RESUMEN
BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.
Asunto(s)
Trastorno Depresivo Mayor , Terapia por Luz de Baja Intensidad , Humanos , Trastorno Depresivo Mayor/terapia , Proyectos Piloto , Electroencefalografía , Estimulación Magnética TranscranealRESUMEN
BACKGROUND: Observational studies have previously shown a possible link between fatty acids and aging-related diseases, raising questions about its health implications. However, the causal relationship between the two remains uncertain. METHODS: Univariable and multivariable Mendelian randomization (MR) was used to analyze the relationship between five types of fatty acids-polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), saturated fatty acid (SFA), Omega-6 fatty acid (Omega-6 FA), and Omega-3 fatty acid (Omega-3 FA) and three markers of aging: telomere length (TL), frailty index (FI), and facial aging (FclAg). The primary approach for Mendelian randomization (MR) analysis involved utilizing the inverse variance weighted (IVW) method, with additional supplementary methods employed. RESULTS: Univariate MR analysis revealed that MUFA, PUFA, SFA, and Omega-6 fatty acids were positively associated with TL (MUFA OR: 1.019, 95% CI: 1.006-1.033; PUFA OR: 1.014, 95% CI: 1.002-1.026; SFA OR: 1.016, 95% CI: 1.002-1.031; Omega-6 FAs OR=1.031, 95% CI: 1.006-1.058). PUFA was also associated with a higher FI (OR: 1.033, 95% CI: 1.009-1.057). In multivariate MR analysis, after adjusting for mutual influences among the five fatty acids, MUFA and PUFA were positively independently associated with TL (MUFA OR: 1.1508, 95% CI = 1.0724-1.2350; PUFA OR: 1.1670, 95% CI = 1.0497-1.2973, while SFA was negatively correlated (OR: 0.8005, 95% CI: 0.7045-0.9096). CONCLUSIONS: Our research presents compelling evidence of a causal association between certain fatty acids and indicators of the aging process. In particular, MUFA and PUFA may play a role in slowing down the aging process, while SFAs may contribute to accelerated aging. These findings could have significant implications for dietary recommendations aimed at promoting healthy aging.
Asunto(s)
Ácidos Grasos Omega-3 , Ácidos Grasos , Grasas de la Dieta , Análisis de la Aleatorización Mendeliana , Ácidos Grasos Insaturados , Ácidos Grasos MonoinsaturadosRESUMEN
Epalrestat, an aldose reductase inhibitor (ARI), has been clinically adopted in treating diabetic neuropathy in China and Japan. Apart from the involvement in diabetic complications, AR has been implicated in inflammation. Here, we seek to investigate the feasibility of clinically approved ARI, epalrestat, for the treatment of rheumatoid arthritis (RA). The mRNA level of AR was markedly upregulated in the peripheral blood mononuclear cells (PBMCs) of RA patients when compared to those of healthy donors. Besides, the disease activity of RA patients is positively correlated with AR expression. Epalrestat significantly suppressed lipopolysaccharide (LPS) induced TNF-α, IL-1ß, and IL-6 in the human RA fibroblast-like synoviocytes (RAFLSs). Unexpectedly, epalrestat treatment alone markedly exaggerated the disease severity in adjuvant induced arthritic (AIA) rats with elevated Th17 cell proportion and increased inflammatory markers, probably resulting from the increased levels of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA). Interestingly, the combined treatment of epalrestat with N-Acetylcysteine (NAC), an anti-oxidant, to AIA rats dramatically suppressed the production of 4-HNE, MDA and inflammatory cytokines, and significantly improved the arthritic condition. Taken together, the anti-arthritic effect of epalrestat was diminished or even overridden by the excessive accumulation of toxic 4-HNE or other reactive aldehydes in AIA rats due to AR inhibition. Co-treatment with NAC significantly reversed epalrestat-induced upregulation of 4-HNE level and potentiated the anti-arthritic effect of epalrestat, suggesting that the combined therapy of epalrestat with NAC may sever as a potential approach in treating RA. Importantly, it could be regarded as a safe intervention for RA patients who need epalrestat for the treatment of diabetic complications.
