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1.
Breast ; 59: 117-123, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34229126

RESUMO

PURPOSE: To investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease. METHODS: Patients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model. RESULTS: We identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC. CONCLUSION: The 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.

2.
BMC Musculoskelet Disord ; 22(1): 602, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193139

RESUMO

OBJECTIVE: The aim of this study was to evaluate the completeness of reporting of exercise adherence and exercise interventions delivered as part of clinical trials of post-operative total knee replacement (TKA) rehabilitation. DESIGN: Scoping review LITERATURE SEARCH: A literature search was conducted in PubMed, EMBASE, AMED, CINAHL, SPORTDiscus and Cochrane Library. STUDY SELECTION CRITERIA: All randomized controlled trials (RCT) that examined post-operative exercise-based interventions for total knee arthroplasty were eligible for inclusion. Studies that were multifactorial or contained exercise interventions for both hip and knee arthroplasty were also included. DATA SYNTHESIS: The definition, type of measurement used and outcome for exercise adherence were collected and analyzed descreptively. Quality of reporting of exercise interventions were assessed using the Consensus for Exercise Reporting Tool (CERT) and the Cochrane Risk of Bias Tool. RESULTS: There were a total of 112 RCTs included in this review. The majority of RCTs (63%, n = 71) did not report exercise adherence. Only 23% (n = 15) of studies provided a definition of adherence. RCTs were of poor quality, with 85% (n = 95) of studies having high or unclear risk of bias. Reporting of exercise interventions was poor, with only 4 items (of 19) (21%) of the CERT adequately reported (88-99%), with other items not fulfilled on at least 60% of the RCTs. There were no RCTs that had fulfilled all the criteria for the CERT. CONCLUSION: The RCTs included in this study poorly reported exercise adherence, as well as description of the post-operative TKA rehabilitation intervention. Future RCTs should use valid and reliable measures of adherence and a proper tool for reporting of exercise interventions (e.g., CERT, TiDER). PRE-REGISTRATION: OSF: https://osf.io/9ku8a/.


Assuntos
Artroplastia do Joelho , Exercício Físico , Terapia por Exercício , Humanos , Cuidados Pós-Operatórios
3.
Brain Tumor Pathol ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34231121

RESUMO

Current conventional treatment strategies for glioblastoma (GBM) have limited efficacy due to the rapid development of resistance to temozolomide (TMZ). It is particularly urgent to develop novel therapeutic strategies that can overcome TMZ resistance and provide patients with better prognoses. Here, a TMZ-resistant GBM cell strain and a mouse model of TMZ resistance are established as valuable tools to explore novel therapeutic strategies against TMZ resistance. Experimentally, p38MAPK inhibitor reduces the accumulation of F4/80+/CD11b+ macrophages/microglia in glioma and prolongs the survivals of glioma-bearing mice. Glioma-associated macrophages/microglia have a significanct expression of PD-L1. p38MAPK inhibitor in combination with PD-L1 antibody can effectively prolongs the survivals of TMZ-resistant GBM-bearing hosts, and differentially reduces the accumulation of circulating monocytes-derived tumor-associated macrophages and PD-L1 abundances of resident glioma-associated microglia. This combination therapy could be a treatment option for patients at the recurrence or chronic TMZ maintenance stages. A clinical study to confirm the safety and effectiveness of this combination therapy is warranted.

