Cucurbitacin E reduces IL-1ß-induced inflammation and cartilage degeneration by inhibiting the PI3K/Akt pathway in osteoarthritic chondrocytes.

BACKGROUND: Osteoarthritis is a degenerative joint disease. Cartilage degeneration is the earliest and most important pathological change in osteoarthritis, and persistent inflammation is one of the driving factors of cartilage degeneration. Cucurbitacin E, an isolated compound in the Cucurbitacin family, has been shown to have anti-inflammatory effects, but its role and mechanism in osteoarthritic chondrocytes are unclear. METHODS: For in vitro experiments, human chondrocytes were stimulated with IL-1ß, and the expression of inflammatory genes was measured by Western blotting and qPCR. The expression of extracellular matrix proteins was evaluated by immunofluorescence staining, Western blotting and saffron staining. Differences in gene expression between cartilage from osteoarthritis patients and normal cartilage were analysed by bioinformatics methods, and the relationship between Cucurbitacin E and its target was analysed by a cellular thermal shift assay, molecular docking analysis and molecular dynamics simulation. For in vivo experiments, knee osteoarthritis was induced by DMM in C57BL/6 mouse knee joints, and the effect of Cucurbitacin E on knee joint degeneration was evaluated. RESULTS: The in vitro experiments confirmed that Cucurbitacin E effectively inhibited the production of the inflammatory cytokine interleukin-1ß(IL-1ß) and cyclooxygenase-2 (COX-2) by IL-1ß-stimulated chondrocytes and alleviates extracellular matrix degradation. The in vivo experiments demonstrated that Cucurbitacin E had a protective effect on the knee cartilage of C57BL/6 mice with medial meniscal instability in the osteoarthritis model. Mechanistically, bioinformatic analysis of the GSE114007 and GSE117999 datasets showed that the PI3K/AKT pathway was highly activated in osteoarthritis. Immunohistochemical analysis of PI3K/Akt signalling pathway proteins in pathological slices of human cartilage showed that the level of p-PI3K in patients with osteoarthritis was higher than that in the normal group. PI3K/Akt were upregulated in IL-1ß-stimulated chondrocytes, and Cucurbitacin E intervention reversed this phenomenon. The cellular thermal shift assay, molecular docking analysis and molecular dynamics experiment showed that Cucurbitacin E had a strong binding affinity for the inhibitory target PI3K. SC79 activated Akt phosphorylation and reversed the effect of Cucurbitacin E on IL-1ß-induced chondrocyte degeneration, demonstrating that Cucurbitacin E inhibits IL-1ß-induced chondrocyte inflammation and degeneration by inhibiting the PI3K/AKT pathway. CONCLUSION: Cucurbitacin E inhibits the activation of the PI3K/AKT pathway, thereby alleviating the progression of OA. In summary, we believe that Cucurbitacin E is a potential drug for the treatment of OA.

Effect of Preventive Nursing on Male Children with Hypospadias in Preventing Postoperative Complications.

OBJECTIVE: To determine the clinical impact of preventive nursing on children with hypospadias and the intervention effect on postoperative complications. STUDY DESIGN: Comparative study. Place and Duration of the Study: Department of Urology Surgery, Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital, Hebei, China, from August 2019 to July 2021. METHODOLOGY: Children with hypospadias who received elective surgery were randomly divided into two groups of forty cases each. The control group received traditional specialised nursing care during the perioperative period, the study group administered preventive care on the control basis. The postoperative rehabilitation, VAS, anxiety and depression score, postoperative complications, and nursing satisfaction were compared between the two groups. RESULTS: The time of first bowel movement, extubation, and hospitalisation in the study group were significantly shorter than in the control group, with statistically significant value (p<0.001). After intervention, the SAS and SDS in the study group were significantly lower than those in the control group, and the difference was statistically significant (p<0.05). The incidence of complications in the study group was 7.50%, lower than the 25% of control group (p = 0.034). The postoperative VAS scores of the study group were significantly lower than those of control group at 6 and 24 hours (p<0.05). Besides, nursing satisfaction in the study group was 97.50%, higher than the 82.50% of the control group (p = 0.025). CONCLUSION: Preventive nursing had a reliable nursing effect on children undergoing hypospadias surgery, which can reduce postoperative complications, alleviate postoperative pain, improve postoperative anxiety and depression, enhance nursing experience, and promote postoperative recovery. KEY WORDS: Preventive care, Hypospadias in male children, Urethroplasty, Complication, Clinical effect.

