Resting-state fMRI reveals changes within the anxiety and social avoidance circuitry of the brain in mice with psoriasis-like skin lesions.

Psoriasis is an autoimmune skin disease that often co-occurs with psychological morbidities such as anxiety and depression, and psychosocial issues also lead psoriasis patients to avoid other people. However, the precise mechanism underlying the comorbidity of psoriasis and anxiety is unknown. Also, whether the social avoidance phenomenon seen in human patients also exists in psoriasis-like animal models remains unknown. In the present study, anxiety-like behaviours and social avoidance-like behaviours were observed in an imiquimod-induced psoriasis-like C57-BL6 mouse model along with typical psoriasis-like dermatitis and itch-like behaviours. The 11.7T resting-state functional magnetic resonance imaging showed differences in brain regions between the model and control group, and voxel-based morphometry showed that the grey matter volume changed in the basal forebrain region, anterior commissure intrabulbar and striatum in the psoriasis-like mice. Seed-based resting state functional connectivity analysis revealed connectivity changes in the amygdala, periaqueductal gray, raphe nuclei and lateral septum. We conclude that the imiquimod-induced psoriasis-like C57-BL6 mouse model is well suited for mechanistic studies and for performing preclinical therapeutic trials for treating anxiety and pathological social avoidance in psoriasis patients.

All-in-one smart dressing for simultaneous angiogenesis and neural regeneration.

Wound repair, along with skin appendage regeneration, is challenged by insufficient angiogenesis and neural regeneration. Therefore, promoting both proangiogenic and neuro-regenerative therapeutic effects is essential for effective wound repair. However, most therapeutic systems apply these strategies separately or ineffectively. This study investigates the performance of an all-in-one smart dressing (ASD) that integrates angiogenic functional materials and multiple biological factors within a light crosslinked hydrogel, forming a multi-functional dressing capable of facilitating simultaneous micro-vascularization and neural regeneration. The ASD uses a zeolite-imidazolate framework 67 with anchored vanadium oxide (VO2@ZIF-67) that allows for the on-demand release of Co2+ with fluctuations in pH at the wound site to stimulate angiogenesis. It can simultaneously release CXCL12, ligustroflavone, and ginsenoside Rg1 in a sustained manner to enhance the recruitment of endogenous mesenchymal stem cells, inhibit senescence, and induce neural differentiation to achieve in situ nerve regeneration. The ASD can stimulate rapid angiogenesis and nerve regeneration within 17 days through multiple angiogenic and neuro-regenerative cues within one dressing. This study provides a proof-of-concept for integrating functional nanomaterials and multiple complementary drugs within a smart dressing for simultaneous angiogenesis and neural regeneration.

CtBP1 transactivates RAD51 and confers cisplatin resistance to breast cancer cells.

Overexpression of RAD51 is found in many cancers including breast cancer and is associated with poor survival. Compared with normal cells, RAD51 promoter is hyperactive in cancer cells indicating that RAD51 is transcriptionally activated. However, little is known about the mechanisms and factors involved in RAD51 transcription regulation. Transcription corepressor, C-terminal binding protein 1 (CtBP1), is an oncogene repressing a panel of tumor suppressors transcription, which contributes to cancer progression. In this study, immunohistochemistry (IHC) revealed that RAD51 expression was positively correlated with CtBP1 expression in breast cancer patient tissues; short hairpin RNA-mediated CtBP1 depletion, chromatin immunoprecipitation, and dual-luciferase reporter assays showed that CtBP1 activated RAD51 transcription in breast cancer cells. Depletion of CtBP1 increased breast cancer cells' sensitivity to cisplatin and, in turn, expression of exogenous RAD51 in the CtBP1-depleted breast cancer cells increased resistance to cisplatin. The results demonstrated that CtBP1 conferred breast cancer cells resistance to cisplatin through transcriptional activation of RAD51.

Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition.

Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.

Corilagin Attenuates Allergy and Anaphylactic Reaction by Inhibiting Degranulation of Mast Cells.