4.
Acupunct Med ; : 9645284211027892, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231397

RESUMO

OBJECTIVE: To screen for differentially expressed serum microRNAs (miRNAs) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) compared with healthy participants and explore the mechanism of acupuncture in the treatment of IBS-D based on miRNAs. METHODS: IBS-D patients that met the Rome III diagnostic criteria and age- and sex-matched healthy participants were enrolled between April 2017 and December 2017. Serum miRNA levels were initially determined using a TaqMan low-density array (TLDA) in pooled samples. Markedly altered miRNAs in IBS-D patients were subsequently validated using quantitative real-time polymerase chain reaction (qRT-PCR) on individual samples. All IBS-D patients accepted the acupuncture therapy for 6 weeks. The disease severity was assessed using the IBS symptom severity scale (IBS-SSS) questionnaire before and after treatment. After acupuncture, the patients' serum was re-analyzed for altered expression of the miRNAs by qRT-PCR. RESULTS: TLDA and qRT-PCR analysis revealed six upregulated miRNAs (miR-1305, miR-575, miR-149-5p, miR-190a-5p, miR-135a-5p, and miR-148a-3p; P < 0.05) and two downregulated miRNAs (miR-194-5p, miR-127-5p; P < 0.05) in IBS-D patients compared with healthy controls. Post acupuncture treatment, total IBS-SSS scores, severity of abdominal pain, duration of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits and disruption in quality of life decreased significantly (P < 0.001). Furthermore, the upregulated miR-148a-3p levels in IBS-D patients also decreased significantly after acupuncture (P < 0.05). CONCLUSIONS: The over-expression or reduced expression of several miRNAs may contribute to IBS-D pathogenesis. Acupuncture might downregulate miR-148a-3p through multiple pathways to alleviate or relieve IBS-D symptoms. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17010860 (Chinese Clinical Trials Registry).

5.
Artigo em Inglês | MEDLINE | ID: mdl-34255920

RESUMO

This study explored the association between age at menarche and the risk of hypertension in Chinese women. A total of 234 867 women aged ≥18 years from the China Hypertension Survey were included in this study. Participants were required to complete a standard questionnaire. Blood pressure and physical examination of the participants were performed by trained medical staff. Spearman correlation analysis was used to explore the correlation between age at menarche and other individual characteristics. Logistic regression was used to estimate the odds ratios for hypertension by age in years at menarche. The average age at menarche in Chinese women was 14.8 years. Women who were older at menarche were more likely to have a higher body mass index, larger waist circumference, smoke, and have a primary education (p < .05). After adjustments, odds ratios (95% confidence interval) for hypertension across age at menarche groups were 0.912 (0.877-0.948), 0.927 (0.893-0.963), 1.00 (reference), 1.061 (1.020-1.102), and 1.129 (1.090-1.169) for those aged ≤13, 14, 15 (reference), 16, and ≥17 years at menarche, respectively. Each 1-year delay in menarche was associated with a 6.2% increase in the prevalence of hypertension (odds ratio, 1.062; 95% confidence interval, 1.053-1.071). The positive association between age at menarche and hypertension was evident among age at recruitment groups, BMI categories, and education levels. This association was stronger in urban women and postmenopausal women. Our findings suggest that late menarche is related to a higher risk of hypertension among Chinese adult women, and this association appeared similar among different subgroups.

6.
PLoS Negl Trop Dis ; 15(7): e0009520, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34264939

RESUMO

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.

7.
Cell Death Dis ; 12(7): 665, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215721

RESUMO

It has been reported that growth differentiation factor 11 (GDF11) protects against myocardial ischemia/reperfusion (IR) injury, but the underlying mechanisms have not been fully clarified. Considering that GDF11 plays a role in the aging/rejuvenation process and that aging is associated with telomere shortening and cardiac dysfunction, we hypothesized that GDF11 might protect against IR injury by activating telomerase. Human plasma GDF11 levels were significantly lower in acute coronary syndrome patients than in chronic coronary syndrome patients. IR mice with myocardial overexpression GDF11 (oe-GDF11) exhibited a significantly smaller myocardial infarct size, less cardiac remodeling and dysfunction, fewer apoptotic cardiomyocytes, higher telomerase activity, longer telomeres, and higher ATP generation than IR mice treated with an adenovirus carrying a negative control plasmid. Furthermore, mitochondrial biogenesis-related proteins and some antiapoptotic proteins were significantly upregulated by oe-GDF11. These cardioprotective effects of oe-GDF11 were significantly antagonized by BIBR1532, a specific telomerase inhibitor. Similar effects of oe-GDF11 on apoptosis and mitochondrial energy biogenesis were observed in cultured neonatal rat cardiomyocytes, whereas GDF11 silencing elicited the opposite effects to oe-GDF11 in mice. We concluded that telomerase activation by GDF11 contributes to the alleviation of myocardial IR injury through enhancing mitochondrial biogenesis and suppressing cardiomyocyte apoptosis.

