapidly making the drugs to market for a rare and sporadic disease. Normally, the repurposing of drugs begins with a screening of FDA-approved drugs using computational tools, which results in a low hit rate. Here, an integrated machine learning-based drug repurposing strategy is developed to significantly reduce the false positive outcomes by introducing the predock machine-learning-based predictions followed by literature and GSEA-assisted validation and drug pathway prediction. The developed strategy is deployed to 1480 FDA-approved drugs and to drugs currently in a clinical trial for IPF to screen them against "TGFB1", "TGFB2", "PDGFR-a", "SMAD-2/3", "FGF-2", and more proteins resulting in 247 total and 27 potentially repurposable drugs. The literature and GSEA validation suggested that 72 of 247 (29.14%) drugs have been tried for IPF, 13 of 247 (5.2%) drugs have already been used for lung fibrosis, and 20 of 247 (8%) drugs have been tested for other fibrotic conditions such as cystic fibrosis and renal fibrosis. Pathway prediction of the remaining 142 drugs was carried out resulting in 118 distinct pathways. Furthermore, the analysis revealed that 29 of 118 pathways were directly or indirectly involved in IPF and 11 of 29 pathways were directly involved. Moreover, 15 potential drug combinations are suggested for showing a strong synergistic effect in IPF. The drug repurposing strategy reported here will be useful for rapidly developing drugs for treating IPF and other related conditions.

3.
ACS Appl Mater Interfaces ; 16(27): 35463-35473, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38946100

RESUMO

Solution-based processing of van der Waals (vdW) one- (1D) and two-dimensional (2D) materials is an effective strategy to obtain high-quality molecular chains or atomic sheets in a large area with scalability. In this work, quasi-1D vdW Ta2Pt3Se8 was exfoliated via liquid phase exfoliation (LPE) to produce a stably dispersed Ta2Pt3Se8 nanowire solution. In order to screen the optimal exfoliation solvent, nine different solvents were employed with different total surface tensions and polar/dispersive (P/D) component (P/D) ratios. The LPE behavior of Ta2Pt3Se8 was elucidated by matching the P/D ratios between Ta2Pt3Se8 and the applied solvent, resulting in N-methyl-2-pyrrolidone (NMP) as an optimal solvent owing to the well-matched total surface tension and P/D ratio. Subsequently, Ta2Pt3Se8 nanowire thin films are manufactured via vacuum filtration using a Ta2Pt3Se8/NMP dispersion. Then, gas sensing devices are fabricated onto the Ta2Pt3Se8 nanowire thin films, and gas sensing property toward NO2 is evaluated at various thin-film thicknesses. A 50 nm thick Ta2Pt3Se8 thin-film device exhibited a percent response of 25.9% at room temperature and 32.4% at 100 °C, respectively. In addition, the device showed complete recovery within 14.1 min at room temperature and 3.5 min at 100 °C, respectively.

4.
Pulse (Basel) ; 12(1): 40-48, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022561

RESUMO

Introduction: Despite its efficacy, conventional center-based cardiac rehabilitation has several limitations which have led to the emergence of home-based programs and intensive cardiac rehabilitation as alternative methods for overcoming these limitations. Alternative methods for primary prevention have been recommended for similar reasons. Lifestyle modification is considered key to success in both primary and secondary prevention. Therefore, this primary prevention study aimed to investigate the efficiency of intensive lifestyle education and home-based programs involving unstructured exercise in urban forests to prevent coronary artery disease (CAD). The availability of urban forests as preventive exercise environments was also examined. Methods: Patients with risk factors for CAD participated in primary prevention using either FBEG (forest-based exercise group (FBEG, n = 11) or CBEG (center-based exercise group (CBEG, n = 17) for 12 weeks. The FBEG was provided with intensive residential lifestyle education and followed a home program that included performing exercise in an urban forest. The CBEG followed a conventional supervised exercise program at a fitness facility. Changes in body composition, cardiometabolic variables, and functional capacity were tested using a 2-way repeated ANOVA measurement. An independent t-test was used to examine the differences in weekly energy expenditure between the two groups. Results: Significant within-group differences were identified in body composition, cardiometabolic variables, and the 10-yr probability of CAD in both groups. However, the functional capacity, weekly energy expenditure, and attendance rate showed between-group differences, with superiority in the FBEG. Conclusion: Intensive lifestyle education and subsequent home-based programs with unstructured exercise in the forest were as effective as a conventional center-based program, with superiority in terms of the change of some variables. Intensive education on experiencing and habituating a healthy lifestyle seemed to play an important role in improving motivation.

