Publications by authors named "Kang Zeng"

143 Publications

Clinical Significance of Serum Oxidative Stress Markers to Assess Disease Activity and Severity in Patients With Non-Segmental Vitiligo.

Front Cell Dev Biol 2021 16;9:739413. Epub 2021 Dec 16.

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Non-segmental vitiligo (NSV) is a chronic autoimmune disease characterized by progressive depigmentation of the skin. Oxidative stress (OS) has been proposed as one among the main principal causes in the development and establishment of a sustained autoimmune state in patients with NSV. However, the disease-associated OS biomarkers in clinical practice are not well studied. In this study, we found significantly reduced antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD)], total antioxidant capacity (TAC), and increased levels of lipid oxidation product malondialdehyde (MDA) and oxidative DNA damage byproduct [8-hydroxy-2-deoxyguanosine (8-OHdG)] in serum of NSV patients compared with healthy controls (HC). Serum TAC, MDA, and 8-OHdG levels were correlated with disease activity in all patients with NSV and much lower in patients receiving conventional treatment in the past 1 year compared to that without treatment. In addition, both serum MDA and 8-OHdG levels were significantly correlated with CXCL10 expression in patients with NSV. And the serum TAC, MDA, and 8-OHdG levels were also correlated with affected body surface area and Vitiligo Area Scoring Index score in patients with NSV. This study demonstrates dysregulated OS status in patients with NSV and provides the evidence that the serum TAC, MDA, and 8-OHdG have a capacity to indicate the activity and severity in patients with NSV.
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http://dx.doi.org/10.3389/fcell.2021.739413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716723PMC
December 2021

The Fgl2 interaction with Tyrobp promotes the proliferation of cutaneous squamous cell carcinoma by regulating ERK-dependent autophagy.

Int J Med Sci 2022 1;19(1):195-204. Epub 2022 Jan 1.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.

Human fibroleukin 2 (Fgl2), a member of the fibrinogen superfamily, can cleave prothrombin to generate thrombin or is secreted in a soluble form as a new type of effector of Tregs with immunomodulatory functions. However, there is little research on the role of Fgl2 in cutaneous squamous cell carcinoma (CSCC) growth. We examined the expression of Fgl2 in samples from CSCC patients and CSCC cell lines. Then, the effect of Fgl2 on CSCC was evaluated and in animals. Regulation of autophagy by Fgl2 was explored in CSCC. Coimmunoprecipitation (Co-IP) and immunofluorescence colocalization experiments were conducted to identify the regulatory effect of Fgl2 on the downstream protein Tyrobp. Then, gain- or loss-of-function analyses and evaluation of Tyrobp expression were performed to validate its role in autophagy and proliferation promoted by Fgl2. Here, our study demonstrated that Fgl2 promoted the proliferation of CSCC cells and . Knocking down Fgl2 reduced CSCC cell proliferation and inhibited autophagy in CSCC. Mechanistically, Fgl2 interacted with Tyrobp and promoted ERK-dependent autophagy, resulting in the proliferation of CSCC cells. Our study suggested that Fgl2 could be a promising prognostic biomarker and useful therapeutic target for CSCC.
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http://dx.doi.org/10.7150/ijms.66929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692121PMC
January 2022

Zinc Oxide Nanoparticles Prime a Protective Immune Response in to Defend Against .

Front Microbiol 2021 10;12:766138. Epub 2021 Dec 10.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling in the invertebrate . larvae were injected with different doses of ZnO-NPs to determine their toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in followed by infection. Then the direct antifungal effect of ZnO-NPs against was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity. Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of infected larvae and decreased the fungal dissemination and burden in the infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae. Prophylactic treatment with lower concentrations of ZnO-NPs protects from infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.
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http://dx.doi.org/10.3389/fmicb.2021.766138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702860PMC
December 2021

Identification of Immunological Biomarkers of Atopic Dermatitis by Integrated Analysis to Determine Molecular Targets for Diagnosis and Therapy.

Int J Gen Med 2021 15;14:8193-8209. Epub 2021 Nov 15.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Purpose: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder associated with immune dysregulation and barrier dysfunction. In this study, we investigated immunological biomarkers for AD diagnosis and treatment using CIBERSORT to identify immune cell infiltration characteristics.

Patients And Methods: Common differentially expressed genes (DEGs) of lesioned (LS) vs non-lesioned (NL) groups were obtained from public datasets (GSE140684 and GSE99802). We performed functional enrichment analysis and selected hub genes from the protein-protein interaction (PPI) network. The hub genes were then subjected to transcription factor (TF), microRNA (miRNA), long non-coding RNA (lncRNA), drug interaction, and protein subcellular localization analyses. We also performed correlation analysis on differentially expressed immune cells, TFs, and hub genes. Receiver operating characteristic (ROC) curve analysis and binomial least absolute shrinkage and selection operator (LASSO) regression analysis were employed to assess the expression of hub genes in the GSE99802, GSE140684, GSE58558, GSE120721, and GSE36842 datasets.