8.
J Neurol ; 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34274994

RESUMO

BACKGROUND AND OBJECTIVE: Exploration of hypermetabolism in amyotrophic lateral sclerosis (ALS) with different ethnicities is needed to understand its metabolic implications for clinical management. We aimed to evaluate the features of hypermetabolism and investigate its association with clinical characteristics and prognosis of ALS in a prospective Chinese cohort. METHODS: This prospective study was conducted at Peking University Third Hospital, China from 2017 to 2020. 343 participants were enrolled initially. After strict screening, 147 matched health controls and 93 patients with ALS were eligible and underwent detailed clinical assessments. Disease severity and progression were evaluated using recognized scales. Metabolic assessments included body composition and metabolic index (MI) [hypermetabolism if MI ≥ 120.0%]. Patients were followed up every 6 months for survival analysis. RESULTS: Compared with controls, hypermetabolism was significantly more prevalent in ALS (p = 0.009). MI was consistently higher in ALS than controls (p = 0.009). Further correlation analysis showed that MI significantly decreased with disease progression, as graded by King's College staging system (p < 0.001). MI was significantly correlated with fat-free mass and fat mass (p = 0.005 and 0.007). Survival analysis showed that hypermetabolism independently indicated a worse prognosis for ALS (HR = 1.020, CI = 1.004-1.036, p = 0.013). CONCLUSION: A significant increase in the prevalence and degree of hypermetabolism was identified in ALS compared with strictly matched controls. Metabolic index, which is significantly associated with disease progression and body composition, is an independent prognostic indicator for a worse survival of ALS.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34199704

RESUMO

Cadmium (Cd) is one of the most important heavy metal toxicants, used throughout the world at the industrial level. It affects humans through environmental and occupational exposure and animals through the environment. The most severe effects of oral exposure to Cd on the male reproductive system, particularly spermatogenesis, have not been discussed. In this study, we observed the damage to the testes and heritable DNA caused by oral exposure to Cd. Adult male Sprague-Dawley rats were divided into four groups: a control group and three groups treated with 5, 10, and 15 mg Cd/kg/day for 17 days by oral gavage. Our results revealed that Cd significantly decreases weight gain in 10 and 15 mg/kg groups, whereas the 5 mg/kg groups showed no difference in weight gain. The histopathology showed adverse structural effects on the rat testis by significantly reducing the thickness of the tunica albuginea, the diameter of the tubular lumen, and the interstitial space among seminiferous tubules and increasing the height of the epithelium and the diameter of the seminiferous tubules in Cd treated groups. Comet assay in epididymal sperms demonstrated a significant difference in the lengths of the head and comet in all the 3 Cd treated groups, indicating damage in heritable DNA, although variations in daily sperm production were not significant. Only a slight decrease in sperm count was reported in Cd-treated groups as compared to the control group, whereas the tail length, percentage of DNA in head, and tail showed no significant difference in control and all the experimental groups. Overall, our findings indicate that Cd toxicity must be controlled using natural sources, such as herbal medicine or bioremediation, with non-edible plants, because it could considerably affect heritable DNA and induce damage to the reproductive system.

10.
Acta Ophthalmol ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34260829

RESUMO

PURPOSE: To monitor the intraocular proangiogenic and profibrotic cytokine profiles within 7 days after intravitreous injection of conbercept (IVC) for patients with proliferative diabetic retinopathy (PDR). METHODS: This prospective, randomized controlled, consecutive, comparative study included 157 eyes with PDR. Participant eyes underwent sham IVC or IVC and subsequent vitrectomy at days 2, 3, 4, 5, 6, 7 postinjection. The intraocular cytokines profiles were measured using beaded assay methods. RESULTS: After IVC, the vascular endothelial growth factor (VEGF)-A level in PDR vitreous decreased rapidly by approximately 10 times at day 2 (p = 0.00001) and kept at a low level at days 3, 4, 5, 6, 7 (p < 0.001, each compared with IVC-sham group). Similar tendency of the change in VEGF-A was observed in aqueous humour. The level of placenta growth factor (PIGF) in aqueous humour decreased 2 days after IVC whereas returned to baseline level after 5 days. The vitreous profibrotic cytokines, tissue growth factor (TGF)-ß1, TGF-ß2, TGF-ß3 and connective tissue growth factor did not increase after IVC in each group. CONCLUSION: We observed a remarkable and rapid decrease in intraocular VEGF-A, temporal decrease in PIGF from day 2 to day 4, increase in VEGF-C and VEGF-D from day 2 onwards, but no profibrotic switch in PDR eyes after IVC. The findings might suggest that ideal vitrectomy timing might be around 3 days after IVC.

