SPRR1B is Related to the Immune Microenvironment and Can Be Used as a Biomarker for the Diagnosis of Psoriasis.

Background: Psoriasis, a chronic inflammatory disorder with an unknown cause, significantly impacts the physical and psychological well-being of patients. However, current biomarkers related to psoriasis lack clinical specificity, sensitivity, and predictive ability. Methods: In this study, we collected skin lesion tissues from 20 psoriasis patients and 20 normal skin samples. Additionally, we obtained four datasets from the GEO database, which included human psoriasis and healthy specimens. We utilized SVM-RFE analysis and the LASSO regression model to identify potential biomarkers. Furthermore, we examined the composition of immune cell types in psoriasis and their correlation with specific genes. Results: Our investigation revealed 57 differentially expressed genes (DEGs), and we identified significantly enriched pathways through KEGG pathway analysis. The results of machine learning and WGCNA suggested that LCE3D and SPRR1B could potentially be used as marker genes for diagnosing psoriasis. RT-PCR and immunohistochemical detection confirmed the abnormally high expression of the SPRR1B gene in psoriasis. Analysis of immune cell infiltration revealed a strong positive correlation between SPRR1B and Macrophages M0 and T cells follicular helper, while showing the strongest negative correlation with resting Mast cells. In addition, we found that silencing SPRR1B in IFN-γ-treated HaCat cells could significantly reduce the increase in IL-17, IL-22, KRT6, and KRT16 caused by IFN-γ. Conclusion: These findings suggest that SPRR1B may have a significant role in the pathogenesis of psoriasis and could be employed as a novel immunomarker for its development.

The potency of common proinflammatory cytokines measurement for revealing the risk and severity of anxiety and depression in psoriasis patients.

OBJECTIVE: Proinflammatory cytokines mediate anxiety and depression in various ways, such as immunity, inflammation, and the hypothalamic-pituitary-adrenal axis. This study intended to further explore the linkage of common proinflammatory cytokine levels with anxiety and depression in psoriasis patients. METHODS: Totally, 150 psoriasis patients and 50 healthy controls (HCs) were included; the serum samples were collected, then common proinflammatory cytokines were measured by ELISA. Hospital Anxiety and Depression Scale (HADS) was assessed. RESULTS: HADS-anxiety (HADS-A) score, HADS-depression (HADS-D) score, TNF-α, IL-1ß, IL-6, IL-12, IL-17A, and IL-23 were all increased in psoriasis patients compared to HCs (all p < 0.05). In psoriasis patients, TNF-α (p = 0.001), IL-12 (p = 0.035), and IL-17A (p < 0.001), but not IL-1ß (p = 0.255), IL-6 (p = 0.248), and IL-23 (p = 0.216), were positively linked to HADS-A score. Meanwhile, TNF-α (p = 0.007) and IL-17A (p = 0.007) were enhanced in psoriasis patients with anxiety in contrast to those without anxiety; whereas IL-1ß (p = 0.178), IL-6 (p = 0.360), IL-12 (p = 0.239), and IL-23 (p = 0.450) were not different. TNF-α (p < 0.001), IL-1ß (p = 0.013), Il-17A (p < 0.001), and IL-23 (p = 0.023), but not IL-6 (p = 0.143) and IL-12 (p = 0.158), were positively linked to HADS-D score. Concurrently, TNF-α (p = 0.015), IL-17A (p < 0.001), and IL-23 (p = 0.017) were climbed in psoriasis patients with depression by comparison to those without depression; whereas IL-1ß (p = 0.113), IL-6 (p = 0.237), IL-12 (p = 0.660) did not differ. CONCLUSION: TNF-α, IL-17A, and IL-23 increments reflect anabatic anxiety and depression in psoriasis patients, uncovering the potency of proinflammatory cytokines measurement for monitoring or even preventing psoriasis patients' anxiety and depression.

ANRIL polymorphisms in psoriasis vulgaris patients in northern China

Background: Psoriasis is a systemic inflammatory disease. The autoimmune response plays a role in the pathogenesis of psoriasis. The long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) can regulate the immune response and participate in the pathogenesis of immune-related diseases, however, the role of ANRIL in the pathogenesis of psoriasis requires further clarification. Objectives: To study the association between ANRIL polymorphisms and psoriasis in the northern Chinese population. Materials & Methods: We genotyped six SNPs in ANRIL in 270 psoriasis vulgaris patients and 271 healthy controls in the northern Chinese population using an improved multiplexed ligation detection reaction method, in order to identify the role of ANRIL in psoriasis. Results: The C allele of rs3217992 and the T allele of rs2518723 were more prevalent in the case group than in the control group. The haplotypes, CTATAA, CCCCGG, and CTCCGG, were associated with risk of psoriasis, while the TCCCGG, TCATAA and CCATAA haplotypes were protective against psoriasis. Based on subgroup analysis, patients with the CT genotype at the rs3217992 and rs2518723 loci had a higher probability of a family history of psoriasis, and patients with the AA genotype had a higher mean age in the rs1333048 and rs10757278 groups, while those with the TT genotype had a higher mean age in the rs1333045 group. Conclusion: Our study identifies an association between ANRIL genetic variants and risk of psoriasis in northern China.