Comparison of clinical effects between microscopic surgery and conventional surgery in children with penile hypospadias and difference analysis of postoperative urodynamics.

Objective: To compare and analyze the clinical effects of microscopic surgery and conventional surgery in children with penile hypospadias and the differences in postoperative urodynamic indexes. Methods: It was a clinical comparative study. A total of 80 children with penile hypospadias admitted to Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from July 2018 to September 2022 were selected and randomly divided into two group. The experimental group were treated with microscopic urethroplasty, while the control group were treated with traditional urethroplasty. The operative effect, operation time, total intraoperative blood loss, postoperative hospital stay and incidence of surgical complications were compared and analyzed between the two groups. All the children were followed up for two years, and the changes in urodynamic parameters including maximum urine flow rate (Qmax), average urine flow rate (Qavc), urine flow time (FT), peak time (TQmax) and residual urine (PVR) were compared before, two weeks after, six months after and two years after surgery. Results: The efficacy of the experimental group was significantly higher than that of the control group (p=0.013). The intraoperative blood loss and postoperative hospital stay in the experimental group were significantly better than those in the control group (p=0.000). The incidences of urinary leakage and urethral stricture in the experimental group were lower than those in the control group (p<0.05). The Qmax level in the experimental group was higher than that in the control group at six months and two years after surgery, while the FT level was lower than that of the control group (p<0.05). Conclusion: Microscopic surgery is a method with significant clinical value in the treatment of penile hypospadias.

Laparoscopic versus Conventional Open Surgery Approach of Tunica Vaginalis for Palpable Cryptorchidism.

OBJECTIVE: To evaluate the advantages of the laparoscopic approach of tunica vaginalis in the treatment of palpable cryptorchidism. STUDY DESIGN: Randomised clinical comparative study. PLACE AND DURATION OF STUDY: Department of Urology Surgery, Baoding Children's Hospital, Baoding, Hebei, China, from July 2019 to June 2020. METHODOLOGY: A total of 80 children admitted with palpable cryptorchidism were selected and randomly divided into two groups i.e. the experimental group and the control group, with 40 cases in each group. The experimental group were treated with a laparoscopic approach of tunica vaginalis, and the control group were treated with conventional open surgery. The perioperative indicators, proportion with testicular external fixation, surgical effect, testicular development (6 months postoperative), and incidence of complications were compared. RESULTS: The postoperative ambulation and discharge time of the experimental group were significantly shorter than the control group (p<0.001). The external fixation rate of the control group was higher than the experimental group (p=0.02). The effective rate of the experimental group was significantly higher than the control group (p=0.03). The re-examination performed, 6 months postoperatively, showed that the testicular volume in the experimental group was significantly higher than in the control group (p=0.03). The incidence of the surgical complications in the experimental group was significantly lower than in the control group (p=0.04). CONCLUSION: Laparoscopic approach of tunica vaginalis is effective in the treatment of palpable cryptorchidism and more conducive to testicular development. It has the advantages of less injury, less complications, quick postoperative recovery, more adequate spermatic cord dissociation, and well-preserved testicular blood supply. KEY WORDS: Laparoscopic approach of tunica vaginalis, Palpable cryptorchidism, Treatment.

Effectiveness of cell- and colony stimulating factor-based therapy for liver cirrhosis: a network meta-analysis of randomized controlled trials.

BACKGROUND AIMS: Cirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis. METHODS: A literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels. RESULTS: Twenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49-3.79, P < 0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00-2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators. CONCLUSIONS: Cell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.

Association between diabetic retinopathy and interleukin-related gene polymorphisms: a machine learning aided meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is a severe complication of diabetes and a common cause of visual loss in adults. We aimed to assess the correlation between IL gene-related SNPs and the incidence of DR and attempted to predict DR with combined mutation site detection. METHODS: A systematic search of databases was performed up to August 2019. Five genetic models were used to analyze associations. Machine learning methods were implemented to improve SNP-related disease prediction. RESULTS: Sixteen trials assessing a total of 7221 patients were included in our meta-analysis. IL6/rs1800795, rs1800796, and IL10/rs1800896 were analyzed. For the IL-6 gene, there was no significant association between rs1800795 and the incidence of DR (allelic model: OR, 1.091; 95% CI, 0.892-1.334; p = .396). There was no significant correlation between rs1800796 (allelic model: OR, 1.135; 95% CI, 0.678-1.901; p = .63), rs1800896 (allelic model: OR, 1.047; 95% CI, 0.788-1.392; p = .752) and the incidence of DR. Unfortunately, the machine learning results also showed that the combined detection of two SNPs could not accurately predict DR occurrence. CONCLUSION: rs1800795 and rs1800796 in the IL-6 gene and rs1800896 in IL-10 gene are not related to the incidence of DR. Mutations in multiple SNPs for each DR patient still need to be specifically assessed to increase prediction accuracy.