11.
Pediatr Blood Cancer ; : e29212, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245210

RESUMO

BACKGROUND: Positron emission tomography (PET)-based measures of baseline total-body tumor burden may improve risk stratification in intermediate-risk Hodgkin lymphoma (HL). MATERIALS AND METHODS: Evaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high-quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan-Meier survival analyses assessed for an association of MTV and TLG with event-free survival (EFS). RESULTS: From the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET-derived parameters were significantly associated with EFS. For each of these, Kaplan-Meier analyses and the log-rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p < .029). In a multivariable model controlling for important covariates including disease bulk and response to chemotherapy, MTV2BP was significantly associated with EFS (p = .012). CONCLUSION: Multiple baseline PET-derived volumetric parameters were associated with EFS. MTV2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk-based treatment algorithms may improve outcomes in intermediate-risk HL.

12.
J Hazard Mater ; 417: 126130, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34229397

RESUMO

Novel composite foam (CMCTS-PUF-s) was prepared by immobilizing carboxymethyl chitosan (CMCTS) on polyurethane foam (PUF) in which amino groups in CMCTS reacted with isocyanate groups in polyurethane prepolymer. The adsorption capacity of the optimal composite foam (CMCTS-PUF-5) reached to 118.2 mg/g with 5% CMCTS loading. The removal rate to methylene blue (MB) was up to 97.1%, which was obviously higher than 18.9% of PUF. After recycling for five times, the removal rate still reached 83.2%, which strongly proved the excellent reusability of immobilizing CMCTS modified PUF. The characterization results of FTIR and TG showed that CMCTS was well loaded on PUF by covalent bond. The Young's modulus and tensile strength of CMCTS-PUF-5 were increased by 252% and 97% compared with that of PUF. MIP characterization result showed the porosity of CMCTS-PUF-5 was 73.99% and the pore sizes were mainly distributed between 50 and 150 µm, which provide sufficient diffusion channels and active sites for MB dyes. The adsorption kinetics and isotherm proved pseudo-second-order kinetic model and Langmuir isotherm model could well describe the adsorption process of CMCTS-PUF-5. Therefore, CMCTS-PUF-s presents excellent recoverability, high stability and attractive adsorption efficiency, shows the potential application in future treatment of dye wastewater.

13.
Int J Mol Med ; 48(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34212983

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to be associated with the progression of coronary artery disease (CAD). In our previous study, the levels of lncRNA uc003pxg.1 were upregulated in patients with CAD compared with those in control subjects. However, the role and underlying mechanism of the effects of uc003pxg.1 in CAD remain unknown. Therefore, the aim of the present study was to investigate the expression pattern and biological function of uc003pxg.1 in CAD. First, uc003pxg.1 expression levels were assessed in peripheral blood mononuclear cells isolated from patients with CAD by reverse transcription­quantitative (RT­q)PCR. The results demonstrated that the levels of uc003pxg.1 were significantly upregulated (~4.6­fold) in samples from 80 patients with CAD compared with those in 80 healthy subjects. Subsequently, the present study demonstrated that small interfering RNA­mediated uc003pxg.1 knockdown inhibited human umbilical vein endothelial cell (HUVEC) proliferation and migration, which was analyzed using the Cell Counting Kit­8, cell cycle, EdU and Transwell assays. Additionally, the results of RT­qPCR and western blot analyses revealed that uc003pxg.1 regulated the mRNA and protein levels of cyclin D1 and cyclin­dependent kinase. Through high­throughput sequencing and dual­luciferase reporter assays, the present study demonstrated that microRNA (miR)­25­5p was a downstream target of uc003pxg.1. Further experiments verified that uc003pxg.1 regulated HUVEC proliferation and migration via miR­25­5p. The results of the present study may enhance the current understanding of the role of lncRNA uc003pxg.1 in CAD.

