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1.
Arch Sex Behav ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020242

RESUMO

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting injectable PrEP among sexually active adult PWUD. The data were collected from adult participants (n = 270) residing in Harris County, TX, who self-reported problematic substance use and who reported oral, anal, or vaginal sex in the six months prior to completing the survey. The survey was distributed and completed online via Qualtrics Panels in March of 2022 and included measures of PrEP and HIV knowledge, PrEP stigma, sexual health self-efficacy, experiences of discrimination, health literacy, and medical mistrust. The majority of participants reported circumstances or behaviors that increased their susceptibility to HIV. Findings indicated that PrEP user stereotypes and PrEP anticipated disapproval by others were associated with interest in using daily oral PrEP and willingness to use long acting injectable PrEP. These results provide insight into reasons for low PrEP uptake among PWUD who live in a high HIV prevalence jurisdiction. Implications for HIV prevention intervention are discussed.

2.
Arch Craniofac Surg ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39020470

RESUMO

Pleomorphic adenoma is a benign tumor that can occur in the salivary glands, most commonly in the parotid gland. While it primarily occurs in the major salivary glands, it can sometimes be found in the minor salivary glands. Within the minor salivary glands, it most often originates in the hard palate and soft palate, and less frequently in the upper lips. Due to its location in the minor salivary glands, most pleomorphic adenoma involve and protrude on the mucosa. A 61-year-old man presented with 1.5 cm exophytic mass on the skin of his upper lip. This mass was exophytic on the skin and did not involve or protrude into the inner lip mucosa. The mass was entirely excised, and a subsequent permanent biopsy diagnosed it as a pleomorphic adenoma. In such situations, it can be challenging to suspect pleomorphic adenoma during a physical examination, leading to potential diagnostic confusion. It might also be mistaken for an inclusion cyst or another type of mass, making it tempting to treat without verifying the pathological results.

3.
J Epidemiol ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38972733

RESUMO

BACKGROUND: Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D. METHODS: Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. RESULTS: Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HRn=5years vs. n=0years 1.11, 95% CI 1.04-1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HRn=5years vs. n=0years 0.81, 95% CI 0.73-0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). CONCLUSIONS: Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

4.
Cell Commun Signal ; 22(1): 365, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020373

RESUMO

BACKGROUND: The homing of human mesenchymal stem cells (hMSCs) is crucial for their therapeutic efficacy and is characterized by the orchestrated regulation of multiple signaling modules. However, the principal upstream regulators that synchronize these signaling pathways and their mechanisms during cellular migration remain largely unexplored. METHODS: miR-29a-3p was exogenously expressed in either wild-type or DiGeorge syndrome critical region 8 (DGCR8) knockdown hMSCs. Multiple pathway components were analyzed using Western blotting, immunohistochemistry, and real-time quantitative PCR. hMSC migration was assessed both in vitro and in vivo through wound healing, Transwell, contraction, and in vivo migration assays. Extensive bioinformatic analyses using gene set enrichment analysis and Ingenuity pathway analysis identified enriched pathways, upstream regulators, and downstream targets. RESULTS: The global depletion of microRNAs (miRNAs) due to DGCR8 gene silencing, a critical component of miRNA biogenesis, significantly impaired hMSC migration. The bioinformatics analysis identified miR-29a-3p as a pivotal upstream regulator. Its overexpression in DGCR8-knockdown hMSCs markedly improved their migration capabilities. Our data demonstrate that miR-29a-3p enhances cell migration by directly inhibiting two key phosphatases: protein tyrosine phosphatase receptor type kappa (PTPRK) and phosphatase and tensin homolog (PTEN). The ectopic expression of miR-29a-3p stabilized the polarization of the Golgi apparatus and actin cytoskeleton during wound healing. It also altered actomyosin contractility and cellular traction forces by changing the distribution and phosphorylation of myosin light chain 2. Additionally, it regulated focal adhesions by modulating the levels of PTPRK and paxillin. In immunocompromised mice, the migration of hMSCs overexpressing miR-29a-3p toward a chemoattractant significantly increased. CONCLUSIONS: Our findings identify miR-29a-3p as a key upstream regulator that governs hMSC migration. Specifically, it was found to modulate principal signaling pathways, including polarization, actin cytoskeleton, contractility, and adhesion, both in vitro and in vivo, thereby reinforcing migration regulatory circuits.