Results: We identified 238 common DEGs and 25 hub genes. Additionally, we predicted TFs, miRNAs, lncRNA, drugs, and protein subcellular localizations. The proportions of activated dendritic cells (DCs) and CD4+ memory T cells were relatively high in the LS skin. Expression levels of the TF FOXC1 were negatively correlated with target genes and the abundance of two immune cell types. The LASSO model showed that GZMB, CXCL1, and CD274 are candidate diagnostic biomarkers.

Conclusion: Our study suggests that downregulated expression of FOXC1 expression may enhance the levels of chemokines, chemokine receptors, T cell receptor signaling molecules, activating CD4+ memory T cells and DCs in AD.
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http://dx.doi.org/10.2147/IJGM.S331119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605491PMC
November 2021

Podophyllotoxin-combined 5-aminolevulinic acid photodynamic therapy significantly promotes HR-HPV-infected cell death.

Photodermatol Photoimmunol Photomed 2021 Nov 15. Epub 2021 Nov 15.

Department of Dermatology and Venereology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Human papillomavirus (HPV) infection and related diseases are difficult clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating condyloma acuminata is remarkable, with high virus clearance and low recurrence rates. Podophyllotoxin (POD) is the first-line drug with a significant therapeutic effect on condyloma acuminata. However, no studies have determined whether POD-combined ALA-PDT improves high-risk (HR)-HPV-infected cell killing. We aimed to investigate whether POD-combined ALA-PDT could promote HPV-infected cell death more effectively than the single treatment and explore the underlying mechanism.

Methods: In HeLa and SiHa cells, flow cytometry, EdU assay and LDH release test were used to detect apoptosis, cell proliferation change and necrosis, respectively. To investigate whether the combined therapy might activate apoptosis and induce endoplasmic reticulum (ER) stress, flow cytometry was used to determine intracellular levels of ROS and calcium, and Western blotting was used to determine the expression of related proteins. Mitochondrial membrane depolarization was detected by JC-1 assay. Immunofluorescence staining and Western blotting were used to detect the activation of autophagy.

Results: Podophyllotoxin -combined ALA-PDT inhibited the proliferation and promoted apoptosis and necrosis more effectively than the single treatment at the same intensity and concentration. The activation of the caspase-dependent apoptosis pathway, ER stress and autophagy was more substantial in POD-combined ALA-PDT than with single treatments.

Conclusion: Podophyllotoxin -combined ALA-PDT effectively promoted cell death through several pathways in HeLa and SiHa cells. This combination might be a promising therapeutic strategy for the HR-HPV infection.
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http://dx.doi.org/10.1111/phpp.12754DOI Listing
November 2021

Case Report: Short-Term Application of Topical Imiquimod Is Practical for Chromoblastomycosis.

Am J Trop Med Hyg 2021 Sep 27;105(6):1696-1697. Epub 2021 Sep 27.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Chromoblastomycosis is a chronic cutaneous fungal infection caused by dematiaceous fungi. It is a therapeutic challenge because of the lack of specific treatments. We describe a refractory case of chromoblastomycosis in which the lesion did not respond to initial treatment, but then use of topical imiquimod cured the lesion successfully.
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http://dx.doi.org/10.4269/ajtmh.21-0735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641331PMC
September 2021

Patterns of multiple human papillomavirus clearance during 5-aminolevulinic acid-based photodynamic therapy in patients with genital warts.

Photodiagnosis Photodyn Ther 2021 Sep 22;35:102454. Epub 2021 Jul 22.

Nanfang hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:

Background: Multiple human papillomavirus infections are commonly encountered in genital warts. Infection can be eliminated using 5-aminolevulinic acid-based photodynamic therapy. The aim of this study was to identify the preponderant genotypes and patterns of human papillomavirus co-infection clearance during photodynamic therapy in patients with genital warts.

Methods: We conducted a retrospective study between January 2020 and February 2021 at two hospitals in Guangzhou, China. Human papillomavirus typing and quantitative detection were performed before starting treatment and after each session of photodynamic therapy.

Results: A total of 97 patients participated in the study. Co-infections with low-risk and high-risk types were common in genital warts. Types 6 was the most common type detected, followed by types 52, 11, 58, 51 and 56. Patients with multiple infections were more likely to have high-risk human papillomavirus infection. The viral load of high-risk human papillomavirus before treatment was significantly lower than that of low-risk human papillomavirus, and decreased faster during therapy. In addition, high-risk types were cleared more readily than low-risk types, and 51.4% of high-risk types were eliminated after three rounds of therapy. A transient increase in viral load, especially low-risk types, was observed after two sessions of therapy.

Conclusions: Low-risk human papillomavirus was preponderant in patients co-infected with low-risk and high-risk types. Photodynamic therapy effectively eliminated multiple human papillomavirus infections. The response to photodynamic therapy was mainly determined by the low-risk types in patients infected with combinations of low-risk and high-risk types.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102454DOI Listing
September 2021

Nanomaterials applied in wound healing: Mechanisms, limitations and perspectives.