14.
Mol Cell Endocrinol ; 535: 111378, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34216644

RESUMO

PURPOSE: We previously found the mutation frequency of cytoskeleton-associated protein 2 (CKAP2) was significantly increased in proliferative diabetic retinopathy (PDR) patients through whole exome sequencing. The present study was conducted to explore the expression and possible mechanism of CKAP2 in PDR patients and human retinal capillary endothelial cells (HRCECs) under high-glucose (HG) conditions. METHODS: Expression of CKAP2 and p53 in the vitreous fluid and fibrovascular membrane (FVM) of PDR patients and HRCECs under HG conditions was observed. Cell proliferation, migration and tubule formation were assessed. Ranibizumab and siRNA transfection were used in the inhibition assay. RESULTS: CKAP2 and p53 were significantly increased in the ocular tissues of PDR patients. HG combined with VEGF treatment significantly up-regulated expression of CKAP2 and p53 in HRCECs. Inhibition of CKAP2 attenuated the abilities of cell proliferation, migration and tube formation under HG conditions. Blocking VEGF or p53 significantly decreased CKAP2 expression, whereas inhibition of CKAP2 failed to alter the level of VEGF or p53. CONCLUSIONS: CKAP2 is involved in the pathogenesis of PDR and regulated by VEGF and p53 under HG conditions.

15.
J Colloid Interface Sci ; 603: 220-232, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34197982

RESUMO

This work synthesized a novel CuS/KTa0.75Nb0.25O3 (KTN) heterojunction composite and firstly applied it in photocatalytic and piezocatalytic reduction of N2 to NH3. XRD, Raman, XPS, SEM, and TEM analyses indicate that CuS nanoparticles closely adhered to the surface of KTN nanorods, which facilitates the migration of electrons between the two semiconductors. Mott-Schottky and valence band XPS analysis shows that KNbO3 shows a higher conduction band than CuS, indicating that CuS mainly acts as electron trappers to capture the photogenerated electrons from KTN. Because of the great enhanced spatial separation of photogenerated charge carriers, the CuS/KTN presents much higher performance than pure KNT, which is further confirmed by 1H NMR analysis of the reaction solution. An interesting finding is that synthesized CuS/KTN not only performs well under light irradiation but also can work in an ultrasonic bath, indicating its great potential in photo/piezocatalytic conversion of N2 to NH3. The optimal 10 %CuS/KTN shows an NH3 production rate of 36.2 µmol L-1 g-1 h-1 under ultrasonic vibration, which reaches 7.4 times that of KTN. The electrons generated by KTN through the piezoelectric effect can be captured by CuS, which endows the electrons a longer life to participate in the reaction, thereby improving the catalytic reaction performance.

16.
Life Sci ; 282: 119824, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34265361

RESUMO

AIM: Berberine (BBR) is an alkaloid extracted from Coptidis Rhizoma, also known as Huang-Lian. Huang-Lian has been used extensively in traditional Chinese medicine for the treatment of various diseases, including diabetes and dementia. Because Alzheimer's disease (AD) is a complex disease that involves various pathophysiological changes, the diverse neuroprotective effects of BBR may be useful for improving the brain's energy state at an early stage of the disease. MAIN METHODS: We performed extracellular flux and 1H NMR-based metabolic profiling analyses to investigate the effects of BBR on metabolic processes in these cells. Pioglitazone (PIO), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist has been studied extensively for the treatment of AD. We explored the combination dosing effects of BBR and PIO in vitro, then leveraged computational methods to explain the experimental finding. KEY FINDINGS: BBR demonstrates potential in modulating the mitochondrial bioenergetics and attenuating dysfunction of the primary energy and glutathione metabolism pathways in an AD cell model. It also suppresses basal respiration and reduces the production of pro-inflammatory cytokines in activated microglial cells. Both experimental and computational observations indicate that BBR and PIO have comparable binding affinities to the PPARγ protein, suggesting both drugs may have some overlapping effects for AD. SIGNIFICANCE: BBR exerts beneficial effects on disrupted metabolic processes in amyloidogenic cells and activated microglial cells, which are important for preventing or delaying early-stage disease progression. The choice of BBR or PIO for AD treatment depends on their respective pharmacokinetic profiles, delivery, efficacy and safety, and warrants further study.

