The occurrence and development mechanisms of esophageal stricture: state of the art review.

BACKGROUND: Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS: A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS: Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION: The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.

Downregulation of Ebp1Khib210 promotes keratinocyte proliferation through induction of TIF-IA-mediated rRNA synthesis.

BACKGROUND: Psoriasis is a prevalent chronic inflammatory dermatosis characterized by excessive proliferation of keratinocytes. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly identified post-translational modification that regulates various biological processes. Abnormal Khib modification has been closely associated with the development of autoimmune diseases. OBJECTIVE: To investigate the abnormal Khib profile and its pathogenic role in psoriasis. METHODS: We utilized liquid chromatography-tandem mass spectrometry to analyze Khib-modified proteins in the epidermis of psoriasis and healthy controls. Mutated cells and mice with downregulated Ebp1Khib210 were generated to investigate its functional effects in psoriasis. RESULTS: The omic analysis revealed dysregulation of Khib modification in psoriatic lesions, exhibiting a distinct profile compared to controls. We observed the downregulation of Ebp1Khib210 in psoriatic lesions and IMQ-induced psoriatic mice. Notably, the expression of Ebp1Khib210 was upregulated in psoriatic patients following effective treatment. Decreased Ebp1Khib210 enhanced keratinocyte viability, proliferation, and survival while inhibiting apoptosis in vitro. Additionally, Pa2g4K210A mice with downregulated Ebp1Khib210 exhibited more severe psoriatic lesions and enhanced keratinocyte proliferation. Moreover, we found that Ebp1K210A mutation increased the interaction between Ebp1 and nuclear Akt, thereby inhibiting MDM2-mediated TIF-IA ubiquitination, and resulting to increased rRNA synthesis and keratinocyte proliferation. The downregulation of Ebp1Khib210 was attributed to inflammation-induced increases in HDAC2 expression. CONCLUSION: Our findings demonstrate that downregulation of Ebp1Khib210 promotes keratinocyte proliferation through modulation of Akt signaling and TIF-IA-mediated rRNA synthesis. These insights into Khib modification provide a better understanding of the pathogenesis of psoriasis and suggest potential therapeutic targets.

Integration and Quantitative Visualization of 3,3',5,5'-Tetramethylbenzidine-Probed Enzyme-Linked Immunosorbent Assay-like Signals in a Photothermal Bar-Chart Microfluidic Chip for Multiplexed Immunosensing.

The photothermal effect shows significant promise for various biomedical applications but is rarely exploited for microfluidic lab-on-a-chip bioassays. Herein, a photothermal bar-chart microfluidic immunosensing chip, with the integration of the conventional 3,3',5,5'-tetramethylbenzidine (TMB)-probed enzyme-linked immunosorbent assay (ELISA)-like system, was developed based on exploiting the photothermal pumping technique for visual bar-chart microfluidic immunosensing. Both the sandwich ELISA-like system and the photothermal pumping protocol were integrated into a single photothermal bar-chart chip. On-chip immunocaptured iron oxide nanoparticles catalyzed the oxidation of the chromogenic substrate, TMB, to produce a sensitive photothermal and chromogenic dual-functional probe, oxidized TMB. As the result of heat generation and the subsequent production of elevating vapor pressure in the sealed microfluidic environment, the on-chip near-infrared laser-driven photothermal effect of the probe served as a dose-dependent pumping force to drive the multiplexed quantitative display of the immunosensing signals as visual dye bar charts. Prostate-specific antigen as a model analyte was tested at a limit of detection of 1.9 ng·mL-1, lower than the clinical diagnostic threshold of prostate cancer. This work presents a new perspective for microfluidic integration and multiplexed quantitative bar-chart visualization of the conventional TMB-probed ELISA signals possibly by means of an affordable handheld laser pointer in a lab-on-a-chip format.

Increased angiogenesis and migration of dermal microvascular endothelial cells from patients with psoriasis.

