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1.
Ann Surg Oncol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020394

RESUMO

PURPOSE: Several randomized controlled trials (RCTs) have investigated observation or axillary radiotherapy (ART) in place of completion axillary lymph node dissection (cALND) for management of positive sentinel nodes (SNs) in clinically node-negative women with breast cancer. The optimal treatment strategy for this population is not known. METHODS: MEDLINE, Embase, and EBM Reviews-NHS Economic Evaluation Database were searched from inception until July 2019. A systematic review and narrative summary was performed of RCTs comparing observation or ART versus cALND in clinically node-negative female breast cancer patients with positive SNs. The Cochrane risk of bias tool for RCTs was used to assess risk of bias. Outcomes of interest included overall survival (OS), disease-free survival (DFS), axillary recurrence, and axillary surgery-related morbidity. RESULTS: Three trials compared observation with cALND, and two trials compared ART with cALND. No studies blinded participants or personnel, and there was heterogeneity in inclusion criteria, study design, and follow-up. Neither observation nor ART resulted in statistically inferior 5- or 8-year OS or DFS compared with cALND. There was also no statistically significant increase in axillary recurrences associated with either approach. Four trials reported morbidity outcomes, and all showed cALND was associated with significantly more lymphedema, paresthesia, and shoulder dysfunction compared with observation or ART. CONCLUSIONS: Women with clinically node-negative breast cancer and positive SNs can safely be managed without cALND.

2.
J Cell Mol Med ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31981312

RESUMO

Recent studies have demonstrated that commercially available lipid-lowering drugs cause various side effects; therefore, searching for anti-hyperlipidaemic compounds with lower toxicity is a research hotspot. This study was designed to investigate whether the marine-derived compound, 5-hydroxy-3-methoxy-5-methyl-4-butylfuran-2(5H)-one, has an anti-hyperlipidaemic activity, and the potential underlying mechanism in vitro. Results showed that the furanone had weaker cytotoxicity compared to positive control drugs. In RAW 264.7 cells, the furanone significantly lowered ox-LDL-induced lipid accumulation (~50%), and its triglyceride (TG)-lowering effect was greater than that of liver X receptor (LXR) agonist T0901317. In addition, it significantly elevated the protein levels of peroxisome proliferator-activated receptors (PPARα) and ATP-binding cassette (ABC) transporters, which could be partially inhibited by LXR antagonists, GSK2033 and SR9243. In HepG2 cells, it significantly decreased oleic acid-induced lipid accumulation, enhanced the protein levels of low-density lipoprotein receptor (LDLR), ABCG5, ABCG8 and PPARα, and reduced the expression of sterol regulatory element-binding protein 2 (~32%). PPARα antagonists, GW6471 and MK886, could significantly inhibit the furanone-induced lipid-lowering effect. Furthermore, the furanone showed a significantly lower activity on the activation of the expression of lipogenic genes compared to T0901317. Taken together, the furanone exhibited a weak cytotoxicity but had powerful TC- and TG-lowering effects most likely through targeting LXRα and PPARα, respectively. These findings indicate that the furanone has a potential application for the treatment of dyslipidaemia.

3.
Biomacromolecules ; 21(1): 56-72, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31271024

RESUMO

Oxygen (O2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O2 release for the long-term. In this paper, we present different O2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O2 generating systems. Then, the applications of O2 generating materials in supporting engineered constructs, supplying high O2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.