The Prognostic and Predictive Value of Dihydropyrimidine Dehydrogenase-Related Indicators in Clinical Outcomes of Chemotherapy in Colorectal Cancer Patients: a Systematic Review and Meta-Analysis.

Colorectal cancer (CRC) is the third most common cancer worldwide. Predictive biomarkers are needed to predict patients' outcomes and to select a chemotherapy regimen. We assessed whether dihydropyrimidine dehydrogenase (DPD)-related indicators can predict CRC patients' outcomes. We searched the studies in PubMed, EmBase, and the Cochrane Library up to March 4, 2018. We mainly analyzed different CRC patients' outcomes according to specific DPD-related indicators. Twenty-five articles were included in the meta-analysis. The results showed that for disease-free survival (DFS), low DPD expression was significantly superior to high expression (I2 = 72%; HR: 1.59; 95%CI: 1.21-2.09; p = 0.001). However, this result had a potential publication bias (Begg's test: p = 0.007; Egger's test: p = 0.004). Among patients treated with chemotherapy, a high thymidylate phosphorylase (TP)/DPD ratio was advantageous for DFS (I2 = 63.7%; HR: 0.65; 95%CI: 0.46-0.92; p = 0.015), and this result did not have a publication bias. For overall survival (OS), low DPD expression was superior to high expression (I2 = 74.4%; HR: 2.11; 95%CI: 1.48-3.00; p < 0.001), although this result had a publication bias (Egger's test: p = 0.003; Begg's test: p = 0.010). There was no difference in OS according to the TP/DPD ratio (I2 = 0%; HR: 0.92; 95%CI: 0.75-1.13; p = 0.420). DFS and OS were better in CRC patients with low DPD expression than in those with high DPD expression. However, because of publication bias, more DPD indicator-related studies, especially with negative results, are still needed. Patients with a high TP/DPD ratio have better DFS but not OS.

Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report.

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=-1.330; 95% confidence interval (CI), -(2.095-0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350-3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157-2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226-2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213-2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

The Comparison of Adipose Stem Cell and Placental Stem Cell in Secretion Characteristics and in Facial Antiaging.

Background. Mesenchymal stem cells are the most commonly used seed cells in biomedical research and tissue engineering. Their secretory proteins have also been proven to play an important role in tissue healing. Methods. We isolated adipose stem cells and placental stem cells and performed analysis examining characteristics. The secretory proteins were extracted from conditioned medium and analyzed by MALDI-TOF/TOF. The antiaging effect of conditioned mediums was evaluated by the results of facial skin application. Results. Adipose stem cells and placental stem cells were found to be very similar in their surface markers and multipotency. The specific proteins secreted from adipose stem cells were more adept at cell adhesion, migration, wound healing, and tissue remodeling, while the proteins secreted by placental stem cells were more adept at angiogenesis, cell proliferation, differentiation, cell survival, immunomodulation, and collagen degradation. While these two types of conditioned medium could improve the facial index, the improvement of Melanin index after injection of the adipose stem cell conditioned medium was much more significant. Conclusion. The results suggest that the secreted proteins are ideal cell-free substances for regeneration medicine, especially in the antiaging field.

The efficacy of conditioned media of adipose-derived stem cells combined with ablative carbon dioxide fractional resurfacing for atrophic acne scars and skin rejuvenation.

