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1.
Sleep Health ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39307579

RESUMO

BACKGROUND: Many individuals use the Internet, including generative artificial intelligence like ChatGPT, for sleep-related information before consulting medical professionals. This study compared responses from sleep disorder specialists and ChatGPT to common sleep queries, with experts and laypersons evaluating the responses' accuracy and clarity. METHODS: We assessed responses from sleep medicine specialists and ChatGPT-4 to 140 sleep-related questions from the Korean Sleep Research Society's website. In a blinded study design, sleep disorder experts and laypersons rated the medical helpfulness, emotional supportiveness, and sentence comprehensibility of the responses on a 1-5 scale. RESULTS: Laypersons rated ChatGPT higher for medical helpfulness (3.79 ± 0.90 vs. 3.44 ± 0.99, p < .001), emotional supportiveness (3.48 ± 0.79 vs. 3.12 ± 0.98, p < .001), and sentence comprehensibility (4.24 ± 0.79 vs. 4.14 ± 0.96, p = .028). Experts also rated ChatGPT higher for emotional supportiveness (3.33 ± 0.62 vs. 3.01 ± 0.67, p < .001) but preferred specialists' responses for sentence comprehensibility (4.15 ± 0.74 vs. 3.94 ± 0.90, p < .001). When it comes to medical helpfulness, the experts rated the specialists' answers slightly higher than the laypersons did (3.70 ± 0.84 vs. 3.63 ± 0.87, p = .109). Experts slightly preferred specialist responses overall (56.0%), while laypersons favored ChatGPT (54.3%; p < .001). ChatGPT's responses were significantly longer (186.76 ± 39.04 vs. 113.16 ± 95.77 words, p < .001). DISCUSSION: Generative artificial intelligence like ChatGPT may help disseminate sleep-related medical information online. Laypersons appear to prefer ChatGPT's detailed, emotionally supportive responses over those from sleep disorder specialists.

3.
Int J Biol Sci ; 20(12): 4731-4749, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309445

RESUMO

Methyltransferase-like (METTL)18 has histidine methyltransferase activity on the RPL3 protein and is involved in ribosome biosynthesis and translation elongations. Several studies have reported that actin polymerization serves as a Src regulator, and HSP90 is involved in forming polymerized actin bundles. To understand the role of METTL18 in breast cancer and to demonstrate the importance of METTL18 in HER-2 negative breast cancer metastasis, we used biochemical, molecular biological, and immunological approaches in vitro (breast tumor cell lines), in vivo (tumor xenograft model), and in samples of human breast tumors. A gene expression comparison of 31 METTL series genes and 22 methyltransferases in breast cancer patients revealed that METTL18 is highly amplified in human HER2-negative breast cancer. In addition, elevated levels of METTL18 expression in patients with HER2-negative breast cancer are associated with poor prognosis. Loss of METTL18 significantly reduced the metastatic responses of breast tumor cells in vitro and in vivo. Mechanistically, METTL18 indirectly regulates the phosphorylation of the proto-oncogene tyrosine-protein kinase Src and its downstream molecules in MDA-MB-231 cells via METTL18-mediated RPL3 methylation, which is also involved in determining HSP90 integrity and protein levels. In confocal microscopy and F/G-actin assays, METTL18 was found to induce actin polymerization via HSP90. Molecular events involving METTL18, RPL3, HSP90, and actin polymerization yielded Src phosphorylated at both tyrosine 419 and tyrosine 530 with kinase activity and oncogenic functions. Therefore, it is suggested that the METTL18-HSP90-Actin-Src regulatory axis plays critical oncogenic roles in the metastatic responses of HER2-negative breast cancer and could be a promising therapeutic target.