4.
Ann Rheum Dis ; 79(3): 408-417, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31871141

RESUMO

OBJECTIVES: The heterogeneity of meniscus cells and the mechanism of meniscus degeneration is not well understood. Here, single-cell RNA sequencing (scRNA-seq) was used to identify various meniscus cell subsets and investigate the mechanism of meniscus degeneration. METHODS: scRNA-seq was used to identify cell subsets and their gene signatures in healthy human and degenerated meniscus cells to determine their differentiation relationships and characterise the diversity within specific cell types. Colony-forming, multi-differentiation assays and a mice meniscus injury model were used to identify meniscus progenitor cells. We investigated the role of degenerated meniscus progenitor (DegP) cell clusters during meniscus degeneration using computational analysis and experimental verification. RESULTS: We identified seven clusters in healthy human meniscus, including five empirically defined populations and two novel populations. Pseudotime analysis showed endothelial cells and fibrochondrocyte progenitors (FCP) existed at the pseudospace trajectory start. Melanoma cell adhesion molecule ((MCAM)/CD146) was highly expressed in two clusters. CD146+ meniscus cells differentiated into osteoblasts and adipocytes and formed colonies. We identified changes in the proportions of degenerated meniscus cell clusters and found a cluster specific to degenerative meniscus with progenitor cell characteristics. The reconstruction of four progenitor cell clusters indicated that FCP differentiation into DegP was an aberrant process. Interleukin 1ß stimulation in healthy human meniscus cells increased CD318+ cells, while TGFß1 attenuated the increase in CD318+ cells in degenerated meniscus cells. CONCLUSIONS: The identification of meniscus progenitor cells provided new insights into cell-based meniscus tissue engineering, demonstrating a novel mechanism of meniscus degeneration, which contributes to the development of a novel therapeutic strategy.

5.
Cell Commun Signal ; 17(1): 160, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796101

RESUMO

Decondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization.

6.
Minerva Cardioangiol ; 67(6): 450-455, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31850725

RESUMO

BACKGROUND: The aim of this study was to evaluate the regrowth and progression of within-stent neointima after stenting as a model of accelerated atherosclerosis and the potential effects of the combination Pycnogenol® and Centellicum® in 12 months' follow-up. METHODS: Progression was defined as the passage from one arterial risk class to next, more advanced risk class in 12 months of follow-up. Each class corresponds to a different risk of cardiovascular events and progression. Three management groups were formed, treated with either standard management (SM), Pycnogenol® 150 mg/day, or a combination of Pycnogenol® 150 mg/day and Centellicum® 450 mg/day. RESULTS: No side effects or tolerability problems were observed. 82 subjects with stented arteries in class 2 were evaluated for the passage into class 3 over 12 months. This group included 82 subjects; there were no dropouts. The management subgroups were comparable at baseline. At 12 months 66.7% of subjects in the SM subgroup progressed to class 3, versus 10.7% in the Pycnogenol® group; progression was seen in 6.7% (P<0.05) of subjects supplemented with the combination. In the second section of the registry study (78 subjects with stented arteries in class 3) we evaluated the percentage of patients passing into class 4. At 12 months 53.6% of subjects using the SM progressed versus 26.9% in the subgroup using Pycnogenol® (P<0.05) and 11.5% in the Pycnogenol®+Centellicum® group (P<0.05). Across all 160 subjects in the three management groups, progression of the stented artery at 12 months was seen in 59.6% of subjects in the SM group versus 18.5% (P<0.05) in the group managed with Pycnogenol® only. The Pycnogenol®+Centellicum® combination further decreased progression down to 8.9% (P<0.05). Oxidative stress was significantly reduced (P<0.05) in the two supplement groups. CONCLUSIONS: In conclusion, the combination Pycnogenol®+Centellicum® appears to reduce the rate of progression of the neointima after stenting.

