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1.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(2): 281-287, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38686408

RESUMO

Alzheimer's disease (AD) is a common and serious form of elderly dementia, but early detection and treatment of mild cognitive impairment can help slow down the progression of dementia. Recent studies have shown that there is a relationship between overall cognitive function and motor function and gait abnormalities. We recruited 302 cases from the Rehabilitation Hospital Affiliated to National Rehabilitation Aids Research Center and included 193 of them according to the screening criteria, including 137 patients with MCI and 56 healthy controls (HC). The gait parameters of the participants were collected during performing single-task (free walking) and dual-task (counting backwards from 100) using a wearable device. By taking gait parameters such as gait cycle, kinematics parameters, time-space parameters as the focus of the study, using recursive feature elimination (RFE) to select important features, and taking the subject's MoCA score as the response variable, a machine learning model based on quantitative evaluation of cognitive level of gait features was established. The results showed that temporal and spatial parameters of toe-off and heel strike had important clinical significance as markers to evaluate cognitive level, indicating important clinical application value in preventing or delaying the occurrence of AD in the future.


Assuntos
Disfunção Cognitiva , Marcha , Aprendizado de Máquina , Humanos , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/diagnóstico , Fenômenos Biomecânicos , Análise da Marcha/métodos , Masculino , Idoso , Feminino , Cognição , Caminhada , Dispositivos Eletrônicos Vestíveis
2.
Cerebellum ; 22(3): 394-430, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35414041

RESUMO

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.


Assuntos
Ataxia Cerebelar , Doenças Cerebelares , Tremor Essencial , Humanos , Marcha Atáxica/etiologia , Tremor , Consenso , Ataxia Cerebelar/complicações , Ataxia/complicações , Doenças Cerebelares/complicações , Marcha/fisiologia
3.
Int J Mol Sci ; 24(4)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36834630

RESUMO

Hepatocellular carcinoma (HCC) is a vital global health problem. The characteristics are high morbidity, high mortality, difficulty in early diagnosis and insensitivity to chemotherapy. The main therapeutic schemes for treating HCC mainly include Tyrosine kinase inhibitors represented by sorafenib and lenvatinib. In recent years, immunotherapy for HCC has also achieved certain results. However, a great number of patients failed to benefit from systemic therapies. FAM50A belongs to the FAM50 family and can be used as a DNA-binding protein or transcription factor. It may take part in the splicing of RNA precursors. In studies of cancer, FAM50A has been demonstrated to participate in the progression of myeloid breast cancer and chronic lymphocytic leukemia. However, the effect of FAM50A on HCC is still unknown. In this study, we have demonstrated the cancer-promoting effects and diagnostic value of FAM50A in HCC using multiple databases and surgical samples. We identified the role of FAM50A in the tumor immune microenvironment (TIME) and immunotherapy efficacy in HCC. We also proved the effects of FAM50A on the malignancy of HCC in vitro and in vivo. In conclusion, we confirmed that FAM50A is an important proto-oncogene in HCC. FAM50A acts as a diagnostic marker, immunomodulator and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Sorafenibe/farmacologia , Microambiente Tumoral , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA
4.
Int J Nurs Pract ; 29(6): e13139, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36879363

RESUMO

AIM: Nursing interventions include the preventive care that can support and guide the nurse's effort to provide asthma interventions for children. Hence, this review was done to assess the effectiveness of nursing interventions for management of childhood asthma. METHODS: We conducted a search in Medline, the Cochrane library, EMBASE, ScienceDirect and Google Scholar from 1964 until April 2022. Meta-analysis was done using a random-effects model and pooled weighted mean difference (WMD) or standardized mean difference (SMD) and/or risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: Fourteen studies were analysed. The pooled RR was 0.49 for emergency visits (95% CI: 0.32 to 0.77) and 0.46 for hospitalizations (95% CI: 0.27 to 0.79). The pooled WMD was -1.20 for number of days with symptoms (95% CI: -3.50 to 1.11), -0.98 for number of nights with symptoms (95% CI: -2.94 to 0.98) and -0.69 for frequency of asthma attacks (95% CI: -1.19 to -0.20). The pooled SMD was 0.39 for quality of life (95% CI: 0.11 to 0.66) and 0.58 for asthma control (95% CI: -0.29 to 1.46). CONCLUSION: Nursing interventions were relatively effective in improving the quality of life and reducing asthma related emergencies, acute attacks and hospitalization amongst childhood asthma patients.


