Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

Green credit policy, government subsidy, and enterprises "shifting from virtual to real".

Taking the green credit policy in 2012 as a quasi-natural experiment, this paper uses the difference-in-differences method to explore the impact of green credit policy on enterprises' financial asset allocation and the moderating effect of government subsidy. We find that green credit policy significantly promotes the financial asset allocation of heavy-polluting enterprises, which is mainly reflected in short-term liquid financial investment, thus supporting the precautionary motivation of holding financial assets. The mechanism analysis shows that green credit policy promotes the financial asset allocation of heavy-polluting enterprises by reducing the scale of debt financing and increasing the financing cost. Government subsidy can significantly weaken the promoting effect of green credit policy on enterprises' financial asset allocation, and there is heterogeneity due to the regional environmental regulation intensity and financial development level. Further analysis shows that the negative moderating effect of government subsidy on green credit policy and enterprises' financial asset allocation significantly promotes the "shifting form virtual to real" of heavy polluting enterprises by reducing financial asset allocation. This paper discusses the impact of green credit policy on financial asset allocation of heavy-polluting enterprises in China and further clarifies the significant role of government subsidy in the process, so as to provide suggestions for government to control the "shifting from real to virtual" of enterprises. The results also provide an important reference for countries, especially developing countries, to implement green credit policy and government subsidy to achieve sustainable economic development.

Metabolic influences on T cell in psoriasis: a literature review.

Psoriasis is a systemic inflammatory disease that frequently coexists with various other conditions, such as essential hypertension, diabetes, metabolic syndrome, and inflammatory bowel disease. The association between these diseases may be attributed to shared inflammatory pathways and abnormal immunomodulatory mechanisms. Furthermore, metabolites also play a regulatory role in the function of different immune cells involved in psoriasis pathogenesis, particularly T lymphocytes. In this review, we have summarized the current research progress on T cell metabolism in psoriasis, encompassing the regulation of metabolites in glucose metabolism, lipid metabolism, amino acid metabolism, and other pathways within T cells affected by psoriasis. We will also explore the interaction and mechanism between psoriatic metabolites and immune cells. Moreover, we further discussed the research progress of metabolomics in psoriasis to gain a deeper understanding of its pathogenesis and identify potential new therapeutic targets through identification of metabolic biomarkers associated with this condition.

Germinal Centre-Related Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type: Report of a Remission Case.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LTs) is a rare and the most aggressive type of the cutaneous B-cell lymphoma with poor prognosis and low therapeutic response. It mostly affects elderly women, with a 5-year survival rate of 50% if not efficiently treated. We present a 28-year-old male patient with indolent PCDLBCL-LT who reached nearly 100% clearance after six rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy sessions.

Recombinant programmed cell death 1 inhibits psoriatic inflammation in imiquimod­treated mice.

Psoriasis is a common chronic inflammatory skin disease. Programmed cell death ligand 1 (PD­L1) and programmed cell death 1 (PD­1) are expressed on immune cells in a number of chronic inflammatory diseases. However, a limited number of studies have investigated the expression and function of the PD­L1 and PD­1 pathway in psoriatic inflammation. The present study used human psoriasis samples and imiquimod­induced murine psoriasis models to investigate the potential role of PD­1 in the modulation of psoriatic inflammation. The results demonstrated that inhibition of PD­1 function with antibodies promoted psoriasis development. PD­1­fragment crystallizable (PD­1­Fc) treatment inhibited psoriatic inflammation and exhibited additive effects with anti­tumor necrosis factor α therapy in imiquimod­induced mouse psoriasis, suggesting that PD­1­Fc treatment may serve as a new therapeutic strategy for psoriasis.

Core-shell nanospheres to achieve ultralow friction polymer nanocomposites with superior mechanical properties.

Core-shell nanospheres have been widely used in catalysis, batteries, medicine, etc. owing to their unique structural characteristics, which exhibit optimal performance and integrated functions of both the core and shell materials. To simultaneously achieve outstanding mechanical properties and remarkable lubrication properties in desirable polymer composites, core-shell nanospheres with polytetrafluoroethylene (PTFE) as the core and poly methyl methacrylate (PMMA) as the shell have been adopted as structural units to form bulk nanocomposites. We demonstrated that the mechanical and lubrication properties of the nanocomposites prepared using core-shell nanospheres as the continuous matrix were dramatically improved. Specifically, when compared with that of pure PTFE, the compressive strength of the PTFE@PMMA nanocomposite obviously increased up to one order of magnitude (from ∼9 to ∼90 MPa), the friction coefficient reduced to 25% (the lowest value was 0.03), and the wear rate decreased up to two orders of magnitude. Moreover, the mechanical and lubrication properties of the nanocomposites could be adjusted by changing the core-shell ratio, and an appropriate core-shell ratio was beneficial for achieving the desired comprehensive properties. It has been proposed that the properties, such as the confinement effect, improved dispersion capacity, etc., imparted by the core-shell structure effectively lead to high dispersion of the reinforcement phase, improvement of the binding force of the transfer film to the friction surface, and interruption of the wear process of the polymer composite.