7.
BMC Complement Altern Med ; 19(1): 335, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775730

RESUMO

BACKGROUND: Concerns have been raised regarding the efficacy and safety resulting from the potential interactions of herbs with Western medications due to the use of both herbs and Western medicine by the general public. Information obtained from the web must be critically evaluated prior to its use in making decisions. DESCRIPTION: This study aimed to construct an herb-drug interaction (HDI) website (https://drug-herb-interaction.netlify.com) with a critically reviewed database. Node.js was used to store the database by running JavaScript. Vue.js is a front-end framework used for web interface development. A total of 135 sets of information related to the interactions of ginseng, ginkgo and dong quai with Western medicine from the literature identified in Medline were collected, followed by critical reviews to prepare nineteen items of information for each HDI monograph. A total of 80 sets of validated HDIs met all criteria and were further assessed at the individual reliability level (likely, possible, and unevaluable) and labeled with the "interaction" item. This query system of the website can be operated in both the Chinese and English languages to obtain all monographs on HDIs in the database, including bilingual interaction data. The database of HDI monographs can be updated by simply uploading a new version of the information Excel file. The designed "smart search" module, in addition to the "single search", is convenient for requesting multiple searches. Among the "likely" interactions (n = 26), 50% show negative HDIs. Ten of these can increase the effect of the Western drug, and the others (n = 3) imply that the HDI can be beneficial. CONCLUSIONS: The current study provides a website platform and 80 sets of validated bilingual HDIs involving ginseng, ginkgo and dong quai in an online database. A search of HDI monographs related to these three herbs can be performed with this bilingual, easy-to-use query website, which is feasible for professionals and the general public. The identified reliability level for each HDI may assist readers' decisions regarding whether taking Western medications concomitant with one of three herbal medicinal foods is safe or whether caution is required due to potentially serious outcomes.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Interações Ervas-Drogas , Multilinguismo , Interface Usuário-Computador , Competência Cultural , Medicamentos de Ervas Chinesas , Ginkgo biloba , Humanos , Internet , Panax , Reprodutibilidade dos Testes
8.
Panminerva Med ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31670494

RESUMO

BACKGROUND: The present registry study investigated effects of the dietary supplement Pycnogenol® on migraine headache attacks and oxidative stress in otherwise healthy subjects with migraine mild-moderate headache (MH) that were considered. To manage MH, these subjects used only a few drugs (anti-emetics, analgesics on demand) and lifestyle changes; only very occasionally they used other, more specific products such as triptans. METHODS: Study GROUPS: one group used only standard management (SM), basically, management on demand. Oral magnesium and riboflavin (vitamin B2) were used with lipoic acid as they are considered useful to improve MH. Another group used the supplement Pycnogenol® (150 mg/day for 8 weeks) in addition to SM. These two groups were compared to a third (non-parallel, observational) group using topiramate (50 mg/day). If needed, subjects were allowed to use rescue medications. RESULTS: 46 subjects were included in the study. 22 used the standard management and 24 were supplemented with Pycnogenol® in association with SM. In addition, 21 subjects were treated with topiramate. Safety with Pycnogenol® was very good. The two main management groups and the third non-parallel group had comparable baseline characteristics. The number of migraine attacks were significantly reduced during the observation period with Pycnogenol® (p<0.05) in comparison with SM. Supplementation was more effective in reducing the use of rescue medications (p<0.05) including analgesics compared to SM. At 8 weeks, the pain score was lower with Pycnogenol in comparison with SM (p<0.05). The working incapacity was significantly lower with Pycnogenol® than in the SM group (P<0.05). The number of migraine attacks was lower with topiramate compared to SM. Pain score, working incapacity and use of rescue medication were lower with topiramate than in SM. However, adverse effects with topiramate, included paresthesia, fatigue, dizziness and nausea even at low dosages complicated management. Some 50% of these side effects require a form of further treatment including medication. Oxidative stress: all included subjects had high oxidative stress at baseline. At 8 weeks, the level of plasma free radicals was significantly lowered with Pycnogenol® (p<0.05), but not in the SM or topiramate group. CONCLUSIONS: In conclusion Pycnogenol® used as prophylaxis appears to reduce pain and the number and severity of symptoms in MH in parallel with a reduction on oxidative stress.

