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1.
Diabetes Metab J ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38763510

RESUMO

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

2.
Front Neurol ; 15: 1323703, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628693

RESUMO

Background: With longer life spans and medical advancements, the rising number of patients with advanced-stage Parkinson's disease (PD) warrants attention. Current literature predominantly addresses dementia and fall management in these patients. However, exploring the impact of swallowing function on patients with advanced PD is crucial. Previous research has demonstrated notable enhancements in the quality of life related to voice for participants following a group singing-intervention program. To further elucidate the effect of individual singing-induced swallowing exercises, our study aimed to investigate the quantitative and qualitative effects of therapeutic singing on swallowing function in patients with advanced PD in comparison to a matched usual care control group. The hypothesis of this study is that therapeutic singing-induced swallowing exercises can assist to maintain swallowing function in patients with advanced PD. Methods: This prospective matched control study compared the effects of a 6-week therapeutic singing-based swallowing intervention on swallowing function and quality of life in patients with advanced PD. The intervention group received individual sessions with a music therapist and conventional individual physical therapy. The control group received the same standard physical therapy for 6 weeks without music intervention. The primary outcome measure was Video Fluoroscopic Dysphagia Scale (VDS). Results: The study revealed that the intervention group maintained swallowing function, whereas the control group experienced deterioration, indicating significant time-dependent changes in Penetration-Aspiration Scale (PAS), National Institutes of Health-Swallowing Safety Scale (NIH-SSS), and VDS. Analysis of PAS and NIH-SSS liquid food scores in both groups showed significant time effects. However, the intervention group exhibited no significant differences between the pre- and post-tests, indicating preservation of the swallowing function. VDS of liquid food indicated an interaction effect between time and group in the pharyngeal phase and total scores. The Swallowing-Quality of Life showed significant time-effect improvement in the intervention group. Conclusion: Therapeutic singing exercises may help maintain swallowing function in advanced PD patients, potentially enhancing quality of life related to swallowing in those with advanced-stage diseases. Clinical trial registration: https://cris.nih.go.kr/cris/search/listDetail.do, identifier KCT0008644.

3.
J Int Med Res ; 52(3): 3000605241233514, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38501996

RESUMO

OBJECTIVE: To compare the kinematic effects of two widely-used prefabricated ankle-foot orthoses (AFOs), the Dyna Ankle (DA) and UD Flex (UD), on the gait cycle of patients with hemiplegia due to cerebral palsy or acquired brain injury. METHODS: This was a retrospective cohort study involving 29 patients. Gait analysis results were assessed under three conditions: barefoot, with the DA, and with the UD. Friedman tests and post hoc analysis with Bonferroni correction were performed to assess differences between the three conditions. RESULTS: The DA significantly improved ankle dorsiflexion during the mid-swing phase, making it more effective in correcting foot drop compared with the UD (DA: 2.28°, UD: 0.44°). Conversely, the UD was more effective in preventing knee flexion during the loading response (DA: 28.11°, UD: 26.72°). CONCLUSIONS: The DA improved ankle dorsiflexion during the swing phase significantly more than that with the UD in patients with hemiplegia. Compared with the DA, the UD more effectively prevented increased knee flexion during the loading response. The choice to prescribe these orthoses should consider individual patient characteristics.


Assuntos
Tornozelo , Órtoses do Pé , Humanos , Hemiplegia , Estudos Retrospectivos , Articulação do Tornozelo
4.
Cells ; 13(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38391956

RESUMO

Central nervous system diseases, particularly neurodegenerative disorders, pose significant challenges in medicine. These conditions, characterized by progressive neuronal loss, have remained largely incurable, exacting a heavy toll on individuals and society. In recent years, in vivo reprogramming using Yamanaka factors has emerged as a promising approach for central nervous system regeneration. This technique involves introducing transcription factors, such as Oct4, Sox2, Klf4, and c-Myc, into adult cells to induce their conversion into neurons. This review summarizes the current state of in vivo reprogramming research in the central nervous system, focusing on the use of Yamanaka factors. In vivo reprogramming using Yamanaka factors has shown promising results in several animal models of central nervous system diseases. Studies have demonstrated that this approach can promote the generation of new neurons, improve functional outcomes, and reduce scar formation. However, there are still several challenges that need to be addressed before this approach can be translated into clinical practice. These challenges include optimizing the efficiency of reprogramming, understanding the cell of origin for each transcription factor, and developing methods for reprogramming in non-subventricular zone areas. Further research is needed to overcome the remaining challenges, but this approach has the potential to revolutionize the way we treat central nervous system disorders.


