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1.
Artigo em Inglês | MEDLINE | ID: mdl-38865075

RESUMO

PURPOSE OF REVIEW: This review assesses the effectiveness and safety of light therapy, particularly green light therapy, as an emerging non-pharmacological treatment for chronic migraine (CM). It aims to highlight alternative or complementary approaches to traditional pharmacological remedies, focusing the need for diverse treatment options. RECENT FINDINGS: Despite sensitivity to light being a defining feature of migraine, light therapy has shown promising signs in providing substantial symptom relief. Studies have provided insights into green light therapy's role in managing CM. These studies consistently demonstrate its efficacy in reducing the frequency, severity, and symptoms of migraines. Additional benefits observed include improvements in sleep quality and reductions in anxiety. Importantly, green light therapy has been associated with minimal side effects, indicating its potential as a suitable option for migraine sufferers. In addition to green light, other forms of light therapy, such as infrared polarized light, low-level laser therapy (LLLT), and intravascular irradiation of blood (ILIB), are also being explored with potential therapeutic effects. Light therapies, especially green light therapy, are recognized as promising, safe, and non-pharmacological interventions for treating CM. They have been shown to be effective in decreasing headache frequency and enhancing the overall quality of life. However, current studies, often limited by small sample sizes, prompt more extensive clinical trials to better understand the full impact of light therapies. The exploration of other light-based treatments, such as LLLT and ILIB, warrants further research to broaden the scope of effective migraine management strategies.

2.
Comput Methods Programs Biomed ; 253: 108251, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38824806

RESUMO

BACKGROUND & OBJECTIVES: Measurement of blood pressure (BP) in ambulatory patients is crucial for at high-risk cardiovascular patients. A non-obtrusive, non-occluding device that continuously measures BP via photoplethysmography will enable long-term ambulatory assessment of BP. The aim of this study is to validate the metasense 2PPG cuffless wearable design for continuous BP estimation without ECG. METHODS: A customized high-speed electronic optical sensor architecture with laterally spaced reflectance pulse oximetry was designed into a simple unobtrusive low-power wearable in the form of a watch. 78 volunteers with a mean age of 32.72 ± 7.4 years (21 to 64), 51% male, 49% female were recruited with ECG-2PPG signals acquired. The fiducial features of the 2PPG morphologies were then attributed to the estimator. A 9-1 K-fold cross-validation was applied in the ML. RESULTS: The correlation for PTT-SBP was 0.971 and for PTT-DBP was 0.954. The mean absolute error was 3.167±1.636 mmHg for SBP and 6.4 ± 3.9 mm Hg for DBP. The ambulatory estimate for SBP and DBP for an individual over 3 days with 8-hour recordings was 0.70-0.81 for SBP and 0.42-0.51 for DBP with a ± 2.65 mmHg for SBP and ±2.02 mmHg for DBP. For SBP, 98% of metasense measurements were within 15 mm Hg and for DBP, 91% of metasense measurements were within 10 mmHg CONCLUSIONS: The metasense device provides continuous, non-invasive BP estimations that are comparable to ambulatory BP meters. The portability and unobtrusiveness of this device, as well as the ability to continuously measure BP could one day enable long-term ambulatory BP measurement for precision cardiovascular therapeutic regimens.


Assuntos
Determinação da Pressão Arterial , Fotopletismografia , Dispositivos Eletrônicos Vestíveis , Humanos , Fotopletismografia/instrumentação , Fotopletismografia/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Determinação da Pressão Arterial/instrumentação , Determinação da Pressão Arterial/métodos , Pressão Sanguínea , Adulto Jovem , Desenho de Equipamento , Reprodutibilidade dos Testes , Eletrocardiografia/instrumentação
3.
Plant Commun ; : 101010, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918950

RESUMO

Genome-wide association study (GWAS) identifies trait-associated loci, but due in part to slow decay of linkage disequilibrium (LD), identifying the causal genes can be a bottleneck. Transcriptome-wide association study (TWAS) addresses this by identifying gene expression-phenotype associations or integrating gene expression quantitative trait loci (eQTLs) with GWAS results. Here, we used self-pollinated soybean (Glycine max [L.] Merr.) as a model to evaluate the application of TWAS in the genetic dissection of traits in plant species with slow LD decay. We generated RNA-Seq data of a soybean diversity panel, and identified the genetic expression regulation of 29,286 genes in soybean. Different TWAS solutions were less affected by LD and robust with source of expression that identified known genes related to traits from different development stages and tissues. A novel gene named pod color L2 was identified via TWAS and functionally validated by genome editing. By introducing the new exon proportion feature, we significantly improved the detection of expression variations resulting from structural variations and alternative splicing. As a result, the genes identified by our TWAS approach exhibited a diverse range of causal variations, including SNP, insertion/deletion, gene fusion, copy number variation, and alternative splicing. Using our TWAS approach, we identified genes associated with flowering time, including both previously known genes and novel genes that had not previously linked to this trait before, providing complementary insights with GWAS. In summary, this study supports the application of TWAS for candidate gene identification in species with low rates of LD decay.