Assuntos
Movimento Celular , Células-Tronco Mesenquimais , MicroRNAs , Transdução de Sinais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Movimento Celular/genética , Transdução de Sinais/genética , Animais , Camundongos
5.
Int J Geriatr Psychiatry ; 39(6): e6106, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39031830

RESUMO

OBJECTIVE: This study examined the relationship between precarious employment (PE) and mental well-being, focusing on age-specific interactions. METHODS: Nationally representative Korean workers (N = 29,961) were surveyed between 2020 and 2021 to collect data on multidimensional PE (categorized as low, moderate, or high) and the WHO-5 well-being index. Workers' ages were classified as young (<35 years), middle-aged (35-54 years), and older (≥55 years). Logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The interaction between PE and age on well-being was examined by including interaction terms in the regression models. RESULTS: The prevalence of poor well-being was 25%, 29%, and 39% for low, moderate, and high precariousness, respectively, whereas it was 26%, 30%, and 39% for young, middle-aged, and older workers, respectively. In the overall sample, the OR (95% CI) of the association between PE and poor well-being was 1.24 (1.17-1.32) for moderate and 1.54 (1.43-1.65) for high precariousness, compared with low precariousness. There was a significant interaction between old age and PE on the odds of poor well-being. Compared with young workers with low PE, middle-aged workers with high PE (OR: 1.85, 95% CI: 1.62-2.10) and older workers with high PE (OR: 2.10, 95% CI: 1.83-2.40) exhibited increased odds of having poor mental well-being. CONCLUSION: PE serves as a social determinant of older workers' psychological well-being. Policy interventions are required to protect older workers' psychological well-being.


Assuntos
Emprego , Saúde Mental , Humanos , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Emprego/estatística & dados numéricos , Emprego/psicologia , Saúde Mental/estatística & dados numéricos , Fatores Etários , Modelos Logísticos , Idoso , Segurança do Emprego
6.
BMC Neurol ; 24(1): 210, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902631

RESUMO

We analyzed the changes in various motor function scores over a four-year period in patients with non-ambulatory spinal muscular atrophy (SMA) during Nusinersen treatment. Patients underwent Hammersmith Infant Neurological Examination (HINE) or Hammersmith Functional Motor Scale Expanded (HFMSE) before treatment, and approximately every 4 months thereafter. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) or Children's Hospital of Philadelphia - Adult Test of Neuromuscular Disorders (CHOP ATEND), Revised Upper Limb Module (RULM), and Motor Function Measure (MFM) were performed based on baseline functional status. Narrative interviews were conducted to explore post-treatment physical improvement regarding activities of daily living (ADLs) and fatigue after ADLs. Based on HFMSE results, 9 patients achieved minimum clinically important differences. Average rates of change (slopes) with corresponding 95% confidence intervals for all assessment tools were in a positive direction. CHOP-INTEND showed the most prominent improvement in children and adolescents followed by HFMSE. Improvements in CHOP-ATEND were most noticeable in adults. Improvements were accompanied by changes in ADLs as observed in the narrative interviews. It is necessary to consider various functional aspects to determine the effectiveness of Nusinersen therapy. The objective assessment of the therapeutic effect of Nusinersen in non-ambulatory SMA requires consideration of functional aspects and the related ADLs.


Assuntos
Atrofia Muscular Espinal , Oligonucleotídeos , Humanos , Masculino , Feminino , Oligonucleotídeos/uso terapêutico , Atrofia Muscular Espinal/tratamento farmacológico , Criança , Pré-Escolar , Adolescente , República da Coreia/epidemiologia , Adulto , Lactente , Resultado do Tratamento , Atividades Cotidianas , Adulto Jovem
7.
Int J Infect Dis ; : 107152, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936655

RESUMO

Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection.

8.
Antibiotics (Basel) ; 13(6)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38927208

RESUMO

Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group.