Assuntos
Reprogramação Celular , Doenças do Sistema Nervoso Central , Animais , Humanos , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição/genética , Sistema Nervoso Central , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/terapia
5.
Front Neurol ; 15: 1330811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419706

RESUMO

Background: Intrathecal baclofen (ITB) therapy, a viable alternative for unsuitable candidates of conventional spasticity medications, is a preferred method of administration over the oral route. Owing to its enhanced bioavailability, ITB ensures a more effective delivery at the target site. Objective: There is a lack of conclusive evidence regarding the use of ITB treatment in managing ambulatory patients with spastic dystonia. Before ITB pump implantation, patients commonly undergo an ITB bolus injection trial to rule out potential adverse reactions and verify the therapeutic effects on hypertonic issues. In this report, we highlight a case of spastic dystonia, particularly focusing on an ambulatory patient who demonstrated significant improvement in both the modified Ashworth scale (MAS) score and gait pattern following the ITB injection trial. Case report: This case report outlines the medical history of a 67-year-old male diagnosed with left-side hemiplegia and spastic dystonia, resulting from his second episode of intracranial hemorrhage in the right thalamus. An ITB injection trial was initiated because the patient was not suitable for continued botulinum toxin injections and oral medications. This was due to the persistent occurrence of spastic dystonia in both the upper and lower extremities. The patient underwent a four-day ITB injection trial with progressively increasing doses, resulting in improved MAS scores and gait parameters, including cadence, step length, step time, stride length, and stride time were increased. Particularly, kinematic gait analysis demonstrates a substantial improvement of increased knee flexion in the swing phase in stiff knee gait pattern. These findings indicated a gradual reduction in spasticity-related symptoms, signifying the positive effect of the ITB injection trial. The patient eventually received an ITB pump implantation. Conclusion: In this post-stroke patient with spastic dystonia, ITB therapy has demonstrated effective and substantial management of spasticity, along with improvement in gait patterns.

6.
Commun Biol ; 7(1): 110, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243116

RESUMO

Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3'-Sialyllactose (3'-SL) in human milk regulates many biological functions. However, its effect on bone metabolism remains unknown. This study aimed to investigate the molecular mechanisms underlying the effect of 3'-SL on bone homeostasis. Treatment of human bone marrow stromal cells (hBMSCs) with 3'-SL enhanced osteogenic differentiation and inhibited adipogenic differentiation of hBMSCs. RNA sequencing showed that 3'-SL enhanced laminin subunit gamma-2 expression and promoted osteogenic differentiation via the phosphatidylinositol 3­kinase/protein kinase B signaling pathway. Furthermore, 3'-SL inhibited the receptor activator of nuclear factor κB ligand-induced osteoclast differentiation of bone marrow-derived macrophages through the nuclear factor κB and mitogen­activated protein kinase signaling pathway, ameliorated osteoporosis in ovariectomized mice, and positively regulated bone remodeling. Our findings suggest 3'-SL as a potential drug for osteoporosis.


Assuntos
Oligossacarídeos , Osteogênese , Osteoporose , Camundongos , Humanos , Animais , Osteogênese/genética , Diferenciação Celular/genética , Osteoporose/tratamento farmacológico , Homeostase
7.
Nat Biotechnol ; 42(3): 484-497, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37188916

RESUMO

Applications of base editing are frequently restricted by the requirement for a protospacer adjacent motif (PAM), and selecting the optimal base editor (BE) and single-guide RNA pair (sgRNA) for a given target can be difficult. To select for BEs and sgRNAs without extensive experimental work, we systematically compared the editing windows, outcomes and preferred motifs for seven BEs, including two cytosine BEs, two adenine BEs and three C•G to G•C BEs at thousands of target sequences. We also evaluated nine Cas9 variants that recognize different PAM sequences and developed a deep learning model, DeepCas9variants, for predicting which variants function most efficiently at sites with a given target sequence. We then develop a computational model, DeepBE, that predicts editing efficiencies and outcomes of 63 BEs that were generated by incorporating nine Cas9 variants as nickase domains into the seven BE variants. The predicted median efficiencies of BEs with DeepBE-based design were 2.9- to 20-fold higher than those of rationally designed SpCas9-containing BEs.


