Interleukin-37 inhibits desmoglein-3 endocytosis and keratinocyte dissociation via upregulation of Caveolin-1 and inhibition of the STAT3 pathway.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially fatal autoimmune bullous disease primarily caused by acantholysis of keratinocytes attributed to pathogenic desmoglein-3 (Dsg3) autoantibodies. Interleukin-37 (IL-37) reportedly plays important roles in a variety of autoimmune diseases, but its role in PV is not clear. OBJECTIVES: To investigate whether IL-37 plays a role in the occurrence and progression of PV. METHODS: HaCaT keratinocytes were stimulated with anti-Dsg3 antibody to establish an in vitro PV model, which was defined as anti-Dsg3 group. Cells incubated with medium without anti-Dsg3 treatment were used as control. IL-37 was cultured with these cells infected with or without lentiviral vector shRNA-Caveolin-1 (sh-Cav-1-LV). Cell dissociation assay and immunocytofluorescence were performed to assess keratinocyte dissociation, keratin retraction and Dsg3 endocytosis. Real-time PCR was used to detect the mRNA level of Cav-1, and western blot was used to determine the protein expression of Cav-1, Dsg3, STAT3 and phosphorylated-STAT3 (p-STAT3). RESULTS: The anti-Dsg3 group showed more cell debris, increased keratin retraction, increased Dsg3 endocytosis, reduced Cav-1 expression and co-localization than the control group, while IL-37 treatment neutralized all of these changes. Interestingly, Cav-1 knockdown supressed the inhibitory effect of IL-37 on keratinocyte dissociation and Dsg3 internalization. The protein expression of p-STAT3 was increased in keratinocytes of the PV model but decreased by IL-37. Re-activation of the STAT3 pathway by colivelin supressed the inhibitory effect of IL-37 on keratinocyte dissociation and Dsg3 internalization, along with upregulation of Cav-1 and Dsg3. CONCLUSIONS: IL-37 inhibited keratinocyte dissociation and Dsg3 endocytosis in an in vitro PV model through the upregulating Cav-1 and inhibiting STAT3 pathway.

IgG4-Related Disease Manifested as Cutaneous Plasmacytosis: A Case Report.

Background: IgG4-related disease (IgG4-RD) is a rare fibroinflammatory disease that has a high tendency to misdiagnosis in clinics. Case Presentation: A 48-year-old man developed a rash with progressive itching 3 years ago after hormone therapy for an ocular "inflammatory pseudotumor". The disease condition of this patient involved multiple organs which involved the skin. The patient was misdiagnosed with other diseases during the period of hospitalization, leading to poor therapeutic effects and repeated skin lesions. The dermatopathological report indicated plasma cell proliferative disorder, with IgG4/IgG exceeding 40% and abnormally elevated serum IgG4 levels. After the patient was diagnosed with IgG4-RD, a series of treatments improved skin lesions, relieved other symptoms, and decreased serum IgG4 levels. Conclusion: IgG4-RD is a highly misdiagnosed disease that deserves the attention of physicians. The patient we reported could be considered a representative case of IgG4-RD that presents with skin lesions. For patients with suspected IgG4-RD, serum IgG4 testing should be performed, and further imaging, serological tests, and pathology examinations are needed to exclude malignancy, infection, and autoimmune diseases.

Spatial network and driving factors of low-carbon patent applications in China from a public health perspective.

Introduction: The natural disasters and climate anomalies caused by increasing global carbon emissions have seriously threatened public health. To solve increasingly serious environmental pollution problems, the Chinese government has committed itself to achieving the goals of peak carbon emissions and carbon neutrality. The low-carbon patent application is an important means to achieve these goals and promote public health. Methods: This study analyzes the basic situation, spatial network, and influencing factors of low-carbon patent applications in China since 2001 at the provincial and urban agglomeration levels using social network analysis based on data from the Incopat global patent database. Results: The following findings are established. (1) From the number of low-carbon patent applications, the total number of low-carbon patent applications in China increased year by year, while the number of applications in the eastern region was larger than those in the central and western regions, but such regional differences had been decreasing. (2) At the interprovincial level, low-carbon patent applications showed a complex and multithreaded network structure. In particular, the eastern coastal provinces occupied the core position in the network. The weighted degree distribution of China's interprovincial low-carbon patent cooperation network is affected by various factors, including economic development, financial support, local scientific research level, and low-carbon awareness. (3) At the urban agglomeration level, the eastern coastal urban agglomerations showed a radial structure with the central city as the core. Urban innovation capability, economic development, low-carbon development awareness, level of technology import from overseas, and informatization level are highly correlated with the weighted degree of low-carbon cooperation networks of urban agglomerations. Discussion: This study provides ideas for the construction and governance of low-carbon technology innovation system and perspectives for theoretical research on public health and high-quality development in China.

Mechanism underlying the effect of SO2-induced oxidation on human skin keratinocytes.

This study aimed to study the effect and mechanism of action of SO2-induced oxidation on human skin keratinocytes.Different concentrations of SO2 derivatives (0, 25, 50, 100, 200, 400, and 800 µM) were used for treating HaCaT keratinocytes for 24 hours. MTT was used to evaluate the effect of each concentration on cell proliferation. HaCaT cells were randomly divided into control and SO2 groups. The control group received no treatment, whereas the SO2 group was treated with SO2 derivatives of selected concentrations for 24 hours. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD), tumor necrosis factor TNF-α (TNF-α), and interleukin-1 (IL-1-ß) in cell supernatants were detected using enzyme-linked immunosorbent assay. Real-time polymerase chain reaction was used to detect the expression of nuclear transcription factor (Nrf2) and heme oxygenase (HO)-1 mRNA. The Western blot analysis was used to test the expression levels of Nrf2, HO-1, activated caspase-3, Bcl-2, Bax, IκB, NF-κB p65 (p65), ERK1/2, p38, phospho-NF-κB p65 (p-p65), p-ERK1/2, and p-p38.SO2 derivatives (100, 200, 400, and 800 µM) could inhibit cell proliferation. SO2 derivatives increased the level of ROS, MDA, TNF-α, IL-1ß, Nrf2, HO-1, and p-p65/p65 and decreased the levels of SOD, IκB, p-ERK1/2/ERK1/2, and p-p38/p38 compared with the control group, but they had no effect on the levels of caspase-3, Bcl-2, and Bax.SO2 could inhibit the proliferation of human skin keratinocytes and induce oxidative stress and inflammation via the activation of the NF-κB pathway to inhibit the ERK1/2 and p38 pathways.