9.
Chem Rev ; 124(13): 8233-8306, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38885684

RESUMO

Interest in energy-to-X and X-to-energy (where X represents green hydrogen, carbon-based fuels, or ammonia) technologies has expanded the field of electrochemical conversion and storage. Solid oxide electrochemical cells (SOCs) are among the most promising technologies for these processes. Their unmatched conversion efficiencies result from favorable thermodynamics and kinetics at elevated operating temperatures (400-900 °C). These solid-state electrochemical systems exhibit flexibility in reversible operation between fuel cell and electrolysis modes and can efficiently utilize a variety of fuels. However, electrocatalytic materials at SOC electrodes remain nonoptimal for facilitating reversible operation and fuel flexibility. In this Review, we explore the diverse range of electrocatalytic materials utilized in oxygen-ion-conducting SOCs (O-SOCs) and proton-conducting SOCs (H-SOCs). We examine their electrochemical activity as a function of composition and structure across different electrochemical reactions to highlight characteristics that lead to optimal catalytic performance. Catalyst deactivation mechanisms under different operating conditions are discussed to assess the bottlenecks in performance. We conclude by providing guidelines for evaluating the electrochemical performance of electrode catalysts in SOCs and for designing effective catalysts to achieve flexibility in fuel usage and mode of operation.

10.
Viruses ; 16(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38932244

RESUMO

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 µg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.


Assuntos
Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Lactente , Pré-Escolar , Adulto , Criança , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Feminino , Sensibilidade e Especificidade , Antígenos Virais/imunologia , Masculino , Proteínas Virais de Fusão/imunologia , Idoso
11.
Endocr J ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38866492

RESUMO

Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves' orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1ß to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1ß, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1ß-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO.

12.
J Clin Psychiatry ; 85(2)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38836859

RESUMO

Objective: We explored depressive symptom trajectories and their associations with underweight and obesity in Korean women.Methods: This prospective cohort study involved 7,691 women enrolled in the Korean Longitudinal Survey of Women and Families, with a follow-up period spanning from 2014 to 2020. Depressive symptoms were evaluated through the 10-item version of the Center of Epidemiologic Studies Depression Scale. Growth mixture modeling was employed to identify trajectories of depressive symptoms. Multinomial logistic regressions were conducted to investigate the correlation between depression trajectories and the evolving risks of underweight and obesity over the study period.Results: Five distinct trajectory classes were observed ("persistent low symptoms": N = 5,236, 68.1%; "decreasing symptoms": N = 930, 12.1%; "transient high symptoms": N = 421, 5.5%; "increasing symptoms" N = 825, 10.7%; and "persistent high symptoms": N = 279, 3.6%). Those with a low socioeconomic status, comorbidity, and who were divorced or widowed were more likely to follow the persistent high symptom trajectory. Among the 5 trajectories, the risks of underweight and obesity steadily increased in women following the trajectory with persistent high symptoms. For these women, the odds ratio (OR) of underweight increased from 2.27 (95% CI, 1.32-3.92) in 2014 to 3.39 (1.91-6.05) in 2020. They were not associated with obesity in 2014 (OR [95% CI]: 1.38 [0.61-3.11]) but exhibited an elevated risk of obesity in 2020 (3.76 [1.97-7.17]).Conclusion: We observed considerable heterogeneity in the trajectories of depressive symptoms among women, and individuals with persistent high depressive symptoms face an escalating risk of both underweight and obesity.


Assuntos
Depressão , Obesidade , Magreza , Humanos , Feminino , Magreza/epidemiologia , República da Coreia/epidemiologia , Obesidade/epidemiologia , Adulto , Estudos Longitudinais , Depressão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Comorbidade
13.
Yonsei Med J ; 65(7): 397-405, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38910302

