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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 6040-6043, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019348

RESUMO

In dental hygienist education, many skills are taught that cannot be acquired without repeated training. To make this training more efficient, we need to measure the students' skills and show correction points in real-time. In this research, we focus on hand scaling work, which is one of the most important tasks of dental hygienists. We developed a measurement system to measure both the motion and force exerted during hand scaling work. This measured data can be used to quantitatively evaluate students' skills. In the experiment, we measured the hand scaling motion of several participants with different levels of job experience, including dental hygienist teachers, dental hygienists, and dental hygienist students. We showed that it is possible to extract from the measured results a quantitative index for discriminating different individual skills.

3.
Sci Rep ; 10(1): 14432, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879408

RESUMO

To examine associations of healthy lifestyle during pregnancy with body mass index (BMI) and risk of overweight or obesity of grandchildren during adolescence and young adulthood. Our study population included 14,001 grandmother-mother-child triads comprised of participants of two ongoing prospective cohort studies of related individuals. We used self-reported grand-maternal gestational weight gain, diet, physical activity, and smoking during pregnancy to create a lifestyle score ranged from 0 to 12, with a higher score indicating healthier lifestyle. Grandchild BMI was self-assessed in follow-up questionnaires. Compared with individuals whose grandmothers had the least healthy lifestyle during pregnancy, individuals whose grandmothers had the most healthy lifestyle had 0.17 (95% CI 0.01, 0.33; P for trend = 0.05) kg/m2 lower BMI and 7% (95% CI 2%, 12%; P for trend = 0.001) lower risk of overweight or obesity during adolescence and young adulthood. The inverse associations between grand-maternal lifestyle and BMI in grandchildren were mainly mediated by maternal pre-pregnancy BMI (mediation effect: 64%; P value = 0.001). Overall, maternal BMI, along with maternal socioeconomic status and lifestyle factors in the second and third generations accounted for all of the inter-generational association (mediation effect: 99%; P value < 0.001). The inverse associations of grand-maternal lifestyle with BMI of offspring were not modified by grand-maternal pre-pregnancy BMI, grandchild age, or grandchild gender. Grandchildren of women who had the healthiest lifestyles during pregnancy defined by no excess gestational weight gain, no smoking, a healthy diet and being physically active, were less likely to be overweight or obese in adolescence and early adulthood.

4.
Bone Joint J ; 102-B(10): 1303-1310, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32993343

RESUMO

AIMS: The most frequent indication for revision surgery in total hip arthroplasty (THA) is aseptic loosening. Aseptic loosening is associated with polyethylene liner wear, and wear may be reduced by using vitamin E-doped liners. The primary objective of this study was to compare proximal femoral head penetration into the liner between a) two cross-linked polyethylene (XLPE) liners (vitamin E-doped (vE-PE)) versus standard XLPE liners, and b) two modular femoral head diameters (32 mm and 36 mm). METHODS: Patients scheduled for a THA were randomized to receive a vE-PE or XLPE liner with a 32 mm or 36 mm metal head (four intervention groups in a 2 × 2 factorial design). Head penetration and acetabular component migration were measured using radiostereometric analysis at baseline, three, 12, 24, and 60 months postoperatively. The Harris Hip Score, University of California, Los Angeles (UCLA) Activity Score, EuroQol five-dimension questionnaire (EQ-5D), and 36-Item Short-Form Health Survey questionnaire (SF-36) were assessed at baseline, three, 12, 36, and 60 months. RESULTS: Of 220 screened patients, 127 were included in this study. In all, 116 received the allocated intervention, and 94 had their results analyzed at five years. Head penetration was similar between liner materials and head sizes at five years, vE-PE versus XLPE was -0.084 mm (95% confidence interval (CI) -0.173 to 0.005; p = 0.064), and 32 mm versus 36 mm was -0.020 mm (95% CI -0.110 to 0.071; p = 0.671), respectively. No differences were found in acetabular component migration or in the patient-reported outcome measures. CONCLUSION: No significant difference in head penetration was found at five years between vE-PE and XLPE liners, nor between 32 mm and 36 mm heads. Cite this article: Bone Joint J 2020;102-B(10):1303-1310.