9.
Curr Eye Res ; : 1-7, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31744338

RESUMO

Background: This study aims to evaluate the risk factors of retinal re-detachment and visual outcome after silicone oil removal (SOR) in silicone oil-filled eyes.Methods: A total of 57 patients who underwent pars plana vitrectomy (PPV) and silicone oil injection for retinal detachment (RD), and subsequently underwent a silicone oil removal procedure. Pre-operative examinations were performed to determine the best-corrected visual acuity (BCVA) using the Snellen chart, while Icare was used to determine the intraocular pressure (IOP). In addition, slit-lamp examination of the anterior segment and lens, fundus pre-set lens examination for the posterior segment, color fundus photography, anterior segment photography and type B-ultrasonic scans were performed.Results: In five of 57 patients (8.77%), the retina re-detached following the removal of silicone oil. The factors for re-detachment were proliferative vitreoretinopathy (PVR) (two cases), the formation of new retinal breaks (two cases), and incomplete membrane peeling (one case). The rate of retinal re-detachment (reRD) was statistically independent of the duration of silicone oil endotamponade (P = .810). BCVA significantly improved following the removal of silicone oil (P = .001). The duration of the silicone oil tamponade was significant in the development of cataract (27 eyes, 47.3%; P = .0008), emulsified oil in the anterior chamber (13 eyes, 22.8%; P = .009), and glaucoma (seven eyes, 12.2%).Conclusion: The improvement of visual acuity was discovered following the removal of the intraocular silicone oil. Although the duration of the intraocular silicone oil endotamponade had no effect on the rate of retinal attachment, a longer duration of silicone oil endotamponade can lead to the development of complications, such as cataract, emulsified oil in the anterior chamber and glaucoma, suggesting that the earlier removal of oil should be performed.

10.
Parkinsonism Relat Disord ; 69: 104-110, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31731260

RESUMO

INTRODUCTION: Gait and balance impairments are cardinal features of Parkinson's disease (PD) that require cognitive input. However, the extent to which specific gait and balance characteristics relate to cognition in PD is unclear. In addition, independent models of gait and balance have not been developed from the same cohort. We aimed to i) develop models of gait and balance in a large PD cohort and ii) determine which gait and balance characteristics best related to cognition. METHODS: One hundred and ninety-eight people with PD were recruited to the Pacific Udall Center. Using six inertial sensors (APDM, Inc.), comprehensive gait measurements were collected over a 2-min continuous walk and comprehensive static balance measures were collected during a 60-second standing task. Six domains of cognition were assessed: global cognition, attention, executive function, language, memory, and visuospatial function. Correlations and hierarchical linear regression determined independent associations. RESULTS: Principal components analysis identified a gait model containing four domains accounting for 80.1% of total variance: pace/turning, rhythm, variability, and trunk. The balance model contained four independent domains accounting for 84.5% of total variance: sway area/jerkiness, sway velocity, sway frequency anteroposterior, and sway frequency mediolateral. Gait domains of pace/turning and variability were strongly associated with attention and executive function. Sway area and jerkiness of balance associated with attention and visuospatial function. CONCLUSIONS: Gait and balance characteristics were associated with specific types of cognition. The specific relationships between gait or balance with cognitive functions suggests shared cerebral cortical circuitry for mobility and cognitive functions.