4.
Hum Vaccin Immunother ; 20(1): 2362449, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38925146

RESUMO

There is limited literature on current human papillomavirus (HPV) vaccination in the Asia-Pacific region. This integrative literature review was conducted to describe HPV vaccination programs in Hong Kong, Indonesia, Japan, South Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Program descriptions, recommendations, f unding, and coverage data were extracted. Twenty-five citations were included. As of 2022, eight of the 10 areas of interest include HPV in their national immunization program (NIP) for school-aged girls; full implementation in Indonesia is expected in 2023 whereas Vietnam's NIP does not include HPV. Singapore also includes HPV vaccination for women (18-26 years). None of the HPV vaccination programs include males. In most areas (n = 7), programs include only one vaccine option. While female HPV NIPs are present in the Asia-Pacific region, opportunities remain to strengthen NIPs in broader populations (e.g., males, catch-up cohorts) to expand public health impact and provide gender equity in HPV vaccination.


Assuntos
Programas de Imunização , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinação , Humanos , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Feminino , Masculino , Adolescente , Ásia , Vacinação/estatística & dados numéricos , Adulto Jovem , Adulto , Cobertura Vacinal/estatística & dados numéricos , Criança , Papillomavirus Humano
5.
Pharmacol Res ; 206: 107279, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942340

RESUMO

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

6.
PLoS One ; 19(5): e0300787, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753634

RESUMO

The Presenilin (Psn) gene is closely related to aging, but it is still unclear the role of Psn genes in skeletal muscle. Here, the Psn-UAS/Mhc-GAL4 system in Drosophila was used to regulate muscle Psn overexpression(MPO) and muscle Psn knockdown(MPK). Drosophila were subjected to endurance exercise from 4 weeks to 5 weeks old. The results showed that MPO and exercise significantly increased climbing speed, climbing endurance, lifespan, muscle SOD activity, Psn expression, Sirt1 expression, PGC-1α expression, and armadillo (arm) expression in aged Drosophila, and they significantly decreased muscle malondialdehyde levels. Interestingly, when the Psn gene is knockdown by 0.78 times, the PGC-1α expression and arm expression were also down-regulated, but the exercise capacity and lifespan were increased. Furthermore, exercise combined with MPO further improved the exercise capacity and lifespan. MPK combined with exercise further improves the exercise capacity and lifespan. Thus, current results confirmed that the muscle Psn gene was a vital gene that contributed to the healthy aging of skeletal muscle since whether it was overexpressed or knocked down, the aging progress of skeletal muscle structure and function was slowed down by regulating the activity homeostasis of Sirt1/PGC-1α pathway and Psn/arm pathway. Exercise enhanced the function of the Psn gene to delay skeletal muscle aging by up regulating the activity of the Sirt1/PGC-1α pathway and Psn/arm pathway.


Assuntos
Longevidade , Músculo Esquelético , Condicionamento Físico Animal , Transdução de Sinais , Animais , Envelhecimento/fisiologia , Envelhecimento/genética , Envelhecimento/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Envelhecimento Saudável/genética , Envelhecimento Saudável/metabolismo , Envelhecimento Saudável/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Sirtuína 1/metabolismo , Sirtuína 1/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
7.
J Pediatr Endocrinol Metab ; 37(6): 505-515, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38700489

RESUMO

OBJECTIVES: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1 , Exercício Físico , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Criança , Insulina/administração & dosagem , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Adolescente , Glicemia/análise , Hipoglicemia/prevenção & controle , Prognóstico
8.
Int J Biol Macromol ; 269(Pt 2): 132216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729483

RESUMO

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.