Assuntos
Artroplastia de Quadril/instrumentação , Vitamina E/farmacologia , Idoso , Feminino , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Polietileno , Falha de Prótese , Inquéritos e Questionários
5.
J Med Chem ; 63(19): 11195-11214, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-32886510

RESUMO

The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activity and other diverse pharmacological activities. To improve activity and targeting, we designed and prepared 41 semisynthetic analogues of WA. Biological evaluation indicated that the most promising compound 13a displayed the most significant effect on HT-29 cells (human colon cancer cells) (IC50 = 0.08 µM). A structure-activity relationship study indicated that α,ß-unsaturated ketones and ester are necessary groups, allowing 13a to undergo Michael addition reactions with mercaptan and selenol. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed that 13a modified selenocysteine 498 (U) residues in the redox centers of TrxR, resulting in enzyme inhibition. Therefore, compound 13a acts as a novel TrxR inhibitor and may be a promising candidate for cancer intervention.

6.
Exp Cell Res ; 396(1): 112280, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961145

RESUMO

Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α expressions were up-regulated in tumor tissues from multiple myeloma patients. miR-411-3p expression was down-regulated in tumor tissues from multiple myeloma patients. Besides, lncRNA ANRIL can interact with miR-411-3p. HIF-1α was confirmed to be a target of miR-411-3p. Correlation analysis showed that lncRNA ANRIL expression was negatively correlated with miR-411-3p expression. HIF-1α expression was negatively correlated with miR-411-3p expression. Further transfection experiments showed that knockdown of ANRIL or overexpression of miR-411-3p significantly inhibited cell proliferation, tumor formation ability and tumor stem cell like property, promoted cell apoptosis in vitro. Finally, miR-411-3p mimic reduced tumor volume, improved survival rate, suppressed malignant proliferation and tumor stem cell like property in U266 xenograft model. Our results demonstrate that lncRNA ANRIL mediated by miR-411-3p promotes the malignant proliferation and tumor stem cell like property of multiple myeloma through regulating HIF-1α.

7.
Methods ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32791337

RESUMO

Internet gaming addiction (IGD) is a common disease in teenagers which usually reflects the abnormalities in brain function or structure. Several computational models have been applied to investigate the characteristic of IGD brain networks, for instance, the conception of brain controllability. The primary objective of this study was to explore the relationship between brain controllability and IGD related clinical behaviour. A sample of 101 subjects, including 49 IGD patients and 52 normal controls, were recruited to undergo MR T1 and DTI scanning. Specifically, the MR images were used to generate the white matter connectivity matrix and the morphometry similarity network. The morphometry similarity network was then divided into several communities using modular decomposition. After, average controllability, modal controllability and synchronizability were calculated through measuring the adjacency matrix. The results indicated that the IGD group had greater synchronizability and modal controllability compared to that of the control group, and different morphological-based brain communities had different controllability properties. Furthermore, the addiction demonstrated the mediating effects between nodal or modular brain controllability as well as anxiety. In conclusion, brain controllability could be a potential biomarker of IGD.

8.
Gerontology ; 66(5): 494-505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841943

RESUMO

BACKGROUND: Cognitive impairment represents a risk factor for falls in older adults. However, cognition is a complex construct comprising several functional domains. The relationship between specific cognitive domain and falls in cognitively healthy older adults is unclear. OBJECTIVES: This study aims to investigate the relationship between falls, attention, and executive function in older adults while considering the three components of attention (alerting, orienting, and executive control) and three components of executive function (updating, inhibition, and shifting). METHODS: Cognitively healthy older adults were recruited (n = 60 for fallers and n = 100 for non-fallers). The participants were assessed on the Attention Network Test (alerting, orienting, and executive control), running memory test (updating), Stroop test (inhibition), and digit switching test (shifting). Confounder-adjusted logistic models were used to examine the associations between falls and specific cognitive functions in cognitively healthy older adults. RESULTS: The results showed that falls were associated with alerting, executive control, and updating. These associations were not attenuated when adjusting for a series of covariates such as age, gender, education, balance, general health, and emotional status. CONCLUSIONS: The results suggest that among cognitively healthy older adults, falls are related to three specific cognitive functions: alerting, executive control, and updating. Disentangling the mechanism and contribution of cognitive deficits in fall risk may provide insights for the development of prevention and rehabilitation strategies for falls in older adults.