Asunto(s)
Acetilcisteína , Artritis Reumatoide , Humanos , Animales , Ratas , Acetilcisteína/uso terapéutico , Leucocitos Mononucleares , Aldehídos , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.
Asunto(s)
Corteza Motora , Humanos , Corteza Motora/fisiología , Inhibición Neural/fisiología , Ácido Glutámico/metabolismo , Estimulación Magnética Transcraneal , Potenciales Evocados Motores/fisiología , Ácido gamma-Aminobutírico/metabolismo , Neurotransmisores/metabolismoRESUMEN
BACKGROUND: Jasmonates (JAs) are one of important phytohormones regulating potato tuber development. It is a complex process and the underlying molecular mechanism regulating tuber development by JAs is still limited. This study attempted to illuminate it through the potential proteomic dynamics information about tuber development in vitro regulated by exogenous JA. RESULTS: A combined analysis of physiological and iTRAQ (isobaric tags for relative and absolute quantification)-based proteomic approach was performed in tuber development in vitro under exogenous JA treatments (0, 0.5, 5 and 50 µΜ). Physiological results indicated that low JA concentration (especially 5 µM) promoted tuber development, whereas higher JA concentration (50 µM) showed inhibition effect. A total of 257 differentially expressed proteins (DEPs) were identified by iTRAQ, which provided a comprehensive overview on the functional protein profile changes of tuber development regulated by JA. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that low JA concentration (especially 5 µM) exhibited the promotion effects on tuber development in various cellular processes. Some cell wall polysaccharide synthesis and cytoskeleton formation-related proteins were up-regulated by JA to promote tuber cell expansion. Some primary carbon metabolism-related enzymes were up-regulated by JA to provide sufficient metabolism intermediates and energy for tuber development. And, a large number of protein biosynthesis, degradation and assembly-related were up-regulated by JA to promote tuber protein biosynthesis and maintain strict protein quality control during tuber development. CONCLUSIONS: This study is the first to integrate physiological and proteomic data to provide useful information about the JA-signaling response mechanism of potato tuber development in vitro. The results revealed that the levels of a number of proteins involved in various cellular processes were regulated by JA during tuber development. The proposed hypothetical model would explain the interaction of these DEPs that associated with tuber development in vitro regulated by JA.
Asunto(s)
Solanum tuberosum , Carbono/metabolismo , Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polisacáridos/metabolismo , Proteómica/métodos , Solanum tuberosum/metabolismoRESUMEN
Potato (Solanum tuberosum L.) as the important food crop worldwide has abundant morphological and genetic diversity. To understand the underlying molecular mechanisms determining phenotypic differences in wild species and cultivated potato, a comparative proteomics approach was applied to analyze leaf proteome alteration among three tetraploid cultivars and three diploid wild species using two-dimensional gel electrophoresis (2-DE). Quantitative image analysis showed a total of 47 protein spots with significantly altered abundance (>3-fold, P < 0.05), and 45 differentially abundant proteins were identified by MALDI-TOF/TOF MS. These proteins exhibited both the qualitative and quantitative changes. Most of them were involved in photosynthesis, cell defense and rescue, protein biosynthesis, which might exhibit the main differences between tetraploid cultivars and diploid wild species. The photosynthesis and protein biosynthesis-related proteins were up-regulated or only present in tetraploid cultivars, suggesting the higher photosynthetic efficiency and more newly synthesized peptides. It might contribute to some superior traits of tetraploid cultivars, such as larger leaf size, greater growth vigor, better tuber yield and quality. However, some cell defense and rescue-related proteins, especially the pathogenesis-related proteins and antioxidant enzymes, were up-regulated or only present in diploid wild species. It might be responsible for stronger resistance to diseases and pests or tolerance to environmental stresses in diploid wild species. This study would provide valuable information for the underlying molecular mechanisms of potato genetic diversity, and help in developing strategies for the utilization of wild species for potato improvement.