OBJECTIVE: To evaluate the effects of conditioned medium of adipose-derived stem cells (ADSC-CM) on efficacy and side effects after fractional carbon dioxide laser resurfacing (FxCR) when treating subjects with facial atrophic acne scars or with skin rejuvenation needs. MATERIALS AND METHODS: Twenty-two subjects were enrolled in the study and divided into two groups. Nine subjects were included in skin rejuvenation group and thirteen subjects were included in acne scar group, and all subjects underwent three sessions of FxCR. ADSC-CM was applied on FxCR site of one randomly selected face side. Evaluations were done at baseline, 1 week after first treatment, and 1 month after each treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, transepidermal water loss (TEWL), and the erythema and melanin index. Biopsies taken from one subject in skin rejuvenation group were analyzed using hematoxylin and eosin, Masson's Trichrome, and Gomori's aldehyde fuchsin staining. RESULTS: ADSC-CM combined with FxCR increased subject satisfaction, elasticity, skin hydration, and skin elasticity and decreased TEWL, roughness, and the melanin index in both acne scars and skin rejuvenation groups. Histologic analysis showed that ADSC-CM increased dermal collagen density, elastin density, and arranged them in order. CONCLUSION: ADSC-CM with FxCR is a good combination therapy for treating atrophic acne scars and skin rejuvenation. TRIAL REGISTRATION: JSPH2012-082 - Registered 14 Feb 2012.

Bone marrow-derived, neural-like cells have the characteristics of neurons to protect the peripheral nerve in microenvironment.

Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that "neural-like cells" may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve.

Antiphotoaging effect of conditioned medium of dedifferentiated adipocytes on skin in vivo and in vitro: a mechanistic study.

Photoaging of skin occurs partially due to decreased synthesis and increased degradation of dermal collagen. Antiphotoaging therapy aims to counteract these effects. This study aimed to investigate whether secretory factors from dedifferentiated adipocytes (DAs) could alleviate photoaging in human dermal fibroblasts (HDFs) and in mice and to clarify the underlying mechanism. DAs were acquired and verified based on cellular biomarkers and multilineage differentiation potential. The concentrations of several cytokines in conditioned medium from DAs (DA-CM) were determined. In vivo pathological changes, collagen types I and III, and matrix metalloproteinase (MMP)-1 and -3 were evaluated following the injection of 10-fold concentrated DA-CM into photoaged mice. In vitro, the effect of DA-CM on stress-induced premature senescence in HDFs was investigated by 5-ethynyl-2'-deoxyuridine (EdU) staining and ß-galactosidase staining. The influence of DA-CM and transforming growth factor-ß1 (TGF-ß1) on the secretion of collagen types I and III, MMP-1, and MMP-3 in HDFs was evaluated by ELISA. In vivo, we found that subcutaneously injected 10-fold concentrated DA-CM increased the expression of collagen types I and III. In vitro, DA-CM clearly mitigated the decreased cell proliferation and delayed the senescence status in HDFs induced by ultraviolet B (UVB). HDFs treated with DA-CM exhibited higher collagen types I and III secretion and significantly lower MMP-1 and MMP-3 secretion. The TGF-ß1-neutralizing antibody could partially reduce the recovery effect. Our results suggest that DAs may be useful for aging skin and their effects are mainly due to secreted factors, especially TGF-ß1, which stimulate collagen synthesis and alleviate collagen degradation in HDFs.

Cardiomyocyte differentiation induced in cardiac progenitor cells by cardiac fibroblast-conditioned medium.

Our previous study showed that after being treated with 5-azacytidine, Nkx2.5(+) human cardiac progenitor cells (CPCs) derived from embryonic heart tubes could differentiate into cardiomyocytes. Although 5-azacytidine is a classical agent that induces myogenic differentiation in various types of cells, the drug is toxic and unspecific for myogenic differentiation. To investigate the possibility of inducing CPCs to differentiate into cardiomyocytes by a specific and non-toxic method, CPCs of passage 15 and mesenchymal stem cells (MSCs) were treated with cardiac ventricular fibroblast-conditioned medium (CVF-conditioned medium). Following this treatment, the Nkx2.5(+) CPCs underwent cardiomyogenic differentiation. Phase-contrast microscopy showed that the morphology of the treated CPCs gradually changed. Ultrastructural observation confirmed that the cells contained typical sarcomeres. The expression of cardiomyocyte-associated genes, such as alpha-cardiac actin, cardiac troponin T, and beta-myosin heavy chain (MHC), was increased in the CPCs that had undergone cardiomyogenic differentiation compared with untreated cells. In contrast, the MSCs did not exhibit changes in morphology or molecular expression after being treated with CVF-conditioned medium. The results indicated that Nkx2.5(+) CPCs treated with CVF-conditioned medium were capable of differentiating into a cardiac phenotype, whereas treated MSCs did not appear to undergo cardiomyogenic differentiation. Subsequently, following the addition of Dkk1 and the blocking of Wnt signaling pathway, CVF-conditioned medium-induced morphological changes and expression of cardiomyocyte-associated genes of Nkx2.5(+) CPCs were inhibited, which indicates that CVF-conditioned medium-induced cardiomyogenic differentiation of Nkx2.5(+) CPCs is associated with Wnt signaling pathway. In addition, we also found that the activation of Wnt signaling pathway was accompanied by higher expression of GATA-4 and the blocking of the pathway inhibited the expression of GATA-4 in CVF-conditioned medium-incubated Nkx2.5(+) CPCs. This finding suggests that Wnt signaling pathway may alter GATA-4 expression and activate the cardiogenic program in the regulation of differentiation. In conclusion, Nkx2.5(+) CPCs have enormous potential for cardiomyogenic differentiation and the CVF-conditioned medium specifically induces CPCs to differentiate into a cardiac phenotype. Wnt signaling pathway is involved in CVF-conditioned medium-induced cardiomyogenic differentiation of Nkx2.5(+) CPCs.