J Control Release 2021 09 14;337:236-247. Epub 2021 Jul 14.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address:

Internal and external factors cause various types of wounds on the skin. Infections, nonhealing chronic wounds, and aesthetic and functional recovery all cause challenges for clinicians. The development of nanotechnology in biomedicine has brought many new materials, methods and therapeutic targets for the treatment of wounds, which are believed to have great prospects. In this work, the nanomaterials applied in different stages to promote wound healing and systematically expounded their mechanisms were reviewed. Then, the difficulties and defects of the present research and suggested methods for improvement were pointed out. Moreover, based on the current application status of nanomaterials in wound treatment, some new ideas for subsequent studies were proposed and the feasibility of intelligent healing by real-time monitoring, precision regulation, and signal transmission between electronic signals and human nerve signals in the future were discussed. This review will provide valuable directions and spark new thoughts for researchers.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.017DOI Listing
September 2021

CAMKK2 Defines Ferroptosis Sensitivity of Melanoma Cells by Regulating AMPK‒NRF2 Pathway.

J Invest Dermatol 2022 01 7;142(1):189-200.e8. Epub 2021 Jul 7.

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address:

Melanoma is the most lethal skin cancer caused by the malignant transformation of epidermal melanocytes. Recent progress in targeted therapy and immunotherapy has significantly improved the treatment outcome, but the survival of patients with advanced melanoma remains suboptimal. Ferroptosis, a cell death modality triggered by iron-dependent lipid peroxidation, reportedly participates in cancer pathogenesis and can mediate the effect of anti-PD-1 immunotherapy in melanoma. However, the detailed regulatory mechanism of ferroptosis remains far from being understood. In this study, we report that CAMKK2 defines the ferroptosis sensitivity of melanoma cells by regulating the AMPK‒NRF2 pathway. We first found that CAMKK2 was prominently activated in ferroptosis. Then we proved that CAMKK2 negatively regulated ferroptosis through the activation of NRF2 and the suppression of lipid peroxidation. Subsequent mechanistic studies revealed that AMPK connected CAMKK2 upregulation to NRF2-dependent antioxidative machinery in ferroptosis. In addition, the suppression of CAMKK2 increased the efficacy of ferroptosis inducer and anti-PD-1 immunotherapy in the preclinical xenograft tumor model by inhibiting the AMPK‒NRF2 pathway and promoting ferroptosis. Taken together, CAMKK2 plays a protective role in ferroptosis by activating the AMPK‒NRF2 pathway. Targeting CAMKK2 could be a potential approach to increase the efficacy of ferroptosis inducers and immunotherapy for melanoma treatment.
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http://dx.doi.org/10.1016/j.jid.2021.05.025DOI Listing
January 2022

Predictors of human papillomavirus persistence or clearance after 5-aminolevulinic acid-based photodynamic therapy in patients with genital warts.

Photodiagnosis Photodyn Ther 2021 Sep 5;35:102431. Epub 2021 Jul 5.

Nanfang hospital, Southern Medical University, Guangzhou, 510515, China.. Electronic address:

Background: Numerous studies have confirmed that 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is an effective treatment for human papillomavirus-associated diseases. In this study, we evaluated the variables associated with human papillomavirus (HPV) persistence or clearance after ALA-PDT in patients with genital warts.

Methods: We performed a retrospective chart review of all patients with genital warts or subclinical HPV infection who received ALA-PDT treatment between January 2019 and December 2020 at Nanfang Hospital and Dermatology Hospital of Southern Medical University and analyzed the predictors of HPV persistence or clearance. HPV genotype and viral load assays were analyzed before treatment and after each session of photodynamic therapy.

Results: Multiple sexual partners, a history of recurrent HPV infection, and severe pain response during photodynamic therapy were associated with higher odds of viral persistence after three rounds of ALA-PDT. Infection with single strains of HPV, and mucosal and subclinical infection were more likely to be cleared after three rounds of photodynamic therapy.

Conclusion: Our findings suggest that patients with multiple sexual partners, a history of recurrent infections, and severe pain response during photodynamic therapy should undergo close surveillance and monitoring, and may need additional photodynamic therapy sessions. Infection with a single strain of HPV, and mucosal or subclinical infections are more likely to be cleared after three courses of ALA-PDT treatment. These findings may improve the efficiency of ALA-PDT in clinical practice.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102431DOI Listing
September 2021

Successful treatment of a patient with recurrent infection of Chromobacterium violaceum.

BMC Infect Dis 2021 May 26;21(1):484. Epub 2021 May 26.

Department of Dermatology, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China.

Background: Chromobacterium violaceum (C. violaceum) is a Gram-negative saprophytic bacterium that is widespread in tropical and subtropical environments, and belongs to conditional pathogenic bacteria. Human infection with C. violaceum is rare, and this can be fatal when the diagnosis and treatment are delayed, especially recurrent infection patients. Since clinicians lack the knowledge for C. violaceum, rapid diagnosis and early appropriate antimicrobial treatment remains challenging.

Case Presentation: A 15-year-old male student was hospitalized for dark abscess, pustules, severe pain in both legs, and fever for 11 days. There were pustules with gray-white pus and red infiltrating plaques on the back, and the subcutaneous nodules could be touched in front of both tibias, with scab, rupture and necrotic tissue of the lower limb. The patient's condition rapidly progressed. Therefore, next-generation sequencing (NGS), pustular secretion and blood culture were concurrently performed. The final diagnosis for this patient was C. violaceum infection by NGS. However, no bacterial or fungal growth was observed in the pustular secretion and blood culture. After 4 weeks of treatment, the patient was discharged from the hospital without any complications associated with C. violaceum infection.