Asunto(s)
Solanum tuberosum , Diploidia , Fotosíntesis , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , TetraploidíaRESUMEN
Purpose: To explore the effect of propofol plus remifentanil for postoperative pain and heart rate management in patients undergoing abdominal hysterectomy. Methods: In this prospective randomized controlled study, 96 patients who underwent abdominal hysterectomy in an affiliated hospital of Fujian Medical University from April 2016 to April 2017 were recruited and randomized into the study group (n = 48) and control group (n = 48) via the random number table method. The control group received remifentanil for anesthesia, and the study group was given propofol plus remifentanil. The postoperative pain and heart rates of patients were compared between the two groups. Results: No significant difference was observed in the heart rate and adrenaline values between the two groups before anesthesia, and the study group had significantly lower adrenaline values and heart rates intraoperatively and 15 min after operation than the control group. Patients in the study group showed shorter time-lapse before independent breathing recovery, extubation, and resuscitation compared to those in the control group. The study group received less patient-controlled intravenous analgesia (PCIA) as compared to the study group within 48 h after operation. In the study group, the numeric rating scale (NRS) scores within 1 h, 2 h, 6 h, 8 h, and 12 h after operation were significantly lower than those in the control group (P < 0.001). Propofol plus remifentanil offer a viable alternative for postoperative pain management and stress alleviation after abdominal hysterectomy with a high safety profile. Further clinical trials are, however, required prior to clinical promotion.
RESUMEN
BACKGROUND: Gut microbiota coupled with their metabolites (bile acids, BAs) get involved in diabetic pathogenesis. Simiao Wan is a famous traditional Chinese formula consisting on Phellodendron chinense C.K.Schneid. (Rutaceae), Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae) and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Poaceae), and used to treat gouty arthritis and hyperuricemia for thousands of years. However, the mechanisms underlying its beneficial efficacy on diabetes still needs to be explored. PURPOSE: Our study was performed to reveal the effects of the 75% ethanol extraction of Simiao Wan (SMW) on diabetes, gut microbiota and bile acids (BAs) in diabetic mice. METHODS: The effects of SMW on diabetes were evaluated in mice treated by high-fat diet (HFD)/streptozotocin (STZ). The 16S rDNA sequencing and BAs metabolomics were performed to assess the changes of BAs profiles and gut microbiota induced by SMW. Western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of SMW. RESULTS: SMW significantly improved insulin resistance and hepatic lipid accumulation in HFD/STZ mice. It remarkably enriched in the bacteria Allobaculum, Clostridium, Akkermansia, Lactobacilus and Bilophila whereas decreased Coprococcus and Halomonas in diabetic mice. Furthermore, the profiles of BAs were also modulated by SMW, indicated by the reduction of conjugated BAs and 12α-OH/non-12α-OH BAs ratio in liver as well as the increase of primary BAs in feces. SMW also activated farnesoid X receptor and inhibited sterol regulatory element-binding protein-1 expression, contributing to its beneficial actions on lipid accumulation in liver. CONCLUSION: Our results showed that SMW exerted its beneficial effects on insulin resistance and hepatic lipid accumulation indirectly through regulating profiles of gut microbe and BAs.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistencia a la Insulina , Animales , Ácidos y Sales Biliares , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal/fisiología , Metabolismo de los Lípidos , Lípidos , Ratones , EstreptozocinaRESUMEN
Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.