Assuntos
Neoplasias da Mama , Metiltransferases , Proto-Oncogene Mas , Receptor ErbB-2 , Quinases da Família src , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Linhagem Celular Tumoral , Animais , Metiltransferases/metabolismo , Metiltransferases/genética , Quinases da Família src/metabolismo , Camundongos , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Camundongos Nus , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética , Fosforilação
4.
JMIR Form Res ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39311496

RESUMO

BACKGROUND: Sleep deprivation in adolescents is a common but serious issue in public health. Adolescents often have a progressive circadian delay and suffer from insufficient sleep during weekdays due to the school schedule. Temporal patterns in internet search activity data can provide relevant information for understanding the characteristic sleep problems of the adolescent population. Here, we investigated the seasonal and weekly pattern of internet search activity on 'insomnia' distinctively observed in adolescents. OBJECTIVE: We aimed to reveal whether adolescents exhibit distinct temporal patterns in internet search activity of 'insomnia' compared to adults. We hypothesized that adolescents exhibit larger variations in the internet search volume of 'insomnia,' particularly in association with the school schedule (e.g., academic vacations and weekends). METHODS: We extracted the daily search volume of 'insomnia' in Korean adolescents (13~18 years old), adults (19 ~ 59 years old), and young adults (19~24 years old) during the year 2016~2019 using NAVER DataLab. NAVER is the most popular search engine in Korea (market share of 72.43%), and NAVER DataLab can provide the daily search volume in various age groups. The daily search volume data of each group was normalized with the annual median of each group. The time series of the search volume was decomposed into the slow fluctuation (over a year) and the fast fluctuation (within a week) using the Fast Fourier Transform. Then, we compared the normalized search volume across months in a year (slow fluctuation) and days in a week (fast fluctuation). RESULTS: In the annual trend, two-way ANOVA revealed a significant (group) x (month) interaction (p < 0.001). The adolescents exhibited much greater seasonal variations across a year than the adult population (coefficient of variation: 0.483 for adolescents vs. 0.131 for adults). The search volume of 'insomnia' in adolescents was notably higher in January, February, and August, which are academic vacation periods in Korea (p < .001). In the weekly pattern, two-way ANOVA revealed a significant (group) x (day) interaction (p < 0.001). The adolescents showed considerably increased search volume on Sunday and Monday (p < .001) compared to the adults. In contrast, the young adults (19~24 years old) demonstrated seasonal and weekly patterns similar to the adults. CONCLUSIONS: Adolescents demonstrated distinctive seasonal and weekly patterns in internet searches on 'insomnia' (i.e., increased search in vacation months and weekend/weekday transition), which are closely associated with the school schedule. Adolescents' sleep concerns might be potentially affected by the disrupted daily routine and the delayed sleep phase during vacations and weekends. As we demonstrated, comparing various age groups in infodemiology and infoveillance data might be helpful in identifying distinctive features in vulnerable age groups.

5.
J Invest Dermatol ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39241981

RESUMO

Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light-induced melanogenesis, as well as its signaling pathway. Operating downstream target of OPN3 in blue light-induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx. [Ca2+] induced activation of CaMKII and MAPK. It also downregulated clusterin expression, leading to the nuclear translocation of PAX3, ultimately affecting melanin synthesis. In addition, blue light interfered with autophagy-mediated regulation of melanosomes by decreasing not only the interaction between CLU and LC3B but the expression of ATF family. These findings demonstrate that the pigmenting effects of blue light are mediated by CaMKII- and MAPK-mediated signaling, as well as CLU-dependent inhibition of autophagy through OPN3-TRPV1-calcium influx, suggesting a new signaling pathway by which blue light regulates melanocyte biology. Furthermore, these results suggest that TRPV1 and CLU could be potential therapeutic targets for blue light-induced pigmentation due to prolonged exposure to blue light.

6.
Nat Genet ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227743

RESUMO

In combination with cell-intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with neoadjuvant chemotherapy and radiotherapy. We developed spatially constrained optimal transport interaction analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid coculture system. We identified enrichment in interleukin-6 family signaling that functionally confers resistance to chemotherapy. Overall, this study demonstrates that characterization of the tumor microenvironment using single-cell spatial transcriptomics allows for the identification of molecular interactions that may play a role in the emergence of therapeutic resistance and offers a spatially based analysis framework that can be broadly applied to other contexts.