Conclusion: Rapid diagnosis and early appropriate antimicrobial treatment is the key to the successful treatment of C. violaceum infection, especially in patients with sepsis symptoms. This case highlights that NGS is a promising tool for the rapid diagnosis of C. violaceum infection, preventing the delayed diagnosis and misdiagnosis of C. violaceum infection in patients who tested negative for pustular secretion and blood culture.
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http://dx.doi.org/10.1186/s12879-021-06216-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157692PMC
May 2021

Chinese guidelines on the clinical application of 5-aminolevulinic acid-based photodynamic therapy in dermatology (2021 edition).

Photodiagnosis Photodyn Ther 2021 Sep 12;35:102340. Epub 2021 May 12.

Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address:

Photodynamic Therapy with 5-aminolevulinic acid (ALA-PDT) has been widely applied in the treatment of skin diseases in China. To further standardize, guide, and promote the clinical applications of ALA-PDT in dermatology, the Chinese Society of Dermatology, Chinese Association of Rehabilitation Dermatology, Photomedicine Therapeutic Equipment Group of Committee on Skin Disease, and Cosmetic Dermatology of China Association of Medical Equipment invited relevant experts engaged in ALA-PDT to revise and update the first edition of "Clinical application of 5-aminolevulinic acid-based photodynamic therapy: an expert consensus statement" and establish a more current edition, to provide an updated reference for Chinese dermatologists in clinical practice. In the guideline, the expert group reached consensus opinions on ALA-PDT with regard to mechanisms of action, therapeutic protocol, clinical applications, adverse reactions and countermeasures, precautions, care, and evaluation of efficacy.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102340DOI Listing
September 2021

Safety and effectiveness of 5-aminolevulinic acid photodynamic therapy combined with fractional micro-plasma radio-frequency treatment for verrucous epidermal nevus: A retrospective study with long-term follow-up.

J Dermatol 2021 Aug 25;48(8):1229-1235. Epub 2021 Apr 25.

Department of Dermatology and Venereology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Verrucous epidermal nevus (VEN) is a benign skin disease that seriously affects appearance. Numerous therapeutic methods have been tried with varying results. However, there are few reports on the treatment of VEN by photodynamic therapy (PDT). This study aimed to evaluate the efficacy and adverse effects of 5-aminolevulinic acid (ALA)-PDT in VEN treatment with a long-term follow-up. A total of 16 patients with VEN received ALA-PDT and were followed up for more than 1 year to observe the treatment effects, adverse reactions, and patients' satisfaction. Complete improvement of lesions was observed in 11 patients (three to six sessions of ALA-PDT). Two patients obtained 90-99% improvement (five sessions) and 50-89% improvement in three patients (three to six sessions). They were satisfied with the treatment effects, with an average satisfaction of 4.19/5 (±0.91). Long-term follow-up ranging 14-50 months showed a low recurrence rate (2/16) and no scar left after ALA-PDT. The results demonstrate that ALA-PDT is an effective and safe therapy in treating VEN with mild adverse reactions and a low risk of scar formation.
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http://dx.doi.org/10.1111/1346-8138.15923DOI Listing
August 2021

A KRAS-responsive long non-coding RNA controls microRNA processing.

Nat Commun 2021 04 1;12(1):2038. Epub 2021 Apr 1.

Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.

Wild-type KRAS (KRAS) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of KRAS overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive lncRNA, KIMAT1 (ENSG00000228709) and show that it correlates with KRAS levels both in cell lines and in lung cancer specimens. Mechanistically, KIMAT1 is a MYC target and drives lung tumorigenesis by promoting the processing of oncogenic microRNAs (miRNAs) through DHX9 and NPM1 stabilization while halting the biogenesis of miRNAs with tumor suppressor function via MYC-dependent silencing of p21, a component of the Microprocessor Complex. KIMAT1 knockdown suppresses not only KRAS expression but also KRAS downstream signaling, thereby arresting lung cancer growth in vitro and in vivo. Taken together, this study uncovers a role for KIMAT1 in maintaining a positive feedback loop that sustains KRAS signaling during lung cancer progression and provides a proof of principle that interfering with KIMAT1 could be a strategy to hamper KRAS-induced tumorigenesis.
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http://dx.doi.org/10.1038/s41467-021-22337-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016872PMC
April 2021

mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(4):438-445

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease. Aberrant mTOR pathway activity is involved in many autoimmune diseases. This study investigated the correlation of mTOR pathway (PI3K/AKT/mTOR/p70S6K) activity with the loss of balance in T helper 2/regulatory T (Th2/Treg) cells in the peripheral blood of PV patients. CD4+ T cells were isolated from 15 PV patients and 15 healthy controls (HCs), the ratios of Th2/CD4+ T cells and Treg/CD4+ T cells, the activity of the mTOR pathway (PI3K/AKT/mTOR/p70S6K), the transcription factors and cytokines of Th2 and Treg cells were detected. Primary CD4+ T cells from PV patients were cultured under Th2- or Treg-polarizing conditions with or without rapamycin in vitro. We found that PV patients showed significantly elevated serum IL-4 when compared with HCs, and serum IL-4 level was positively correlated with the titer of anti-Dsg1/3 antibody and disease severity, while the serum TGF-β level was negatively correlated with the titer of anti-Dsg3 antibody and disease severity. Meanwhile, PV patients showed increased Th2/CD4+ T cell ratio; decreased Treg/CD4+ T cell ratio; elevated mRNA of PI3K, AKT, mTOR and protein of PI3K (P85), AKT, p-AKT (Ser473), mTOR, p-mTOR (Ser2448), p-p70S6K (Thr389), GATA3; reduced protein of forkhead box protein 3. Rapamycin inhibited Th2 cell differentiation and promoted Treg cell differentiation in vitro. These data suggest a close association between mTOR pathway activation and the loss of balance in Th2/Treg cells in peripheral blood of PV patients. Inhibiting mTORC1 can help restore the Th2/Treg balance.
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http://dx.doi.org/10.1093/abbs/gmab008DOI Listing
March 2021

Circular RNA profiles and the potential involvement of down-expression of hsa_circ_0001360 in cutaneous squamous cell carcinogenesis.

FEBS Open Bio 2021 04 11;11(4):1209-1222. Epub 2021 Mar 11.

Institute of Dermatology, Guangzhou Medical University, China.

Circular RNAs (circRNAs) act as sponges of noncoding RNAs and have been implicated in many pathophysiological processes, including tumor development and progression. However, their roles in cutaneous squamous cell carcinoma (cSCC) are not yet well understood. This study aimed to identify differentially expressed circRNAs and their potential functions in cutaneous squamous cell carcinogenesis. The expression profiles of circRNAs in three paired cSCC and adjacent nontumorous tissues were detected with RNA sequencing and bioinformatics analysis. The candidate circRNAs were validated by PCR, Sanger sequencing and quantitative RT-PCR in another five matched samples. The biological functions of circRNAs in SCL-1 cells were assessed using circRNA silencing and overexpression, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS), flow cytometry, transwell and colony formation assays. In addition, the circRNA-miRNA-mRNA interaction networks were predicted by bioinformatics. In summary, 1115 circRNAs, including 457 up-regulated and 658 down-regulated circRNAs (fold change ≥ 2 and P < 0.05), were differentially expressed in cSCC compared with adjacent nontumorous tissues. Of four selected circRNAs, two circRNAs (hsa_circ_0000932 and hsa_circ_0001360) were confirmed to be significantly decreased in cSCC using PCR, Sanger sequencing and quantitative RT-PCR. Furthermore, hsa_circ_0001360 silencing was found to result in a significant increase of the proliferation, migration and invasion but a significant decrease of apoptosis in SCL-1 cells in vitro, whereas hsa_circ_0001360 overexpression showed the opposite regulatory effects. hsa_circ_0001360 was predicted to interact with five miRNAs and their corresponding genes. In conclusion, circRNA dysregulation may play a critical role in carcinogenesis of cSCC, and hsa_circ_0001360 may have potential as a biomarker for cSCC.
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http://dx.doi.org/10.1002/2211-5463.13114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016141PMC
April 2021

The mechanism of 5-aminolevulinic acid photodynamic therapy in promoting endoplasmic reticulum stress in the treatment of HR-HPV-infected HeLa cells.

Photodermatol Photoimmunol Photomed 2021 Jul 8;37(4):348-359. Epub 2021 Feb 8.

Department of Dermatology and Venereology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: 5-aminoketovaleric acid, as a precursor of the strong photosensitizer protoporphyrin IX (PpIX), mainly enters the mitochondria after entering the cell, and the formed PpIX is also mainly localized in the mitochondria. So at present the research on the mechanism of 5-aminoketovalerate photodynamic therapy (ALA-PDT) mainly focuses on its impact on mitochondria. There are few reports on whether ALA-PAT can affect the endoplasmic reticulum and trigger endoplasmic reticulum stress (ERS).

Aims/objectives: Here we investigated the effects of ALA-PDT on endoplasmic reticulum and its underlying mechanisms in high-risk human papillomavirus (HR-HPV) infection.

Materials And Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALAPDT, and cell viability, ROS production, the level of Ca2+ in the cytoplasm and apoptosis were evaluated by CCK8, immunofluorescence and flow cytometry, respectively. The protein expression of the markers of ERS and autophagy and CamKKβ-AMPK pathway was examined by western blot.

Results: The results showed that ALA-PDT inhibited cell viability of HeLa cells in vitro; ALA-PDT induced autophagy in HeLa cells ; ALA-PDT induced autophagy via the Ca2+-CamKKβ-AMPK pathway, which could be suppressed by the inhibition of ERS;ALA-PDT induced ERS-specific apoptosis via the activation of caspase 12.