11.
Minerva Cardioangiol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31633315

RESUMO

BACKGROUND: This 'concept' registry evaluated the efficacy of Pycnogenol® and the combination Pycnogenol® and Centella Asiatica (Centellicum®) in controlling the increasing number of arterial/cardiac calcifications in subjects with asymptomatic atherosclerosis. METHODS: The study included 3 groups of 30 males with asymptomatic coronary calcifications. Group one was followed with standard management (SM); Group 2 used SM and Pycnogenol® (150 mg/day); Group 3 used the combination Pycnogenol® (150 mg/day) + Centellicum® (450 mg/day). All subjects took cardioaspirin (Bayer, 100 mg/day). RESULTS: No drop outs, no clinical events were observed in 12 months. The 3 groups had comparable demographic and medical characteristics. No tolerability problems and no side effects from supplementation were reported. After 12 months, oxidative stress was significantly decreased (p<0.05) in both groups taking Pycnogenol®. The evaluation of the number of calcifications > 1 mm indicated a trend in controls using SM towards a progressive increase in calcifications. At 12 months the decrease in the number of calcifications with the combined supplements (Pycnogenol® and Centellicum®) (group 3) was -9.952% and thus significantly better that in the other two groups (p<0.05). Pycnogenol® alone was more effective than SM alone in controlling the variation in calcifications (p<0.05). Considering a 34,88% increase in SM subjects, the total absolute difference between SM (34.8%) and the decrease observed in group 3 (-9.95%) was 44,75% (p<0.02). This indicates that supplementation with the combined supplements blocks the increase in calcified areas and, possibly, in time may decrease the number of calcified spots. CONCLUSIONS: This study shows that there is a significant activity of the complex Pycnogenol®+ Centellicum® in reducing the progressive diffusion of central cardiovascular calcifications - associated with advanced plaques - in a relatively short period of time. Longer studies - focusing also on events - may better evaluate the efficacy of these standardized supplements combination on the evolution of atherosclerosis.

12.
Minerva Cardioangiol ; 67(5): 392-398, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31637898

RESUMO

BACKGROUND: Raynaud syndrome (RS) is associated with vasospasm of the hand and fingers as a response to cold or stress. RS may cause discomfort and color changes (pallor, cyanosis, erythema, as single symptoms, but usually in combination, localized to one or more fingers). The aim of this 4-week registry study was the evaluation of subjects with mild, primary RS and their treatment with a standard management (SM) plan in comparison with SM associated with supplementation with Pycnogenol®. METHODS: A group of 67 females with mild, primary RS was included. All subjects were working in shops with refrigerators. No skin lesions were present. The age range was between 30 and 40; the vasospastic changes were symmetrical; no other physical findings were present. RESULTS: The two groups, receiving standard management (N.=33) or SM+Pycnogenol®, 100 mg/day, (N.=34) were comparable at inclusion. Considering the main symptoms, the decrease in coldness, burning pain, paresthesias and irregular color changes was more significant with Pycnogenol® (P<0.05) at 4 weeks. At thermography, low temperature areas and discrepancies in temperature and color were decreased with Pycnogenol® more than in controls (P<0.05). In the Pycnogenol® group, one subject (2.94%) decided to use drug treatment (PGE1) in 4 weeks in comparison with 5 controls (15.15%). The lowest finger temperature improved from 20.3° C at inclusion to 26.4° C at 4 weeks (+30.04%) with Pycnogenol® in comparison with lower values (from 20.5 to 23.1 [+12.7%] in controls [P<0.05]). The fingertip skin flux increased significantly (+ 1.55 flux units) with Pycnogenol® (P<0.05), in controls just by +0.14 (ns). Supplementation with Pycnogenol® decreased oxidative stress and increased transcutaneous oxygen pressure (TcPO2) more than in controls. Compliance and tolerability were optimal. CONCLUSIONS: This pilot registry study suggests that Pycnogenol® may be used with significant advantages in primary, mild RS. Subjects using Pycnogenol® may control their symptoms and may avoid the need for more complex and, potentially dangerous or expensive treatments.

13.
J Xray Sci Technol ; 27(6): 1021-1031, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31640109

RESUMO

PURPOSE: To test the feasibility of differentiate gastric cancer from gastric stromal tumor using a radiomics study based on contrast-enhanced CT images. MATERIALS AND METHODS: The contrast-enhanced CT image data of 60 patients with gastric cancer and 40 patients with gastric stromal tumor confirmed by postoperative pathology were retrospectively analyzed. First, CT images were read by two senior radiologists to acquire subjective CT signs model, including perigastric fatty infiltration, perigastric enlarged lymph nodes, the enhancement and growth modes of gastric tumors. Second, the manual segmentation of gastric tumors from the CT images was performed by the two radiologists to extract radiomics features via ITK-SNAP software, and to construct radiomics signature model. Finally, a diagnostic model integrated with subjective CT signs and radiomics signatures was constructed. The diagnostic efficacy of three models in differentiating gastric cancer from gastric stromal tumor was compared by using receiver operating characteristic curves (ROC). RESULTS: There are statistically significant differences between the gastric cancer and gastric stromal tumor in the perigastric enlarged lymph nodes, growth mode and radiomics signature (p < 0.05). The area under ROC curve (AUC), sensitivity and accuracy of subjective CT signs model were the lowest among the three models. While the combined model yields the highest AUC value (0.903), specificity (93.33%) and accuracy (86.00%) among the three models (p = 0.03). CONCLUSION: The diagnostic model integrating subjective CT signs and radiomics signature can improve the diagnostic accuracy of gastric tumors.