Assuntos
Ácidos Alcanossulfônicos , Sistemas CRISPR-Cas , Aprendizado Profundo , Sistemas CRISPR-Cas/genética , Edição de Genes , Proteína 9 Associada à CRISPR/genética , Proteína 9 Associada à CRISPR/metabolismo , RNA Guia de Sistemas CRISPR-Cas
8.
Endocrinol Metab (Seoul) ; 38(5): 568-577, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37816500

RESUMO

BACKGRUOUND: Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. METHODS: We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. RESULTS: The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. CONCLUSION: CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Calcificação Vascular , Humanos , Diabetes Mellitus Tipo 2/complicações , Doenças Cardiovasculares/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Cálcio , Estudos de Coortes , Angiografia Coronária/métodos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Medição de Risco/métodos
9.
Nutr Res Pract ; 17(3): 464-474, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37266123

RESUMO

BACKGROUND/OBJECTIVES: Estimation of energy demand using resting energy expenditure (REE) is a reasonable approach for optimizing glycemic control and weight management in patients with type 2 diabetes mellitus (T2DM). This study aimed to compare REE predictions and objective measurements in patients with T2DM in Korea. SUBJECTS/METHODS: This study enrolled 36 participants with T2DM (age range, 20-60 years). Anthropometric variables including height, weight, waist-hip ratio, blood pressure, body fat, body fat percentage, and total body weight were measured using bioimpedance. REE was evaluated using indirect calorimetry. The measured REE values were compared to values estimated using five predictive equations: the Harris-Benedict, Mifflin, Owen, Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO), and Schofield equations. This study evaluated the associations between measured REE values and anthropometric/clinical data, including height, weight, and age, using multivariate linear regression. RESULTS: The mean measured REE value was 1891.79 ± 288.03 kcal/day (male), 1,502.00 ± 202.96 kcal/day (female). REE estimates generated from the Mifflin equation showed the largest differences from measured REE values, whereas estimates derived from the FAO/WHO equation were the closest to the measured REE values. This study also identified associations between measured REE values and various anthropometric/clinical variables. CONCLUSION: The accuracy of REE prediction equations is critically important in promoting the efficacy of dietary counseling and the effective treatment of diabetes. Our results indicate the need for additional studies informing more suitable methods for determining the energy requirements of Korean patients with T2DM.

10.
Nat Methods ; 20(7): 999-1009, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37188955

RESUMO

Recently, various small Cas9 orthologs and variants have been reported for use in in vivo delivery applications. Although small Cas9s are particularly suited for this purpose, selecting the most optimal small Cas9 for use at a specific target sequence continues to be challenging. Here, to this end, we have systematically compared the activities of 17 small Cas9s for thousands of target sequences. For each small Cas9, we have characterized the protospacer adjacent motif and determined optimal single guide RNA expression formats and scaffold sequence. High-throughput comparative analyses revealed distinct high- and low-activity groups of small Cas9s. We also developed DeepSmallCas9, a set of computational models predicting the activities of the small Cas9s at matched and mismatched target sequences. Together, this analysis and these computational models provide a useful guide for researchers to select the most suitable small Cas9 for specific applications.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes
11.
J Korean Med Sci ; 38(16): e128, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37096311

RESUMO

BACKGROUND: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. METHODS: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. RESULTS: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. CONCLUSION: Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.


Assuntos
Pré-Eclâmpsia , Trofoblastos , Recém-Nascido , Gravidez , Humanos , Feminino , Trofoblastos/metabolismo , Placenta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Leucócitos Mononucleares/metabolismo , Nucleosídeo Difosfato Quinase D/metabolismo
12.
Toxins (Basel) ; 15(4)2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37104217

RESUMO

The genus Hapalochlaena, including the blue-lined octopus Hapalochlaena fasciata (H. fasciata), is highly toxic. Venomous, blue-lined octopuses were recently found in Korea, but their toxicity, toxin composition, and distribution remain largely unknown. Here we estimated the geographic distribution of the organisms along the Korean coast and clarified their toxicity. Tetrodotoxin (TTX) was present in all three specimens of H. fasciata examined, although the toxicity varied largely between individuals. The mean TTX concentration in the whole body of the three specimens was 6.5 ± 2.2 µg/g (range 3.3-8.5 µg/g). Among the body parts examined, the salivary glands exhibited the highest concentration (22.4 ± 9.7 µg/g). From 2012 to 2021, 26 individuals were obtained nearly every month from different regions of the Korean coast. A non-fatal case of a blue-lined octopus bite was reported along the Korean coast in June 2015. This is the first report on the widespread distribution of blue-lined octopuses on the Korean coast and TTX detection. The widespread distribution of the TTX-bearing H. fasciata along the Korean coast within the temperate zone indicates that the species may soon become a serious health issue in Korea. The toxicity of this species is also a potentially significant human health risk.