Asunto(s)
Insulina , Lipólisis , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Insulina/metabolismo , Lipólisis/fisiología , Hígado/metabolismo , Ratones , Espectrometría de Masas en TándemRESUMEN
The objective of our overview of systematic reviews was to critically analyze the evidence from existing systematic reviews investigating the effectiveness and safety of low-level laser therapy (LLLT) in patients with breast cancer-related lymphedema (BCRL). In addition, an updated and comprehensive systematic review was conducted, which aimed to provide updated evidence about this topic. PubMed, EMBASE, and Cochrane Library databases were systematically searched for systematic reviews and randomized controlled trials (RCTs) investigating the effectiveness and safety of LLLT in patients with BCRL. The methodological quality for each of included systematic reviews or RCTs was assessed using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) tool or Cochrane risk of bias tool, respectively. The updated systematic review separately compared the effectiveness of LLLT to each of active or negative interventions. Data were pooled with random-effects models for each outcome per comparison. The evidence quality of outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) or GRADE-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) for quantitative studies and qualitative studies, respectively. Seven systematic reviews and ten RCTs met the eligibility criteria. Conflicting results regarding the effectiveness of LLLT were presented by the overview of systematic reviews. The AMSTAR 2 showed that the methodological quality of included systematic reviews was low or critically low quality due to one or more critical weaknesses. The GRADE and GRADE-CERQual showed that the evidence quality was low to very low for most outcomes. The updated systematic review showed that LLLT may offer additional benefits as compared to compression therapies (pneumatic compression or compression bandage), placebo laser, or no treatment for patients with BCRL. However, when compared to other types of active interventions, LLLT did not improve outcomes significantly. None of the treatment-related adverse event was reported. Many trials had a high or unclear risk of bias for two or more items, and our updated systematic review showed low quality of evidence per outcome using GRADE approach. Due to insufficient data and poor quality of evidence, there is uncertain to reach these conclusions that LLLT is superior to another active or negative intervention and is safe. More RCTs of high methodological quality, with large sample sizes and long-term follow-up, are needed to inform clinical guidelines and routine practice.
Asunto(s)
Neoplasias de la Mama , Terapia por Luz de Baja Intensidad , Linfedema , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Terapia por Luz de Baja Intensidad/efectos adversos , Revisiones Sistemáticas como AsuntoRESUMEN
Background: There are 9 traditional Chinese medicines (TCMs) combined with standard quadruple (SQ) available for the treatment of Helicobacter pylori (Hp)-associated gastritis, but their relative efficacy and best options in clinical decision making are unknown due to a lack of high-quality head-to-head randomized controlled trials (RCTs). This study aimed to explore which formulas are the most effective and/or safest for Hp-associated gastritis. Methods: We performed a search of electronic databases including PubMed, Web of Science, Cochrane Library, Embase, Chinese databases and South Korean database from inception to March 2022 to identify all relevant RCTs on the comparison between TCM combined with SQ and SQ for Hp-associated gastritis. Efficacy outcomes were the eradication rate of Hp and therapeutic response rate, and safety outcome was incidence of adverse reactions. Publication bias was assessed quantitatively using Egger's regression analysis and qualitatively using trim-and-fill method. Quality assessment was performed using Cochrane Risk of Bias, version 2 (ROB 2) tool. The Bayesian methods were applied to compare each treatment. Results: A total of 55 trials with 6,187 patients were involved. The experimental group included 9 TCMs combined with SQ. The control group was SQ. The pair-wise meta-analysis demonstrated that compared with control group, 8 TCMs combined with SQ could statistically improve the eradication rate of Hp in patients with gastritis, 9 TCMs combined with SQ could significantly improve the therapeutic response rate. Additionally, Banxia Xiexin decoction combined with SQ (BXS) could statistically decrease the incidence of adverse reactions. The network meta-analysis results showed that BXS, Xiangsha Liujunzi combined with SQ (XSS), and Huangqi Jianzhong decoction combined with SQ (HQS) was the best measures to effectively eradicate Hp, enhance therapeutic effect, and decrease adverse reactions, respectively. The results of trim-and-fill method indicated that the results were stable and less affected by publication bias. Conclusions: Compared with SQ, TCM combined with SQ generally has a better clinical effect and higher safety in patients with Hp-associated gastritis. BXS, XSS, and HQS are recommended based on the patient's condition and needs in clinical practice. Further high-quality double-blinded RCTs are warranted to validate the conclusions.