Concentrated Hypoxia-Preconditioned Adipose Mesenchymal Stem Cell-Conditioned Medium Improves Wounds Healing in Full-Thickness Skin Defect Model.

In recent years, the bioactive factors were utilized in exercise and athletic skin injuries. In this research, the concentrated conditioned medium of hypoxia-preconditioned adipose mesenchymal stem cells, which is rich in bioactive factor, is applied in full-thickness skin defect model to evaluate the therapeutic efficacy. Adipose mesenchymal stem cells were harvested from the abdominal subcutaneous adipose tissues. The surface markers and the potential of differentiation were analyzed. The conditioned medium of hypoxia-preconditioned stem cells was collected and freeze-dried and then applied on the rat full-thickness skin defect model, and the healing time of each group was recorded. Haematoxylin and eosin staining of skin was assessed by microscope. The characteristics of adipose mesenchymal stem cells were similar to those of other mesenchymal stem cells. The concentration of protein in freeze-dried conditioned medium in 1 mL water was about 15 times higher than in the normal condition medium. In vivo, the concentrated hypoxia-preconditioned conditioned medium can reduce the wound size and accelerate the skin wound healing. The concentrated hypoxia-preconditioned adipose mesenchymal stem cell-conditioned medium has great effect on rat model of wound healing, and it would be an ideal agent for wound care in clinical application.

Interferon regulatory factor-1 together with reactive oxygen species promotes the acceleration of cell cycle progression by up-regulating the cyclin E and CDK2 genes during high glucose-induced proliferation of vascular smooth muscle cells.

BACKGROUND: The high glucose-induced proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of diabetic vascular diseases. In a previous study, we confirmed that Interferon regulatory factor-1 (Irf-1) is a positive regulator of the high glucose-induced proliferation of VSMCs. However, the mechanisms remain to be determined. METHODS: The levels of cyclin/CDK expression in two cell models involving Irf-1 knockdown and overexpression were quantified to explore the relationship between Irf-1 and its downstream effectors under normal or high glucose conditions. Subsequently, cells were treated with high glucose/NAC, normal glucose/H2O2, high glucose/U0126 or normal glucose/H2O2/U0126 during an incubation period. Then proliferation, cyclin/CDK expression and cell cycle distribution assays were performed to determine whether ROS/Erk1/2 signaling pathway was involved in the Irf-1-induced regulation of VSMC growth under high glucose conditions. RESULTS: We found that Irf-1 overexpression led to down-regulation of cyclin D1/CDK4 and inhibited cell cycle progression in VSMCs under normal glucose conditions. In high glucose conditions, Irf-1 overexpression led to an up-regulation of cyclin E/CDK2 and an acceleration of cell cycle progression, whereas silencing of Irf-1 suppressed the expression of both proteins and inhibited the cell cycle during the high glucose-induced proliferation of VSMCs. Treatment of VSMCs with antioxidants prevented the Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression in high glucose conditions. In contrast, under normal glucose conditions, H2O2 stimulation and Irf-1 overexpression induced cell proliferation, up-regulated cyclin E/CDK2 expression and promoted cell cycle acceleration. In addition, overexpression of Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were treated with U0126, the specific Erk1/2 inhibitor abolished the proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression under high glucose or normal glucose/H2O2 conditions. CONCLUSIONS: These results demonstrate that the downstream effectors of Irf-1 are cyclin E/CDK2 during the high glucose-induced proliferation of VSMCs, whereas they are cyclin D1/CDK4 in normal glucose conditions. The Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression are associated with ROS/Erk1/2 signaling pathway under high glucose conditions.