7.
Medicine (Baltimore) ; 103(37): e39696, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39287298

RESUMO

BACKGROUND: Shoulder impingement syndrome (SIS) is a common condition that causes chronic shoulder pain. The effectiveness of acupuncture in treating chronic shoulder pain has been documented in previous studies; however, existing systematic reviews and meta-analyses have often excluded Chinese databases and combined different types of acupuncture interventions, such as electroacupuncture, warm acupuncture, pharmacopuncture, and acupotomy. Thus, this study specifically examines the exclusive impact of manual acupuncture on SIS. METHODS: Several databases, including PubMed, Cochrane Central, Embase, 1 Chinese database (China National Knowledge Infrastructure), and 5 Korean databases (ScienceON, Oriental Medicine Advanced Searching Integrated System, KoreaMed, Korean Studies Information Service System, and KMBASE), were systematically searched for relevant studies. The quality of the included studies was evaluated using the Cochrane Assessment Tool for Risk of Bias Version 2. Data collected from the selected studies were synthesized for meta-analysis. The primary outcome was a pain scale score, and the secondary outcomes were shoulder function and disability. RESULTS: This study included 5 randomized controlled trials. The primary outcome assessment revealed significantly reduced pain (standardized mean difference [SMD] = -0.50, 95% confidence interval [CI] = -0.74 to -0.27) and improvements in shoulder function and disability (SMD = -0.57, 95% CI = -0.96 to -0.19). A subgroup analysis based on treatment duration indicated that short-term acupuncture treatment (≤4 weeks) exhibited a high level of confidence with low heterogeneity (SMD = -0.37, 95% CI = -0.73 to -0.02). CONCLUSION: Manual acupuncture is effective for relieving pain and improving shoulder function and disability in patients with SIS. However, further research is necessary to validate these findings owing to the limited number of patients and heterogeneity among the studies reviewed.


Assuntos
Terapia por Acupuntura , Síndrome de Colisão do Ombro , Humanos , Síndrome de Colisão do Ombro/terapia , Terapia por Acupuntura/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor de Ombro/terapia , Resultado do Tratamento , Medição da Dor
8.
Spine J ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39271021

RESUMO

BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) combined with uncinate process resection and laminoplasty combined with foraminotomy (LPF) have been used to achieve cervical cord and root decompression in patients with combined cervical myeloradiculopathy (CMR). PURPOSE: To compare the clinical and radiographic outcomes of ACDF with those of LPF for the treatment of CMR. STUDY DESIGN/SETTING: Propensity score-matched retrospective cohort study PATIENT SAMPLE: Patients with CMR who underwent ACDF or LPF and were followed up for at least 2 years. OUTCOME MEASURES: C2-C7 lordosis, C2-C7 sagittal vertical axis, and cervical range of motion (ROM) were determined. The visual analog scale (VAS) scores for neck and arm pain, neck disability index (NDI), and Japanese Orthopedic Association (JOA) scores were analyzed. METHODS: The radiographic and clinical outcomes of the two groups were compared. RESULTS: Eighty-four patients were included (n=42 in each group) after application of the inclusion criteria and propensity score matching. A significant decrease in C2-C7 lordosis (p<0.001) and ROM (p<0.001) was observed in the LPF and ACDF groups, respectively. LPF was associated with a significant decrease in C2-C7 lordosis (p<0.001), while ACDF caused a significant decrease in cervical ROM (p<0.001). ACDF effectively improved neck pain VAS (p<0.001) and NDI (p<0.001), while neck pain did not significantly improve after LPF (p=0.103). Furthermore, neck pain VAS (p=0.026) and NDI (p=0.021) at postoperative 6 months, were significantly greater in the LPF group than in the ACDF group, while the difference was not statistically significant at 2 years postoperatively (neck pain VAS, p=0.502; NDI, p=0.085). Arm pain VAS and JOA score both significantly improved after LPF (p=0.003 and 0.043, respectively) or ACDF (p<0.001 and 0.039, respectively), and postoperative results were not significantly different between the two groups. CONCLUSION: LPF and ACDF yielded similar outcomes for arm pain and neurological recovery. More immediate neck pain improvement was observed with ACDF, while neck pain after 2 years postoperatively was similar between the LPF and ACDF groups. Furthermore, increased postoperative loss of lordosis was observed in the LPF group, whereas decreased postoperative ROM was observed in the ACDF group. These findings should be considered when deciding the surgical method for patients with CMR. LEVEL OF EVIDENCE: III.