BACKGROUND This study evaluated the anti-allergic activity of corilagin and also postulates the possible mechanism of its action. MATERIAL AND METHODS Corilagin was given orally at dose of 10, 20, and 40 mg/kg/day. All the animals (guinea pigs, rats, and mice) were sensitized for allergy such as eosinophilia and leukocytosis induced by milk; degranulation of mast cell by compound 48/80; and passive and active anaphylaxis. Moreover, the antagonistic effect was determined by estimating the effect of corilagin on contraction of guinea pig tracheal chain and ileum induced by Ach and histamine, respectively. RESULTS There was a significant decrease in the leukocyte and eosinophil counts in the corilagin-treated group compared to the negative control group. Treatment with corilagin significantly protects the degranulation of mast cells, and it also has significant anti-muscarinic and antihistaminic activity by reducing the muscle contraction induced by Acetylcholine (Ach) and histamine in guinea pig tracheal chain and ileum. CONCLUSIONS Corilagin possess anti-anaphylactic and anti-allergic activity by inhibiting the release of mediators from mast cells and by decreasing the serum concentration of immunoglobulin E (IgE).

Acute and chronic toxicity of a polyherbal preparation - Jueyin granules.

BACKGROUND: The potential toxicity of Chinese herbal medicine has attracted more attention in recent years. Jueyin granules (JYG), a polyherbal formula, have been proven to be an effective agent for treating psoriasis in both animal models and clinical research. However, little is known about the possible acute and chronic toxicity of JYG. The objective of this study was to investigate the safety of JYG in ICR mice and Wistar rats. METHODS: To examine the acute toxicity of JYG, ICR mice were randomly divided into an experimental group and a control group, each comprising 20 mice (10 male and 10 female). The experimental group was fed JYG solution at a dose of 21.5 g/kg, equivalent to 143 times the clinical human dosage, for 14 days, whereas control animals were fed distilled water. In the chronic toxicity test, Wistar rats were divided into four groups, each comprising 40 rats (20 male and 20 female). For 6 months, the experimental animals were given JYG at a dose of 7.5, 3.75 and 1.875 g/kg, whereas control animals were given distilled water. The animals' body weight, food and water consumptions were monitored weekly. In addition, their biochemical and hematological parameters, histopathology, and body and organ weights were all measured at specific observation time points. RESULTS: According to the results of the acute toxicity test, no mortality was found and no abnormal pathological changes in major organs were observed in mice treated with JYG. In the chronic toxicity test, JYG did not cause significant abnormalities in the physiological parameters or pathological changes in the major organs of the rats. CONCLUSION: The results indicated that JYG at the given doses did not induce any harmful effects in animals. Thus, it is reasonable to conclude that JYG is safe at the studied dosage levels and causes no acute or chronic toxicity in animal models.

Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.

BACKGROUND: Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro-/anti-inflammatory factors on transforming growth factor-ß(TGF-ß) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. METHODS: SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. RESULTS: Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. CONCLUSION: The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.

[Relation between Chinese Medical Constitutions of Female Patients with Late-onset Acne: an Epidemiological Investigation].

OBJECTIVE: To explore the correlation between syndrome types of late-onset acne female patients and constitutions of Chinese medicine (CM). METHODS: A questionnaire was performed in 365 late-onset acne female patients and 135 healthy subjects (as the control) using Professor WANG Qi's. methods and Standards for Chinese Medical Constitutions Classification. RESULTS: Their CM constitutions were sequenced as damp-heat constitution, yin-deficiency constitution, balanced constitution, yang-deficiency constitution, blood-stasis constitution, qi-stagnation constitution, qi-deficiency constitution, phlegm-damp constitution, inherited special constitution, with statistical difference when compared with those of the control group ( χ2 = 85.206, P < 0.01). In the 365 female late-onset acne patients, 114 (31.23%) were with Chongren imbalance syndrome, 108 (29.59%) were with blood stasis or coagulated phlegm syndrome, 83 (22.74%) were with dampness heat syndrome, and 60 (16.44%) were with wind heat syndrome. There was statistical difference in CM constitution distributions among different CM syndrome types (χ2 = 105.671, P < 0.01). The distribution of CM medical constitutions was different between the two groups. Biased constitutions were often seen in the patient group, while balanced constitution was often seen in the control group. Binary Logistic regression analysis indicated that influencing factors covered sweet food, light diet, roasted food, coffee, stress, work pressure, and family pressure. Of them light diet was one protective factor, while the rest were adverse factors. CONCLUSION: The etiology and syndrome types of female late-onset acne female patients were associated with CM constitution.