Assuntos
Octopodiformes , Animais , Humanos , Tetrodotoxina/toxicidade , Peçonhas , Glândulas Salivares , República da Coreia
13.
Sci Rep ; 13(1): 6004, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045900

RESUMO

Polydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury.


Assuntos
Polidesoxirribonucleotídeos , Traumatismo por Reperfusão , Humanos , Polidesoxirribonucleotídeos/uso terapêutico , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia/etiologia
14.
Diabetes Obes Metab ; 25(8): 2096-2104, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37016484

RESUMO

AIMS: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium-glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients with glycated haemoglobin (HbA1c) of 7.0-10.0%, entered a 2-week placebo run-in period, and were randomized to receive once-daily enavogliflozin (0.1, 0.3 or 0.5 mg) or placebo for 12 weeks. The primary efficacy endpoint was the change in HbA1c from baseline at week 12. RESULTS: Overall, 194 patients were included in the full analysis set [placebo, n = 46; enavogliflozin (0.1 mg, n = 49; 0.3 mg, n = 50; 0.5 mg, n = 49)]. Patients receiving 0.1, 0.3 and 0.5 mg enavogliflozin showed significantly reduced HbA1c compared with those receiving placebo at week 12 (-0.79%, -0.89%, -0.92% and -0.08%, respectively; p < .001 vs. placebo). Mean changes in fasting plasma glucose from baseline at week 12 were -30.5, -31.1, -35.0 and 4.9 mg/dl in patients receiving enavogliflozin doses and placebo, respectively. The proportion of patients achieving HbA1c <7.0% at week 12 was significantly higher in the three enavogliflozin groups than in the placebo group (42.9%, 44.0%, 61.2% and 17.4%, respectively). A higher proportion of patients showed HbA1c reduction by >0.5% after receiving enavogliflozin doses than those receiving placebo (61.2%, 72.0%, 65.3% and 26.1%, respectively). There were no significant differences in incidences of adverse events of hypoglycaemia and genital infection between the groups. CONCLUSIONS: Once-daily enavogliflozin monotherapy for 12 weeks is an effective, safe, and well-tolerated treatment for Korean patients with type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Resultado do Tratamento , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Quimioterapia Combinada , Método Duplo-Cego , República da Coreia/epidemiologia , Glicemia
15.
Commun Biol ; 6(1): 466, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37117485

RESUMO

Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. CRISPR-Cas9 nuclease causes double-strand breaks (DSBs) in the targeted DNA that induces toxicity, whereas CRISPR interference (CRISPRi) using dead Cas9 (dCas9) suppresses the target gene expression without DSBs. Delivery of dCas9-sgRNA targeting CAG repeat region does not damage the targeted DNA in HEK293T cells containing CAG repeats. When this study investigates whether CRISPRi can suppress mutant HTT (mHTT), CRISPRi results in reduced expression of mHTT with relative preservation of the wild-type HTT in human HD fibroblasts. Although both dCas9 and Cas9 treatments reduce mHTT by sgRNA targeting the CAG repeat region, CRISPRi delays behavioral deterioration and protects striatal neurons against cell death in HD mice. Collectively, CRISPRi can delay disease progression by suppressing mHtt, suggesting DNA DSB-free CRISPRi is a potential therapy for HD that can compensate for the shortcoming of CRISPR-Cas9 nuclease.


Assuntos
Doença de Huntington , Camundongos , Humanos , Animais , Doença de Huntington/genética , Doença de Huntington/terapia , Doença de Huntington/metabolismo , Quebras de DNA de Cadeia Dupla , Células HEK293 , Corpo Estriado/metabolismo
16.
J Clin Med ; 12(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902759

RESUMO

This study was performed to review which mHealth apps that improve brace-wearing compliance are currently available, and to carry out their quality assessments by listing their functionalities. We found ten mHealth apps in the literature review and commercial mHealth apps market (Google Play and App store). Then, the quality of these apps was evaluated by their transparency, health content, excellent technical content, security/privacy, issues of usability, and subjective ratings (THESIS) scale, and the functionalities of the included apps were reviewed. Regarding these functionalities, four categories (data acquisition, compliance enhancement, educational components, and additional functionalities) and twelve subcategories were identified. The mean overall quality of the apps was 3.00 out of 5. Although four of the apps achieved a score of 3.0 or more for their overall quality, indicating an acceptable quality, none of the apps scored higher than 4.0, which indicated a high or excellent quality. According to the sections, the transparency section had the highest rating (3.92) and the security/privacy section received the lowest rating (2.02). Given that the overall quality of current mHealth apps was not high, and their potential to motivate patients with idiopathic scoliosis to adhere to their bracing treatment, it is necessary to develop high-quality apps with appropriate functionalities for supporting brace treatment.

