首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.

Background

Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow–derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds. Our objective was to evaluate feasibility, safety and initial clinical outcome of autologous BMDC therapy associated with standard treatment in patients with VLUs.

Methods

We conducted an open-label, single-arm, prospective pilot clinical trial in four patients with six chronic VLUs. The study protocol was approved by the institutional and national review boards and ethics committees. Bone marrow was harvest, processed and then administered by multiple injections into the ulcers. All patients received standard treatment and non-healing characteristics of the VLUs were confirmed at study entry.

Results

Ulcer size and wound pain evaluated 12 months after BMDC treatment were significantly reduced (P < 0.05). BMDC treatment was safe and well tolerated in long-term follow-up.

Discussion

Despite the low number of patients studied, our results showed that autologous BMDC treatment could be a useful, feasible and safe procedure to enhance ulcer healing. However, randomized controlled trials with more patients are needed to address this question and translate this approach into clinical practice.  相似文献   

2.
3.

Background and aims

It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1).

Methods

Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Pancreatic pathological scoring, serum levels of amylase and inflammatory factors, as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activity in the pancreas were evaluated.

Results

Our data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas. Moreover, BMSCs increased the level of HO-1 in the serum and pancreatic tissue in rats with SAP. In addition, the protective effect of BMSCs was partially neutralized by the HO-1 activity inhibitor ZnPP, suggesting a key role of HO-1 in the therapeutic effect of BMSCs on SAP.

Conclusions

BMSCs ameliorated SAP, probably by inducing expression of HO-1, which can exert anti-inflammatory and anti-oxidant effects, reduce apoptosis and promote angiogenesis.  相似文献   

4.

Background aims

EBV type II latency tumors, such as Hodgkin lymphoma (HL), Non-Hodgkin lymphoma (NHL) and nasopharyngeal carcinoma, express a limited array of EBV antigens including Epstein-Barr nuclear antigen (EBNA)1, latent membrane protein (LMP)1, LMP2, and BamH1-A right frame 1 (BARF1). Adoptive immunotherapy for these malignancies have focused on EBNA1, LMP1 and LMP2 because little is known about the cellular immune response to BARF1.

Methods

To investigate whether BARF1 is a potential T-cell immunotherapy target, we determined the frequency of BARF1-specific T-cell responses in the peripheral blood of EBV-seropositive healthy donor and patients with EBV-positive malignancies, mapped epitopes and evaluated the effector function of ex vivo–generated BARF1-specific T-cell lines.

Results

BARF1-specific T cells were present in the peripheral blood of 12/16 (75%) EBV-positive healthy donors and 13/20 (65%) patients with EBV-positive malignancies. Ex vivo expanded BARF1-specific T-cell lines contained CD4- and CD8-positive T-cell subpopulations, and we identified 23 BARF1 peptides, which encoded major histocompatibility complex class I– and/or II–restricted epitopes. Epitope mapping identified one human leukocyte antigen (HLA)-A*02-restricted epitope that was recognized by 50% of HLA-A*02, EBV-seropositive donors and one HLA-B*15(62)-restricted epitope. Exvivo expanded BARF1-specific T cells recognized and killed autologous, EBV-transformed lymphoblastoid cell lines and partially HLA-matched EBV-positive lymphoma cell lines.

Discussion

BARF1 should be considered as an immunotherapy target for EBV type II (and III) latency. Targeting BARF1, in addition to EBNA1, LMP1 and LMP2, has the potential to improve the efficacy of current T-cell immunotherapy approaches for these malignancies.  相似文献   

5.

Background aims

Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non–small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies.

Methods

We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U.S. clinical trials. We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (version 5.1.0), extracted the data using a standard data extraction form, synthesized the data using meta-analysis and finally rated the evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

Thirty-two RCTs with 2250 patients were included, and most trials had unclear risk of bias. The merged risk ratios values and their 95% confidence intervals of meta-analysis for objective response rate, disease control rate, 1- and 2-year overall survival rates, 1- and 2-year progression-free survival rates were as following: 1.45 (1.31–1.61), 1.26 (1.16–.37), 1.42 (1.23–1.63), 2.06 (1.36–3.12), 1.93 (1.38–2.69) and 3.30 (1.13–9.67). Compared with chemotherapy alone, all differences were statistically significant. CIK cells could increase the CD3+ T cells, CD3+ CD4+ T cells, NK cells and the ratio of CD4+/CD8+ T cells. The chemotherapy with CIK cells had a lower risk of hematotoxicity, gastrointestinal toxicity, liver injury and a higher fever than that of chemotherapy alone. The evidence quality was “moderate” to “very low.”