Psoriasis displays both increased angiogenesis and microvascular dilation in the skin, while human dermal microvascular endothelial cells (HDMECs) are involved in angiogenesis and microvascular dilation. Whether the functions of HDMECs are altered in psoriatic skin versus healthy skin remain unknown. Here, we isolated HDMECs from the skin of 10 patients with psoriasis and 10 healthy subjects and compared angiogenesis, proliferation, migration and cell metabolism between psoriatic HDMECs and normal HDMECs. We found that the morphology of primary HDMECs was comparable between psoriatic HDMECs and normal HDMECs. After passage, psoriatic HDMECs displayed larger cell size and wider intercellular space. In addition to DiI-Ac-LDL (DiI-labelled acetylated low-density lipoprotein) uptake, expression levels of CD31, vWF (von Willebrand factor) and LYVE-1 were comparable in psoriatic HDMECs versus normal HDMECs. However, psoriatic HDMECs exhibited increased tube formation (numbers of nodes and meshes, p < 0.05) and migration (numbers of migrated cells, p < 0.001) and reductions in proliferation (growth rates, p < 0.05) and energy metabolism (oxygen consumption rate and extracellular acidification rate, p < 0.05) compared with normal HDMECs. Therefore, psoriatic HDMECs display an increased angiogenesis and migration and decreased proliferation and metabolic activity, suggesting a pathogenic role of HDMECs in psoriasis.

The effects of human dermal-derived mesenchymal stem cells on the keratinocyte proliferation and apoptosis in psoriasis.

Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperproliferation. Mesenchymal stem cells (MSCs) regulate inflammation and vascular proliferation in the psoriasis lesions. Whether dermal-derived mesenchymal stem cells (DMSCs), the main MSCs in the dermis, regulate keratinocyte proliferation and apoptosis remains unknown. In the present study, we assessed the proliferation and apoptosis of keratinocytes cocultured with DMSCs isolated from either normal or psoriatic involved skin. Cell growth and apoptotic rates were determined using Cell Count Kit-8 and annexin V-FITC staining, respectively. In addition, EDU kit was also used to measure the rate of keratinocyte proliferation. Our results showed that psoriatic DMSCs (pDMSCs) were more potent than normal DMSCs (nDMSCs) in stimulating keratinocyte proliferation. In contrast, the apoptotic rate and expression levels of caspase-3 protein were lower in pDMSC-treated than nDMSC-treated keratinocytes (p < 0.001). Moreover, significantly higher contents of IL-6, IL-8, TNF-α and IFN-γ were found in the culture medium of pDMSCs than in that of nDMSCs. In conclusion, pDMSCs were more potent than nDMSCs in stimulation of keratinocyte proliferation and secretion of proinflammatory cytokines, but weaker in promoting apoptosis.

Dermal mesenchymal stem cells promoted adhesion and migration of endothelial cells by integrin in psoriasis.

The unusual dilatation of dermal capillaries and angiogenesis played important roles in psoriasis. Some genes and proteins of dermal mesenchymal stem cells (DMSCs) from psoriasis are abnormal and related to the function of endothelial cells (ECs). The present study was aimed to evaluate whether psoriatic DMSCs could affect adhesion and migration of ECs through neovascularization-related integrins in psoriasis. Human DMSCs, collected from psoriasis lesions and healthy skin, respectively, were cocultured with human umbilical vein endothelial cells (HUVECs). The expression levels of three integrins, that is, αvß3, αvß5, and α5ß1 in HUVECs were tested by quantitative real-time polymerase chain reaction and Western blot analysis. The adhesion and migration of HUVECs were detected by adhesion assay and migration assay. The results showed that in psoriasis group, the expression of αVß3 and α5ß1 of HUVECs markedly increased 2.50- and 3.71-fold in messenger RNA levels, and significantly increased 1.63- and 1.92-fold in protein levels, comparing to healthy control group (all p < .05). But ß5 was not significantly different between the two groups (p > .05). In addition, compared with control, psoriatic DMSCs promoted HUVECs adhesion by 1.62-fold and migration by 2.91-fold (all p < .05). In conclusion, psoriatic DMSCs impact HUVECs adhesion and migration by upregulating the expression of integrins αVß3 and α5ß1.

The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis.

Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing. The results of our study presented that the DMSCs promoted HaCaT cells apoptosis both in early apoptotic state (13.8 vs. 2.9, p < 0.05) and late apoptotic state (4.2 vs. 0.7, p < 0.05). The expression of apoptosis associated proteins caspase-3 (3.51 vs. 1.99, p < 0.05) and lymphoid enhancer-binding factor 1 (3.10 vs. 0.83, p < 0.05) were upregulated. However, the cell cycle protein cyclin E1 was similar (9.38 vs. 9.05, p > 0.05). Moreover, 33 genes with the function of induced cell apoptosis were highly expressed in DMSCs, including insulin-like growth factor-binding protein 4 (2828.13), IGFBP7 (1805.69), cathepsin D (1694.34), cathepsin B (CTSB, 1641.40) and dickkopf WNT signaling pathway inhibitor 1 (DKK1, 384.79). This study suggested DMSCs induce the apoptosis of keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer.

Multi-omics study in monozygotic twins confirm the contribution of de novo mutation to psoriasis.

BACKGROUND: Genome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.0 in Chinese population. Although rare variations still account for a small proportion of phenotypic variances in complex diseases, their effect on phenotypes is large. Recently, more and more studies focus on the low-frequency functional variants and have achieved a certain amount of success. METHOD: Whole genome sequencing and sanger sequencing was performed on 8 MZ twin pairs discordant for psoriasis to scan and verified the de novo mutations (DNMs). Additionally, 665 individuals with about 20 years' medical history versus 2054 healthy controls and two published large population studies which had about 8 years' medical history (including 10,727 cases versus 10,582 controls) were applied to validate the enrichment of rare damaging mutations in two DNMs genes. Besides, to verify the pathogenicity of candidate DNM in C3, RNA-sequencing for CD4+, CD8+ T cells of twins and lesion, non-lesion skin of psoriasis patients were carried out. Meanwhile, the enzyme-linked immunosorbent assay kit was used to detect the level of C3, C3b in the supernatant of peripheral blood. RESULT: A total of 27 DNMs between co-twins were identified. We found six of eight twins carry HLA-C∗0602 allele which have large effects on psoriasis. And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele. In the replication stage, we found 2 loss-of-function (LOF) variants of C3 only in 665 cases with about 20 years' medical history and gene-wise analysis in 665 cases and 2054 controls showed that the rare missense mutations in C3 were enriched in cases (OR = 1.91, P = 0.0028). We further scanned the LOF mutations of C3 in two published studies (about 8 years' medical history), and found one LOF mutation in the case without carrying HLA-C*0602. In the individual with DNM in C3, RNA sequencing showed the expression level of C3 in skin was significant higher than healthy samples in public database (TPM fold change = 1.40, P = 0.000181) and ELISA showed protein C3 in peripheral blood was higher (~2.2-fold difference) than the other samples of twins without DNM in C3. CONCLUSION: To the best of our knowledge, this is the first report that DNM in C3 is the likely pathological mutations, and it provided a better understanding of the genetic etiology of psoriasis and additional treatments for this disease.

Psoriasis-associated angiogenesis is mediated by EDIL3.

The dermal mesenchymal stem cells (DMSCs) from psoriasis display higher expression level of epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3), while EDIL3 can bind integrins, including αvß3 and αvß5, to regulate angiogenesis. To assess the role of EDIL3 derived from DMSCs of psoriasis (P-DMSCs) in angiogenesis, in vitro, EDIL3 of DMSCs from psoriasis was silenced by interfering EDIL3. Then the efficacy of silencing EDIL3 was tested by fluorescent flag, qRT-PCR and western blotting. And, in vitro, the relationship of EDIL3 in DMSCs with the angiogenesis of HUVECs were investigated through co-culture system. In vivo, EDIL3 recombinant protein was injected into IMQ cream-induced psoriasis-like skin lesions of mouse and EDIL3-associated tube formation were determined using Image J software. Our results showed the capacity of the adhesion, migration and tube formation of HUVECs in all psoriatic DMSCs groups were significantly higher compared with the control and si-EDIL3 groups (all P<0.05) in vitro. Moreover, under stimulated by EDIL3 recombinant protein, EDIL3-associated tube formation was dramatically elevated in vivo (P<0.01). In this study, EDIL3 could promote the adhesion, migration and tube formation of ECs and participant in the angiogenesis pathogenesis of psoriasis through affecting biological function on ECs both in vitro and in vivo. The results suggest a potential role of the critical pro-angiogenic factor EDIL3 in psoriasis therapy.