RESUMO

PURPOSE: Orbital fibroblasts play key roles in the pathogenesis of Graves' orbitopathy (GO), and previous findings have shown that endoplasmic reticulum (ER) stress and autophagy also contribute to GO. In this study, we investigated the presently unclear roles of inositol-requiring enzyme 1 (IRE1) and related autophagy processes in the pro-fibrotic mechanism of GO. MATERIALS AND METHODS: Orbital adipose/connective tissues were obtained from eight GO patients and six normal individuals during surgery. GO fibroblasts were transfected with IRE1 small-interfering RNA and treated with bafilomycin A1 (Baf-A1) to evaluate the inhibitory effects of ER stress and autophagy, and protein-expression levels were analyzed through western blotting after stimulation with transforming growth factor (TGF)-ß. RESULTS: TGF-ß stimulation upregulated IRE1 in GO orbital fibroblasts, whereas silencing IRE1 suppressed fibrosis and autophagy responses. Similarly, Baf-A1, an inhibitor of late-phase autophagy, decreased the expression of pro-fibrotic proteins. CONCLUSION: IRE1 mediates autophagy and the pro-fibrotic mechanism of GO, which provides a more comprehensive interpretation of GO pathogenesis and suggests potential therapeutic targets.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Endorribonucleases , Fibroblastos , Oftalmopatia de Graves , Proteínas Serina-Treonina Quinases , Humanos , Autofagia/fisiologia , Oftalmopatia de Graves/metabolismo , Oftalmopatia de Graves/patologia , Oftalmopatia de Graves/genética , Fibroblastos/metabolismo , Endorribonucleases/metabolismo , Endorribonucleases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Estresse do Retículo Endoplasmático/genética , Fator de Crescimento Transformador beta/metabolismo , Fibrose , Masculino , RNA Interferente Pequeno/genética , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Feminino , Células Cultivadas , Adulto , Pessoa de Meia-Idade
14.
Am J Gastroenterol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934496

RESUMO

INTRODUCTION: New terminologies of metabolic dysfunction-associated steatotic liver disease (MASLD) have been developed. We assessed hepatocellular carcinoma (HCC) risk across MASLD and/or alcohol intake. METHODS: We included participants aged 40-79 years receiving a national health checkup from 2009 to 2010 in the Republic of Korea, classified as follows: non-MASLD, MASLD, MASLD with increased alcohol intake (MetALD; weekly alcohol 210-420 g for male and 140-350 g for female individuals), and alcohol-associated liver disease (ALD; excessive alcohol intake with weekly alcohol ≥420 g for male or ≥350 g for female individuals). The primary outcome was HCC incidence. HCC risk was estimated using multivariable Cox proportional hazard models. RESULTS: Among 6,412,209 participants, proportions of non-MASLD, MASLD, MetALD, and ALD cases were 59.5%, 32.4%, 4.8%, and 3.4%, respectively. During follow-up (median 13.3 years), 27,118 had newly developed HCC. Compared with non-MASLD, the HCC risk increased from MASLD (adjusted hazard ratio [aHR] 1.66, 95% confidence interval [CI] 1.62-1.71) and MetALD (aHR 2.17, 95% CI 2.08-2.27) to ALD (aHR 2.34, 95% CI 2.24-2.45) in a stepwise manner. Furthermore, the older and non-cirrhosis subgroups were more vulnerable to detrimental effects of MASLD and/or alcohol intake, concerning HCC risk. Among the older, female, and cirrhosis subgroups, MetALD poses similar HCC risks as ALD. DISCUSSION: HCC risk increased from MASLD and MetALD to ALD in a stepwise manner, compared with non-MASLD. For an effective primary prevention of HCC, a comprehensive approach should be required to modify both metabolic dysfunction and alcohol intake habit.

15.
Mol Med Rep ; 30(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38757335

RESUMO

Thrombin, which plays a crucial role in hemostasis, is also implicated in cancer progression. In the present study, the effects of the thrombin­targeting recombinant tyrosine­sulfated madanin­1 on cancer cell behavior and signaling pathways compared with madanin­1 wild­type (WT) were investigated. Recombinant madanin­1 2 sulfation (madanin­1 2S) and madanin­1 WT proteins were generated using Escherichia coli. SKOV3 and MDA­MB­231 cells were treated with purified recombinant proteins with or without thrombin stimulation. Migration and invasion of cells were analyzed by wound healing assay and Transwell assay, respectively. Thrombin markedly increased cell migration and invasion in both SKOV3 and MDA­MB­231 cells, which were significantly suppressed by madanin­1 2S (P<0.05). Madanin­1 2S also significantly suppressed thrombin­induced expression of phosphorylated (p)­Akt and p­extracellular signal­regulated kinase in both cell lines (P<0.05), whereas madanin­1 WT had no effect on the expression levels of these proteins in MDA­MB­231 cells. Furthermore, madanin­1 2S significantly reversed the effects of thrombin on E­cadherin, N­cadherin and vimentin expression in MDA­MB­231 cells (P<0.05), whereas madanin­1 WT did not show any effect. In conclusion, madanin­1 2S suppressed the migration and invasion of cancer cells more effectively than madanin­1 WT. It is hypothesized that inhibiting thrombin via the sulfated form of madanin­1 may be a potential candidate for enhanced cancer therapy; however, further in vivo validation is required.