Conclusions: Our study demonstrated that ALA-PDT could exert a killing effect by inducing HeLa cell apoptosis, including endoplasmic reticulum-specific apoptosis. Meanwhile, ERS via the Ca2+ -CamKKβ-AMPK pathway promoted the occurrence of autophagy in HeLa cells. Inhibition of autophagy could increase the apoptosis rate of HeLa cells after ALA-PDT, suggesting that autophagy may be one of the mechanisms of PDT resistance; The Ca2+-CamKKβ-AMPK pathway and autophagy may be targets to improve the killing effect of ALA-PDT in treating HR-HPV infection.
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http://dx.doi.org/10.1111/phpp.12663DOI Listing
July 2021

Rare cases of PAMI syndrome in both father and son with the same missense mutation in PSTPIP1 gene and literature review.

J Dermatol 2021 Apr 17;48(4):519-528. Epub 2021 Jan 17.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

PSTPIP1-associated myeloid-related proteinaemia inflammatory (PAMI) syndrome has been described as a rare and distinct clinical phenotype of PSTPIP1-associated inflammatory diseases. We report PSTPIP1 mutation in both father and son who have leukopenia and acne-like lesions. Through whole-exome sequencing on blood DNA, it is found a heterozygous mutation of PSTPIP1 gene c.748G>A on the father and son. The diagnosis of PAMI is made based on DNA sequencing results and clinical characteristics of typical lesions, leukopenia, and the markedly increased serum S100A8/A9 (calprotectin).
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http://dx.doi.org/10.1111/1346-8138.15706DOI Listing
April 2021

Pre-exposure to protects against subsequent lethal fungal infections.

Virulence 2020 12;11(1):1674-1684

Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA, USA.

Commensal fungi are an important part of human microbial community, among which and are two common opportunistic pathogens. Unlike the high pathogenicity of is reported to show low pathogenicity to the host. Here, by using a infection model, we were able to confirm the much lower virulence of than . Interestingly, pre-exposure to live (LCG) protects the larvae against subsequent various lethal fungal infections, including and . Inconsistently, heat-inactivated (HICG) pre-exposure can only protect against or re-infection, but not . Mechanistically, LCG or HICG pre-exposure enhanced the fungicidal activity of hemocytes against or . Meanwhile, LCG pre-exposure enhanced the humoral immunity by modulating the expression of fungal defending proteins in the cell-free hemolymph, which may contribute to the protection against . Together, this study suggests the important role of in enhancing host immunity, and demonstrates the great potential of model in studying the innate immune responses against infections.
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http://dx.doi.org/10.1080/21505594.2020.1848107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714416PMC
December 2020

Dihydroartemisinin administration improves the effectiveness of 5-aminolevulinic acid-mediated photodynamic therapy for the treatment of high-risk human papillomavirus infection.

Photodiagnosis Photodyn Ther 2021 Mar 4;33:102078. Epub 2020 Nov 4.

Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou 510091, China.

Aims And Background: High-risk human papillomavirus (HR-HPV) infection has been confirmed to be highly related to diseases such as Bowenoid papulosis, cervical cancer, and cervical intraepithelial neoplasia. 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of HR-HPV infection-related diseases. Dihydroartemisinin (DHA) is one of artemisinin derivatives, and has inhibitory effects on a variety of cancer cells. For now, there is no published study focusing on the combination use of ALA-PDT with DHA to improve clinical efficacy of HR-HPV infection-related diseases. So in this study, we will examine the effectiveness of combined treatment of ALA-PDT and DHA for HR-HPV infection as well as its underlying mechanism.

Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALA-PDT or/and DHA, and cell viability, long proliferation, ROS production and apoptosis were evaluated by CCK8, colony-forming assay, immunofluorescence and flow cytometry, respectively. The protein expression of NF-κB-HIF-1α-VEGF pathway and NRF2-HO-1 pathway was examined by western blot.

Results: The results showed that DHA could enhance the effect of ALA-PDT on cell viability long proliferation, ROS production and apoptosis in HeLa cells. We also found that DHA inhibited NF-κB-HIF-1α-VEGF pathway which was activated by ALA-PDT. Besides, ALA-PDT combined with DHA activated NRF2-HO-1 pathway.

Conclusion: Although the NRF2 - NO-1 pathway as a resistance mechanism remains unresolved, DHA has the potential to enhance the effect of ALA-PDT for HPV infection-related diseases through inhibiting NF-κB - HIF-1α - VEGF pathway.
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http://dx.doi.org/10.1016/j.pdpdt.2020.102078DOI Listing
March 2021

Antifungal Photodynamic Activity of Hexyl-Aminolevulinate Ethosomes Against Biofilm.