RESUMEN
BACKGROUND: No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment. METHODS: This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance. RESULTS: Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6). CONCLUSION: Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.
Asunto(s)
COVID-19 , COVID-19/prevención & control , Personal de Salud , Humanos , Pandemias/prevención & control , Equipos de Seguridad , Terapia por RelajaciónRESUMEN
OBJECTIVE: To explore the application of Jianpi Xiaoai recipe combined with cisplatin and Adriamycin in the treatment of endometrial cancer (EC) and its effect on the disease control rate (DCR). METHODS: The data of 120 EC patients treated in People's Hospital of Rizhao from February 2019 to February 2020 were retrospectively analyzed. They were equally split into experimental group and control group according to the order of admission. All patients were treated with neoadjuvant intra-arterial chemotherapy (continuous infusion of the uterine artery for 5 days before surgery, with 20 mg of cisplatin mixed with 2000 mg of normal saline and 10 mg of Adriamycin mixed with 500 ml of normal saline daily), while the experimental group was treated with Jianpi Xiaoai recipe at the same time to compare the short-term efficacy, immune function indexes, incidence of adverse reactions, and HEC-1-B (human endometrial adenocarcinoma cells) cell inhibition rates between the two groups. RESULTS: The DCR and objective remission rate (ORR) in the experimental group were markedly higher compared with the control group (P < 0.05). The immune function indexes after treatment were remarkably better in the experimental group than in the control group (P < 0.05). Compared with the control group, the incidence of adverse reactions in the experimental group was notably lower (P < 0.05), while the HEC-1-B inhibition rates after treatment were obviously higher (P < 0.05). CONCLUSION: Jianpi Xiaoai recipe combined with cisplatin and Adriamycin can increase the HEC-1-B cell inhibition rate in EC patients, improve their immune function, reduce the possibility of adverse reactions, and enhance the therapeutic effect, which is worthy of clinical application and popularization.
RESUMEN
In recent years, a comprehensive study of complex disease with multi-view datasets (e.g., multi-omics and imaging scans) has been a focus and forefront in biomedical research. State-of-the-art biomedical technologies are enabling us to collect multi-view biomedical datasets for the study of complex diseases. While all the views of data tend to explore complementary information of disease, analysis of multi-view data with complex interactions is challenging for a deeper and holistic understanding of biological systems. In this paper, we propose a novel generalized kernel machine approach to identify higher-order composite effects in multi-view biomedical datasets (GKMAHCE). This generalized semi-parametric (a mixed-effect linear model) approach includes the marginal and joint Hadamard product of features from different views of data. The proposed kernel machine approach considers multi-view data as predictor variables to allow a more thorough and comprehensive modeling of a complex trait. We applied GKMAHCE approach to both synthesized datasets and real multi-view datasets from adolescent brain development and osteoporosis study. Our experiments demonstrate that the proposed method can effectively identify higher-order composite effects and suggest that corresponding features (genes, region of interests, and chemical taxonomies) function in a concerted effort. We show that the proposed method is more generalizable than existing ones. To promote reproducible research, the source code of the proposed method is available at.
Asunto(s)
Algoritmos , Osteoporosis , Adolescente , Encéfalo/diagnóstico por imagen , Humanos , Modelos Lineales , Osteoporosis/diagnóstico por imagen , Programas InformáticosRESUMEN
AIMS: To investigate the change of stress hormones, oxidative stress and insulin resistance (IR) in women with gestational diabetes mellitus (GDM) after supplement whey protein, in an attempt to gain insights into the prevention and treatment of GDM. MATERIALS AND METHODS: 60 GDM women were recruited in this study, and 30 women received a preload drink containing 20 g whey protein as group GDM-W, and the other 30 women received control flavoring drink as group GDM, and the trial lasted for 14 days. Plasma epinephrine (E), noradrenaline (NE), and cortisol were detected; we also determined levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess IR. RESULTS: In the GDM-W group, postprandial blood glucose was decreased significantly on 3, 5, 7, and 14 days (all p < .05), plasma 2 h insulin was increased by 7.2, 8.6, and 20.5% on days 5, 7, and 14 (p < .05, .05, .01). HOMA-IR was decreased significantly on day 14 (p < .05). MDA was decreased by 20.7% on day 14 (p < .01), and anti-oxidative enzymes' SOD was decreased by 13.4% on day 14 (p < .05) and GSH was decreased by 16.7 and 29.1% on days 7 and 14 (both p < .05). Stress hormones E and cortisol were decreased by 10.8 and 19.8%, respectively, on day 14 (p < .05). There was no significant difference in NE between the two groups within 14 days. CONCLUSIONS: Whey protein supplementation may improve hyperglycemia by alleviating stress disorder and oxidative stress injury in GDM women. This trial was registered at chictr.org.cn/as ChiCTR1800020413.
