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1.

Background

The intra-articular implantation of mesenchymal stromal cells (MSCs) as a treatment for knee osteoarthritis (OA) is an emerging new therapy. In this study, patients with knee OA received intra-articular implantations of autologous bone marrow–derived MSCs. We sought to assess the safety and efficacy of this implantation.

Materials and Methods

This was a phase 1/2 single-center, triple-blind, randomized controlled trial (RCT) with a placebo control. The subjects consisted of patients with knee OA randomly assigned to either an intra-articular implantation of MSCs (40?×?106 cells) or 5 mL normal saline (placebo). Patients were followed up for 6 months after the implantations. The pain level and function improvements for patient-reported outcomes were assessed based on a visual analog scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and its subscales, walking distance, painless walking distance, standing time and knee flexion compared with the placebo group at 3 and 6 months following the implantations.

Results

Overall, 43 patients (Kellgren-Lawrence grades 2, 3 and 4) were assigned to either the MSCs (n?=?19) or placebo (n?=?24) group. Patients who received MSCs experienced significantly greater improvements in WOMAC total score, WOMAC pain and physical function subscales and painless walking distance compared with patients who received placebo. There were no major adverse events attributed to the MSC therapy.

Conclusion

This randomized, triple-blind, placebo-controlled RCT demonstrated the safety and efficacy of a single intra-articular implantation of 40?×?106 autologous MSCs in patients with knee OA. Intra-articular implantation of MSCs provided significant and clinically relevant pain relief over 6 months versus placebo and could be considered a promising novel treatment for knee OA. We propose that further investigations should be conducted over an extended assessment period and with a larger cohort.  相似文献   
2.
The purpose of this study was to examine the effectiveness and specificity of a classroom-based psychosocial intervention after war. All students (n=2500) of six villages in Southern Lebanon designated as most heavily exposed to war received a classroom-based intervention delivered by teachers, consisting of cognitive-behavioural and stress inoculation training strategies. A random sample of treated students (n=101) and a matched control group (n=93) were assessed one month post-war and one year later. Mental disorders and psychosocial stressors were assessed using the Diagnostic Interview for Children and Adolescents - Revised with children and parents. War exposure was measured using the War Events Questionnaire. The prevalence of major depressive disorder (MDD), separation anxiety disorder (SAD) and post-traumatic stress disorder (PTSD) was examined pre-war, one month post-war (pre-intervention), and one year post-war. Specificity of treatment was determined by rating teachers’ therapy diaries. The rates of disorders peaked one month post-war and decreased over one year. There was no significant effect of the intervention on the rates of MDD, SAD or PTSD. Post-war MDD, SAD and PTSD were associated with pre-war SAD and PTSD, family violence parameters, financial problems and witnessing war events. These findings have significant policy and public health implications, given current practices of delivering universal interventions immediately post-war.  相似文献   
3.
Generating appropriate cartilage for clinical applications to heal skeletal tissue loss is a major health concern. In this regard, cell-based approaches offer a potential therapeutic strategy for cartilage repair, although little is known about the precise mechanism of chondrogenesis. Unrestricted somatic stem cell (USSC) is considered as a suitable candidate because of its potential for differentiating into multiple cell types. Recent studies show that microRNAs (miRNAs) are involved in several biological processes including development and differentiation. To identify the chondro-specific miRNA signature, miRNA patterns of USSCs and differentiated chondrocytes were investigated using microarrays and validation by qPCR. Prior to these analyses, chondrogenic commitment of differentiated USSCs was verified by immunocytochemistry, specific staining and evaluation of some main chondrogenic marker genes. Various in silico explorations (for both putative targets and signalling pathways) and empirical analyses (miRNA transfections followed by qPCR of some chondrogenic indicators) were carried out to support our results. Transient modulation of multiple chondro-miRs (such as mir-630, mir-624 and mir-376) with chondrocyte targets (such as TGFbR, MAP3K, collagens, SMADs and cadherins) as mediators of chondrogenic signalling pathways including cell-cell interactions, TGF-beta, and MAPK signalling suggests a mechanism for genetic induction of chondrogenic differentiation. In conclusion, this research reveals more details about the allocation of USSCs into the chondrocytes through identification of miRNA signature which modulates targets and pathways required for chondrogenic lineage and could provide guidelines for future clinical treatments and anti-miRNA therapies.  相似文献   
4.