14.
Neurol Res ; 41(12): 1090-1096, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31584351

RESUMO

Background: Serum C-reactive protein (CRP) has been reported to be associated with risk of ischemic vascular disease including ischemic stroke. Genome-wide association studies have revealed several gene variants related to CRP concentration. Methods: We investigated genetic variants in CRP-related genes associated with ischemic stroke in a nested case-control study with 138 ischemic stroke cases and 276 controls. We sequenced the whole coding region of six CPR-related genes and selected eligible SNPs. Three genetic models (additive, dominant and recessive) were calculated by a multivariable conditional logistic regression to estimate the association between SNPs and risk of ischemic stroke. We also calculated gene-environment interactions by using a crossover analysis. Results: Three out of 10 eligible SNPs were shown to be associated with risk of ischemic stroke. rs1800947 in CRP gene (additive model: OR = 2.08, 95% CI: 1.00-4.23) and rs1169288 in HNF1A gene (additive model: OR = 1.45, 95% CI: 1.03-2.06) were associated with an increased risk of ischemic stroke. rs440446 in APOE gene (additive model: OR = 0.63, 95%CI: 0.44-0.88) was associated with a decreased risk of ischemic stroke. Genetic risk scores models including SC-GRS and OR-GRS both showed a significant association with risk of ischemic stroke. These three SNPs interacted with smoking and red meat intake. Conclusions: Our study showed genetic variants of CRP-related genes were associated with risk of ischemic stroke. Our findings could provide useful data for the etiology of ischemic stroke.

15.
Exp Mol Med ; 51(10): 118, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586040

RESUMO

MicroRNAs (miRNAs, miR) play a key role in the pathogenesis of osteoarthritis (OA). Few studies have examined the regulatory role of P21-activated kinases (PAKs), a family of serine/threonine kinases, in OA. The aim of this study was to determine whether miR-455-3p can regulate cartilage degeneration in OA by targeting PAK2. MiR-455-3p knockout mice showed significant degeneration of the knee cartilage. MiR-455-3p expression increased and PAK2 expression decreased in the late stage of human adipose-derived stem cell (hADSC) chondrogenesis and in chondrocytes affected by OA. Furthermore, in both miR-455-3p-overexpressing chondrocytes and PAK2-suppressing chondrocytes, cartilage-specific genes were upregulated, and hypertrophy-related genes were downregulated. A luciferase reporter assay confirmed that miR-455-3p regulates PAK2 expression by directly targeting the 3'-untranslated regions (3'UTRs) of PAK2 mRNA. IPA-3, a PAK inhibitor, inhibited cartilage degeneration due to OA. Moreover, suppressing PAK2 promoted R-Smad activation in the TGF/Smad signaling pathway in chondrocytes. Altogether, our results suggest that miR-455-3p promotes TGF-ß/Smad signaling in chondrocytes and inhibits cartilage degeneration by directly suppressing PAK2. These results thus indicate that miR-455-3p and PAK2 are novel potential therapeutic agents and targets, respectively, for the treatment of OA.