9.
BMJ ; 370: m2206, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641435

RESUMO

OBJECTIVE: To examine the associations between the intake of total and individual whole grain foods and the risk of type 2 diabetes. DESIGN: Prospective cohort studies. SETTING: Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2017), and Health Professionals Follow-Up Study (1986-2016), United States. PARTICIPANTS: 158 259 women and 36 525 men who did not have type 2 diabetes, cardiovascular disease, or cancer at baseline. MAIN OUTCOME MEASURES: Self-reports of incident type 2 diabetes by participants identified through follow-up questionnaires and confirmed by a validated supplementary questionnaire. RESULTS: During 4 618 796 person years of follow-up, 18 629 participants with type 2 diabetes were identified. Total whole grain consumption was categorized into five equal groups of servings a day for the three cohorts. After adjusting for lifestyle and dietary risk factors for diabetes, participants in the highest category for total whole grain consumption had a 29% (95% confidence interval 26% to 33%) lower rate of type 2 diabetes compared with those in the lowest category. For individual whole grain foods, pooled hazard ratios (95% confidence intervals) for type 2 diabetes in participants consuming one or more servings a day compared with those consuming less than one serving a month were 0.81 (0.77 to 0.86) for whole grain cold breakfast cereal, 0.79 (0.75 to 0.83) for dark bread, and 1.08 (1.00 to 1.17) for popcorn. For other individual whole grains with lower average intake levels, comparing consumption of two or more servings a week with less than one serving a month, the pooled hazard ratios (95% confidence intervals) were 0.79 (0.75 to 0.83) for oatmeal, 0.88 (0.82 to 0.94) for brown rice, 0.85 (0.80 to 0.90) for added bran, and 0.88 (0.78 to 0.98) for wheat germ. Spline regression showed a non-linear dose-response association between total whole grain intake and the risk of type 2 diabetes where the rate reduction slightly plateaued at more than two servings a day (P<0.001 for curvature). For whole grain cold breakfast cereal and dark bread, the rate reduction plateaued at about 0.5 servings a day. For consumption of popcorn, a J shaped association was found where the rate of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day. The association between higher total whole grain intake and lower risk of type 2 diabetes was stronger in individuals who were lean than in those who were overweight or obese (P=0.003 for interaction), and the associations did not vary significantly across levels of physical activity, family history of diabetes, or smoking status. CONCLUSION: Higher consumption of total whole grains and several commonly eaten whole grain foods, including whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, and wheat germ, was significantly associated with a lower risk of type 2 diabetes. These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Dieta Saudável , Grãos Integrais , Adulto , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia
10.
Sci Rep ; 10(1): 11188, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636402