Cross-sectional study reveals that HLA-C*07:02 is a potential biomarker of early onset/lesion severity of psoriasis.

Psoriasis is a common chronic autoimmune skin disease, with T cells playing a predominant role in its pathogenesis. Here, we aimed to investigate the relation of T-cell repertoires (TCR) and major histocompatibility complex (MHC) in psoriatic patients to further understand mechanisms in disease pathogenesis. We conducted a cross-sectional study involving nine pairs of monozygotic twins with inconsistent psoriasis and examined the TCR diversity and MHC haplotype of the individuals using multiple-PCR and high-throughput sequencing. Additionally, 665 psoriatic patients were applied to validate the relation of human leucocyte antigen (HLA) class I allele HLA-C*07:02 and early onset or lesion severity of psoriasis. The immune diversity was lower in psoriatic patients compared with unaffected individuals within the twin pairs, although the difference was not significant. The clonotypes of TCR significantly decreased in psoriatic patients with high PASI score and early onset. HLA-C*07:02, a haplotype associated with psoriasis, was positively correlated with the diversity of the TCRV gene. Moreover, HLA-C*07:02 clustered in patients with high PASI and early onset. In the replication stage, we found that the PASI and onset age in psoriasis with HLA-C*07:02 were significantly different from those without HLA-C*07:02 and without HLA-C*06:02. Our observations indicate that HLA-C*07:02 is positively correlated with the diversity of TCRV gene in psoriasis and maybe a potential biomarker of early onset/severe lesions of psoriasis.

An effective method of isolating microvascular endothelial cells from the human dermis.

Dermal microvascular endothelial cells (DMECs) play central roles in inflammation and angiogenesis and have become important cell models for studying various skin diseases. However, primary DMECs are difficult to culture and often contaminated by mesenchymal stem cells, fibroblasts, and other stromal cells. Surgically removed superfluous foreskin was first cut into pieces, digested with two types of enzymes, and dispersed into single cells. Cells obtained from the dermis were then subjected to Percoll density gradient centrifugation and cells located between densities 1.033 and 1.047 g/ml were further purified with endothelial growth medium containing decreasing concentrations of puromycin. Obtained HDMECs were identified by microscopy, flow cytometry, quantitative reverse-transcription polymerase chain reaction, western blot analysis, and immunofluorescent staining. The expression of CD31 (PECAM-1), CD34, VEGFR2, VWF (Von Willebrand Factor), VE-Cadherin (CD144), and NOS was positive. HDMECs were found to have abilities of angiogenesis and uptake of acetylated low-density lipoprotein. Growth curves and cell viability were analyzed, and a growth pattern consisting of the "latency phase-logarithmic growth phase-stagnation phase" was determined. In this study, a simple, rapid, effective, and low-cost method is established to isolate HDMECs from the foreskin with a purity of over 91% and high viability. The method showed good repeatability and allowed a stable passage. This study provides technical support and theoretical guidance for studying the physiological characteristics of HDMECs, the pathogenesis of the skin associated, and other microvascular diseases.

Psoriatic Dermal-derived Mesenchymal Stem Cells Reduce Keratinocyte Junctions, and Increase Glycolysis.

Although it is known that psoriatic dermal-derived mesenchymal stem cells (DMSCs) dysregulate keratinocyte proliferation, the biological activity profile of keratinocytes influenced by psoriatic DMSCs remain unknown. In the present study, we assessed the impact of psoriatic DMSCs on keratinocyte proliferation, differentiation, and glucose metabolism in normal human epidermal keratinocytes co-cultured with or without psoriatic DMSCs. Co-culture of normal human epidermal keratinocytes with psoriatic DMSCs downregulated expression levels of proteins associated with cell junction assembly (alpha-actinin-1, catenin beta-1, poliovirus receptor-related protein 4 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), while upregulating proteins associated with keratinocyte proliferation and differentiation (involucrin, isoform 2 of Histone-binding protein, isoform 3 of Telomeric repeat-binding factor 2 and keratin 13). Moreover, co-culture of normal human epidermal keratinocytes with psoriatic DMSCs stimulated keratinocyte proliferation and glycolysis, but reduced keratinocyte junctions. Taken together, these results demonstrate that psoriatic DMSCs increase keratinocyte proliferation and glycolysis, and reduce cell junctions, suggesting a pathogenic role of psoriatic DMSCs in epidermal hyperplasia, aberrant differentiation, and reduction in turnover time of keratinocytes in psoriasis.