Front Microbiol 2020 11;11:2052. Epub 2020 Sep 11.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Biofilm formation is responsible for the development of chronic and recurrent infections. The generation of biofilms is commonly accompanied by high resistance to conventional antifungal drugs, which can increase up to 1,000-fold. Fortunately, antimicrobial photodynamic therapy (aPDT) has shown excellent potential to treat biofilm infections. However, the current most commonly used photosensitizer (PS), aminolevulinic acid (ALA), is hydrophilic, unstable, and has low permeability, leading to unsatisfactory effects on biofilm eradication. To solve these problems, more stable lipophilic PSs and more effective permeability carriers could be considered as two effective solutions. Hexyl-aminolevulinate (HAL) has good bioavailability as a PS, and we proved in a previous study that ethosomes (ES), lipid-based nanocarriers, promote percutaneous drug penetration. In our previous study, a HAL-ES system presented superior photodynamic effects compared to those of ALA or HAL alone. Therefore, here, we aim to evaluate the biological effects of HAL-ES-mediated aPDT on biofilm. An XTT sodium salt assay showed that aPDT using 0.5% HAL decreased biofilm activity by 69.71 ± 0.43%. Moreover, aPDT with 0.5% HAL-ES further decreased biofilm activity by 92.95 ± 0.16% and inhibited growth of 25.71 ± 1.61% within 48 h, mostly its effect on the hyphae growth, which correlated with a three-fold increase in plasma membrane permeabilization. Notably, HAL-ES-mediated aPDT significantly reduced the sessile minimum inhibitory concentration 50 (SMIC50) of fluconazole to <2.0 μg/ml, and the 21-day survival rate of biofilm-infected mice increased from 6.7 to 73.3%. It also significantly reduced the drug resistance and pathogenicity of biofilm. These results demonstrate that HAL-ES-mediated aPDT could be an effective therapy for biofilm infections; while also serving as a particularly promising effective treatment for cutaneous or mucocutaneous candidiasis and the prevention of progression to systemic candidiasis.
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http://dx.doi.org/10.3389/fmicb.2020.02052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518189PMC
September 2020

A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum.

Lupus 2020 Dec 7;29(14):1854-1865. Epub 2020 Oct 7.

Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Central South University, Changsha, China.

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR'97), 2012 Systemic Lupus International Collaborating Clinics (SLICC'12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR'19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC'12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR'19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.
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http://dx.doi.org/10.1177/0961203320959716DOI Listing
December 2020

Human spermbots for patient-representative 3D ovarian cancer cell treatment.

Nanoscale 2020 Oct;12(39):20467-20481

Institute for Integrative Nanosciences, Leibniz IFW Dresden, Helmholtzstraße 20, 01069 Dresden, Germany. and Research Centre for Materials, Architectures and Integration of Nanomembranes (MAIN), Rosenbergstraße 6, TU Chemnitz, 09126 Chemnitz, Germany and Material Systems for Nanoelectronics, TU Chemnitz, Reichenhainer Straße 70, 09126 Chemnitz, Germany and School of Science, TU Dresden, 01062 Dresden, Germany.

Cellular micromotors are attractive for locally delivering high concentrations of drug, and targeting hard-to-reach disease sites such as cervical cancer and early ovarian cancer lesions by non-invasive means. Spermatozoa are highly efficient micromotors perfectly adapted to traveling up the female reproductive system. Indeed, bovine sperm-based micromotors have shown potential to carry drugs toward gynecological cancers. However, due to major differences in the molecular make-up of bovine and human sperm, a key translational bottleneck for bringing this technology closer to the clinic is to transfer this concept to human material. Here, we successfully load human sperm with Doxorubicin (DOX) and perform treatment of 3D cervical cancer and patient-representative ovarian cancer cell cultures, resulting in strong anticancer cell effects. Additionally, we define the subcellular localization of the chemotherapeutic drug within human sperm, using high-resolution optical microscopy. We also assess drug effects on sperm motility and viability over time, employing sperm samples from healthy donors as well as assisted reproduction patients. Finally, we demonstrate guidance and release of human drug-loaded sperm onto cancer tissues using magnetic microcaps, and show the sperm microcap loaded with a second anticancer drug, camptothecin (CPT), which unlike DOX is not suitable for directly loading into sperm due to its hydrophobic nature. This co-drug delivery approach opens up novel targeted combinatorial drug therapies for future applications.
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http://dx.doi.org/10.1039/d0nr04488aDOI Listing
October 2020

Mesenchymal stem cells transplantation in systemic lupus erythematosus treatment.

Dermatol Ther 2020 11 10;33(6):e14262. Epub 2020 Sep 10.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

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http://dx.doi.org/10.1111/dth.14262DOI Listing
November 2020

A novel GNAS mutation inherited from probable maternal mosaicism causes two siblings with pseudohypoparathyroidism type 1A.

J Pediatr Endocrinol Metab 2020 Sep;33(9):1219-1224

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objectives Objectives Pseudohypoparathyroidism type 1A (PHP1A) is caused by maternal inheritance of GNAS mutations. It is characterized by the resistance to several hormones, primarily the parathyroid hormone (PTH), and the features of Albright's hereditary osteodystrophy. Case presentation Here, we present a family comprised two affected brothers with PHP1A and identify a novel mutation (c.277C>T) in the GNAS gene. The siblings developed a slightly different presentation in the same clinical condition. Although both patients presented with PTH resistance, which is the hallmark of PHP, the proband showed the thyroid-stimulating hormone resistance with the progression of heterotopic ossification from skin and subcutaneous tissue into deep connective tissue, while the younger brother with normocalcemia did not show the resistance to other hormones. The patients may inherit the mutation from their mother who presumably carries the mutation as a mosaicism. Conclusions Our case highlights the significance of considering mosaicism as an explanation for apparent de novo cases of pseudohypoparathyroidism.
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http://dx.doi.org/10.1515/jpem-2019-0476DOI Listing
September 2020

5-aminolevulinic acid photodynamic therapy and excision surgery for nevoid basal cell carcinoma syndrome with multiple basal cell carcinomas and PTCH1 mutation.