Asunto(s)
Catecolaminas/sangre , Diabetes Gestacional/dietoterapia , Hidrocortisona/sangre , Hiperglucemia/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Proteína de Suero de Leche/administración & dosificación , Adulto , Glucemia/análisis , Diabetes Gestacional/sangre , Diabetes Gestacional/fisiopatología , Epinefrina/sangre , Femenino , Edad Gestacional , Glutatión/sangre , Humanos , Resistencia a la Insulina , Malondialdehído/sangre , Norepinefrina/sangre , Embarazo , Superóxido Dismutasa/sangreRESUMEN
OBJECTIVE: To investigate the effectiveness of alpha activity neurofeedback training over the parietal lobe in GAD patients. METHODS: Twenty-six female patients who had been diagnosed as GAD according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition, DSM-V) criteria were included in this study. Patients were randomized into two groups: the left parietal lobe training group (LPL group, n = 13) and the right parietal lobe training group (RPL group, n = 13), and then received ten 40-minute alpha training sessions in the relevant area. Evaluations included severity of anxiety (by State-Trait Anxiety Inventory, STAI) and depression (by Beck Depression Inventory, BDI-II) after the fifth training session and the last training session. RESULTS: The scores of STAI-S decreased significantly two weeks after the fifth training session in both groups (LPL group: from 47.15 ± 10.65 to 38.69 ± 8.78, p<.05; RPL group: from 44.92 ± 12.37 to 37.31 ± 6.41, p < .05) and decreased further at the four weeks' time point after the last training session (LPL group: 35.15 ± 9.24; RPL group: 29.85 ± 6.18). Compared with baseline, the scores of STAI-T, BDI-II and ISI decrease at two weeks, no significant difference found between LPL group and RPL group. The scores of STAI-T, BDI-II and ISI decreased at four weeks when compared with two weeks, and no significant difference found between LPL group and RPL group. CONCLUSION: Neurofeedback training of alpha activity over the parietal lobe is effective in GAD patients, especially the anxiety trait and depressive symptoms.