Background

Avascular necrosis (AVN) of femoral head is a progressive bone disease due to ischemia of femoral head; patients experience pain and they can not do normal activity. There is not an effective way to treat the cause of this disease. In recent studies, treatment of this disease using pluripotent stem cell–derived mesenchyme is safe and effective, but this method needs more investigation. In this study, the safety and efficacy of CD133+ cells were evaluated as a novel method of stem cell therapy to treat AVN.

Methods

In this prospective quasi-experimental study, the participants were selected among patients with AVN who were referred to the Royan Cell Therapy Center. Autologous bone marrow–derived CD133+ cells were injected into the necrotic site of the femoral head during core decompression (CD). The Visual Analogue Scale (VAS), Harris Hip Score (HHS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and walking distance (WD) were measured before and 2, 6 and 12 months after CD.

Results

Overall, nine patients (six men and three women) were investigated in this study. Their mean age was 26 years old. All of them significantly improved in VAS, HHS, WOMAC and WD scores and they could do more activity without pain. Also, imaging findings demonstrated significant reductions in joint injuries. Significant complications were not seen in patients.

Discussion

This prospective quasi-experimental study demonstrated that, in patients with AVN, a single bone marrow–derived CD133+ cell injection into the necrotic site of the femoral head during CD is safe and effective in providing significant, clinically relevant pain relief and patients could do more activity over 2, 6 and 12 months. This pilot study suggested further clinical trials over an extended assessment period to approve bone marrow–derived CD133+ cell injection to treat AVN.  相似文献   
5.
In natural habitats, especially in arid areas, plants are often simultaneously exposed to multiple abiotic stresses, such as salt, osmotic and heat stresses. However, most analyses of gene expression in stress responses examine individual stresses. In this report, we compare gene expression in individual and combined stresses. We show that combined stress treatments with salt, mannitol and heat induce a unique pattern of gene expression that is not a simple merge of the individual stress responses. Under multiple stress conditions, expression of most heat and salt stress‐responsive genes increased to levels similar to or higher than those measured in single stress conditions, but osmotic stress‐responsive genes increased to lower levels. Genes up‐regulated to higher levels under multiple stress condition than single stress conditions include genes for heat shock proteins, heat shock regulators and late embryogenesis abundant proteins (LEAs), which protect other proteins from damage caused by stresses, suggesting their importance in multiple stress condition. Based on this analysis, we identify candidate genes for engineering crop plants tolerant to multiple stresses.  相似文献   
6.
The functional response of Cydonia vicina nilotica Muls. (Coleoptera: Coccinellidae) to six densities of Aphis craccivora Koch (Homoptera: Aphididae) nymphs on broad bean (Viciafaba Linn.) was investigated in the laboratory. A linear relationship between the rate of consumption and prey density was observed with r^2 values between 0.58 and 0.97. Plotting prey density against prey killed by four larval instars, and adult males and females of C. vicina nilotica fit well with the type Ⅱ model of Holling' s disc equation. Adult females consumed the highest number of prey, followed by fourth instars and adult males. Based on the functional response data, the model predicts a maximum of 144.9, 116.3, 86.2, 80.0, 72.5 and 20.0 nymphs to be consumed per day by an individual adult female, fourth instar, adult male, third, second and first instars, respectively. The differences in the responses of the predator to aphid densities are discussed.  相似文献   
7.
8.