Different epigenome regulation and transcriptome expression of CD4+ and CD8+ T cells from monozygotic twins discordant for psoriasis.

OBJECTIVES: Psoriasis is an immunodeficient skin disorder, and its exact pathogenesis is unclear. Monozygotic twins are presumed to be genetically identical, and their phenotypic differences may be due to transcriptional regulation or epigenome factors. To explain the inconsistency between twins, we have collected 3 pairs of monozygotic twins who are discordant for psoriasis. METHODS: Reduced representation of bisulfite sequencing and RNA sequencing was conducted using the peripheral blood of the twins to find the genes playing important roles in psoriasis pathogenesis. RESULTS: As a result, we found methylation diversity in four genes (MAST3, MTOR, PM20D1 and ZNF99), and we also found 9 differentially expressed genes (PPAN-P2RY11, PIGV, RPS18, TMEM121, KIF21A, KCNH2, WNT10B, PRX and CDH24) by RNA sequencing. According to the conjoint analysis of methylation and the mRNA results, PTPN6, CCL5, NFATC1 and PRF1 were found to be closely related to psoriasis. We then annotated the genes to explore the associations between these genes and psoriasis. CONCLUSIONS: These findings provide a better understanding of psoriasis that can improve the diagnosis and treatment of the disease.

Photothermal Microfluidic Sensing Platform Using Near-Infrared Laser-Driven Multiplexed Dual-Mode Visual Quantitative Readout.

The application of different sensing principles in microfluidic devices opens up further possibilities for the development of point-of-care testing (POCT). Herein, the photothermal sensing principle is introduced in microfluidic paper-based analytical devices (µPADs) to develop a photothermal microfluidic sensing platform using near-infrared (NIR) laser-driven multiplexed dual-mode visual quantitative readout. Prussian blue (PB) as the analyte-associated photothermal agent was in situ synthesized in thermoresponsive poly(N-isopropylacrylamide) hydrogels to serve as the on-chip photothermal sensing element. The NIR laser-driven photothermal effect of PB triggered not only on-chip dose-dependent heat generation but also phase transition-induced dye release from the hydrogels, simultaneously enabling both thermal image- and distance-based dual-mode visual quantitative readout of the analyte concentration in a multiplexed manner. Both the on-chip temperature elevation value of the hydrogels and the traveling distance of released dye solutions were proportional to the concentration of PB. With the detection of silver ions in environmental water as a proof-of-concept study, the photothermal µPAD can detect silver ions at a concentration as low as 0.25 µM with high selectivity and satisfactory accuracy. The photothermal microfluidic sensing platform holds great potential for POCT with promising integratability and broad applicability, owing to the combination of synergistic advantages of the photothermal sensing principle, µPADs, and photothermally responsive hydrogels.

Comparison of two commonly used methods for stimulating T cells.

OBJECTIVE: Although several methods have been reported and used for in vitro T cell amplification, there are no consistent reports on the optimal stimulation conditions and the characterization of these stimulated T cells. The current study aimed to determine the optimal conditions for efficient T cell amplification by two commonly used methods involving CD3/CD28 antibody and phytohemagglutinin (PHA), respectively. RESULTS: Orthogonal design and CCK8 assay showed that 5 µg/mL CD3, 5 µg/mL CD28, and 100 ng/mL IL2 for the first method and 50 µg/mL PHA for the second method was optimal for T cell stimulation. Flow cytometry demonstrated that the percentage of CD8+ in the stimulated groups significantly increased, while the percentage of CD4+/CD8+ was significantly decreased compared with the unstimulated group. The percentage of CD4+ showed no significant difference among the three groups. Notably, there was no significant difference between the two stimulated groups. In addition, the percentage of apoptotic cells was significantly increased in the stimulated groups compared with the unstimulated group, but showed no remarkable difference between the PHA and CD3/CD28 stimulation groups. Glycolysis analysis showed that the glycolytic capacity and glycolytic reserve were both significantly increased in the PHA and CD3/CD28 groups compared with the unstimulated group, with no significant difference noted between the stimulated groups. CONCLUSIONS: Although both stimulation methods showed similar efficacies, we suggest the PHA method might be better considering its easy application and cost-effective nature.