5.
Epidemiol Health ; : e2024062, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39026431

RESUMO

Objectives: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. Methods: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into 3 lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway-adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. Results: The integration of each AEP-AOP component for PHMG and CMIT/MIT led to the development of an AEP-AOP model, wherein disinfectants released from humidifiers in aerosol or gaseous form reached target sites, causing respiratory damage through molecular initiating events and key events. The model demonstrated high reliability and relevance to the pathogenesis of respiratory diseases. Conclusion: The AEP-AOP model developed in this study provides strong evidence that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38894601

RESUMO

OBJECTIVE: The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project (NSHAP) integrated 1940 Census data into its extensive dataset, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly-introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition. METHOD: We analyzed 777 respondents who were children in 1940 (age<17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment. RESULTS: Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function. DISCUSSION: The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed.

7.
J Endocrinol ; 262(3)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38913537

RESUMO

Osteosarcopenia, which refers to the concomitant presence of osteoporosis and sarcopenia, is expected to increase in the rapidly progressive aging world, with serious clinical implications. However, the pathophysiology of osteosarcopenia has not been fully elucidated, and no optimal treatment specific to osteosarcopenia is available. The RANKL-RANK pathway is widely used as a therapeutic target for osteoporosis. Growing evidence supports the importance of the RANKL-RANK pathway, not only in bone, but also in muscle, and the therapeutic potential of targeting this pathway in muscle diseases has been noted. The muscles and bones closely communicate with each other through various secretory factors called myokines and osteokines. This review covers the roles of the RANKL-RANK pathway in the bone and muscle and their reciprocal interactions. Moreover, we will suggest future directions to move forward for the treatment of osteosarcopenia to prepare for an upcoming aging society.


Assuntos
Osso e Ossos , Osteoporose , Ligante RANK , Sarcopenia , Transdução de Sinais , Humanos , Sarcopenia/metabolismo , Ligante RANK/metabolismo , Osso e Ossos/metabolismo , Osteoporose/metabolismo , Transdução de Sinais/fisiologia , Animais , Músculo Esquelético/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Envelhecimento/metabolismo , Envelhecimento/fisiologia
8.
Complement Med Res ; : 1-8, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744266

RESUMO

BACKGROUND: Neck reflex points or Adler-Langer points are commonly used in neural therapy to detect so-called interference fields. Chronic irritations or inflammations in the sinuses, teeth, tonsils, or ears are supposed to induce tension and tenderness of the soft tissues and short muscles in the upper cervical spine. The individual treatment strategy is based on the results of diagnostic Adler-Langer point palpation. This study investigated the inter- and intra-rater reliability and explored treatment effects. METHODS: We performed a randomized controlled trial with 104 inpatients (80.8% female, 51.8 ± 12.74 years) of a German department for internal and integrative medicine. Patients were randomized to individual neural therapy according to the pathological findings (n = 48) or no treatment (n = 56). In each patient, three experienced raters (20-45 years of experience in neural therapy) and two novice raters (medical students) rated Adler-Langer points rigidity on a standardized rating scale ("strong," "weak," "none"). The patients independently evaluated the tenderness on palpation of the eight points using the same scale. Pressure pain thresholds were assessed at the eight Adler-Langer points. All patients were retested after 30 min. The five raters were blinded to treatment allocation and assessments of the other raters. Video recordings were obtained to assess the consistency of the areas tested by the different raters. RESULTS: Agreement between patients and raters (Cohen's kappa = 0.161-0.400) and inter-rater reliability were low (Fleiss kappa = 0.132-0.150). Moreover, the individual agreement (pre-post comparisons in untreated patients) was similarly low even in experienced raters (Cohen's kappa = 0.099-0.173). Video documentation suggests that raters do not place their fingers in the correct segments (percentage of correct position: 42.0-60.6%). Pressure pain thresholds at five of the eight Adler-Langer points showed significant changes after treatment compared to none in the control group. CONCLUSION: Under this artificial experimental setting, this method of Adler-Langer point palpation has not proven to be a reliable diagnostic tool. But it could be shown that, as claimed by the method, the tenderness in five of eight Adler-Langer points decreased after neural therapy.