[Effect of Shengji Huayu Recipe on the expression of MMP-3 and TIMP-1 in skin ulcer tissue of diabetic rats].

OBJECTIVE: To study the effect of Shengji Huayu Recipe (SHR)on the expression of MMP-3 and TIMP-1 in the skin ulcer tissue of diabetic rats. METHODS: The skin ulcer model was established in diabetic mice. Different compatibility proportions of SHR [the ratio of Shengji Recipe (SJR) to Huayu Recipe (HYR) = 2:1, 1:1, and 1:2, respectively] were used to intervene. The expression of MMP-3 protein in the skin ulcer of diabetic rats was detected by Western blot method,and TIMP-1 protein was detected by immunohistochemical assay. RESULTS: At each time point, there was no statistical difference in the blood glucose level among groups (P > 0.05). But all of them increased significantly,when compared with those of the normal wound group (P < 0.01). As for the difference between after would area treatment and before would area treatment, better effect was obtained in the SHR No. 3 group and the normal ulcer group than in the diabetic ulcer model group (P < 0.05). Results of Western blot showed that the MMP-3 protein expression was higher in the SHR No. 2 group than in the SHR No.3 group (P < 0.05). Immunohistochemical results showed that TIMP-1 protein expression was lower in the SHR No. 2 group than in the SHR No. 3 group and the diabetic ulcer model group (P < 0.05). TIMP-1 protein expression was higherin the SHR No. 3 group than in the SHR No. 2 group (P < 0.01). CONCLUSION: Using SHR No.3 was conducive to the promotion of wound healing in early wound repair stage, and using SHR No. 2 might be conducive to inhibiting the formation of pathological scar.

[Research on different expressions of peripheral blood Th1/Th2 cells in psoriasis patients of blood heat syndrome and of blood stasis syndrome].

OBJECTIVE: To explore the correlation between the pathogenesis of psoriasis patients of blood heat syndrome (BHS) and blood stasis syndrome (BSS) and peripheral blood Th1/Th2 cells axis drift, and to observe different expressions of peripheral blood Th1/Th2 cells between healthy subjects and psoriasis patients of BHS and BSS. METHODS: There were 15 patients in the BHS group and 15 in the BSS group. There were 16 patients in the healthy control group. The expressions of CD4+ gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry (FACS). The Th1 main cytokines such as IFN-gamma and Th2 cytokines such as IL-4 in the serum of psoriasis patients of different syndromes were detected by enzyme-linked immunosorbent assay (ELISA). The Psoriasis Area and Severity Index score (PASI) were conducted. RESULTS: FACS results showed that the expression level of CD4+ IFN-gamma+ in the PBMCs was significantly higher in the BHS group than in the BSS group and the healthy control group (P < 0.05). Besides, it was positively correlated with the PASI (P < 0.05). ELISA results showed that the peripheral serum level of IFN-gamma was significantly higher in the BHS group than in the BSS group and the healthy control group (P < 0.05). The plasma level of IFN-gamma was positively correlated with the PASI score in the BHS group (P < 0.05). The plasma level of IFN-gamma was negatively correlated with the PASI score in the BSS group (P < 0.05). The peripheral serum level of IL-4 was significantly lower in the BHS group than in the BSS group and the healthy control group (P < 0.05). CONCLUSIONS: Peripheral Th1 cells had dominant state in psoriasis patients of BHS. When psoriasis patients of BHS were transformed to BSS or to the normal level, the expression of peripheral blood Th1 cells decreased.

Rapid analysis of Radix Astragali using a portable Raman spectrometer with 1064-nm laser excitation and data fusion with PLS-DA.