Asunto(s)
Depresión , Neurorretroalimentación , Ansiedad/terapia , Trastornos de Ansiedad/terapia , Depresión/terapia , Femenino , Humanos , Escalas de Valoración PsiquiátricaRESUMEN
Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C16H14O4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Chalconas/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Osteosarcoma/tratamiento farmacológico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Neoplasias Óseas/enzimología , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Activación Enzimática , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Osteosarcoma/enzimología , Osteosarcoma/patología , Fosforilación , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Osteosarcoma (OS) is a primary bone tumor associated with locally aggressive growth and early metastatic potential that typically occurs in children and adolescents. Chinese traditional medicine Cinnamomum cassia Presl has been shown to have significant tumor-killing effect, in which cinnamaldehyde (CA) is the main active ingredient. PURPOSE: To explore the anticancer effect of CA on the osteosarcoma cells and the possible molecular mechanism. METHODS: Crystal violet assay, MTT assay and colony-forming assay were used to confirm the inhibitory role of CA in the proliferation of 143B and MG63 osteosarcoma cells. Hoechst 33258 staining and flow cytometry were used to observe apoptosis. The migration and invasion role of OS cells were evaluated using transwell assays and wound healing assays. Western blotting was used to analyse the protein expression levels. Nude mice were inoculated with 143B cells to establish an orthotopic OS tumor animal model and to investigate the effects of CA on OS tumors. RESULTS: According to crystal violet assay, MTT assay and colony-forming assay, CA significantly inhibited cell proliferation. Hoechst 33258 staining and flow cytometry analysis showed that CA-induced apoptosis in a concentration-dependent manner. In addition, transwell assays and wound healing assays showed that CA inhibited the migration and invasion of osteosarcoma cells. In vivo mouse models, CA inhibited the growth of osteosarcoma. The potential mechanisms could be that CA inhibited the transcriptional activity of Wnt/ß-catenin and PI3K/Akt of the osteosarcoma. CONCLUSION: CA may inhibit the proliferation, migration, invasion and promote apoptosis of OS cells by inhibiting Wnt/ß-catenin and PI3K/Akt signaling pathways. CA may be a potentially effective anti-tumor drug.
Asunto(s)
Acroleína/análogos & derivados , Antineoplásicos Fitogénicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , beta Catenina/antagonistas & inhibidores , Acroleína/química , Acroleína/farmacología , Animales , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Células Tumorales Cultivadas , beta Catenina/metabolismoRESUMEN
BACKGROUND: In recent years, clinical studies about Yangxin Decoction combined acupuncture (YXDA) for the treatment of Qi Deficiency and Blood Stasis type of Chest Bi-Syndrome (CBS-QDBS) has been increased, but the results are different. The aim of this study is to investigate the effect of YXDA on blood lipid metabolism (BLMB) in patients with CBS-QDBS. METHODS: We will collect any randomized controlled trials that assess the effect of YXDA on BLMB in CBS-QDBS from PUBMED, EMBASE, Cochrane Library, PsycINFO, CINAHL, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure. All of these databases will be searched from their initial time to the present. All language limitation will be imposed. Literature selection, information collection, and risk of bias assessment will be performed independently by two authors, respectively. All data analysis will be undertaken using RevMan 5.3 Software. RESULTS: This study will summarize the systematic nature of the literature search and its methods for assessing study quality and analyzing all relevant outcome data. Considering the inconsistent results, this study will improve the existing evidence on the effect of YXDA on BLMB in CBS-QDBS. CONCLUSION: The findings of this study will present the latest evidence of YXDA on BLMB in patients with CBS-QDBS. STUDY REGISTRATION: INPLASY202070047.
Asunto(s)
Terapia por Acupuntura/métodos , Dolor en el Pecho/terapia , Medicamentos Herbarios Chinos/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Qi , Terapia Combinada , Medicamentos Herbarios Chinos/farmacología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de InvestigaciónRESUMEN
In the natural environment, attended sounds tend to be perceived much better than unattended sounds. However, the physiological mechanism of how our neural systems direct the state of perceptual attention to prepare for the detection of upcoming acoustic stimuli before auditory stream segregation remains elusive. In this study, based on the direct intracerebral recordings from the auditory cortex in eight epileptic patients with refractory focal seizures, we investigated the neural processing of auditory attention by comparing the local field potentials before 'attentional' and 'distracted' conditions. Here we first showed a distinct build-up of slow, negative cortical potential in Heschl's gyrus. The amplitude increased steadily, starting from 600 to 800 ms before presentation of the tone until the onset of the evoked component P/N 60-80 when the patients were in the attentional condition. Because of their specific topographical distribution and modality-specific properties, we named these 'auditory preparatory potentials', which are also associated with increased gamma oscillations (30-150 Hz) and desynchronized low frequency activity (below 30 Hz). Thus, our findings suggest that the auditory cortex is pre-activated to facilitate the perception of forthcoming sound events, and contribute to the understanding of the neurophysiological mechanisms of auditory perception from a new perspective.