9.
Dement Neurocogn Disord ; 23(2): 95-106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38720825

RESUMO

Background and Purpose: Ventricle enlargement has been implicated in the pathophysiology of Alzheimer's disease (AD). We studied the relationship between ventricular size and cognitive function in patients with AD. We focused on the effect of the initial ventricle size on the rate of cognitive decline in patients with AD. Methods: A retrospective analysis of probable clinical AD participants with more than 2 magnetic resonance imaging images was performed. To measure ventricle size, we used visual rating scales of (1) Cardiovascular Health Study (CHS) score and (2) conventional linear measurement method. Results: Increased clinical dementia rating (CDR) was correlated with a decreased Mini-Mental Status Examination (MMSE) score, and increased medial temporal lobe atrophy (MTLA) and global ventricle size (p<0.001, p<0.001, p=0.021, respectively). There was a significant correlation between the change in cognitive function in the group (70%-100%ile) with a large initial ventricle size (p=0.021 for ΔCDR, p=0.01 for ΔMMSE), while the median ventricle size (30%-70%ile) showed correlation with other brain structural changes (MTLA, frontal atrophy [FA], and white matter) (p=0.036 for initial MTLA, p=0.034 for FA). Conclusions: In this study, the initial ventricle size may be a potential new imaging biomarker for initial cognitive function and clinical progression in AD. We found a relationship between the initial ventricle size and initial AD-related brain structural biomarkers.

10.
Medicina (Kaunas) ; 60(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38792920

RESUMO

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02-0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86-182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Biomarcadores Tumorais/análise , Idoso , Intervalo Livre de Doença , Quimioterapia Adjuvante/métodos , Prognóstico , Receptor ErbB-2/análise , Análise de Sobrevida
11.
Nat Commun ; 15(1): 4198, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760344

RESUMO

During HIV infection, specific RNA-protein interaction between the Rev response element (RRE) and viral Rev protein is required for nuclear export of intron-containing viral mRNA transcripts. Rev initially binds the high-affinity site in stem-loop II, which promotes oligomerization of additional Rev proteins on RRE. Here, we present the crystal structure of RRE stem-loop II in distinct closed and open conformations. The high-affinity Rev-binding site is located within the three-way junction rather than the predicted stem IIB. The closed and open conformers differ in their non-canonical interactions within the three-way junction, and only the open conformation has the widened major groove conducive to initial Rev interaction. Rev binding assays show that RRE stem-loop II has high- and low-affinity binding sites, each of which binds a Rev dimer. We propose a binding model, wherein Rev-binding sites on RRE are sequentially created through structural rearrangements induced by Rev-RRE interactions.


Assuntos
HIV-1 , Conformação de Ácido Nucleico , RNA Viral , Produtos do Gene rev do Vírus da Imunodeficiência Humana , HIV-1/metabolismo , HIV-1/genética , Sítios de Ligação , Produtos do Gene rev do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene rev do Vírus da Imunodeficiência Humana/química , Produtos do Gene rev do Vírus da Imunodeficiência Humana/genética , RNA Viral/metabolismo , RNA Viral/química , RNA Viral/genética , Cristalografia por Raios X , Ligação Proteica , Modelos Moleculares , Humanos , Elementos de Resposta
12.
Environ Sci Pollut Res Int ; 31(24): 35938-35951, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38743333

RESUMO

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (ß2-MG), N-acetyl-ß-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for ß2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.


Assuntos
Exposição Ocupacional , Humanos , República da Coreia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Teorema de Bayes , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Taxa de Filtração Glomerular , Poluentes Ambientais , Biomarcadores/urina , Medição de Risco
13.
BMC Musculoskelet Disord ; 25(1): 422, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811932