Abstract Root fatty acid composition, photosynthesis, leaf water potentials, stomatal resistances, leaf specific weights, and root: shoot ratios of soybean were measured in two temperature regimes. Groups of soybean plants were grown in controlled chambers of the Duke University Phytotron under two thermoperiods. One group of the plants was grown from seed for 3 weeks in either 29/23°C or 17/11°C thermoperiods, and another group was grown for 2 weeks in 29/23°C and then transferred to the 17/11°C thermoperiod where it remained for 8 days. Broccoli was also grown in either 29/23°C or 17/11°C thermoperiods. Soybean roots contained more unsaturated fatty acids than broccoli roots, although broccoli roots showed a larger increase in unsaturation than soybean roots with decreased temperature. The fatty acid unsaturation in the roots of soybean began to increase rapidly after the temperature regime was changed. The increase was in the new roots produced in the cold regime rather than in the pre-existing roots. The soybean leaf water and osmotic potentials decreased about 0.4 MPa, beginning one day after the transfer from 29/23°C to 17/11°C, but recovered significantly after 8 d. Plants grown at 17/11 °C had lower rates of photosynthesis and adaxial stomatal resistances, but higher root: shoot ratios and specific leaf weights compared to plants grown at 29/23°C. Plants grown and maintained at 29/23°C showed a steady increase in photosynthetic rates over the 8-d experimental period, whether rates were measured in 1 mol m?3 or 9 mol m?3 oxygen. Plants transferred to 17/11°C however maintained constant rates of photosynthesis at 1 mol m?3 O2, whereas at 9 mol m?3 rates declined for 2 d then were constant for the remaining 6 d of the experimental period. These results suggest that changes in membrane fatty acid unsaturation is an important aspect of plant acclimation to chilling temperatures in terms of maintaining root permeability and water uptake. However, the degree of unsaturation is not a good indicator of differences in chilling tolerance among species. The apparent acclimation of photorespiration to a constant percentage of photosynthesis suggests a role of photorespiration in the plant.  相似文献   
9.
The effects on water status and growth of controlled cycles of water stress applied at various stages of development were studied on a semi-dwarf spring wheat (Triticum aestivum L.). The plants were grown in controlled environment chambers of the Duke University Phytetron at 24/18°C with a 12-h photo-period at about 600 μE m?2 s?1. Groups of plants were subjected to severe water stress by withholding irrigation, beginning at the 7th leaf, early anthesis, or early dough stages of development. A second cycle started 9 to 13 days after termination of the first cycle and maintained until the flag leaf water potential reached –25 bars at each of the growth stages. The lower leaves showed sign of wilting as indicated by curling in the first drying cycle at –7 bars and in the second cycle at –9 bars of leaf water potential during all stages of growth. Although these leaves recovered completely upon rewatering, onset of senescence was accelerated by three days in stressed plants. A preliminary drying cycle did not increase the ability of the plants to withstand subsequent stress because of severity of stress. Water stress of –25 bars at all three stages of growth reduced seed yield. The reduction was greater when a second stress cycle was also applied. Stress applied during early anthesis stage produced the smallest and the least number of seeds. The lack of osmotic adjustment probably was due to very rapid and severe development of water stress.  相似文献   
10.
The effect of osmotic potentials, 0 to ?13.5 atm (?1.37 M Pa), on the germination of three safflower varieties (Carthamus tinctorius L.) was studied at a controlled temperature (30±2°C) using a non-electrolyte substance, polyethelene glycol 6000. The varieties were cv. Ute, cv. Iranian local 3151, and cv. Iranian local 2811. The percent germination of the three varieties averaged over all osmotic potentials were: 86, 77 and 61 for local 3151, local 2811 and “Ute”, respectively. The Ute variety had the highest, and the local 3151 variety had the lowest rate of germination reduction. The variations among the varieties in the percent and rate of germination were due to osmotic effects of the media.  相似文献   
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