Assuntos
Movimento Celular , Proteínas Recombinantes , Trombina , Humanos , Caderinas/metabolismo , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Trombina/antagonistas & inibidores , Trombina/farmacologia , Tirosina/metabolismo , Tirosina/farmacologia
16.
Pharmacol Biochem Behav ; 240: 173787, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705285

RESUMO

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies.


Assuntos
Terapia Comportamental , Recompensa , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Terapia Comportamental/métodos , Animais , Comportamento Aditivo/terapia
17.
Int J Mol Sci ; 25(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38732255

RESUMO

This research aimed to explore the healing impacts of Melittin treatment on gastrocnemius muscle wasting caused by immobilization with a cast in rabbits. Twenty-four rabbits were randomly allocated to four groups. The procedures included different injections: 0.2 mL of normal saline to Group 1 (G1-NS); 4 µg/kg of Melittin to Group 2 (G2-4 µg/kg Melittin); 20 µg/kg of Melittin to Group 3 (G3-20 µg/kg Melittin); and 100 µg/kg of Melittin to Group 4 (G4-100 µg/kg Melittin). Ultrasound was used to guide the injections into the rabbits' atrophied calf muscles following two weeks of immobilization via casting. Clinical measurements, including the length of the calf, the compound muscle action potential (CMAP) of the tibial nerve, and the gastrocnemius muscle thickness, were assessed. Additionally, cross-sectional slices of gastrocnemius muscle fibers were examined, and immunohistochemistry and Western blot analyses were performed following two weeks of therapy. The mean regenerative changes, as indicated by clinical parameters, in Group 4 were significantly more pronounced than in the other groups (p < 0.05). Furthermore, the cross-sectional area of the gastrocnemius muscle fibers and immunohistochemical indicators in Group 4 exceeded those in the remaining groups (p < 0.05). Western blot analysis also showed a more significant presence of anti-inflammatory and angiogenic cytokines in Group 4 compared to the others (p < 0.05). Melittin therapy at a higher dosage can more efficiently activate regeneration in atrophied gastrocnemius muscle compared to lower doses of Melittin or normal saline.


Assuntos
Meliteno , Músculo Esquelético , Atrofia Muscular , Regeneração , Animais , Coelhos , Meliteno/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Regeneração/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Masculino
18.
Vaccines (Basel) ; 12(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38793764

RESUMO

This is a cross-sectional serosurveillance study for RSV. Between June and September of 2021, a total of 150 sera were collected from 30 individuals in each age group (<5, 5-18, 19-49, 50-64, and ≥65 years). Seroprevalence was estimated using enzyme-linked immunosorbent assays targeting two stabilized prefusion F (preF; DS-Cav1 and SC-TM) and G proteins. The overall seroprevalence was low in young children and older adults, despite them having a higher risk of severe RSV infection. There was a remarkable difference in age-stratified seroprevalence rates between anti-preF and anti-G protein antibodies. Given the high disease burden and low seroprevalence in both infants and old adults, RSV vaccination would be crucial for pregnant women and people aged over 60 years.

19.
Pract Radiat Oncol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697347

RESUMO

PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.

20.
Front Immunol ; 15: 1385135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756783

RESUMO

Background: The assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy. Methods: This prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination. Results: A total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p<0.001). NAb titers against BQ.1.1, BN.1, and XBB.1 were significantly higher at 9 months post-vaccination than baseline in both groups, whereas NAb against EG.5 was negligible at all time points. The T-cell immune response (median spot forming unit/106 cells) was highly cross-reactive at both baseline (wild-type/BA.5/XBB.1.5, 38.3/52.5/45.0 in SARS-CoV-2-naïve individuals; 51.6/54.9/54.9 in SARS-CoV-2-infected individuals) and 4 weeks post-vaccination, with insignificant boosting post-vaccination. Conclusion: Remarkable cross-reactive neutralization was observed against BQ.1.1, BN.1, and XBB.1 up to 9 months after BA.4/5 bivalent vaccination, but not against EG.5. The T-cell immune response was highly cross-reactive.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Imunidade Humoral , SARS-CoV-2 , Vacinação , Humanos , Masculino , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Feminino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Idoso , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Linfócitos T/imunologia
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