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Introduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation. Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content. Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes. Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.
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The crude polysaccharide of Bletilla striata in this study was extracted by water extraction and alcohol precipitation and further purified by gel column to yield the purified component Bletilla striata polysaccharide (BSP). Its structure and innate immune regulation activity were studied. BSP mainly comprises mannose and glucose, with a monosaccharide molar ratio of 2.9:1 and a weight-average molecular weight of 28,365 Da. It is a new low-molecular-weight water-soluble neutral glucomannan. BSP contains a â 6)-ß-Manp-(1â, â4)-ß-Glcp-(1â, â4)-ß-Manp-(1 â and â3)-α-Manp-(1 â linear main chain, containing ß-Glcp-(1 â and ß-Manp-(1 â two branched chain fragments were connected to the Man residue at position 4. BSP can enhance the anti-infection ability of Caenorhabditis elegans against Pseudomonas aeruginosa, significantly improve the phagocytic ability of RAW264.7 macrophages, stimulate the secretion of NO and TNF-α, and have good innate immune regulation activity. These findings guide the use of Bletilla striata polysaccharides with immunomodulatory action.
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Imunidade Inata , Mananas , Orchidaceae , Animais , Mananas/química , Mananas/farmacologia , Mananas/isolamento & purificação , Camundongos , Orchidaceae/química , Células RAW 264.7 , Imunidade Inata/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/imunologia , Peso Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificaçãoRESUMO
Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.
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Ferroptosis, a type of programmed cell death, occurs when there is oxidative stress and lipid peroxides. This condition is marked by lipid peroxidation that relies on iron and the reduction of cellular defences against oxidation. To investigate the effect of UVB irradiation on ferroptosis of human keratinocytes HaCaT cells, the cells were pretreated with Ferrostatin 1 (Fer-1, 10 µM), an ferroptosis inhibitor and then irradiated with UVB (20 mJ/cm2 ) for 30 min to detect related indexes of ferroptosis through MTT assay, quantitative real-time polymerase chain reaction, flow cytometry, reactive oxygen species (ROS) assay, western blotting. Results showed that UVB significantly reduced cell activity, promoted apoptosis and ROS level, whereas Fer-1 significantly increased cell activity, and reduced apoptosis and ROS level. In addition, UVB significantly reduced levels of ferroptosis-related proteins and skin barrier-related proteins, and increased levels of γ-H2AX and iron, whereas Fer-1 significantly increased their protein levels, and reduced levels of γ-H2AX and iron. Conjoint analysis of transcriptomic and proteomic revealed that UVB significantly reduced the levels of TIMP metallopeptidase inhibitor 3 (TIMP3), and coagulation factor II thrombin receptor (F2R), whereas Fer-1 significantly promoted the levels of TIMP3, and F2R. Therefore, our results indicated that Fer-1 significantly ameliorates UVB-induced damage of HaCaT cells by regulating the levels of TIMP3 and F2R.
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Ferroptose , Células HaCaT , Humanos , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Apoptose , Queratinócitos/metabolismo , Ferro , Raios Ultravioleta/efeitos adversosRESUMO
A compound's overall contour impacts its ability to elicit biological response, rendering access to distinctly shaped molecules desirable. A natural product's framework can be modified, but only if it is abundant and contains suitably modifiable functional groups. Here we introduce a programmable strategy for concise synthesis of precisely altered scaffolds of scarce bridged polycyclic alkaloids. Central to our approach is a scalable catalytic multi-component process that delivers diastereo- and enantiomerically enriched tertiary homoallylic alcohols bearing differentiable alkenyl moieties. We used one product to launch progressively divergent syntheses of a naturally occurring alkaloid and its precisely expanded, contracted and/or distorted framework analogues (average number of steps/scaffold of seven). In vitro testing showed that a skeleton expanded by one methylene in two regions is cytotoxic against four types of cancer cell line. Mechanistic and computational studies offer an account for several unanticipated selectivity trends.
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Alcaloides Indólicos , Catálise , Alcaloides Indólicos/química , Alcaloides Indólicos/síntese química , Humanos , Linhagem Celular Tumoral , Estereoisomerismo , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Estrutura Molecular , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Background: Vitiligo is a common clinical disorder caused by the destruction of epidermal melanocytes, which is often associated with autoimmune mechanisms. Autophagy plays a crucial role in maintaining cellular homeostasis and exhibits close associations with various autoimmune disorders. While dysautophagy of melanocytes is associated with vitiligo pathogenesis, there is a lack of studies on autophagy-related genes (ARGs) in blood samples from individuals with vitiligo. Methods: Blood samples from individuals with vitiligo and healthy controls were compared to identify differentially expressed genes (DEGs), which were subsequently subjected to further analysis. Then, miRNAs correlated with core genes were predicted by five distinct online tools, and those miRNAs that appeared in three or more tools at the same time were chosen for further enrichment analysis. Furthermore, in vitro experiments of targeting core genes were conducted. Results: The results showed that there were a total of 30 ARGs among DEGs, with 13 up-regulated genes and 17 down-regulated genes. Based on the functional enrichment analysis of DEGs and projected miRNAs, we hypothesized that autophagy and apoptosis may synergistically contribute to the progression of vitiligo, with the TNFSF10/hsa-let-7a-5p axis potentially playing an important role that should not be ignored. In addition, epigallocatechin-3-gallate (EGCG) was found to be the common component in BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI, which were discovered to be potential in vitiligo treatment by inducing cell autophagy and apoptosis targeting TNFSF10. Conclusion: It was the first time that TNFSF/hsa-let-7a-5p was discovered to be involved in the development of vitiligo through autophagy and apoptosis. Meanwhile, we observed that BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI were promising to treat vitiligo by regulating autophagy and apoptosis via TNFSF10. These findings could lead to new directions for investigating the pathogenesis and therapy of vitiligo.