Tetrandrine enhances the anticancer effects of arsenic trioxide in vitro.

Arsenic trioxide (As2O3), an effective agent to treat leukemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden death have been implicated in the cardiotoxicity of As2O3. The present study was designed to assess whether the combination of As2O3 and tetrandrine could generate a more powerful anti-cancer effect. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed for detecting the proliferation of HepG2 and A549 cells treated with tetrandrine and As2O3. Fluorescent microscopy measurements and flow cytometry were carried out to evaluate the apoptosis in HepG2 cells. The cell cycle arrest of HepG2 cells was also determined by flow cytometry. The cell proliferation assay in HepG2 and A549 cells indicated that tetrandrine significantly enhanced the inhibit effect of As2O3. In addition, the following Isobolograms further demonstrated that combining As2O3 with tetrandrine generated synergism action. Tetrandrine also enhanced the apoptosis, necrosis and cell cycle arrest in As2O3-treated HepG2 cells. Our present study showed that tetrandrine can dramatically enhance the anti- cancer effect induced by As2O3. Combining As2O3 with tetrandrine would be a novel strategy to treat cancer in clinical practice.

Resveratrol protects against vinorelbine-induced vascular endothelial cell injury.

Vinorebine (VNR), a second-generation vinca alkaloid antitumor drug, caused serious local venous toxicities, such as venous irritation, phlebitis and necrotizing vasculitis. This study investigated whether resveratrol (RES), a naturally occurring polyphenol compound, could reduce the vascular injury induced by VNR. Human vascular endothelial cell line ECV-304 cells were exposed to VNR for 10 min and then cells were cultured with serum-free medium with or without RES for 24 h. MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphe-nyl-2-tetrazolium bromide) assay was used to detect the cell viability. Reactive oxygen species (ROS) was measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The activity of superoxide dismutase (SOD) was assessed by SOD detection kit. VNR decreased the viability of ECV-304 cells in a dose-dependent manner. Moreover, VNR caused cell apoptosis, the generation of intracellular ROS and the reduction of intracellular SOD. Interestingly, pretreatment with RES for 2 h increased the cell viability in a dose-dependent manner. Cell apoptosis, the intracellular ROS generation and the reduction of intracellular SOD induced by VNR were also attenuated when cells were pretreated with RES for 2 h. These results demonstrated that RES would protect against vascular endothelial cell injury induced by VNR. So the use of RES together with VNR may be a possible therapeutic approach to avoid the vascular injury induced by VNR.

Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro.

The clinical use of doxorubicin (DOX), a potent antineoplastic agent, is limited by its serious side-effects, which include acute and chronic cumulative dose-related cardiotoxicity. Berberine (BER), a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay was used to detect the cell viability of A549, HeLa and HepG2 cells after each cell line was treated with DOX, BER or a combination of DOX and BER for 24 h. Apoptosis was evaluated by acridine orange staining. The results showed that BER and DOX exhibited dose-dependent inhibitory effects on A549 and HeLa cells which were likely mediated by inducing apoptosis. The same result was found in the combination group. Isobologram illustration and combination index (CI) analyses revealed that the combination of DOX and BER generates synergistic effects in A549 (CI=0.61) and HeLa (CI=0.73) cells. These findings indicate that BER sensitizes cells to the anticancer effects of DOX.

Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice.

Doxorubicin, a very potent and often used anti-cancer drug, is largely limited due to the dose-related toxic effects. The present study investigated whether berberine, a natural product alkaloid, can reduce the liver injury induced by doxorubicin. Mice of either gender were randomly divided into four groups: the control group, doxorubicin group, berberine group, and berberine+doxorubicin group. In the tests, body weight, general condition and mortality of the mice were observed, and serum alanine aminotransferase and aspartate transaminase levels were determined to evaluate liver function. Furthermore, the liver was excised for determination of the weight changes, as well as histopathological analysis in the tissues. Mortality rate and significant decline in body weight, and increased plasma alanine aminotransferase and aspartate transaminase activities were observed in doxorubicin-treated mice. These changes were significantly prevented by pretreatment with berberine. Histopathological studies showed that doxorubicin caused structural injuries, such as vascular congestion, inflammatory cell infiltration, hepatocellular degeneration and necrosis, fibrosis in the liver. These histopathological changes were largely attenuated by berberine pretreatment. These findings indicate that berberine has the hepatoprotective effect on doxorubicin-induced liver injury in mice.