9.
Integr Med Res ; 13(3): 101071, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39263445

RESUMO

Background: Korean red ginseng extract (KRGE) (Family: Araliaceae) is one of the most widely used traditional herbs in Asia. Multiple studies have shown that KRGE has anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. Methods: Sprague-Dawley rats were divided into five groups for PTU-induced hypothyroidism and six groups for LT4-induced hyperthyroidism. At the experiment's conclusion, rats were sacrificed, and blood, thyroid gland, and liver samples were collected. Body weight was recorded weekly, and serum hormone levels were assessed using enzyme-linked immunoassay. Thyroid gland and liver tissues were stained with hematoxylin and eosin. KRGE was prepared in 0.5% CMC and stored at 4 °C before administration. Results: In the LT4-induced hyperthyroidism model, KRGE prevented decreases in body weight, thyroid gland weight, liver weight, serum glucose, and thyroid hormone levels compared to the PTU group. It also reduced increases in T3, T4, and serum aspartate aminotransferase levels after LT4 treatment. Additionally, KRGE improved thyroid gland and liver histopathology, effects not observed in the PTU-induced hypothyroidism model. Conclusion: All things considered, our research points to KRGE's potential protective role in rat hyperthyroidism caused by LT4 by lowering thyroid hormone production.

10.
Cureus ; 16(9): e68954, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252936

RESUMO

Background Osteoarthritis (OA) is a prevalent and exhausting condition often requiring long-term management. While there is a steady growth in the use of collagen-based treatment for OA, there is a lack of studies assessing the safety and efficacy of repeated administration of injectable atelocollagen for OA. Objective This study aims to evaluate the clinical efficacy and safety of repeated administration of injectable atelocollagen in reducing knee pain for patients with knee OA. Methods Clinical records of 91 patients from five hospitals were reviewed for this retrospective study. All 91 patients had received repeated administration of injectable atelocollagen (CartiPRO®, Dalim Tissen Co., Ltd., South Korea) as a treatment for knee OA for seven months. The efficacy of injectable atelocollagen was evaluated by physicians at least 30 days after the last administration, with outcomes categorized as "effective", "moderately effective", or "not effective". For analysis purposes, both "effective" and "moderately effective" were grouped as "effective" while "not effective" was classified as "ineffective". Safety was assessed by monitoring the incidence of adverse events (AEs) reported within six months following the re-administration of atelocollagen. Results Among the 91 patients, 96.7% (88 patients) experienced effective pain relief following the re-administration of CartiPRO®, with 3.3% (three patients) reporting ineffectiveness. In terms of safety assessment, 35 patients reported AEs, totaling up to 44 events, with no serious or unexpected device-related AEs. Conclusion The repeated use of atelocollagen was found to be both safe and effective in managing knee pain for patients with knee OA. These findings support the repeated use of injectable atelocollagen as a reliable treatment option for managing knee OA pain in clinical practice.

11.
Exp Mol Med ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39261656

RESUMO

The regulatory role of the inhibitor of NF-kB kinase ε (IKKε) in postmyocardial infarction (MI) inflammation remains uncertain. Using an MI mouse model, we examined the cardiac outcomes of IKKε knockout (KO) mice and wild-type mice. We employed single-cell RNA sequencing (scRNA-seq) and phosphorylated protein array techniques to profile cardiac macrophages. IKKε KO mice exhibited compromised survival, heightened inflammation, pronounced cardiac fibrosis, and a reduced ejection fraction. A distinct cardiac macrophage subset in IKKε KO mice exhibited increased fibrotic marker expression and decreased phosphorylated p38 (p-p38) levels, indicating an enhanced macrophage-myofibroblast transition (MMT) post-MI. While cardiac inflammation is crucial for initiating compensatory pathways, the timely resolution of inflammation was impaired in the IKKε KO group, while the MMT in macrophages accelerated post-MI, leading to cardiac failure. Additionally, our study highlighted the potential of 5-azacytidine (5-Aza), known for its anti-inflammatory and cardioprotective effects, in restoring p-p38 levels in stimulated macrophages. The administration of 5-Aza significantly reduced the MMT in cardiac macrophages from the IKKε KO group. These findings underscore the regulation of the inflammatory response and macrophage transition by the IKKε-p38 axis, indicating that the MMT is a promising therapeutic target for ischemic heart disease.