Hemophagocytic lymphohistiocytosis presenting with annular erythema multiforme-like eruptions in a patient with angioimmunoblastic T cell lymphoma: A case report.

Angioimmunoblastic T cell lymphoma (AITL)-associated hemophagocytic lymphohistiocytosis (HLH) rarely occurs with annular erythema multiforme-like rashes. The present case report describes a patient who was misdiagnosed with erythema multiforme at an early stage of the disease due to annular erythema multiforme-like eruptions. However, antihistamine treatment was ineffective. The patient progressed rapidly with high fever, hepatosplenomegaly and pharyngitis. The number of copies of Epstein-Barr virus DNA continuously increased. Accompanied by the swelling of lymph nodes, the blood cell count decreased. Further bone-marrow examination and biopsy of the lymph nodes were conducted. The patient was eventually diagnosed with AITL-associated HLH, and treated with etoposide together with cyclophosphamide, doxorubicin, vincristine and prednisolone. The patient was successfully treated with several courses of chemotherapy. In view of the fact that AITL-associated HLH with annular erythema multiforme-like rashes is relatively rare worldwide and is associated with a high mortality rate, the data on previous cases were reviewed with the hope of providing clinical bases for early diagnosis and treatment of AITL-associated HLH.

Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy.

Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induces tumor infiltration by both CD8+ and CD4+ T cells to suppress melanoma progression, and combining NRF2 inhibition with anti-PD-1 treatment enhanced its anti-tumor function. Our studies identify a critical and targetable PD-L1 upstream regulator and provide an alternative strategy to inhibit the PD-1/PD-L1 signaling in melanoma treatment.

C19, a C-terminal peptide of CKLF1, decreases inflammation and proliferation of dermal capillaries in psoriasis.

Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology. Chemokine-like factor 1 (CKLF1), a human cytokine that is a functional ligand for CCR4, displays chemotactic activities in a wide spectrum of leukocytes and plays an important role in psoriasis development. In previous study, our laboratory found that the expression of CKLF1 increased in psoriatic lesions. C19 as a CKLF1's C-terminal peptide has been reported to exert inhibitory effects on a variety of diseases. However, the protective roles of C19 in endothelial cells proliferation and inflammatory cells chemotaxis remain elusive in psoriasis. In this study we examined the protective effect of C19 on both the cellular model and the animal model. The effects of C19 on endothelial cells proliferation and inflammatory cells chemotaxis were investigated in cultured human umbilical vein endothelial cells (HUVECs) and imiquimod-induced psoriasiform inflammation of BALB/c mice based on techniques including immunohistochemical analysis, quantitative real-time PCR (qRT-PCR), western blot, transwell, and EdU assay. This study shows that CKLF1-C19 significantly protects against psoriasis by inhibiting the infiltration of inflammatory cells and proliferation of microvascular cells, possibly via inhibiting MAPK pathways.

Immune Signatures in Patients with Psoriasis Vulgaris of Blood-Heat Syndrome: A Systematic Review and Meta-Analysis.

Objective. To determine whether immunological serum markers IFN-γ, IL-4, IL-17, IL-23, IL-6, TNF-α, and IL-10 are elevated or decreased in patients compared with healthy controls. Methods. A complete search of the literature on this topic within the past 30 years was conducted across seven databases. Seventeen studies including 768 individuals were identified. Differences in serum marker levels between subjects and controls were pooled as MDs using the random-effects model. Results. The pooled MDs were higher in patients than in healthy controls for IFN-γ (MD 24.9, 95% CI 12.36-37.43), IL-17 (MD 28.92, 95% CI 17.44-40.40), IL-23 (MD 310.60, 95% CI 4.96-616.24), and TNF-α (MD 19.84, 95% CI 13.80-25.87). Pooled IL-4 (MD -13.5, 95% CI -17.74--9.26) and IL-10 (MD -10.33, 95% CI -12.03--8.63) levels were lower in patients. Conclusion. The pooled analyses suggest that levels of IFN-γ, IL-17, IL-23, and TNF-α are significantly elevated and that levels of IL-4 and IL-10 are significantly decreased in sera of patients with psoriasis vulgaris of blood-heat syndrome. Measuring progression of blood-heat syndrome of psoriasis vulgaris will require additional high-quality data, with a low risk of bias and adequate sample sizes, before and after antipsoriatic therapy.