16.
Orthop Traumatol Surg Res ; 105(7): 1351-1359, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31588033

RESUMO

BACKGROUND: Rotating-hinge knee replacements are usually reserved for revision surgeries, when the extent of soft tissue loss makes a constrained implant more suitable. They remain an uncommon choice in primary surgery when the soft tissue loss is not as extensive. METHODS: We completed a systematic review and meta-analysis to assess patients who underwent a Total Knee Replacement (TKR) with the rotating-hinge prosthesis in the primary setting. We searched PubMed and Embase for articles published in the ten years prior June 2017: Prosthesis survival rates, causes of failure, and clinical/functional scores were the primary outcomes. Twenty-one articles met the inclusion criteria for meta-analysis. Articles were grouped into (1) non-tumour (n=11) and (2) tumour indications (n=10). Survival data was summarized in forest plots, generated using Stata. RESULTS: We found that for certain indications the prosthesis has impressive survival rates and functional outcomes. Short-term (1-5 year) prosthesis survival in non-tumour cases was 92% (95% CI, 87-98%) and 77% (95% CI, 68-87%) in tumour cases. Mid-term (6-10 year) survival was 82% (95% CI, 74-89%) and 69% (95% CI, 57-81%) in non-tumour and tumour studies respectively. In analysis of clinical scores, patients showed a significant improvement in their pain score. Infection was the most commonly cited cause of prosthesis failure in both non-tumour and tumour studies, attributing to 31.5% and 37.6% of failures respectively. Aseptic loosening, dislocation and fracture were also commonly cited complications. CONCLUSION: We concluded that the rotating-hinge knee prosthesis is a viable option in primary surgery when there is extensive soft tissue destruction surrounding the joint. LEVEL OF EVIDENCE: I.

17.
Minerva Med ; 110(6): 524-529, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578841

RESUMO

BACKGROUND: In association with standard management, natural pharmaceutical standard (PS) supplements may play an important role in managing and preventing mild-to-moderate symptoms of asthma, a significant health issue that impacts patients and the healthcare system. Quercetin is a natural flavonoid with important biological properties (anti-inflammatory, antihistamine and anti-oxidative actions). METHODS: In this pilot registry, we evaluated the effects of quercetin formulated with the Phytosome® delivery system (Quercefit™, QFit)+standard management (SM) in otherwise healthy subjects with mild-moderate asthmatic attacks and rhinitis. Subjects used either QFit 1 or 2 tabs/day in association with SM or SM only (control group). After 30 days of management, we evaluated the presence of the main signs/symptoms of asthma according to the GINA classification system also considering the need of rescue medication, nasal drops, the use of inhalers, the rhinitis score and oxidative stress. RESULTS: QFit+SM showed superior results compared with SM alone in controlling, preventing and reducing daily and night symptoms, in maintaining higher peak expiratory flow (PEF) and in decreasing PEF variability. The supplementary use of QFit improved additional measures of asthma management, decreasing the use of inhalers, nasal drops, rescue medications and improving the rhinitis score. QFit produced a significantly more evident reduction in oxidative stress compared with SM; Qfit showed a very good safety profile. CONCLUSIONS: This preliminary supplement, concept registry shows a potential protective and preventive effect of quercetin on attacks frequency and in controlling the most common signs/symptoms of asthma in the milder cases of the disease.