12.
Small ; : e2403133, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221667

RESUMO

Due to its small hole-effective mass, flexibility, and transparency, copper iodide (CuI) has emerged as a promising p-type alternative to the predominantly used n-type metal oxide semiconductors. However, the lack of effective doping methods hinders the utility of CuI in various applications. Sulfur (S)-doping through liquid iodination is previously reported to significantly enhance electrical conductivity up to 511 S cm-1. In this paper, the underlying doping mechanism with various S-dopants is explored, and suggested a method for controlling electrical conductivity, which is important to various applications, especially thermoelectric (TE) materials. Subsequently, electric and TE properties are systematically controlled by adjusting the carrier concentration from 3.0 × 1019 to 4.5 × 1020 cm-3, and accurately measured thermal conductivity with respect to carrier concentration and film thickness. Sulfur-doped CuI (CuI:S) thin films exhibited a maximum power factor of 5.76 µW cm-1 K-2 at a carrier concentration of 1.3 × 1020 cm-3, and a TE figure of merit (ZT) of 0.25. Furthermore, a transparent and flexible TE power generator is developed, with an impressive output power density of 43 nW cm-2 at a temperature differential of 30 K. Mechanical durability tests validated the potential of CuI:S films in transparent and flexible TE applications.

13.
Int J Mol Sci ; 25(16)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39201257

RESUMO

This study investigated the effects of Lycium chinense Mill (LCM) extract on obesity and diabetes, using both in vitro and high-fat diet (HFD)-induced obesity mouse models. We found that LCM notably enhanced glucagon-like peptide-1 (GLP-1) secretion in NCI-h716 cells from 411.4 ± 10.75 pg/mL to 411.4 ± 10.75 pg/mL compared to NT (78.0 ± 0.67 pg/mL) without causing cytotoxicity, implying the involvement of Protein Kinase A C (PKA C) and AMP-activated protein kinase (AMPK) in its action mechanism. LCM also decreased lipid droplets and lowered the expression of adipogenic and lipogenic indicators, such as Fatty Acid Synthase (FAS), Fatty Acid-Binding Protein 4 (FABP4), and Sterol Regulatory Element-Binding Protein 1c (SREBP1c), indicating the suppression of adipocyte differentiation and lipid accumulation. LCM administration to HFD mice resulted in significant weight loss (41.5 ± 3.3 g) compared to the HFD group (45.1 ± 1.8 g). In addition, improved glucose tolerance and serum lipid profiles demonstrated the ability to counteract obesity-related metabolic issues. Additionally, LCM exhibited hepatoprotective properties by reducing hepatic lipid accumulation and diminishing white adipose tissue mass and adipocyte size, thereby demonstrating its effectiveness against hepatic steatosis and adipocyte hypertrophy. These findings show that LCM can be efficiently used as a natural material to treat obesity and diabetes, providing a new approach for remedial and therapeutic purposes.


Assuntos
Fármacos Antiobesidade , Dieta Hiperlipídica , Hipoglicemiantes , Lycium , Obesidade , Extratos Vegetais , Animais , Camundongos , Lycium/química , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Dieta Hiperlipídica/efeitos adversos , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Humanos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Camundongos Endogâmicos C57BL , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
14.
Mayo Clin Proc ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093271

RESUMO

OBJECTIVE: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. PATIENTS AND METHODS: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. RESULTS: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). CONCLUSION: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored.

15.
Adv Healthc Mater ; : e2401466, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087398

RESUMO

Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.