Conclusions

The available moderate evidences indicate that chemotherapy with CIK cells, especially autologous CIK cells, can significantly improve the tumor responses, 1- and 2-year overall and progression-free survival rates in patients with advanced NSCLC. This treatment does have a high risk of fever. The optimal use may be treatment with one or two cycles and in combination with vinorelbine and cisplatin, paclitaxel and cisplatin, or docetaxel and cisplatin.  相似文献   

6.

Background

Neo-vascularization, an indispensible phenomenon for tissue regeneration, facilitates repair and remodeling of wound tissues. This process is impaired in chronic wounds due to reduced number and recruitment of endothelial cells (ECs), thereby necessitating development of newer strategies to enhance the EC repertoire as a therapeutic approach.

Methods

We explored the ‘plasticity’ of Wharton's jelly derived–mesenchymal stromal cells (WJ-MSCs) using an anti-inflammatory drug-mediated enhanced trans-differentiation into ECs, based on our observation of temporal decrease in COX-2 expression during trans-differentiation of MSCs into ECs at day 7 and 14 along with mature ECs.

Results

At a physiological level, an increased DiI-labeled acetylated-low density lipoprotein (DiI-Ac-LDL) uptake, proliferation, migration and chick chorio allantoic membrane (CAM)-vasculogenesis occurred while at a molecular level significant up-regulation in messenger RNA (mRNA) and protein expression of endothelial-specific markers, Vegfr2, Pecam, eNOS, VE-Cadh and Tie-2, along with an activated p-VEGFR2 and its downstream mediators were observed in celecoxib-preconditioned ECs as compared with WJ-MSCs. Green fluorescent protein (GFP)-expressing stable WJ-MSCs and trans-differentiated EC-D14 in the absence/presence of celecoxib were generated using antibiotic selection for intradermal transplantation at the wound site on a murine ‘excisional splinting wound’ model. Engraftment of transplanted human cells in immunosuppressant-treated mice was confirmed by a significant increase in the expression levels of human gene-specific endothelial markers at the regenerated wound sites. Morphometrically, increased vascularity and percent wound closure were observed in regenerated wounds of mice transplanted with celecoxib-preconditioned-EC-D14.

Conclusion

Cox-2 inhibition led to an enhanced trans-differentiation of WJ-MSCs into ECs that, when transplanted, accelerated the skin regeneration by engraftment and neo-vascularization at the wound bed, suggesting a plausible new therapeutic role of celecoxib.  相似文献   

7.

Background

Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs.

Methods

In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate–expanded human bone marrow–derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1β and tumor necrosis factor (TNF)α concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1β and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis.

Results

Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1β protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon.

Conclusions

In conclusion, we observed a good safety profile for bone marrow–derived platelet lysate–expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.  相似文献   

8.

Background

The isolation of lymphocytes – and removal of platelets (PLTs) and red blood cells (RBCs) – from an initial blood sample prior to culture is a key enabling step for effective manufacture of cellular therapies. Unfortunately, currently available methods suffer from various drawbacks, including low cell recovery, need for complex equipment, potential loss of sterility and/or high materials/labor cost.

Methods

A newly developed system for selectively concentrating leukocytes within precisely designed, but readily fabricated, microchannels was compared with conventional density gradient centrifugation with respect to: (i) ability to recover lymphocytes while removing PLTs/RBCs and (ii) growth rate and overall cell yield once expanded in culture.

Results

In the optimal embodiment of the new microfluidic approach, recoveries of CD3+, CD19+ and CD56+ cells (85%, 89% and 97%, respectively) were significantly higher than for paired samples processed via gradient-based separation (51%, 53% and 40%). Although the removal of residual PLTs and RBCs was lower using the new approach, its enriched T-cell fraction nevertheless grew at a significantly higher rate than the gradient-isolated cells, with approximately twice the cumulative cell yield observed after 7 days of culture.