Assuntos
Asma , Qualidade de Vida , Criança , Humanos , Asma/terapia , Hospitalização
5.
Insect Mol Biol ; 31(6): 722-733, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35789509

RESUMO

Intracellular calcium (Ca2+ ) is vital for signal transduction in many cellular events. Several Ca2+ -binding proteins mediate the transduction of intracellular calcium signals. The EF-hand motifs containing neuronal calcium sensor (NCS) proteins are mainly expressed in the nervous system, where they have important roles in the regulation of a variety of neuronal functions. NCS1 has four EF-hand motifs and well-defined neuronal development functions in a variety of eukaryotes. However, NCS2 has only been identified in invertebrates such as insects and nematodes thus far. The functions of NCS2 remain largely unknown. Here, we identified an orthologous NCS2 in the hemipteran Nilaparvata lugens. Based on qRT-PCR, this gene was found to be primarily expressed in the brain. Knockdown of NCS2 in each nymphal instar by RNA interference led to lethality and caused aggradation and disordered arrangement of lipid droplets in the ovaries and testes of adults, which were associated with the absence of mature oocytes in female ovaries and reduction of spermiation in male adults. Our findings revealed a novel function for NCS2 as a regulator in development and reproduction and suggested that this protein had an important role in modulating lipid droplet remodelling in ovary and testis of N. lugens adults.


Assuntos
Hemípteros , Muda , Feminino , Masculino , Animais , Muda/genética , Cálcio/metabolismo , Hemípteros/genética , Oogênese , Oócitos/metabolismo , Proteínas de Insetos/metabolismo
6.
Int J Mol Sci ; 23(5)2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35270018

RESUMO

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is an essential enzyme that transfers electrons from NADPH to cytochrome P450 monooxygenases. CPR is involved in cuticular hydrocarbon (CHC) synthesis in insects and is vital for insect development and survival. Here, we clarify the physiological function of a CPR gene in Nilaparvata lugens, an important rice pest, by using RNA interference. CPR gene knockdown leads to the functional loss of waterproofing and water retention in the integument of female adults, which causes significantly reduced body weight and a lethal phenotype. Scanning electron microscopy shows that the lipid layer on the outermost surface of the abdominal cuticle becomes thin in dsCPR-injected adults. Furthermore, CHC profile analysis reveals that CPR knockdown significantly decreases the contents of CHCs with a carbon chain length ≥ C27 in adult females. Moreover, we find that CPR knockdown generates a deficient phenotype in ovaries with deformed oocytes and a complete failure of egg-laying. These findings suggest that CPR plays multiple functional roles in CHC biosynthesis and embryo development in insects.


Assuntos
Hemípteros , Animais , Feminino , Hemípteros/genética , Hemípteros/fisiologia , Insetos/genética , Tegumento Comum , NADP , Ovário
7.
Biochem Biophys Res Commun ; 549: 207-213, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33684697

RESUMO

DNA transfection is routinely used for delivering expression of gene of interest to target cells. Transfected DNA has been known to activate cellular DNA sensor(s) and innate immune responses, but the effects of such responses on transfected DNA are not fully understood. STING (stimulator of interferon genes) is an important adaptor protein in cellular innate immune response to various DNA and RNA stimuli and upon activation induces significant type I interferon responses. In this work, we characterized the effects of STING on gene expression driven by transfected double-stranded DNA. We observed that gene expression from transfected DNA was repressed in the presence of overexpressed STING, but increased if endogenous STING was knocked down through RNA interference. Endogenous chromosomal genes and chromosome-integrated exogenous genes were not affected by such STING-mediated restriction, which did not depend on DNA circularity or linearity, promoter used, or bacterial sequences in transfected DNA. Mechanistically, STING-mediated repression of transfected DNA correlates with reduced mRNA levels, and partially involves the induction of interferon ß production by STING. Collectively, these data indicate that episomal double-stranded DNA is targeted by STING-mediated cell defense.