Radix Astragali is a medicinal herb with various physiological activities. There were high similarities among Radix Astragali samples from different regions owing to similarities in their major chemical compositions. Raman spectroscopy is a non-invasive and non-des- tructive technique that can be used in in-situ analysis of herbal samples. Dispersive Raman scattering, excited at 1064 nm, produced minimal fluorescence background and facilitated easy detection of the weak Raman signal. By moving the portable Raman probe point-by- point from the centre of the Radix Astragali sample to the margin, the spectral fingerprints, composed of dozens of Raman spectra representing the entire Radix Astragali samples, were obtained. Principal component analysis and partial least squares discriminant analysis (PLS-DA) were applied to the Radix Astragali spectral data to compare classification results, leading to efficient discrimination between genuine and counterfeit products. Furthermore, based on the PLS-DA model using data fusion combined with different pre- processing methods, the samples from Shanxi Province were separated from those belonging to other habitats. The as-proposed combination method can effectively improve the recognition rate and accuracy of identification of herbal samples, which can be a valuable tool for the identification of genuine medicinal herbs with uneven qualities and various origins.

DNA methylation of microRNA-365-1 induces apoptosis of hair follicle stem cells by targeting DAP3.

Background: DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Nevertheless, the precise role of DNA methylation in chemotherapeutic drug-induced alopecia remains unclear. This study examined the role and novel processes of DNA methylation in regulating of chemotherapeutic drug-induced alopecia. Methods: A mouse model of cyclophosphamide (CTX)-induced alopecia was established. Hematoxylin-eosin staining and immunohistochemical staining for the Ki67 proportion and a mitochondrial membrane potential assay (JC-1) were performed to assess the structural integrity and proliferative efficiency of the hair follicle stem cells (HFSCs). Immunofluorescence staining and real-time fluorescence quantitative PCR (RT-qPCR) were performed to determine the expression levels of key HFSC markers, namely Lgr5, CD49f, Sox9, CD200, and FZD10. Differential DNA methylation levels between the normal and CTX-induced model groups were determined through simple methylation sequencing and analyzed using bioinformatics tools. The expression levels of miR-365-1, apoptosis markers, and DAP3 were detected through RT-qPCR and western blotting. In parallel, primary mouse HFSCs were extracted and used as a cell model, which was constructed using 4-hydroperoxycyclophosphamide. The luciferase reporter gene assay was conducted to confirm miR-365-1 binding to DAP3. To measure the expression of relevant indicators, superoxide dismutase (SOD) and malondialdehyde (MDA) kits were used. Methylation-specific PCR (MS-PCR) was performed to determine DNA methylation levels. The regulatory relationship within HFSCs was confirmed through plasmid overexpression of miR-365-1 and DAP3. Result: In the alopecia areata model, a substantial number of apoptotic cells were observed within the hair follicles on the mouse backs. Immunofluorescence staining revealed that the expression of HFSC markers significantly reduced in the CTX group. Both RT-qPCR and western blotting demonstrated a noteworthy difference in DNA methyltransferase expression. Simple methylation sequencing unveiled that DNA methylation substantially increased within the dorsal skin of the CTX group. Subsequent screening identified miR-365-1 as the most differentially expressed miRNA. miR-365-1 was predicted and confirmed to bind to the target gene DAP3. In the CTX group, SOD and ATP expression markedly reduced, whereas MDA levels were significantly elevated. Cellular investigations revealed 4-HC-induced cell cycle arrest and decreased expression of HFSC markers. MS-PCR indicated hypermethylation modification of miR-365-1 in the 4-HC-induced HFSCs. The luciferase reporter gene experiment confirmed the binding of miR-365-1 to the DAP3 promoter region. miR-365-1 overexpression dramatically reduced apoptotic protein expression in the HFSCs. However, this effect was slightly reversed after DAP3 overexpression in lentivirus. Conclusion: This study explored the occurrence of miR-365-1 DNA methylation in chemotherapeutic drug-induced alopecia. The results unveiled that miR-365-1 reduces cell apoptosis by targeting DAP3 in HFSCs, thereby revealing the role of DNA methylation of the miR-365-1 promoter in chemotherapeutic drug-induced alopecia.

Effectiveness and mechanism of the Chinese medicine Weiren Xiaoyou formula in improving palmoplantar warts.