Discussion

The standardization of each step of cellular therapy manufacturing would enable an accelerated translation of research breakthroughs into widely available clinical treatments. The high-throughput approach described in this study – requiring no ancillary pumping mechanism nor expensive disposables to operate – may be a viable candidate to standardize and streamline the initial isolation of lymphocytes for culture while also potentially shortening the time required for their expansion into a therapeutic dose.  相似文献   

9.

Background

Chronic wounds present a major challenge in modern medicine. Even under optimal conditions, the healing process may lead to scarring and fibrosis. The ability of mesenchymal stem cells (MSCs) to differentiate into other cell types makes these cells an attractive therapeutic tool for cell transplantation. Both tissue-engineered construct and MSC therapy are among the current wound healing procedures and potential care. Chitosan has been widely applied in tissue engineering because of its biocompatibility and biodegradability.

Aim

The aim of the current work was to compare the efficiency of MSCs and chitosan dressing, alone or in combination treatment on wound healing.

Methods

This study was conducted on 15 rabbits, which were randomly divided in 3 groups based on the type of treatment with MSCs, chitosan dressing and combination of both. A full–thickness skin defect was excised from the right and left side of the back of each animals. Defects on right sides were filled with treatments and left side defects were left as control. Evaluation of the therapeutic effectiveness was performed through a variety of clinical and microscopical evaluations and measurements of the process of wound healing on days 7, 14, 21, and 28. Histological evaluation of wound healing was classified by different scoring systems.

Results

The data indicated that wounds treated with bone marrow derived MSC had enhanced cellularity and better epidermal regeneration. During the early stages of wound healing, the closure rate of bone marrow derived MSC-treated wounds were significantly higher than other treatments (P < 0.05). Although the MSCs in the wound edges enhance the healing of the full–thickness wound, the healing process of chitosan treatment was slower than the control group.

Conclusion

This study revealed advanced granulation tissue formation and epithelialization in wounds treated with MSCs, and may suggests this treatment as an effective applicant in wound healing process. Chitosan scaffold dressings, whether alone or in combination with MSCs, have worsened the wound healing as compared to the control group.  相似文献   

10.

Background

The incidence of systemic infections by Saccharomyces cerevisiae has increased in recent years, especially among immunocompromised patients. Amphotericin B, voriconazole or echinocandins have been used with favorable outcome against systemic infections by this fungus. However, clinical experience is limited and no in vivo studies have been conducted.

Aims

We evaluated the in vitro activity of nine antifungal compounds against S. cerevisiae and the in vivo efficacy of those three antifungals showing the highest in vitro activity by using a murine model of systemic infection.

Methods

Minimal inhibitory concentrations (MICs) were determined by the microdilution method against three strains of S. cerevisiae. After intravenous infection with 5 × 107 CFUs, animals received liposomal amphotericin B (5 mg/kg), voriconazole (25 mg/kg) or anidulafungin (5 mg/kg). Treatment efficacy was assessed by determining of CFUs/g in liver, kidney, brain, lung and spleen.

Results

5-Fluorocytosine was the most in vitro active compound followed by amphotericin B, voriconazole and anidulafungin. The in vivo study showed that liposomal amphotericin B was the most effective drug driving highest fungal clearance.

Conclusions

All treatments reduced the fungal load in comparison to the control group, being liposomal amphotericin B the most effective drug followed by anidulafungin and finally voriconazole.  相似文献   

11.

Background

Acute kidney injury (AKI) is a common clinical problem raising the urgent needs to develop new strategies for treatment. The present study investigated the therapeutic potential of human umbilical cord – mesenchymal stem cells (HUC-MSCs) transplantation against renal ischemia/reperfusion injury (IRI) in rats.

Methods

Twenty four male Wistar rats were assigned into two main groups, sham group (control group) and I/R group. I/R group was injected in the tail vein with either phosphate buffer saline (PBS) or HUC-MSCs.