Assuntos
DNA/metabolismo , Proteínas de Membrana/metabolismo , Sequência de Bases , Cromossomos Humanos/genética , Regulação da Expressão Gênica , Células HEK293 , Humanos , Interferon beta/metabolismo , Transfecção
8.
J Med Virol ; 93(8): 4939-4948, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33666247

RESUMO

This study aimed to explore the value of baseline serum exosome-derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg-IFN). A total of 120 treatment-naïve HBeAg-positive CHB patients who received Peg-IFN therapy (48 weeks) were enrolled. Next-generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg-IFN treatment outcome, and qRT-PCR was used to validate them. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. Thirty-three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (nonresponse group). In the identification cohort, 40 serum exosome-derived miRNAs were differentially expressed between the response group (four patients) and the nonresponse group (four patients). In the confirmation cohort, the expression levels of serum exosomal miR-194-5p (p < .001) and miR-22-3p (p < .001) were significantly downregulated in the response group (29 patients) compared to the nonresponse group (83 patients). Multivariate analysis identified baseline serum exosomal miR-194-5p, miR-22-3p, alanine aminotransferase (ALT), and HBV DNA as independent predictors of HBeAg seroconversion (all p < .05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR-194-5p and miR-22-3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR-194-5p and miR-22-3p further improved the predictive performance with an AUROC of 0.82. Baseline serum exosomal miR-194-5p and miR-22-3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg-IFN.


Assuntos
Exossomos/metabolismo , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Interferon Tipo I/uso terapêutico , MicroRNAs/metabolismo , Polietilenoglicóis/uso terapêutico , Soroconversão/efeitos dos fármacos , Adulto , Antivirais/uso terapêutico , Biomarcadores/sangue , Feminino , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Humanos , Masculino , MicroRNAs/sangue , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento
10.
Acta Biochim Biophys Sin (Shanghai) ; 51(4): 431-440, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30811522

RESUMO

Chronic hepatitis B virus (HBV) infection remains a global public health problem. HBV-encoded X protein (HBx) is a multifunctional regulator that is required to initiate and maintain productive HBV infection, and is involved in HBV-related hepatocellular carcinoma (HCC). Inhibitors that interfere with the functions of HBx could be useful not only for the inhibition of HBV replication but also for the prevention or treatment of HBV-related HCC. To screen molecules that target HBx on a large scale remains a technical challenge due to a lack of sensitive and high-throughput system. In this work, we established an in vitro bioluminescent reporter system for screening HBx-targeting molecules. The system is based on a secretory fusion protein that combines HBx and NanoLuc (HBx-Nluc). The measured activity of NanoLuc in the culture supernatant of HBx-Nluc-expressing cells directly reflects the level of secreted HBx-Nluc. HBx protein-targeting intracellular anti-HBx single-chain variable fragment and RNA-targeting shRNA significantly reduced the secreted NanoLuc activity in HBx-Nluc-expressing cells. This system is simple and sensitive, and compatible with continuous non-disruptive screening, suggesting its potential usefulness for high-throughput screening and evaluating HBx-targeting molecules.


Assuntos
Luciferases/metabolismo , Luminescência , Nanotecnologia/métodos , Transativadores/metabolismo , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/metabolismo , Células HEK293 , Células Hep G2 , Hepatite B/diagnóstico , Hepatite B/genética , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , Humanos , Luciferases/genética , Microscopia de Fluorescência , Nanoestruturas , Reprodutibilidade dos Testes , Transativadores/genética , Proteínas Virais Reguladoras e Acessórias
11.
Hepatology ; 66(6): 1894-1909, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28646551

RESUMO

Angiogenesis has been proven to play an important role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying HCC angiogenesis is not well understood. In this study, Prospero-related homeobox 1 (PROX1) was identified as a novel proangiogenic factor in HCC cell lines and tissues. A strong positive correlation was found between the levels of PROX1 and microvessel density in HCC tissues. Knockdown of PROX1 expression in HCC cells significantly inhibited the in vitro capillary tube formation by human vascular endothelial cells and in vivo angiogenesis of HCC, while overexpression of PROX1 in HCC cells induced the opposite effects. PROX1 and nuclear factor κB p65 expression levels were positively correlated in both HCC tissues and cell lines. PROX1 enhances the nuclear accumulation of p65 and stabilizes p65 by recruiting ubiquitin-specific protease 7 to prevent p65 ubiquitination. Consequently, PROX1 activated nuclear factor κB signaling and selectively promoted expression of the proangiogenic interleukin-8 (IL-8) by epigenetically stimulating the IL-8 promoter. Finally, progression of high PROX1 expression HCC in tumor xenograft mice could be effectively contained by an anti-IL-8 monoclonal antibody. CONCLUSIONS: We have identified PROX1 as a crucial promoter of HCC angiogenesis; our study provides an insight into PROX1's function in HCC progression and the potential therapeutic application of anti-IL-8 antibody in high PROX1 expression HCC patients. (Hepatology 2017;66:1894-1909).