Background: Palmoplantar warts (PWs) are a usual skin disease associated with human papillomavirus (HPV) that can affect patients' quality of life. The traditional Chinese medicine (TCM) Weiren Xiaoyou formula (WRXYF) is a relatively gentle and effective therapy that has achieved good therapeutic effects in clinical practice, but its mechanism has not yet been studied. Methods: A meta-analysis was carried out to identify the potential advantages of topical TCM for PW treatment. Clinical cases suggested that WRXYF was an effective therapeutic agent against PWs. Network pharmacology was utilized to predict potential targets for the main bioactive compound, tanshinone IIA (Tan IIA), in WRXYF. High-performance liquid chromatography with electrospray mass spectrometry (HPLC/ESI-MS) was applied to detect major components. The bioactivity of Tan IIA against PWs was then validated with quantitative polymerase chain reaction (q-PCR), fluorescence in situ hybridization (FISH), electron microscopy and Western blotting. Results: A meta-analysis was conducted on 10 randomized clinical trials (RCTs) involving 2260 participants suggested that topical TCM could more effectively treat PWs than conventional medications. Network pharmacology identified Tan IIA as a candidate agent from 17 major compounds assessed by HPLC/ESI-MS because of its stable binding with 10 PW targets. HPV2, HPV27, and HPV57 were the main infectious strains in tissues obtained from PW patients and in HPV-infected HaCaT cells. Tan IIA treatment effectively destroyed viral particles and reduced the viral copy numbers of the three HPV subtypes. The results shown that Tan IIA has the ability to halt the cell cycle of HPV-infected HaCaT cells specifically in the G0/G1 phase. A total of 6 cell cycle-related proteins were regulated after Tan IIA treatment, demonstrating the role of Tan IIA in inhibiting the cell cycle. Conclusion: Tan IIA, the primary bioactive constituent in WRXYF, enhances PWs by halting the cell cycle in the G0/G1 phase via modulation of the p53 signaling pathway.

SERPINB4 Promotes Keratinocyte Inflammation via p38MAPK Signaling Pathway.

Psoriasis is a chronic inflammatory skin disease characterized by infiltration of inflammatory cells and excessive proliferation of epidermal keratinocytes. SERPINB4, as a serine protease inhibitor, has been clearly expressed in the skin lesions and serum of patients with psoriasis, but the specific mechanism of action is not yet clear. Here, we showed that SERPINB4 expression was increased in skin lesions from the imiquimod (IMQ)-treated mice and M5-(a mixture of five proinflammatory cytokines: IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α) treated human immortalized keratinocyte (HaCaT). Knockdown of SERPINB4 by short hairpin RNA attenuated the M5-induced keratinocyte inflammation. Conversely, lentiviral expression of SERPINB4 promoted keratinocyte inflammation. Finally, we observed that SERPINB4 stimulation activated the p38MAPK signaling pathway. Taken together, these results suggest that SERPINB4 has a critical role in psoriasis pathogenesis.

Selective IgA Deficiency with Multiple Autoimmune Comorbidities: A Case Report and Literature Review.

Case: Individuals with Selective Immunoglobulin-A Deficiency (SIgAD) are often asymptomatic, and symptomatic SIgAD patients often have autoimmune comorbidities. A 48-year-old Han Chinese man presented with abdominal discomfort, hematochezia, and a large tumor in the anogenital region. The primary diagnosis of SIgAD was based on the patient's age, serum IgA concentration (0.067 g/L), and the evidence of chronic respiratory infection. No other immunoglobulin deficiency or evidence of immunosuppression was present. The primary diagnosis of giant condyloma acuminatum was based on human papilloma virus-6-positive laboratory results and histological characteristics. The tumor and adjacent skin lesions were resected. Hemoglobin concentration fell to 5.50 g/dL, and an emergency erythrocyte transfusion was performed. The body temperature increased to 39.8 ºC, suggesting a transfusion reaction, and 5 mg dexamethasone was administered intravenously. Hemoglobin concentration stabilized at 10.5 g/dL. The clinical signs and laboratory results indicated autoimmune hemolytic anemia, systemic lupus erythematosus, and Hashimoto's thyroiditis. Abdominal discomfort and hematochezia subsided. Though uncommon, the manifestation of multiple autoimmune comorbidities can occur in SIgAD patients. Further research is needed regarding the causes of SIgAD and the autoimmune disorders that often occur as comorbidities.

Research on the wound healing effect of Shengji Huayu Formula ethanol extract-derived fractions in streptozotocin-induced diabetic ulcer rats.

BACKGROUND: Diabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions. METHODS: A diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts. RESULTS: It was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established. CONCLUSION: SHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.

Identification of IRF1 as a Novel Pyroptosis-Related Prognostic Biomarker of Atopic Dermatitis.