Assuntos
Carvão Vegetal , Lignina , Óleo de Gergelim , Lignina/química , Carvão Vegetal/química , Adsorção , Óleo de Gergelim/química , Benzo(a)pireno/química , Cinética
9.
BMC Med Educ ; 24(1): 542, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750452

RESUMO

BACKGROUND: Simulation is widely utilized in medical education. Exploring the effectiveness of high-fidelity simulation of clinical research within medical education may inform its integration into clinical research training curricula, finally cultivating physician-scientist development. METHODS: Standard teaching scripts for both clinical trial and cross-sectional study simulation were designed. We recruited undergraduates majoring in clinical medicine at 3th grade into a pre-post intervention study. Additionally, a cross-sectional survey randomly selected medical undergraduates at 4th or 5th grade, medical students in master and doctor degree as external controls. Self-assessment scores of knowledge and practice were collected using a 5-point Likert scale. Changes in scores were tested by Wilcoxon signed-rank test and group comparisons were conducted by Dunn's tests with multiple corrections. Multivariable quantile regressions were used to explore factors influencing the changes from baseline. RESULTS: Seventy-eight undergraduates involved the clinical trial simulation and reported improvement of 1.60 (95% CI, 1.48, 1.80, P < 0.001) in knowledge and 1.82 (95% CI, 1.64, 2.00, P < 0.001) in practice score. 83 undergraduates involved in the observational study simulation and reported improvement of 0.96 (95% CI, 0.79, 1.18, P < 0.001) in knowledge and 1.00 (95% CI, 0.79, 1.21, P < 0.001) in practice. All post-intervention scores were significantly higher than those of the three external control groups, P < 0.001. Higher agreement on the importance of clinical research were correlated with greater improvements in scores. Undergraduates in pre-post study showed high confidence in doing a future clinical research. CONCLUSION: Our study provides evidence supporting the integration of simulation into clinical research curriculum for medical students. The importance of clinical research can be emphasized during training to enhance learning effect.


Assuntos
Pesquisa Biomédica , Currículo , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Educação de Graduação em Medicina/métodos , Estudos Transversais , Feminino , Masculino , Pesquisa Biomédica/educação , Competência Clínica , Treinamento por Simulação , Avaliação Educacional
10.
Mol Biol Evol ; 41(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38768215

RESUMO

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.


Assuntos
Genoma de Planta , Seleção Genética , Adaptação Fisiológica/genética , Altitude
11.
World J Clin Cases ; 12(13): 2173-2181, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38808336

RESUMO

BACKGROUND: Multidrug-resistant Gram-negative bacteria, exacerbated by excessive use of antimicrobials and immunosuppressants, are a major health threat. AIM: To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia, and to provide theoretical reference for clinical diagnosis and treatment. METHODS: This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022. After bacteriological culture, the patients' airway secretions were collected to confirm the presence of Gram-negative bacilli. The patients were divided into the experimental and control groups according to the medication used. The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous, nebulization, or intravenous combined with nebulization, with a daily dosage of 1.5-3.0 million units. The control group consisted of 26 patients who received standard dosages of other antibiotics (including sulbactam sodium for injection, cefoperazone sodium sulbactam for injection, tigecycline, meropenem, or vaborbactam). RESULTS: Of the 28 patients included in the research group, 26 patients showed improvement, treatment was ineffective for two patients, and one patient died, with the treatment efficacy rate of 92.82%. Of the 26 patients in the control group, 18 patients improved, treatment was ineffective for eight patients, and two patients died, with the treatment efficacy rate of 54.9%; significant difference was observed between the two groups (P < 0.05). The levels of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in both groups were significantly lower after treatment than before treatment (P < 0.05), and the levels of WBC, PCT, and CRP in the research group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, there were no significant changes in aspartate aminotransferase, creatinine, and glomerular filtration rate in both groups, while total bilirubin and alanine aminotransferase decreased after treatment (P < 0.05) with no difference between the groups. In patients with good clinical outcomes, the sequential organ failure assessment (SOFA) score was low when treated with inhaled polymyxin sulfate, and specific antibiotic treatment did not improve the outcome. Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes. CONCLUSION: Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable. Moreover, the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions, providing new ideas for clinical administration.