18.
Front Cell Dev Biol ; 7: 161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508417

RESUMO

Long non-coding RNAs (lncRNAs) play pivotal roles in diseases such as osteoarthritis (OA). However, knowledge of the biological roles of lncRNAs is limited in OA. We aimed to explore the biological function and molecular mechanism of HOTTIP in chondrogenesis and cartilage degradation. We used the human mesenchymal stem cell (hMSC) model of chondrogenesis, in parallel with, tissue biopsies from normal and OA cartilage to detect HOTTIP, CCL3, and miR-455-3p expression in vitro. Biological interactions between HOTTIP and miR-455-3p were determined by RNA silencing and overexpression in vitro. We evaluated the effect of HOTTIP on chondrogenesis and degeneration, and its regulation of miR-455-3p via competing endogenous RNA (ceRNA). Our in vitro ceRNA findings were further confirmed within animal models in vivo. Mechanisms of ceRNAs were determined by bioinformatic analysis, a luciferase reporter system, RNA pull-down, and RNA immunoprecipitation (RIP) assays. We found reduced miR-455-3p expression and significantly upregulated lncRNA HOTTIP and CCL3 expression in OA cartilage tissues and chondrocytes. The expression of HOTTIP and CCL3 was increased in chondrocytes treated with interleukin-1ß (IL-1ß) in vitro. Knockdown of HOTTIP promoted cartilage-specific gene expression and suppressed CCL3. Conversely, HOTTIP overexpression reduced cartilage-specific genes and increased CCL3. Notably, HOTTIP negatively regulated miR-455-3p and increased CCL3 levels in human primary chondrocytes. Mechanistic investigations indicated that HOTTIP functioned as ceRNA for miR-455-3p enhanced CCL3 expression. Taken together, the ceRNA regulatory network of HOTTIP/miR-455-3p/CCL3 plays a critical role in OA pathogenesis and suggests HOTTIP is a potential target in OA therapy.

19.
J Vis Exp ; (150)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31524862

RESUMO

Viruses within the genus Lyssavirus are zoonotic pathogens, and at least seven lyssavirus species are associated with human cases. Because bats are natural reservoirs of most lyssaviruses, a lyssavirus surveillance program of bats has been conducted in Taiwan since 2008 to understand the ecology of these viruses in bats. In this program, non-governmental bat conservation organizations and local animal disease control centers cooperated to collect dead bats or bats dying of weakness or illness. Brain tissues of bats were obtained through necropsy and subjected to direct fluorescent antibody test (FAT) and reverse transcription polymerase chain reaction (RT-PCR) for detection of lyssavirus antigens and nucleic acids. For the FAT, at least two different rabies diagnosis conjugates are recommended. For the RT-PCR, two sets of primers (JW12/N165-146, N113F/N304R) are used to amplify a partial sequence of the lyssavirus nucleoprotein gene. This surveillance program monitors lyssaviruses and other zoonotic agents in bats. Taiwan bat lyssavirus is found in two cases of the Japanese pipistrelle (Pipistrellus abramus) in 2016-2017. These findings should inform the public, health professionals, and scientists of the potential risks of contacting bats and other wildlife.

20.
Zoonoses Public Health ; 66(7): 805-812, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31478316

RESUMO

Tickborne diseases (TBDs) such as Lyme disease (LD), babesiosis, ehrlichiosis and Rocky Mountain spotted fever cause substantial morbidity and even mortality in the USA. Data indicate that Hispanic populations may be at greater risk for occupational exposure to ticks and disseminated LD; however, information on knowledge and practices of Hispanic populations regarding TBDs is limited. We surveyed 153 Hispanic and 153 non-Hispanic residents of Maryland and Virginia to assess awareness of TBDs, prevention practices and risk of tick encounters. Hispanic respondents were less likely than non-Hispanics to report familiarity with LD symptoms (21% vs. 53%, p < 0.001) and correctly identify ticks as vectors of LD (40% vs. 85%, p < 0.001). Although there was no significant difference in overall proportion of respondents who routinely take one or more preventive measures to prevent tick bites (59% vs. 61%, p = 0.65), Hispanics were more likely to report showering after coming indoors (36% vs. 25%, p = 0.04) but less likely to conduct daily tick checks compared with non-Hispanics (17% vs. 35%, p < 0.001). History of tick bite or finding a tick crawling on oneself or a household member in the past year did not significantly differ between Hispanics and non-Hispanics (19% vs. 24%, p = 0.26). Notably, after controlling for Hispanic/non-Hispanic ethnicity, primary language (English vs. Spanish) was a significant predictor of whether an individual had knowledge of LD symptoms, correctly identified ticks as vectors for LD and performed daily tick checks. These results provide guidance for future development of more targeted and effective TBD prevention education for both Hispanic and non-Hispanic communities.

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