Results

The HUC-MSCs improved kidney injury induced by I/R as demonstrated by enhancement of the kidney function via decreasing serum levels of creatinine, urea and uric acid. The therapeutic efficacy of HUC-MSCs were found to be mediated through anti-oxidant activity as indicated by significant reduction in total malondialdehyde (MDA) and significant increment in the levels of reduced glutathione (GSH), catalase (CAT) and glutathione-S-transferase (GST).

Conclusion

The present work suggests that HUC-MSCs may be an effective therapeutic agent against renal IRI. The recorded data showed improvement of renal functions and urine albumin in HUC-MSCs than IRI group with positive antioxidant efficacy of HUC-MSCs through scavenging free radicals and supporting the antioxidant enzymes.  相似文献   

12.

Background

Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear.

Aim of the work

To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat.

Material & methods

Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10 mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy.

Results

In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells.

Conclusion

Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal.  相似文献   

13.

Objective

A new method was presented to prepare clinical-grade human adipose-derived stromal stem cells (ASCs) and its safety in vitro, such as biological characteristics and genetic features alteration were investigated.

Methods

The morphology of the ASCs which were cultured in vitro using serum-free medium was observed. Cell cycle and CD markers profile were tested by flow cytometry, while karyotype was analyzed by the chromosome G-banding technology. Growth factors expression was tested by ELISA and tumor-related genes were analyzed by the real-time PCR, respectively.

Results

ASCs were adult stem cells with spindle shape. The proliferation ratio of ASCs began to slow down after 10 passages, and was significant after 15 passages. Cell cycle analysis revealed that the percentage of G2 phase and S phase cells was stable. There was no obvious missing, translocation or dislocation in terms of karyotype. Expression level of tumor relevant genes and cytokines at different passages had no significant difference.

Conclusions

The clinical-grade ASCs prepared with this new method, less than ten passages, was safe for clinical trials.  相似文献   

14.

Background

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgr) catalyzes the synthesis of mevalonate, a key compound for the synthesis of cholesterol in humans and ergosterol in fungi. Since the Hmgr enzymes of Saccharomyces cerevisiae, Schizosaccharomyces pombe and Candida glabrata are similar to the Hmgr enzymes of mammals, fungal Hmgr enzymes have been proposed as a model for studying antifungal agents.

Aims

To examine the correlation between inhibiting Um-Hmgr enzyme and the viability, sterols synthesis and mating in Ustilago maydis.

Methods

Using in silico analysis, the ORF codifying for Um-Hmgr was identified and the protein characteristics were deduced. The effect of the competitive inhibitors of Um-Hmgr on the viability of this basidiomycota, the synthesis of its sterols, and its mating were evaluated.

Results

The Umhmgr gene (XP_011389590.1) identified putatively codifies a protein of 1443 aa (ca. MW = 145.5 kDa) that has a possible binding domain in the endoplasmic reticulum (ER) and high identity with the Hmgr catalytic domain of humans and other yeasts. The inhibition of Um-Hmgr caused a decrease of viability and synthesis of sterols, and also the inhibition of mating. The activity of Um-Hmgr is mainly located in the membrane fraction of the fungus.

Conclusions

Given our results we believe U. maydis is a valid model for studying synthetic inhibitors with lipid-lowering or antifungal activity. Additionally, we propose the Hmgr enzyme as an alternative molecular target to develop compounds for treating both phytopathogenic and pathogenic human fungi.  相似文献   

15.

Background

Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options.

Aims

The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2 μg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8 μg/ml), (3) caspofungin-resistant strains (MIC ≥ 8 μg/ml), and (4) micafungin-resistant strains (MIC ≥ 8 μg/ml).

Methods

Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done.

Results

The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible.

Conclusions

Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents.  相似文献   

16.

Background

Invasive candidiasis by Candida albicans is associated with high morbidity and mortality, due in part to the late implementation of an appropriate antifungal therapy hindered by the lack of an early diagnosis.

Aims

We aimed to evaluate the in vitro antifungal activity of the antibodies against C. albicans germ tubes (CAGTA) raised in a rabbit model of candidemia.

Methods

We measured the effect of CAGTA activity by colorimetric XTT and crystal violet assays, and colony forming units count, both on C. albicans planktonic cells and during the course of biofilm formation and maturation. Viability and cell morphology were assessed by optical, fluorescent or scanning electron microscopy.