Comparative analysis of molecular activity in dermal mesenchymal stem cells from different passages.

Mesenchymal stem cells (MSCs) are used for tissue regeneration in several pathological conditions, including autoimmune diseases. However, the optimal sources and culture requirements for these cells are still under investigation. Here, we compared mRNA expression in dermal MSCs (DMSCs) at passage (P) 3 and P5 to provide a reference for future studies related to DMSCs expansion. In normal DMSCs, the expression of three of eight genes associated with basic cellular activity were different at P5 compared to that at P3: PLCB4 and SYTL2 were upregulated by 4.30- and 6.42-fold, respectively (P < 0.05), whereas SATB2 was downregulated by 39.25-fold (P < 0.05). At the same time, genes associated with proliferation, differentiation, inflammation, and apoptosis were expressed at similar levels at P3 and P5 (P > 0.05). In contrast, in DMSCs isolated from psoriatic patients we observed differential expression of three inflammation-associated genes at P5 compared to P3; thus IL6, IL8, and CXCL6 mRNA levels were upregulated by 16.02-, 31.15-, and 15.04-fold, respectively. Our results indicate that normal and psoriatic DMSCs showed different expression patterns for genes related to inflammation and basic cell activity at P3 and P5, whereas those for genes linked to proliferation, differentiation, and apoptosis were mostly similar.

Comparison of microarray and RNA-Seq analysis of mRNA expression in dermal mesenchymal stem cells.

OBJECTIVE: We characterized mRNA expression profiles in normal and psoriatic human dermal mesenchymal stem cells (DMSCs) to provide a reference for future investigation of differential gene expression in DMSCs. RESULTS: Microarray and RNA sequencing (RNA-Seq) analyses both identified 23 differentially expressed genes using both platforms. The results showed comparable upregulation or downregulation for 14/23 genes using either platform and a 100 % coincidence rate was found by real-time PCR. For all of the differentially expressed genes that were verified by real-time PCR, the coincidence rate for RNA-Seq and real-time PCR was significantly higher than that for microarray analysis and real-time PCR (83.3 vs. 37.5 %, P < 0.0001). Furthermore, RNA-Seq revealed the presence of over 2300 novel transcription tags. CONCLUSION: Relative to microarray analysis, RNA-Seq is more accurate in identifying differentially expressed genes in DMSCs.

Biological characteristics and gene expression pattern of bone marrow mesenchymal stem cells in patients with psoriasis.

Mesenchymal stem cells (MSCs) have immunoregulatory and proangiogenic effects and are suggested to be involved in the pathological processes of immune-related diseases, including psoriasis. Biological characteristics of bone marrow MSCs (BMSCs) from patients with autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, but not psoriasis, have been characterized. We compared the gene expression profile and biological characteristics of BMSCs from patients with psoriasis and healthy controls. Although the phenotype, differentiation potential and ability to support CD34(+) cell proliferation were similar to those of normal BMSCs, psoriatic BMSCs showed aberrant proliferative activity, increased apoptosis rate and a characteristic gene expression profile. These aberrations may develop after the abnormal immune response in psoriasis and result in BMSC dysfunction. The functionally deficient BMSCs may then fail to suppress overactive immune cells, thereby contributing to the pathogenesis of psoriasis.

Construction methods and biomedical applications of PVA-based hydrogels.

Polyvinyl alcohol (PVA) hydrogel is favored by researchers due to its good biocompatibility, high mechanical strength, low friction coefficient, and suitable water content. The widely distributed hydroxyl side chains on the PVA molecule allow the hydrogels to be branched with various functional groups. By improving the synthesis method and changing the hydrogel structure, PVA-based hydrogels can obtain excellent cytocompatibility, flexibility, electrical conductivity, viscoelasticity, and antimicrobial properties, representing a good candidate for articular cartilage restoration, electronic skin, wound dressing, and other fields. This review introduces various preparation methods of PVA-based hydrogels and their wide applications in the biomedical field.