17.
Seizure ; 91: 346-359, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34284303

RESUMO

BACKGROUND: Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated antibodies, and AE-related seizures are still unclear. AIMS: This research evaluated the relationship between AE, AE-related seizures, and neuronal antibodies, as well as the morbidity of AE with early incidence. METHODS: The PubMed, Embase, Cochrane, and Web of Science databases were searched. Pooled estimates and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Of the 4,869 citations identified, 100 articles were reviewed in full, and 42 subgroups were analyzed. The overall incidence of AE patients with seizures was 42% (95% CI: 0.40-0.44), and among them, the incidence of epilepsy in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients was 73% (95% CI: 0.70-0.77). Subsequently, we found that the prevalence of AE as the cause of epilepsy within the pooled period was 1% (95% CI: 0.01-0.02), while the overall positive rate of neuronal antibodies in epilepsy patients was 4% (95% CI: 0.03-0.05). Additionally, the detection rates of different antibodies among epilepsy patients were as follows: anti-NMDAR, 1%; anti-leucine-rich glioma inactivated 1 (LGI1), 1%; anti-contactin-associated protein-like 2 (CASPR2), 2%. CONCLUSION: Based on our findings, neuronal antibodies may serve as a bridge to study AE and immune-related epilepsy. To further understand the differences in outcomes following different treatment measures, and to provide more information for public health policy and prevention, more research is needed to improve the accuracy of estimations.

18.
BMC Ophthalmol ; 21(1): 281, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284740

RESUMO

BACKGROUND: Dysfunction of lacrimal gland (LG) gains increasing attention in patients with thyroid-associated ophthalmopathy (TAO), while the underlying pathological change is still not fully established. This study aimed to evaluate the utility of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in non-invasively detecting microstructural alterations of LG in patients with TAO, as well as in discriminating disease activity. METHODS: Thirty TAO patients and 15 age- and sex- matched healthy controls, who underwent rs-EPI-based DTI, were retrospectively enrolled. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of LG, and clinical-endocrinological variables were collected and compared. The correlations between FA and ADC values of LG and serum thyroid biochemical markers were also assessed. RESULTS: TAO group showed significantly lower FA (P < 0.001) and higher ADC (P = 0.014) of LG than healthy group. Active subgroup had significantly lower FA (P < 0.001) and higher ADC (P < 0.001) than inactive subgroup. In TAO group, FA of LG was significantly and negatively correlated with TRAb (r=-0.475, P = 0.008), while ADC of LG showed no significant correlation (P > 0.05). The area under receiver operating characteristic curve of FA was significantly greater than that under curve of ADC for discriminating disease activity (0.832 vs. 0.570, P = 0.009). CONCLUSIONS: rs-EPI-based DTI is a useful tool to characterize the microstructural change of LG in patients with TAO. The derived metrics, particularly FA, can help to reveal disease activity.

19.
Int J Mol Sci ; 22(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205274

RESUMO

The fragile X syndrome (FXS) is an X-chromosome-linked neurodevelopmental disorder with severe intellectual disability caused by inactivation of the fragile X mental retardation 1 (FMR1) gene and subsequent loss of the fragile X mental retardation protein (FMRP). Among the various types of abnormal synaptic function and synaptic plasticity phenotypes reported in FXS animal models, defective synaptic retinoic acid (RA) signaling and subsequent defective homeostatic plasticity have emerged as a major synaptic dysfunction. However, the mechanism underlying the defective synaptic RA signaling in the absence of FMRP is unknown. Here, we show that RARα, the RA receptor critically involved in synaptic RA signaling, directly interacts with FMRP. This interaction is enhanced in the presence of RA. Blocking the interaction between FMRP and RARα with a small peptide corresponding to the critical binding site in RARα abolishes RA-induced increases in excitatory synaptic transmission, recapitulating the phenotype seen in the Fmr1 knockout mouse. Taken together, these data suggest that not only are functional FMRP and RARα necessary for RA-dependent homeostatic synaptic plasticity, but that the interaction between these two proteins is essential for proper transcription-independent RA signaling. Our results may provide further mechanistic understanding into FXS synaptic pathophysiology.

20.
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