Assuntos
Carcinoma Hepatocelular/metabolismo , Proteínas de Homeodomínio/metabolismo , Interleucina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Neovascularização Patológica , Proteínas Supressoras de Tumor/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Humanos , Interleucina-8/antagonistas & inibidores , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Camundongos , Camundongos Nus , Terapia de Alvo Molecular , Estabilidade Proteica , Distribuição Aleatória , Fator de Transcrição RelA/metabolismo , Ativação Transcricional , Peptidase 7 Específica de Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Biochem Biophys Res Commun ; 492(1): 18-26, 2017 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-28821433

RESUMO

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5+) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5-) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Metástase Neoplásica , Fator de Transcrição RelA/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/deficiência , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Movimento Celular , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estabilidade Proteica
14.
Acta Biochim Biophys Sin (Shanghai) ; 48(12): 1094-1100, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27827798

RESUMO

Global adoption of hepatitis B virus (HBV) vaccines has greatly reduced new HBV infections. Current HBV vaccines are liquid suspensions containing recombinant hepatitis B surface antigen (HBsAg) particles mixed with aluminum phosphate or aluminum hydroxide. Refrigeration (2-8°C) as recommended for vaccine transport and storage may be unachievable in certain HBV-prevalent developing countries or regions. In this study, we stored yeast-expressed HBsAg and aluminum hydroxide separately at the standard (4°C) and elevated temperature (25, 37, or 45°C) for 14, 23, and 30 days, then mixed them and used the mixture to vaccinate mice with a prime-boost program. The antisera from all the vaccinated mice successfully inhibited HBV infection of HepG2 cells stably expressing HBV receptor sodium taurocholate cotransporting polypeptide. Furthermore, no serum HBsAg was detected in vaccinated mice on Day 1 post-hydrodynamic injection (HDI) of an HBV replicon plasmid and onwards, accompanied with an increasing anti-HBsAg antibody (HBsAb) level. In contrast, serum HBsAg in phosphate-buffered saline (PBS)-injected mice peaked on Day 4 post-HDI and was cleared on Day 14 post-HDI, which coincided with appearance of HBsAb on Day 7 post-HDI, suggesting a typical HBV acute infection process. HBV DNA peaked on Day 4 post-HDI in vaccinated mice, its level significantly lower than that in PBS-injected mice on Day 7 post-HDI, and showed a higher clearance rate. Taken together, we conclude that storing recombinant HBsAg at 25, 37, or 45°C for 14-30 days does not impair its immunogenicity in mice.


Assuntos
Antígenos de Superfície da Hepatite B/genética , Temperatura Alta , Saccharomyces cerevisiae/genética , Animais , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Células Hep G2 , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
15.
Zhongguo Gu Shang ; 37(2): 196-206, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38425073

RESUMO

OBJECTIVE: To investigate whether Bushen Huoxue recipe can protect articular cartilage by regulating Akt/mTOR signaling pathway to promote the autophagy of chondrocytes in ovariectomized rats. METHODS: Among 30 SPF 12-week-old female SD rats weighing (247.0±7.0) g, 6 were randomly selected as the blank control group, and the remaining rats were randomly divided into model group, BSHXR-L group, BSHXR-M group and BSHXR-H group, with 6 rats in each group. The protective effect of Bushen Huoxue recipe on articular cartilage injury in rats was determined by visual observation score, muscovine O-solid green staining and immunohistochemistry. The expression of autophagy related proteins was detected by Western-blot, and the relative expression of Akt, mTOR and downstream autophagy genes was detected by qPCR. RESULTS: After modeling, BSHXR (L, M, H) groups could alleviate the histological damage of cartilage. Immunohistochemistry showed that the expression of Collagen-Ⅱand Aggrecan gradually increased, and the expression of MMP-13 gradually decreased, and the differences between BSHXR-M and BSHXR-H groups and model group were statistically significant (P<0.05). The results of Western-blot showed that the autophagy pathway proteins p-Akt/Akt and p-mTOR/mTOR were inhibited in the BSHXR(L, M, H) groups, and the expressions of downstream proteins Beclin-1 and LC3Ⅱwere gradually increased, while p62 was gradually decreased, showing a dose effect. QPCR results showed that BSHXR(L, M, H) groups could promote the relative expression of Beclin-1 and LC3ⅡmRNA, and inhibit the relative expression of p62, Akt, mTOR mRNA, and the differences were statistically significant compared with model group (P<0.05). CONCLUSION: Bushen Huoxue recipe can enhance the cartilage autophagy response by inhibiting the Akt/mTOR signaling pathway, and then protect the cartilage.