17.
J Int Med Res ; 51(3): 3000605231162452, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36988314

RESUMO

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene were first described as a cause of Rett syndrome. MECP2 duplication can cause intellectual disability, developmental delay, severe feeding difficulties, and recurrent infections. Here, we report a Korean family with MECP2 duplication syndrome, which was previously misdiagnosed as cerebral palsy. A man in his early 30 s visited our clinic with intellectual disability, speech impairment, epilepsy, and progressive spasticity. He had been previously misdiagnosed with cerebral palsy, and had received orthopedic surgeries such as musculotendinous lengthening and derotational osteotomy. After the surgeries, he received comprehensive rehabilitation. Upon carefully checking his family history, we noted that his younger brother had similar symptoms. Next-generation sequencing revealed whole exon duplication in MECP2 in both the patient and his brother; their mother also had this genetic mutation but was asymptomatic. Early diagnosis is essential for improving the success of MECP2 duplication syndrome treatment. Individuals with MECP2 duplication syndrome should be referred to specialists to manage multidisciplinary symptoms and to regularly check for complications that are common in this syndrome.


Assuntos
Paralisia Cerebral , Deficiência Intelectual , Deficiência Intelectual Ligada ao Cromossomo X , Humanos , Masculino , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/genética , Erros de Diagnóstico , Deficiência Intelectual/genética , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteína 2 de Ligação a Metil-CpG/genética , Adulto
18.
Foods ; 12(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36900547

RESUMO

Human norovirus (HNoV) GII.4 and Vibrio parahaemolyticus may be found in sea squirts. Antimicrobial effects of floating electrode-dielectric barrier discharge (FE-DBD) plasma (5-75 min, N2 1.5 m/s, 1.1 kV, 43 kHz) treatment were examined. HNoV GII.4 decreased by 0.11-1.29 log copy/µL with increasing duration of treatment time, and further by 0.34 log copy/µL when propidium monoazide (PMA) treatment was added to distinguish infectious viruses. The decimal reduction time (D1) of non-PMA and PMA-treated HNoV GII.4 by first-order kinetics were 61.7 (R2 = 0.97) and 58.8 (R2 = 0.92) min, respectively. V. parahaemolyticus decreased by 0.16-1.5 log CFU/g as treatment duration increased. The D1 for V. parahaemolyticus by first-order kinetics was 65.36 (R2 = 0.90) min. Volatile basic nitrogen showed no significant difference from the control until 15 min of FE-DBD plasma treatment, increasing after 30 min. The pH did not differ significantly from the control by 45-60 min, and Hunter color in "L" (lightness), "a" (redness), and "b" (yellowness) values reduced significantly as treatment duration increased. Textures appeared to be individual differences but were not changed by treatment. Therefore, this study suggests that FE-DBD plasma has the potential to serve as a new antimicrobial to foster safer consumption of raw sea squirts.

19.
Ann Rehabil Med ; 47(1): 1-3, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36800676
20.
Healthcare (Basel) ; 11(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36611608

RESUMO

This study aimed to objectively assess YouTube videos' quality, reliability, and information delivery capability regarding novel spinal muscular atrophy treatments. Using the keywords "nusinersen", "spinraza", "ridisplam", "evrysdi", "onasemnogene abeparvovec", and "zolgensma", we were able to retrieve and screen 360 videos before settling on a final sample of 99 on 25 September 2022. Then, two independent raters used the mDISCERN and GQS instruments to evaluate the videos' reliability and quality and the Information Delivery Capability (IDC) score to assess the videos' accuracy and patient-friendliness. The quality, reliability, and information delivery capability of the videos about the new treatment for SMA were quite heterogeneous, with an average mDISCERN, GQS, and IDC score of 3.172 ± 0.899, 2.980 ± 1.025, and 4.141 ± 1.747, respectively. In-depth analysis showed that healthcare expert videos that explained contents while showing infographic supplements had good quality, reliability, and information delivery capability. As YouTube is already a dominant media platform, the public may obtain new information about novel therapeutics for SMA through YouTube. It is necessary to consider how SMA patients and caregivers can choose trusted sources with reliable information on YouTube, and our results can provide clues. Additionally, experts should strive to provide more accurate, reliable, and patient-oriented videos.

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