Photodiagnosis Photodyn Ther 2020 Dec 21;32:101968. Epub 2020 Aug 21.

Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong Provice, 510095, China. Electronic address:

This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS.
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http://dx.doi.org/10.1016/j.pdpdt.2020.101968DOI Listing
December 2020

Short-Term Intravenous Infusion of Cyclophosphamide in the Treatment of Refractory Pemphigus Vulgaris: A Retrospective Study.

Dermatology 2021 19;237(2):185-190. Epub 2020 Aug 19.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China,

Background: Pemphigus is an autoimmune disease of the skin and mucous membranes. Glucocorticoids have been the most effective drug for the treatment of pemphigus; however, some patients are insensitive to glucocorticoid therapy. Cyclophosphamide has been extensively used in the treatment of pemphigus.

Objectives: To observe and evaluate the efficacy and safety of high-dose glucocorticoid with weekly intravenous cyclophosphamide in the treatment of refractory pemphigus vulgaris insensitive to glucocorticoids.

Methods: Clinical data of 19 patients with refractory pemphigus vulgaris (insensitive to glucocorticoid) who were treated with high-dose glucocorticoids(1.5 mg/kg/day prednisone) and weekly intravenous infusion of cyclophosphamide, and 24 patients who were sensitive to glucocorticoid therapy received a medium dose of glucocorticoid alone (1 mg/kg/day prednisone) were retrospectively analyzed.

Results: By the time the disease was brought under control, the average total dose of cyclophosphamide was 2.02 g. Comparison between the glucocorticoid-insensitive and glucocorticoid-sensitive groups showed that the average time to disease control was 2.68 vs. 2 weeks, and the average daily dosage of steroid was 1.33 ± 0.53 vs. 0.90 ± 0.28 mg/kg. At the 12- and 18-month follow-ups, the recurrence rate of the glucocorticoid-insensitive group was significantly lower than that of the sensitive group (5.3 vs. 37.5%, 15.8 vs. 45.8%). No serious adverse reactions were observed.

Conclusion: High-dose glucocorticoid plus weekly intravenous infusion of cyclophosphamide safely, effectively, and rapidly controlled the conditions of the patients with refractory pemphigus who were insensitive to glucocorticoids, shortened the duration of hospitalization, avoided the risk of complications that could be caused by further increasing the dose of glucocorticoids (>1.5 mg/kg/day), and lowered the recurrence rate within 18 months.
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http://dx.doi.org/10.1159/000508671DOI Listing
November 2021

Bilateral asymmetrical herpes-zoster with Ramsay hunt syndrome in an immunocompetent adult.

Virol J 2020 08 15;17(1):123. Epub 2020 Aug 15.

Department of Dermatology and Venereology, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.

Background: Bilateral herpes zoster (BHZ) is an atypical presentation of herpes zoster (HZ), with few cases reported before. Ramsay Hunt syndrome (RHS) is an uncommon complication of VZV infection. Cases of BHZ with RHS in immunocompetent adults have been reported rarely.

Case Presentation: We described an immunocompetent adult who suffered from left-sided thoracic herpes zoster and contralateral RHS simultaneously, and summarizes the characteristics of BHZ.

Conclusions: Cases of BHZ with RHS in immunocompetent adults have not been reported previously. Antivirus - glucocorticoid combination therapy showed a good effect in this case.
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http://dx.doi.org/10.1186/s12985-020-01392-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429785PMC
August 2020

Soluble fibrinogen-like protein 2 in condyloma acuminatum lesions.

Authors:
Mei Zeng Kang Zeng

J Infect Dev Ctries 2020 06 30;14(6):589-596. Epub 2020 Jun 30.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Introduction: An imbalance in type 1 (Th1) and type 2 (Th2) T helper cells is associated with the development and recurrence of condyloma acuminatum (CA); however, the mechanisms underlying this imbalance remain unknown. We investigated soluble fibrinogen-like protein 2 (sFGL2), which is an effector of regulatory T cells (Tregs), to determine its role in the Th1/Th2 imbalance of CA.

Methodology: Lesion and blood samples were obtained from 30 CA patients, and these samples were compared with genital skin and blood samples from 20 control subjects. Serum sFGL2, mRNA, and protein levels were estimated using ELISA, quantitative real-time polymerase chain reaction, and western blot, respectively. Immunohistochemical analyses were also conducted.

Results: Compared to controls, CA patients had decreased serum sFGL2 levels. However, sFGL2 mRNA and protein levels in the lesions of CA patients were significantly increased. Interleukin (IL)-4 and Foxp3 mRNA levels were upregulated, and interferon (IFN)-γ levels were downregulated in CA patients compared to those in controls. Additionally, the sFGL2 mRNA level positively correlated with Foxp3 and IL-4 levels and negatively correlated with IFN-γ and IL-17 levels.

Conclusion: sFGL2 contributes to the underlying Th1/Th2 imbalance in CA pathogenesis.
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http://dx.doi.org/10.3855/jidc.12282DOI Listing
June 2020
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