RESUMO

BACKGROUND: In Germany, exercise therapy represents the most commonly prescribed physiotherapy service for non-specific, chronic low back pain (NSCLBP). So far, little is known about current practice patterns of German physiotherapists in delivering this intervention. Thus, the aim of this study was to investigate the appropriateness of exercise therapy delivered to NSCLBP patients in German physiotherapy care and to identify practitioner-related drivers of appropriate exercise delivery. METHODS: We used a vignette-based, exploratory, cross-sectional, online-survey study design (76-items; data collection between May and July 2023). Eligible participants were required to hold a professional degree in physiotherapy and were required to be practicing in Germany. Access links to anonymous online surveys were spread via established German physiotherapy networks, educational platforms, social media, e-mail lists, and snowball sampling. Appropriateness of exercise therapy was calculated by an equally weighted total score (400 points) including scales on shared-decision-making, exercise dose selection, pain knowledge and self-management promotion. "Appropriate exercise delivery" was determined by a relative total score achievement of > 80%. "Partly appropriate exercise delivery" was determined by a relative total score achievement of 50-79%, and "inappropriate exercise delivery" by a score achievement of < 50%. Practitioner-related drivers of exercise appropriateness were calculated by bivariate and multiple linear regression analyses. RESULTS: 11.9% (N = 35) of 298 physiotherapists' exercise delivery was considered "appropriate", 83.3% (N = 245) was "partly appropriate", and 4.8% (N = 14) was "inappropriate". In the final multiple regression model, most robust parameters positively influencing appropriate delivery of exercise therapy were increased scientific literacy (B = 10.540; 95% CI [0.837; 20.243]), increased average clinical assessment time (B = 0.461; 95% CI [0.134; 0.789]), increased self-perceived treatment competence (B = 7.180; 95% CI [3.058; 11.302], and short work experience (B = - 0.520; 95% CI [-0.959; - 0.081]). CONCLUSION: Appropriate exercise delivery in NSCLBP management was achieved by only 11.9% of respondents. However, the vast majority of 95.2% of respondents was classified to deliver exercise therapy partly appropriate. Long work experience seemed to negatively affect appropriate exercise delivery. Positive influences were attributed to scientific literacy, the average clinical assessment time per patient as well as the perceived treatment competence in NSCLBP management. REGISTRATION: Open science framework: https://doi.org/10.17605/OSF.IO/S76MF .


Assuntos
Dor Crônica , Terapia por Exercício , Dor Lombar , Humanos , Dor Lombar/terapia , Estudos Transversais , Alemanha , Terapia por Exercício/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Dor Crônica/terapia , Fisioterapeutas , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
14.
Diabetes Metab J ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38650099

RESUMO

Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were -1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and ß-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion: Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

15.
Biomol Ther (Seoul) ; 32(3): 369-378, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38589021

RESUMO

Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

16.
Exp Mol Med ; 56(4): 1013-1026, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38684915

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it kills cancer cells while sparing normal cells. However, many cancers, including pancreatic ductal adenocarcinoma (PDAC), exhibit intrinsic or acquired resistance to TRAIL, and the molecular mechanisms underlying TRAIL resistance in cancers, particularly in PDAC, remain unclear. In this study, we demonstrated that glutamine (Gln) endows PDAC cells with resistance to TRAIL through KDM4C-mediated epigenetic regulation of cFLIP. Inhibition of glutaminolysis significantly reduced the cFLIP level, leading to TRAIL-mediated formation of death-inducing signaling complexes. Overexpression of cFLIP dramatically rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Alpha-Ketoglutarate (aKG) supplementation significantly reversed the decrease in the cFLIP level induced by glutaminolysis inhibition and rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Knockdown of glutamic-oxaloacetic transaminase 2, which facilitates the conversion of oxaloacetate and glutamate into aspartate and aKG, decreased aKG production and the cFLIP level and activated TRAIL-induced apoptosis. AKG-mediated epigenetic regulation was necessary for maintaining a high level of cFLIP. Glutaminolysis inhibition increased the abundance of H3K9me3 in the cFLIP promoter, indicating that Gln-derived aKG production is important for Jumonji-domain histone demethylase (JHDM)-mediated cFLIP regulation. The JHDM KDM4C regulated cFLIP expression by binding to its promoter, and KDM4C knockdown sensitized PDAC cells to TRAIL-induced apoptosis. The present findings suggest that Gln-derived aKG production is required for KDM4C-mediated epigenetic regulation of cFLIP, which leads to resistance to TRAIL.


Assuntos
Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Glutamina , Histona Desmetilases com o Domínio Jumonji , Neoplasias Pancreáticas , Ligante Indutor de Apoptose Relacionado a TNF , Humanos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Glutamina/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ácidos Cetoglutáricos/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Aspartato Aminotransferase Citoplasmática/metabolismo , Aspartato Aminotransferase Citoplasmática/genética , Animais , Regiões Promotoras Genéticas
17.
Soc Sci Med ; 348: 116768, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537452

RESUMO

The children's mental health landscape is rapidly changing, and youth with mental health conditions (MHCs) are overrepresented in the child welfare system. Mental health is the largest unmet health need in child welfare, so MHCs may affect the likelihood of system reentry. Concerns regarding mental health contribute to calls for expanded supports, yet systems contact can also generate risk of continued child welfare involvement via surveillance. Still, we know little about how expanded supports at the state-level shape child welfare outcomes. Using the Adoption and Foster Care Analysis Reporting System (AFCARS), we examine the association between MHCs and system reentry within 36 months among youth who reunified with their families in 2016 (N = 41,860). We further examine whether this association varies across states and White, Black, and Latinx racial and ethnic groups via two- and three-way interactions. Results from multilevel models show that, net of individual and state-level factors, MHCs are associated with higher odds of reentry. This relationship is stronger for youth in states that expanded Medicaid by 2016 and with higher Medicaid/CHIP child participation rates. The results also show evidence of the moderating role of state-level factors, specifically student-to-school counselor ratio, diverging across racial and ethnic groups. Our results suggest a need for systems of care to better support youth mental health and counteract potential surveillance.