Association between Psoriasis and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Psoriasis is considered a systemic inflammatory disorder. Previous studies have reported conflicting positive or negative correlations between psoriasis and chronic obstructive pulmonary disease. We performed a meta-analysis to determine whether there is an associated risk between psoriasis and chronic obstructive pulmonary disease. We performed a complete 30-year literature search of MEDLINE, Embase, and Cochrane Central Register databases on this topic. Four observational studies with a total of 13,418 subjects were identified. The odds ratios of chronic obstructive pulmonary disease in subjects with psoriasis/mild-to-moderate psoriasis were analyzed using the random-effects model, while the odds ratios of chronic obstructive pulmonary disease in subjects with severe psoriasis and current smoking in subjects with psoriasis were analyzed using the fixed-effect model. We found that psoriasis patients were at a greater risk of developing chronic obstructive pulmonary disease than the general population (odds ratio, 1.90; 95% confidence interval, 1.36-2.65) and that the association between of psoriasis and with chronic obstructive pulmonary disease was stronger among patients with severe psoriasis (odds ratio, 2.15; 95% confidence interval, 1.26-3.67). Psoriasis patients should be advised to cease smoking to reduce their risk of COPD. Moreover, identification of this potential risk may enable earlier implementation of preventive measures for reduction comorbidity and mortality rates.

Chemokine-like factor 1-derived C-terminal peptides induce the proliferation of dermal microvascular endothelial cells in psoriasis.

Psoriasis is an inflammatory disease characterized by the abnormal proliferation of skin cells, including dermal microvascular endothelial cells. Recently, chemokine-like factor 1 (CKLF1) was found to participate in the local inflammation and cell proliferation. To explore its role in the pathogenesis of psoriasis, the expression of both CKLF1 and its receptor (CCR4) was determined in the psoriatic lesions. Also, the effect of the C-terminal peptides (C19 and C27) of CKLF1 on the proliferation of human umbilical vein endothelial cells was studied in vitro. By immunohistochemistry and immunofluorescence, the expression of both CKLF1 and CCR4 was determined in the psoriatic lesions. The effect of C-terminal peptides on human umbilical vein endothelial cells (HUVECs) was studied in vitro by the evaluation of cell proliferation and apoptosis. The in vivo assessment was performed accordingly through the subcutaneous injection peptides on BALB/c mice. The results showed that, by immunohistochemistry, both CKLF1 and CCR4 were increasingly expressed in psoriatic lesions as compared to normal skins. Moreover, the primary umbilical vein endothelial cells exhibited higher proliferation ratio under the C19 or C27 stimulation, which was even enhanced by the addition of psoriatic sera or TNF-α. Furthermore, the enhancement of peptide simulation was accompanied with the activation of ERK1/2-MAPKs pathway. In addition, such effect of C19 and C27 was mirrored by the hyperproliferation of cutaneous microvessels in BALB/c mice that were subcutaneously injected with the two peptides. Therefore, we concluded that CKLF1 plays a role in the pathogenesis of psoriasis by promoting the proliferation of microvascular endothelial cells that possibly correlates with ERK1/2-MAPKs activation.

Receptor interacting protein 1 involved in ultraviolet B induced NIH3T3 cell apoptosis through expression of matrix metalloproteinases and reactive oxygen species production.

BACKGROUND: Receptor interacting protein 1 (RIP1), which plays a key role in apoptosis, cell survival and programmed cell necrosis, is one of the most important proteins in the RIP family. The purpose of this study was to investigate the roles of RIP1 in the apoptosis, the generation of reactive oxygen species (ROS) and the expression of matrix metalloproteinases (MMPs) induced by ultraviolet B (UVB) in fibroblasts. METHODS: siRNA targeting RIP1 was used to silence RIP1 expression in the NIH3T3 fibroblasts. The mRNA and protein levels of MMP-1 and MMP-3, caspase-3 and -8 activities, and ROS activities were determined by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), immunoblotting, caspase activity assay, immunofluorescence, and flow cytometry. RESULTS: The mRNA and protein expressions of MMP-1 and MMP-3 were significantly increased in RIP1 deficient NIH3T3 cells at 24 hours after UVB treatment. At 24 hours after exposure to UVB, RIP1 deficient NIH3T3 cells presented apoptotic morphology, and the apoptosis rate was significantly increased accompanied by pronounced increase in caspase-8 and -3 activities. ROS production was inhibited by UVB at 12 hours in RIP1 deficient NIH3T3 cells. CONCLUSION: RIP1 is involved in NIH3T3 cell damage induced by UVB via participating in the apoptosis, expression of MMPs and ROS production.