Assuntos
Cartilagem Articular , Condrócitos , Medicamentos de Ervas Chinesas , Ratos , Feminino , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Autofagia/genética
16.
Digit Health ; 10: 20552076241257054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817844

RESUMO

Objective: This study aims to validate the reliability and validity of gait analysis using smartphones in a controlled environment. Methods: Thirty healthy adults attached smartphones to the waist and thigh, while an inertial measurement unit was fixed at the shank as a reference device; each participant was asked to walk six gait cycles at self-selected low, normal, and high speeds. Thirty-five cerebral small vessel disease patients were recruited to attach the smartphone to the thigh, performing single-task (ST), cognitive dual-task (DT1), and physical dual-task walking (DT2) to obtain gait parameters. Results: The results from the healthy group indicate that, regardless of whether attached to the thigh or waist, the smartphones calculated gait parameters with good reliability (ICC2,1 > 0.75) across three different walking speeds. There were no significant differences in the gait parameters between the smartphone attached to the thigh and the IMU across all three walking speeds (P > 0.05). However, significant differences were observed between the smartphone at the waist and the IMU during the stance phase, swing phase, stance time, and stride length at high speeds (P < 0.05). At the same time, measurements of other gait parameters were similar (P > 0.05). Patients demonstrated significant differences in the cadence, stride time, stance phase, swing phase, stance time, stride length, and walking speed between ST and DT1 (P < 0.05). Significant differences were observed in the stance phase, swing phase, stride length, and walking speed between ST and DT2 (P < 0.05). Conclusions: This study demonstrates the feasibility of using built-in smartphone sensors for gait analysis in a controlled environment.

17.
Discov Med ; 36(185): 1169-1179, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38926103

RESUMO

BACKGROUND: In recent years, a gene-editing technology known as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has been developed and is progressively advancing into clinical trials. While current antiviral therapies are unable to eliminate the Hepatitis B virus (HBV), it stands as a prime target for the CRISPR/Cas9 technology. The objective of this study was to enhance the efficacy of CRISPR/Cas9 in suppressing HBV replication, lowering HBsAg and HBeAg levels, and eliminating covalently closed circular DNA (cccDNA). METHODS: To enhance the anti-HBV effectiveness of CRISPR/Cas9, our study delved into a dual-guide RNA (gRNA) strategy. After evaluating the antiviral activities of multiple gRNAs that effectively impeded HBV replication, we identified three specific gRNAs-namely 10, 4, and 21. These gRNAs were selected for their targeting of distinct yet conserved regions within the HBV genome. RESULTS: In HBV-stable cell lines, namely HepAD38, and HBV infection models of HepG2-NTCP cells, our investigation revealed that the co-application of gRNA-10 with either gRNA-4 or gRNA-21 within the CRISPR/Cas9 system demonstrated heightened efficacy in impeding HBV replication, reducing the levels of HBsAg, HBeAg, and cccDNA levels, along with a more pronounced promotion of HBsAg clearance when compared to the use of a single gRNA. CONCLUSIONS: The CRISPR/Cas9 system employing dual gRNAs has proven highly effective in both suppressing HBV replication and facilitating HBsAg clearance. This promising outcome suggests that it holds potential to emerge as a novel approach for achieving the functional cure of patients with HBV infection.