16.
J Ethnopharmacol ; 335: 118681, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39121929

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (P. ginseng) C.A. Meyer. Has been studied for decades for its various biological activities, especially in terms of immune-regulatory properties. Traditionally, it has been known that root, leaves, and fruits of P. ginseng were eaten for improving body's Qi and homeostasis. Also, these were used to protect body from various types of infectious diseases. However, molecular mechanisms of immunomodulatory activities of ginseng berries have not been systemically studied as often as other parts of the plant. AIM OF THE STUDY: The aim of this research is to discover the regulatory effects of P. ginseng berries, more importantly, their ginsenosides, on innate immune responses and to elucidate the molecular mechanism. MATERIALS AND METHODS: Ginseng berry concentrate (GBC) was orally injected into BALB/c mice for 30 days, and spleens were extracted for evaluation of immune-regulatory effects. Murine macrophage RAW264.7 cells were used for detailed molecular mechanism studies. Splenic natural killer (NK) cells were isolated using the magnetic-activated cell sorting (MACS) system, and the cytotoxic activity of isolated NK cells was measured using a lactate dehydrogenase (LDH) release assay. The splenic immune cell population was determined by flow-cytometry. NF-κB promoter activity was assessed by in vitro luciferase assay. Expression of inflammatory proteins and cytokines of the spleen and RAW264.7 cells were evaluated using western blotting and real-time PCR, respectively. RESULTS: The GBC enhanced cytotoxic activity of NK cells and the immune-regulation-related splenic cell population. Moreover, GBC promoted NF-κB promoter activity and stimulated the NF-κB signaling cascade. In spleen and RAW264.7 cells, expression of pro-inflammatory cytokines was increased upon GBC application, while expression of anti-inflammatory cytokines decreased. CONCLUSIONS: These results suggest that P. ginseng berry can stimulate innate immune responses and help maintain a balanced immune condition, mostly due to the action of its key ginsenoside Re, along with other protopanaxadiol- and protopanaxatriol-type ginsenosides. Such finding will provide a new insight into the field of well-being diet research as well as non-chemical immune modulator, by providing nature-derived and plant-based bioactive materials.


Assuntos
Citocinas , Frutas , Ginsenosídeos , Células Matadoras Naturais , Macrófagos , Camundongos Endogâmicos BALB C , NF-kappa B , Panax , Regulação para Cima , Animais , Panax/química , Ginsenosídeos/farmacologia , NF-kappa B/metabolismo , Camundongos , Células RAW 264.7 , Citocinas/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/imunologia , Regulação para Cima/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Transdução de Sinais/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/citologia , Baço/imunologia , Extratos Vegetais/farmacologia , Masculino
19.
Front Cardiovasc Med ; 11: 1424551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036505

RESUMO

Background: The alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds. Methods: To determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases. Results: We observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10-21. Conclusions: We suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.

20.
Artigo em Inglês | MEDLINE | ID: mdl-39082701

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To clarify whether clinical outcomes of anterior cervical discectomy and fusion (ACDF), is affected by presence of spinal canal-cord mismatch (SCCM). SUMMARY OF BACKGROUND DATA: SCCM is considered a factor that would moderately influence surgeons to perform posterior surgery since it could widen the spinal canal, while an anterior approach could only remove degenerative pathologies grown into the spinal canal. METHODS: We retrospectively reviewed 186 patients who underwent ACDF and had been followed-up for >2 years. Patients with spinal cord occupation ratio (SCOR) of ≥0.7 were classified into the SCCM group, while those with a SCOR of <0.7 were included in the no-SCCM group. Patient demographics, cervical sagittal parameters, neck pain visual analog scale (VAS), arm pain VAS, and Japanese Orthopedic Association (JOA) score were assessed. JOA score was the primary outcome of the study. RESULTS: One-hundred and forty-seven patients (79.0%) were included into the no-SCCM group, while 39 patients (21.0%) were classified into the SCCM group. Postoperative radiographic parameters including C2-C7 lordosis, C2-C7 sagittal vertical axis, and range of motion did not significantly differ between the two groups. Neck pain VAS, arm pain VAS, and JOA score (no-SCCM group, from 13.7±2.5 to 14.6±2.3, P<0.001; SCCM group, from 13.8±1.6 to 15.0±2.0, P<0.001) significantly improved after the operation in both groups, and results were not significantly different between the two groups. Furthermore, SCOR was not significantly associated with JOA recovery rate at 2 years postoperatively in linear regression analysis. CONCLUSION: Clinical and radiographic outcomes of ACDF were not affected by the presence of SCCM. Furthermore, SCOR was not significantly associated with neurologic recovery at 2 years of follow-up. Therefore, ACDF can be safely and effectively applied for treating cervical myelopathy, regardless of the presence of SCCM, when other factors favor the anterior approach. LEVEL OF EVIDENCE: 3.

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