Results

CAGTA ≥50 μg/ml caused a strong inhibition of C. albicans blastospores growth, and DiBAC fluorescent staining evidenced a fungicidal activity. Moreover, electron microscopy images revealed that CAGTA induced morphological alterations of the surface of C. albicans germ tubes grown free as well as in biofilm. Interestingly, CAGTA ≥80 μg/ml reduced the amount of C. albicans biofilm, and this effect started at the initial adhesion stage of the biofilm formation, during the first 90 min.

Conclusions

This is the first report showing that CAGTA reduce C. albicans growth, and impair its metabolic activity and ability to form biofilm in vitro. The antigens recognized by CAGTA could be the basis for the development of immunization protocols that might protect against Candida infections.  相似文献   

17.

Objective

Observe anti-inflammatory effect and the effect on acute pharyngitis rats model induced by ammonia water of compound Lobelia oral liquid, providing experimental basis for its clinical use.

Methods

Use egg white establish foot swelling rats model and use carboxymethyl cellulose establish white blood cell migration rats model. Then observe the anti-inflammatory effect of compound Lobelia oral liquid. Use 15% ammonia spray at pharyngeal establish acute pharyngitis rats model, Visual observation and conduct grading of pharyngeal tissue stimulation in rats, measure the levels of TNF-α and IL-6 in serum. Pharyngeal tissue was taken to observe the morphological changes.

Result

All dose groups of compound Lobelia oral liquid can reduce the rate of foot swelling of rats at all time points (P?<?0.01 or P?<?0.05), and significantly reduce the number of white blood cells of rats (P?<?0.01); And improve the local hyperemia degree, reduce secretion, reduce local swelling of pharyngeal tissue, reduce the serum TNF-α and IL-6 levels of acute pharyngitis rats with different degrees (P?<?0.01 or P?<?0.05).

Conclusion

Compound Lobelia oral liquid has a good anti-inflammatory effect on foot swelling and white blood cell migration rats model, as well as significant improvement effect on acute pharyngitis rats model.  相似文献   

18.

Background

We evaluated the effect of 45 days of rosuvastatin or pravastatin treatment on the distribution of HDL subfractions in HIV-1-infected individuals receiving boosted protease inhibitors (PIs) with cardiovascular risk.

Methods

The distribution of HDL subclasses by gradient gel electrophoresis was blindly assessed in 74 HIV-1-infected individuals receiving boosted PIs at baseline and at day 45 of statin treatment, and compared with the distribution obtained in 63 healthy normolipidemic individuals taken as controls.

Results

No significant modification appeared in HDL distribution between the two arms of statins for the HIV-1-infected individuals. Nevertheless, when compared to controls, HDL subfractions showed a significantly lower HDL2b proportion and significantly higher proportions of HDL2a and HDL3b (P < 0.001).

Conclusion

No difference was observed in HDL distribution between pravastatin and rosuvastatin after 45 days treatment, in HIV-1-infected individuals under PIs. Nevertheless, when compared to healthy normolipidemic subjects, HDL distribution is clearly different, with a distribution in HIV-infected individuals under PIs associated with an increased cardiovascular risk.  相似文献   

19.
20.

Background

Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)–secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote wound healing in vivo.

Methods

To this end, MSCs were isolated from the peripheral blood of healthy horses, a physiologically relevant large animal model appropriate for translational wound-healing studies. Conditioned medium (CM) from cultured equine MSCs was analyzed using liquid chromatography-mass spectrophotometry (LC-MS/MS) to identify secreted proteins of interest. Double-stranded RNA-mediated interference (RNAi) was used to silence the genes encoding selected proteins, and the effects of CM from these transfected MSCs on migration of cultured equine DF cells in vitro and full-thickness wounds in mice were evaluated.

Results

We found that MSC-derived plasminogen activator inhibitor-1 (PAI-1) and tenascin-C significantly increased DF migration in vitro and improved wound healing in vivo by decreasing time to wound closure.

Discussion

These results suggest that in a complex wound environment, MSC-secreted factors PAI-1 and tenascin-C contribute to the positive effect of therapeutically applied MSC CM on wound healing.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号