Assuntos
Sistemas CRISPR-Cas , Vírus da Hepatite B , RNA Guia de Sistemas CRISPR-Cas , Replicação Viral , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Humanos , Replicação Viral/genética , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas/genética , Células Hep G2 , Edição de Genes/métodos , DNA Circular/genética , DNA Circular/metabolismo , DNA Viral/genética , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/metabolismo , Antivirais/farmacologia , Hepatite B/virologia , Hepatite B/genética , Hepatite B/terapia
18.
Medicine (Baltimore) ; 102(46): e36019, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37986309

RESUMO

Based on the importance of chronic inflammation in the pathogenesis of periodontitis and diabetes, the bidirectional relationship between these 2 diseases has been widely confirmed. However, the molecular mechanisms of bidirectional relationship still need to be studied further. In this study, gene expression profile data for diabetes and periodontitis were obtained from Gene Expression Omnibus (GEO) database. Integrative analytical platform were constructed, including common differentially expressed genes (cDEGs), Gene Ontology-Kyoto Encyclopedia of Genes and Genomes (GO-KEGG), and protein-protein interaction. Hub genes and essential modules were detected via Cytoscape. Key hub genes and signaling pathway that mediate chronic inflammation were validated by qPCR and Western blot. Eleven cDEGs were identified. Function analysis showed that cDEGs plays an important role in inflammatory response, cytokine receptor binding, TNF signaling pathway. As hub genes, CXCR4, IL1B, IL6, CXCL2, and MMP9 were detected based on the protein-protein interactions network. IL1B, CXCR4 mRNA were up-regulated in gingivitis samples compared with normal tissues (P < .05). Western blot indicated that the levels of TNF were enhanced in gingivitis of type 2 diabetes compared with normal tissues (P < .01). Hub gene and TNF signaling pathway are helpful to elucidate the molecular mechanism of the bidirectional relationship between periodontitis and diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Gengivite , Periodontite , Humanos , Perfilação da Expressão Gênica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Biomarcadores , Periodontite/genética , Inflamação , Biologia Computacional
19.
J Inflamm Res ; 16: 197-207, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660376

RESUMO

Aim: The early prognosis evaluation of acute-on-chronic liver failure (ACLF) is important to decrease its mortality. We aimed to develop a new score to accurately predict the outcome of patients with ACLF. Methods: A derivation set of 408 patients with hepatitis B virus-related ACLF (HBV-ACLF) based on the Asian Pacific Association for the Study of the Liver criteria is used to develop a prognostic score that was validated in 209 patients with HBV-ACLF and 195 patients with non-HBV-ACLF. Results: Seven factors were significantly related to the 28-day mortality and constituted a new score (CHINAT-CD4 = 0.320 × ln (creatinine) + 0.668 × hepatic encephalopathy score + 0.745 × ln (international normalized ratio) + 0.476 × ln (neutrophil) + 0.251 × ln (aspartate aminotransferase) + 0.411 × ln (total bilirubin) - 0.605 × ln (CD4+ T cells count)). The C-indices of the new score for the 28-/90-day mortality (0.810/0.806) outperformed those of the other seven scores (p≤0.05). The results were confirmed in a validation set (0.798/793 for HBV-ACLF; 0.790/0.788 for non-HBV-ACLF). The novel score based on CD4+ T cell count showed high predictive performance for the 28-/90-day mortality of ACLF. Conclusion: The novel score based on CD4+ T cell count can accurately predict the 28-/90-day mortality for patients with ACLF.

20.
Sensors (Basel) ; 12(12): 16920-36, 2012 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-23223150

RESUMO

An infrared ceiling sensor network system is reported in this study to realize behavior analysis and fall detection of a single person in the home environment. The sensors output multiple binary sequences from which we know the existence/non-existence of persons under the sensors. The short duration averages of the binary responses are shown to be able to be regarded as pixel values of a top-view camera, but more advantageous in the sense of preserving privacy. Using the "pixel values" as features, support vector machine classifiers succeeded in recognizing eight activities (walking, reading, etc.) performed by five subjects at an average recognition rate of 80.65%. In addition, we proposed a martingale framework for detecting falls in this system. The experimental results showed that we attained the best performance of 95.14% (F1 value), the FAR of 7.5% and the FRR of 2.0%. This accuracy is not sufficient in general but surprisingly high with such low-level information. In summary, it is shown that this system has the potential to be used in the home environment to provide personalized services and to detect abnormalities of elders who live alone.


Assuntos
Acidentes Domésticos , Comportamento/fisiologia , Raios Infravermelhos , Monitorização Ambulatorial , Acidentes por Quedas , Atividades Cotidianas , Adulto , Algoritmos , Desenho de Equipamento , Feminino , Humanos , Masculino , Privacidade
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