Time trends of contact allergy to a modified European baseline series in Beijing between 2001 and 2006.

BACKGROUND: Monitoring trends of sensitivity rates in a population is useful for epidemiological surveillance. The time trends for sensitivity rates of allergens have not previously been reported in China. OBJECTIVES: The aim of the present study was to determine the prevalence and trends of contact allergy in patients with suspected allergic contact dermatitis in Beijing, China. PATIENTS/METHODS: A retrospective analysis of all patch test data from our database was performed. A total of 1354 patients with suspected allergic contact dermatitis between 2001 and 2006 were studied. Patch tests with 20 allergens or mixtures of allergens were performed and analysed. RESULTS: Sensitivity to potassium dichromate (50.1%) was most frequent, and sensitivity to imidazolidinyl urea (3.0%) was least frequent. Increasing trends in sensitivity rates for 10 allergens with significant linear regression were observed (p < 0.05), including mercapto mix, black rubber mix, potassium dichromate, formaldehyde, epoxy resin, benzocaine, ethylenediamine dihydrochloride, paraben mix, tixocortol-21-pivalate, and sesquiterpene lactone mix. Sensitivity rates for the other 10 allergens remained stable or showed only a trend (fragrance mix) towards an increase (p(trend) > 0.05). CONCLUSIONS: High sensitivity rates were observed in the study. Significant increasing trends in sensitivity rates for 10 allergens, probably reflecting increasing changes in exposure, were found.

Proteome analysis of ultraviolet-B-induced protein expression in vitro human dermal fibroblasts.

BACKGROUND: Ultraviolet-B (UVB) radiation can result in acute photodamage, photoaging and skin cancer through the induction of reactive oxygen species, DNA damage, activation of signaling pathways, and regulation of gene expression. In this study, we investigated UVB-induced alterations in protein expression in human dermal fibroblasts. METHODS: Skin fibroblasts were irradiated with 100 mJ/cm² UVB, and cell viability was monitored by the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectroscopy were used to identify differentially expressed proteins. The mRNA and levels of identified proteins were detected using a quantitative real-time polymerase chain reaction assay and Western blot. RESULTS: UVB decreased the viability of skin fibroblasts. In UVB-treated cells, eighteen differentially expressed proteins were identified. Among these proteins, the amounts of receptor-interacting protein (RIP) and vimentin were significantly up-regulated. However, their mRNA levels decreased and remained relatively stable, respectively. CONCLUSIONS: The differential expression of RIP and vimentin was validated in UVB-irradiated fibroblasts. RIP may promote cell injury, and vimentin may contribute to the resistance of cells to UVB-induced damage.

Ultraviolet B-induced apoptosis of human skin fibroblasts involves activation of caspase-8 and -3 with increased expression of vimentin.

BACKGROUND: After irradiation with a high dose of ultraviolet B (UVB), cells undergo apoptosis. Caspase-8 and -3 are key mediators of apoptosis in many cells. Vimentin, an important cytoskeleton component, can be cleaved by caspase-3, -6, -7 and -8. Cell apoptosis is promoted via caspase-triggered proteolysis of vimentin. In this study, we explored the roles of caspase-8 and -3 and the changes in vimentin expression in UVB-induced apoptosis of human dermal fibroblasts. METHODS: Skin fibroblasts were irradiated with 150 mJ/cm(2) UVB and cell death was monitored by the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and Hoechst staining. Caspase-8 and -3 activities were detected by the caspase activity assay. Vimentin expression was assessed by immunofluorescence and Western blot. RESULTS: Caspase-8 and -3 were activated by 150 mJ/cm(2) UVB irradiation. Caspase-8 and -3 activities changed in a time-dependent way after UVB irradiation to induce apoptosis of fibroblasts, and caspase-8 and -3 interacted with each other in this process. However, their substrate, vimentin, showed an enhanced expression over time after UVB irradiation. CONCLUSIONS: UVB-triggered apoptosis of fibroblasts was dependent on the activation of caspase-8 and -3 with an increased expression of vimentin.