The effect of conditioned media of adipose-derived stem cells on wound healing after ablative fractional carbon dioxide laser resurfacing.

OBJECTIVE: To evaluate the benefits of conditioned medium of Adipose-derived stem cells (ADSC-CM) on wound healing after fractional carbon dioxide laser resurfacing (FxCR) on human skin. MATERIALS AND METHODS: Nineteen subjects were treated with FxCR on the bilateral inner arms. ADSC-CM was applied on FxCR site of one randomly selected arm. Transepidermal water loss (TEWL), skin color, and gross-elasticity of FxCR site on both arms were measured. Skin samples were taken by biopsy from three subjects 3 weeks after treatment for histopathological manifestations and mRNA expressions of procollagen types I and III, elastin genes were noted. RESULTS: The index of erythema, melanin, and TEWL of the ADSC-CM-treated skin were significantly lower than those of the control side. The mRNA expression of type III procollagen in ADSC-CM-treated group at 3 weeks posttreatment was 2.6 times of that of the control group. CONCLUSION: Application of allograft ADSC-CM is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.

Proteome analysis of Physcomitrella patens exposed to progressive dehydration and rehydration.

Physcomitrella patens is an extremely dehydration-tolerant moss. However, the molecular basis of its responses to loss of cellular water remains unclear. A comprehensive proteomic analysis of dehydration- and rehydration-responsive proteins has been conducted using quantitative two-dimensional difference in-gel electrophoresis (2D-DIGE), and traditional 2-D gel electrophoresis (2-DE) combined with MALDI TOF/TOF MS. Of the 216 differentially-expressed protein spots, 112 and 104 were dehydration- and rehydration-responsive proteins, respectively. The functional categories of the most differentially-expressed proteins were seed maturation, defence, protein synthesis and quality control, and energy production. Strikingly, most of the late embryogenesis abundant (LEA) proteins were expressed at a basal level under control conditions and their synthesis was strongly enhanced by dehydration, a pattern that was confirmed by RT-PCR. Actinoporins, phosphatidylethanolamine-binding protein, arabinogalactan protein, and phospholipase are the likely dominant players in the defence system. In addition, 24 proteins of unknown function were identified as novel dehydration- or rehydration-responsive proteins. Our data indicate that Physcomitrella adopts a rapid protein response mechanism to cope with dehydration in its leafy-shoot and basal expression levels of desiccation-tolerant proteins are rapidly upgraded at high levels under stress. This mechanism appears similar to that seen in angiosperm seeds.

Steroids in the treatment of IgA nephropathy to the improvement of renal survival: a systematic review and meta-analysis.

BACKGROUND: Studies have shown that steroids can improve kidney survival and decrease the risk of proteinuria in patients with Immunoglobulin A nephropathy, but the overall benefit of steroids in the treatment of Immunoglobulin A nephropathy remains controversial. The aim of this study was to evaluate the benefits and risks of steroids for renal survival in adults with Immunoglobulin A nephropathy. METHODOLOGY AND PRINCIPAL FINDINGS: We searched the Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE and EMBASE databases. All eligible studies were measuring at least one of the following outcomes: end-stage renal failure, doubling of serum creatinine and urinary protein excretion. Fifteen relevant trials (n = 1542) that met our inclusion criteria were identified. In a pooled analysis, steroid therapy was associated with statistically significant reduction of the risk in end-stage renal failure (RR: 0.46, 95% CI: 0.27 to 0.79), doubling of serum creatinine (RR = 0.34, 95%CI = 0.15 to 0.77) and reduced urinary protein excretion (MD = -0.47 g/day, 95%CI = -0.64 to -0.31). CONCLUSIONS/SIGNIFICANCE: We identified that steroid therapy was associated with a decrease of proteinuria and with a statistically significant reduction of the risk in end-stage renal failure. Moreover, subgroup analysis also suggested that long-term steroid therapy had a higher efficiency than standard and short term therapy.