12.
Small ; : e2401701, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705844

RESUMO

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

13.
Inflammation ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735906

RESUMO

Intervertebral disc degeneration (IVDD) is a common disorder associated with chronic inflammation and cell death. In this study, an IVDD rat model was created through Interleukin-1ß (IL-1ß) injection. The degeneration of intervertebral disc tissues was assessed using magnetic resonance imaging (MRI), followed by hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. RNA sequencing was performed to identify differentially expressed genes (DEGs) between the IVDD model and control rats. The expression levels of DEGs (DEAD-box polypeptide 3 (DDX3), lysine-specific demethylase 5D (KDM5D), interferon-induced gene-1 (IFIT1), ribosomal protein S10 (RPS10), tenomodulin (TNMD), and pentraxin 3 (PTX3)) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The regulatory effect of DDX3 on pyroptosis in IL-1ß-treated nucleus pulpous (NP) cells was assessed after transfection with siRNA of DDX3. A total of 601 DEGs were identified from the IVDD model rat, and were abundant in extracellular matrix (ECM) organization, ECM-receptor interaction, and inflammatory pathways, including the PI3K-Akt, TNF, and AMPK signaling pathways. DDX3, KDM5D, and IFIT1 levels were notably elevated, whereas RPS10, TNMD, and PTX3 levels were decreased in the IL-1ß-induced IVDD rat model. Moreover, silencing DDX3 promoted cell proliferation and abolished IL-1ß-induced cell apoptosis and pyroptosis. This study revealed the role of DDX3 in IVDD pyroptosis, providing potential target for IVDD management.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38738556

RESUMO

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models. METHODS: Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3-related inflammatory factors. Subsequently, the effects of 4-OI on the IRG1-itaconic acid-NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP-1 cells) via in vitro experiments. RESULTS: Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4-OI inhibited the activation of the IRG1-itaconic acid-NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. INTERPRETATION: 4-OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD-derived PBMCs and in a human macrophage model. Thus, 4-OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

15.
Immunol Cell Biol ; 102(5): 365-380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572664

RESUMO

Staphylococcus aureus is a significant bacterial pathogen in both community and hospital settings, and the escalation of antimicrobial-resistant strains is of immense global concern. Vaccination is an inviting long-term strategy to curb staphylococcal disease, but identification of an effective vaccine has proved to be challenging. Three well-characterized, ubiquitous, secreted immune evasion factors from the staphylococcal superantigen-like (SSL) protein family were selected for the development of a vaccine. Wild-type SSL3, 7 and 11, which inhibit signaling through Toll-like receptor 2, cleavage of complement component 5 and neutrophil function, respectively, were successfully combined into a stable, active fusion protein (PolySSL7311). Vaccination of mice with an attenuated form of the PolySSL7311 protein stimulated significantly elevated specific immunoglobulin G and splenocyte proliferation responses to each component relative to adjuvant-only controls. Vaccination with PolySSL7311, but not a mixture of the individual proteins, led to a > 102 reduction in S. aureus tissue burden compared with controls after peritoneal challenge. Comparable antibody responses were elicited after coadministration of the vaccine in either AddaVax (an analog of MF59) or an Alum-based adjuvant; but only AddaVax conferred a significant reduction in bacterial load, aligning with other studies that suggest both cellular and humoral immune responses are necessary for protective immunity to S. aureus. Anti-sera from mice immunized with PolySSL7311, but not individual proteins, partially neutralized the functional activities of SSL7. This study confirms the importance of these SSLs for the survival of S. aureus in vivo and suggests that PolySSL7311 is a promising vaccine candidate.


Assuntos
Proteínas de Bactérias , Infecções Estafilocócicas , Vacinas Antiestafilocócicas , Staphylococcus aureus , Superantígenos , Animais , Staphylococcus aureus/imunologia , Vacinas Antiestafilocócicas/imunologia , Superantígenos/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/prevenção & controle , Camundongos , Proteínas de Bactérias/imunologia , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/sangue , Feminino , Proteínas Recombinantes de Fusão/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Estudos de Viabilidade , Vacinação , Antígenos de Bactérias/imunologia , Camundongos Endogâmicos BALB C , Adjuvantes Imunológicos
16.
Chem Biol Interact ; 395: 111010, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38679114