RESUMO

Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. However, the mechanism by which EA treats ileitis-induced VH is not clearly known. To assess the effects of EA on ileitis-induced VH and confirm whether EA attenuates VH through spinal PAR-2 activation and CGRP release, goats received an injection of 2,4,6-trinitro-benzenesulfonic-acid (TNBS) solution into the ileal wall. TNBS-injected goats were allocated into VH, Sham acupuncture (Sham-A) and EA groups, while goats treated with saline instead of TNBS solution were used as the control. Goats in EA group received EA at bilateral Hou-San-Li acupoints for 0.5 h at 7 days and thereafter repeated every 3 days for 6 times. Goats in the Sham-A group were inserted with needles for 0.5 h at the aforementioned acupoints without any hand manipulation and electric stimulation. Visceromotor responses to colorectal distension, an indicator of VH, were recorded by electromyography. The terminal ileum and thoracic spinal cord (T11) were sampled for evaluating ileitis at days 7 and 22, and distribution and expression-levels of PAR-2, CGRP and c-Fos on day 22. TNBS-treated-goats exhibited apparent transmural-ileitis on day 7, microscopically low-grade ileitis on day 22 and VH at days 7-22. Goats of Sham-A, VH or EA group showed higher (P < 0.01) VH at days 7-22 than the Control-goats. EA-treated goats exhibited lower (P < 0.01) VH as compared with Sham-A or VH group. Immunoreactive-cells and expression-levels of spinal PAR-2, CGRP and c-Fos in the EA group were greater (P < 0.01) than those in the Control group, but less (P < 0.01) than those in Sham-A and VH groups on day 22. Downregulation of spinal PAR-2 and CGRP levels by EA attenuates the ileitis and resultant VH.

11.
J Appl Microbiol ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590882

RESUMO

AIMS: Sustainable agriculture requires effective and safe biofertilizers and biofungicides with low environmental impact. Natural ecosystems that closely resemble the conditions of biosaline agriculture may present a reservoir for fungal strains that can be used as novel bioeffectors. METHODS AND RESULTS: We isolated a library of fungi from the rhizosphere of three natural halotolerant plants grown in the emerging tidal salt marshes on the southeast coast of China. DNA barcoding of 116 isolates based on the rRNA ITS1 and 2 and other markers (tef1 or rpb2) revealed 38 fungal species, including plant pathogenic (41%), saprotrophic (24%), and mycoparasitic (28%) taxa. The mycoparasitic fungi were mainly species from the hypocrealean genus Trichoderma, including at least four novel phylotypes. Two of them, representing the taxa Trichoderma arenarium sp. nov. (described here) and T. asperelloides, showed effective antagonistic activity against five phytopathogenic fungi, and significant growth promotion on tomato seedlings under the conditions of saline agriculture. CONCLUSIONS: Trichoderma spp. of salt marshes play the role of natural biological control in young soil ecosystems with a putatively premature microbiome. SIGNIFICANCE AND IMPACT: The saline soil microbiome is a rich source of halotolerant bioeffectors that can be used in biosaline agriculture.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 977-982, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552968

RESUMO

OBJECTIVE: To investigated the clinical and pathological characteristics of related-renal damage in patients with POEMS syndrome. METHODS: Five patients diagnosed as POEMS syndrome in our hospital were selected. Their clinical manifestation, pathological characteristics of kidney and laboratory examination were analyzed retrospectively. Among the 5 patients, three males and two females with a median age of 50 years old. The mean interval before diagnosis was 13.0±7.2 months. RESULTS: All the patients showed neuropathy, endocrinopathy, monoclonal plasma cell-proliferative disorder, skin changes and extravascular volume overload, in which 4 patients showed organomegaly. Proteinuria was found in 5 patients, and microhematuria was found in 4 patients. Moreover, 4 patients showed an elevated blood urea, while 2 patients showed creatinine elevation. 1 patient at chronic kidney disease (CKD)-G1 stage, 2 patients at CKD-G2 stage, and 1 patient at CKD-G3b stage, moreover, 1 patient at CKD-G5 stage. Endothelial injury and mesangial lesion were the main characteristics of renal pathology. 3 patients were pathologically diagnosed as thrombotic microangiopathy kidney damage, while 2 patients as light chain amyloidosis. CONCLUSION: POEMS syndrome is a multi-systemic disease with complex clinical manifestations. 5 patients had different degrees of renal insufficiency. Endothelial injury and mesangial lesion are the main features of renal pathology.