Purpose: The aim of this study was to characterize key biomarkers associated with pyroptosis in atopic dermatitis (AD). Materials and methods: To identify the differentially expressed pyroptosis-related genes (DEPRGs), the gene expression profiles GSE16161 and GSE32924 from the Gene Expression Omnibus (GEO) database were utilized. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the potential biological functions and involved pathways. Furthermore, protein-protein interaction network analyses were performed to identify hub genes. The types and proportions of infiltrating immune cells were detected by immune filtration analysis using CIBERSORT. A 12-axis competing endogenous RNA (ceRNA) network was constructed utilizing the miRNet database. Immunohistochemistry (IHC) further validated the differential expression of a key gene IRF1 in the skin tissues collected from AD patients. The collection of skin tissue from human subjects in this study were reviewed and approved by the IRB of Yueyang Integrated Chinese and Western Medicine Hospital (KYSKSB2020-125). Results: The study identified a total of 76 DEPRGs, which were enriched in genes associated with the inflammatory response and immune regulation. There was a higher percentage of activated dendritic cells and a lower percentage of resting mast cells in AD samples. PVT1 expression was associated with upregulation of hub genes including CXCL8, IRF1, MKI67, and TP53 in the ceRNA network and was correlated with activated dendritic cells in AD. As a transcription factor, IRF1 could regulate the production of downstream inflammatory factors. The IHC study revealed that IRF1 was overexpressed in the skin tissues of AD patients, which were consistent with the results of the bioinformatic study. Conclusions: IRF1 and its related genes were identified as key pyroptosis-related biomarkers in AD, which is a crucial pathway in the pathogenesis of AD.

Langmuir-Blodgett-Mediated Formation of Antibacterial Microneedles for Long-Term Transdermal Drug Delivery.

Microneedles (MNs) have become versatile platforms for minimally invasive transdermal drug delivery devices. However, there are concerns about MN-induced skin infections with long-term transdermal administration. Using the Langmuir-Blodgett (LB) technique, a simple method for depositing antibacterial nanoparticles of various shapes, sizes, and compositions onto MNs is developed. This strategy has merits over conventional dip coating techniques, including controlled coating layers, uniform and high coverage, and a straightforward fabrication process. This provides MNs with a fast-acting and long-lasting antibacterial effect. This study demonstrates that antibacterial MNs achieve superior bacterial elimination in vitro and in vivo without sacrificing payload capacity, drug release, or mechanical strength. It is believed that such a functional nanoparticle coating technique offers a platform for the expansion of MNs function, especially in long-term transdermal drug delivery fields.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9.

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION: Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Temporal smad7 transgene induction in mouse epidermis accelerates skin wound healing.

The expression of Smad7, a tumor growth factor-ß (TGFß) antagonist, is increased during cutaneous wound healing. To assess this significance, we temporally induced Smad7 transgene expression in wounded skin in gene-switch-Smad7 transgenic (Smad7 tg) mice. Smad7 induction in epidermal keratinocytes caused an increase in keratinocyte proliferation with reduced Smad2 activation, indicating that Smad7 abrogated TGFß-mediated growth inhibition. Additionally, wounded skin from Smad7 tg mice exhibited accelerated re-epithelialization, with increased activation of extracellular signal-regulated kinase (Erk), and an in vitro migration assay revealed that Erk activation contributed to Smad7-mediated keratinocyte migration. Notably, epidermis-specific Smad7 transgene expression also has a profound effect on the wound stroma, resulting in reduced inflammation, angiogenesis, and production of type I collagen. Reduced Smad2 activation was observed in wounded stroma from Smad7 transgenic (Smad7 tg) mice, possibly owing to fewer infiltrated TGFß-producing leukocytes compared to those in wounds from control mice. Because Smad7 is not secreted, these effects could reflect functional changes in Smad7 tg keratinocytes. Supporting this notion, the activation of NF-κB, a nonsecreted protein complex that transcriptionally activates inflammatory cytokines, was reduced in wounded epidermis from Smad7 tg mice compared to that in wounded wild-type epidermis. In sum, epidermal Smad7 overexpression accelerated wound healing through its direct effects on keratinocyte proliferation and migration, and through indirect effects on wound stroma.