RESUMO

The incidence and mortality rate of myocardial infarction are increasing per year in China. The polarization of macrophages towards the classically activated macrophages (M1) phenotype is of utmost importance in the progression of inflammatory stress subsequent to myocardial infarction. Poly (ADP-ribose) polymerase 1(PARP1) is the ubiquitous and best characterized member of the PARP family, which has been reported to support macrophage polarization towards the pro-inflammatory phenotype. Yet, the role of PARP1 in myocardial ischemic injury remains to be elucidated. Here, we demonstrated that a myocardial infarction mouse model induced cardiac damage characterized by cardiac dysfunction and increased PARP1 expression in cardiac macrophages. Inhibition of PARP1 by the PJ34 inhibitors could effectively alleviate M1 macrophage polarization, reduce infarction size, decrease inflammation and rescue the cardiac function post-MI in mice. Mechanistically, the suppression of PARP1 increase NLRC5 gene expression, and thus inhibits the NF-κB pathway, thereby decreasing the production of inflammatory cytokines such as IL-1ß and TNF-α. Inhibition of NLRC5 promote infection by effectively abolishing the influence of this mechanism discussed above. Interestingly, inhibition of NLRC5 promotes cardiac macrophage polarization toward an M1 phenotype but without having major effects on M2 macrophages. Our results demonstrate that inhibition of PARP1 increased NLRC5 gene expression, thereby suppressing M1 polarization, improving cardiac function, decreasing infarct area and attenuating inflammatory injury. The aforementioned findings provide new insights into the proinflammatory mechanisms that drive macrophage polarization following myocardial infarction, thereby introducing novel potential targets for future therapeutic interventions in individuals affected by myocardial infarction.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Macrófagos , Infarto do Miocárdio , NF-kappa B , Poli(ADP-Ribose) Polimerase-1 , Animais , Masculino , Camundongos , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , NF-kappa B/metabolismo , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Regulação para Cima/efeitos dos fármacos
17.
J Integr Med ; 22(3): 279-285, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38688809

RESUMO

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.


Assuntos
Injúria Renal Aguda , Medicamentos de Ervas Chinesas , Taxa de Filtração Glomerular , Humanos , Masculino , Injúria Renal Aguda/tratamento farmacológico , Feminino , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Pessoa de Meia-Idade , Taxa de Filtração Glomerular/efeitos dos fármacos , Idoso , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto , Creatinina/sangue
18.
Curr Opin Neurobiol ; 86: 102874, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582021

RESUMO

The metabolic signals that regulate sleep and the metabolic functions that occur during sleep are active areas of research. Prior studies have focused on sugars and nucleotides but new genetic evidence suggests novel functions of lipid and amino acid metabolites in sleep. Additional genetic studies of energetic signaling pathways and the circadian clock transcription factor network have increased our understanding of how sleep responds to changes in the metabolic state. This review focuses on key recent insights from genetic experiments in humans and model organisms to improve our understanding of the interrelationship between metabolism and sleep.


Assuntos
Sono , Humanos , Sono/fisiologia , Sono/genética , Animais , Metabolismo Energético/fisiologia , Metabolismo Energético/genética , Relógios Circadianos/fisiologia , Relógios Circadianos/genética , Ritmo Circadiano/fisiologia , Ritmo Circadiano/genética
19.
Life Sci Alliance ; 7(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599770

RESUMO

Translational regulation by non-coding RNAs is a mechanism commonly used by cells to fine-tune gene expression. A fragment derived from an archaeal valine tRNA (Val-tRF) has been previously identified to bind the small subunit of the ribosome and inhibit translation in Haloferax volcanii Here, we present three cryo-electron microscopy structures of Val-tRF bound to the small subunit of Sulfolobus acidocaldarius ribosomes at resolutions between 4.02 and 4.53 Å. Within these complexes, Val-tRF was observed to bind to conserved RNA-interacting sites, including the ribosomal decoding center. The binding of Val-tRF destabilizes helices h24, h44, and h45 and the anti-Shine-Dalgarno sequence of 16S rRNA. The binding position of this molecule partially overlaps with the translation initiation factor aIF1A and occludes the mRNA P-site codon. Moreover, we found that the binding of Val-tRF is associated with steric hindrance of the H69 base of 23S rRNA in the large ribosome subunit, thereby preventing 70S assembly. Our data exemplify how tRNA-derived fragments bind to ribosomes and provide new insights into the mechanisms underlying translation inhibition by Val-tRFs.


Assuntos
RNA de Transferência , Ribossomos , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/metabolismo , Microscopia Crioeletrônica , Ribossomos/genética , RNA de Transferência/genética , RNA de Transferência/química , RNA de Transferência/metabolismo , Valina/análise , Valina/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-38669479

RESUMO

Healthy sleep is vital for humans to achieve optimal health and longevity. Poor sleep and sleep disorders are strongly associated with increased morbidity and mortality. However, the importance of good sleep continues to be underrecognized. Mechanisms regulating sleep and its functions in humans remain mostly unclear even after decades of dedicated research. Advancements in gene sequencing techniques and computational methodologies have paved the way for various genetic analysis approaches, which have provided some insights into human sleep genetics. This review summarizes our current knowledge of the genetic basis underlying human sleep traits and sleep disorders. We also highlight the use of animal models to validate genetic findings from human sleep studies and discuss potential molecular mechanisms and signaling pathways involved in the regulation of human sleep.

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