Assuntos
Síndrome POEMS , Paraproteinemias , Insuficiência Renal , Feminino , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
ACS Synth Biol ; 9(7): 1753-1762, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32579850

RESUMO

Carotenoids, a variety of natural products, have significant pharmaceutical and commercial potential. Phytoene dehydrogenase (CrtI) is the rate-limit enzyme for carotenoid synthesis, whose catalysis specificity results in various carotenoids. However, the structural characteristics of CrtI for controlling the catalysis specificity on dehydrogenation steps are still unclear, which limited the development of CrtI function. Here we confirmed two mutation sites H136 and H453 in the mutant library of CrtI from Blakeslea trispora, which markedly regulated catalytic specificity. Interestingly, the sequence alignment features at H136 and H453 were consistent with the phylogenetic analysis of CrtI families. Subsequently, the functions of saturated mutants at H136 and H453 were clustered by principal component analysis (PCA) and k-means. According to the clustering results, diversiform mutants with specific dehydrogenation function provided important application value for carotenoid product customization. Meanwhile, this study also enriched the theory of enzyme evolution and guided the functional development of enzymes.

14.
Endocrinology ; 161(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32591825

RESUMO

Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D-depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D-depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.

16.
Autophagy ; : 1-22, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32432943

RESUMO

SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases. ABBREVIATION: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1.

19.
Biomed Res Int ; 2020: 7650354, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32337276

RESUMO

Transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into spinal cord injury (SCI) may alleviate neuropathic pain and promote functional recovery. The underlying mechanism likely involves activation of glial cells and regulation of inflammatory factors but requires further validation. SCI was induced in 16 ICR mice using an SCI compression model, followed by injection of lentiviral vector-mediated green fluorescent protein- (GFP-) labeled hUC-MSCs 1 week later. Behavioral tests, histological evaluation, and inflammatory factor detection were performed in the treatment (SCI+hUC-MSCs) and model (SCI) groups. Histological evaluation revealed GFP expression in the spinal cord tissue of the treatment group, implying that the injected MSCs successfully migrated to the SCI. The Basso, Beattie, and Bresnahan (BBB) scores showed that motor function gradually recovered over time in both groups, but recovery speed was significantly higher in the treatment group than in the model group. The pain threshold in mice decreased after SCI but gradually increased over time owing to the self-repair function of the body. The corresponding pain threshold of the treatment group was significantly higher than that of the model group, indicating the therapeutic and analgesic effects of hUC-MSCs. Expression of IL-6 and TNF-α in the spinal cord tissue of the treated group decreased, whereas glial cell line-derived neurotrophic factor (GDNF) expression along with ED1 expression increased compared with those in the model group, suggesting that SCI activated ED1 inflammatory macrophages/microglia, which were subsequently reduced by hUC-MSC transplantation. hUC-MSCs are speculated to enhance the repair of the injured spinal cord tissue and exert an analgesic effect by reducing the secretion of inflammatory factors IL-6 and TNF-α and upregulating the expression of GDNF.

20.
Mater Sci Eng C Mater Biol Appl ; 109: 110427, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228983

RESUMO

Bone defects in load bearing areas require bone reconstruction with strong biomaterial having mechanical characteristics like cortical bone. Bioceramics are biomaterials that support bone formation as well as provide adequate mechanical properties. A strontium substitution of the bioceramic is expected to further increase its bioactivity by enhancing osteogenesis and protect the bone from osteoclastic resorption. The study involves development, characterization and in vivo testing of a newly developed strontium substituted hydroxyapatite based bioceramic scaffold (SrHAB) with sufficient biomechanical properties. Optimal concentration of strontium ion required for enhanced osteogenic differentiation was identified by comparing three compositions of SrHAB scaffold; namely Sr10HAB, Sr30HAB and Sr50 HAB for their Alkaline phosphatase activity in vitro. The selected Sr10HAB scaffold demonstrated in vivo bone formation with osteogenic differentiation of stromal derived mesenchymal stem cells (MSC) from human and ovine sources in ectopic and ovine models. Thus, Sr10HAB scaffold has a potential for application in load bearing bone requirements of orthopaedics and dentistry.

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