Assuntos
Grupos Raciais , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adoção/psicologia , Proteção da Criança/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Etnicidade/psicologia , Família/psicologia , Cuidados no Lar de Adoção/estatística & dados numéricos , Cuidados no Lar de Adoção/psicologia , Medicaid/estatística & dados numéricos , Transtornos Mentais/etnologia , Transtornos Mentais/terapia , Saúde Mental , Grupos Raciais/estatística & dados numéricos , Grupos Raciais/psicologia , Estados Unidos , Negro ou Afro-Americano , Brancos , Hispânico ou Latino
18.
Genes (Basel) ; 15(3)2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38540439

RESUMO

Corylopsis Siebold & Zucc. (Hamamelidaceae) is widely used as a horticultural plant and comprises approximately 25 species in East Asia. Molecular research is essential to distinguish Corylopsis species, which are morphologically similar. Molecular research has been conducted using a small number of genes but not in Corylopsis. Plastid genomes of Corylopsis species (Corylopsis gotoana, Corylopsis pauciflora, and Corylopsis sinensis) were sequenced using next-generation sequencing techniques. Repeats and nucleotide diversity that could be used as DNA markers were also investigated. A phylogenetic investigation was carried out using 79 protein-coding genes to infer the evolutionary relationships within the genus Corylopsis. By including new plastomes, the overall plastid genome structure of Corylopsis was similar. Simple sequence repeats of 73-106 SSRs were identified in the protein-coding genes of the plastid genomes, and 33-40 long repeat sequences were identified in the plastomes. The Pi value of the rpl33_rps18 region, an intergenic spacer, was the highest. Phylogenetic analysis demonstrated that Corylopsis is a monophyletic group and Loropetalum is closely related to Corylopsis. C. pauciflora, C. gotoana, and C. spicata formed a clade distributed in Japan, whereas C. sinensis, C. glandulifera, and C. velutina formed a clade that was distributed in China.


Assuntos
Genomas de Plastídeos , Hamamelidaceae , Filogenia , Evolução Biológica , Plastídeos/genética , Hamamelidaceae/genética
19.
J Med Food ; 27(3): 231-241, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38502788

RESUMO

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.


Assuntos
Produtos Biológicos , Oryza , Transtornos do Sono-Vigília , Camundongos , Animais , Depressão/tratamento farmacológico , Natação , Ácido gama-Aminobutírico , Modelos Animais de Doenças , Estresse Psicológico/tratamento farmacológico
20.
Diabetes Res Clin Pract ; 210: 111639, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38548106

RESUMO

AIMS: To evaluate the impact of remnant cholesterol (remnant-C) on chronic kidney disease (CKD) incidence in newly-diagnosed type 2 diabetes. METHODS: This retrospective cohort study used Korean National Health Insurance Service data on 212,836 patients with newly-diagnosed type 2 diabetes between 2009 and 2014. We conducted cox regression analysis to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for developing CKD according to remnant-C tertile. RESULTS: During a median follow-up duration of 5.23 years, 6,850 CKD cases developed. In the fully adjusted model, HRs and 95 % CIs for incident CKD increased in the highest tertile of baseline remnant-C compared to the lowest (HR [95 % CI]; 1.234 [1.159-1.314]). This association was more prominent in patients with hypertension or low-income status (P for interaction < 0.05). Increased HRs in the highest tertile of remnant-C was sustained in type 2 diabetes patients within target range of conventional lipid profile such as low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL and < 70 mg/dL (1.165 [1.041-1.304] and 1.308 [1.063-1.609]), high-density lipoprotein cholesterol (HDL-C) (1.243 [1.155-1.338]) and triglyceride (1.168 [1.076-1.268]), respectively. CONCLUSIONS: In newly-diagnosed type 2 diabetes patients, higher remnant-C is independently associated with CKD incidence, even when conventional lipid values are well-controlled.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Incidência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de Risco , Colesterol , Triglicerídeos , HDL-Colesterol
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