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OBJECTIVE: To detect serum metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMP-1), cyclooxygenase-2 (COX-2), and T helper cells 1-T helper cells 2 (Th1-Th2) levels in asthma patients and assess their clinical significance. METHODS: A total of 72 patients experiencing acute asthma (acute group), 66 stable asthma patients (stable group), and 60 healthy volunteers (control group) were included in this study. The levels of TIMP-1, COX-2, and Th1-Th2 in patients with acute asthma were measured following treatment with budesonide aerosol inhalation. In addition, the levels of MMP-9, TIMP-1, COX-2 and Th1-Th2 were compared in patients with different severity of acute asthma before and after treatment. RESULTS: The serum levels of MMP-9, TIMP-1, and COX-2 showed an increasing trend in the control, stable, and acute groups, while levels of Th1-Th2 showed a sequential decreasing trend, and the differences were statistically significant. Comparison of lung function indexes among the three groups of patients established a negative correlation between serum MMP-9 and its forced vital capacity% predicted (FEV%pred), TIMP-1, and COX-2, and FEV%pred and forced expiratory volume in 1 s-forced vital capacity (FEV1/FVC) levels, but a positive correlation between Th1-Th2 and FEV1/FVC levels in the acute group. A significant difference was observed on comparing the levels of serum MMP-9, TIMP-1, COX-2, and Th1-Th2 in patients with different conditions in the acute group. Specifically, as the condition worsened, a significant increase in serum MMP-9, TIMP-1, and COX-2 levels but a significant decrease in Th1-Th2 levels was observed. After treatment, we observed a significant decrease in serum MMP-9, TIMP-1, and COX-2 levels but a significant increase in Th1-Th2 levels in the acute group. CONCLUSION: The serum levels of MMP-9, TIMP-1, COX-2, and Th1-Th2 are valuable indicators reflecting the condition of asthma patients and could be considered promising clinical monitoring indicators.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Relevância Clínica , Ciclo-Oxigenase 2/uso terapêutico , Metaloproteinase 9 da Matriz , Inibidor Tecidual de Metaloproteinase-1/uso terapêuticoRESUMO
Skin cutaneous melanoma, SKCM, is one of the most aggressive treatment-resistant tumours. Despite the fact that the BRAF oncogene and immunological checkpoints such as PD-1/PD-L1 and CTLA-4 have enhanced the therapeutic efficacy of SKCM, the subsequent resistance mechanisms and remedies have raised concerns. Chemokines have a significant role in the immunological milieu of tumor, which may increase the efficacy of checkpoint blockade and serve as a possible therapeutic intervention route. However, there is still no chemokine-based typing and risk model to provide a prognosis and therapeutic efficacy assessment for SKCM patients. In this study, we verified the distinct differences of prognostic stratification as well as immune characteristics between two chemokine-related clusters in SKCM patients. Two clusters of DEGs were discovered to be primarily enriched in B and T cell receptor signaling pathways as well as TNF signaling via NF-kappa-B. Based on 14 prognosis-related DEGs from aforementioned two clusters (CCL8, GBP2, GBP4, SRNG, HLA-DMB, RARRES3, HLA-DQA1, PARP12, APOL3, IRF1, HLA-DRA, UBE2L6, IL2RA and CD38), a chemokine-related 14-gene prognostic model was established. At the same time, researchers explored differences between the low-risk and high-risk groups in clinical traits, the proportion of infiltration of 22 different types of immune cells, and how well medications worked. The risk score model's immunotherapy and prognostic predictions were also confirmed in testing groups. Based on the finding, we can claim that there is a clear link between chemokines and TME in SKCM. The risk score may perform as a trustworthy prediction model, giving therapeutic benefits for both chemotherapy and immunotherapy, as well as being beneficial for clinical decision making in SKCM patients.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Prognóstico , Quimiocinas/genética , Melanoma Maligno CutâneoRESUMO
OBJECTIVES: Dendritic cells are one of the first host cells that cryptococcus encounters. However, the correlations among cryptococcus, dendritic cells, and long noncoding RNA remain unclear. This study was undertaken to investigate the effects of long noncoding RNAs on dendritic cells with cryptococcus infection. MATERIALS AND METHODS: We treated dendritic cells with cryptococcus and then detected expression of CD80, CD86, and major histocompatibility complex class II in dendritic cells with a real-time fluorescent quantitative polymerase chain reaction assay. We used nextgeneration sequencing and bioinformatics analysis to determine the competitive endogenous RNA mechanisms, confirmed via real-time polymerase chain reaction, dual luciferase reporter, and RNA-binding protein immunoprecipitation assays. RESULTS: After treatment of dendritic cells with 1 × 108 CFU/mL cryptococcus for 12 hours, dendritic cell viability was normal, whereas mRNA expression levels of CD80, CD86, and major histocompatibility complex class II in dendritic cells were substantially increased. With next-generation sequencing, we discovered 4 small nucleolar RNA host genes (snhg1, snhg3, snhg4, and snhg16) in cryptococcus-treated dendritic cells compared with wild-type dendritic cells. Bioinformatics analysis combined with real-time polymerase chain reaction led us to speculate that cryptococcus may affect the maturation and apoptosis of dendritic cells by regulating snhg1-miR-145a-3p-Bcl2. Further polymerase chain reaction, dual luciferase reporter, and RNA-binding protein immunoprecipitation experiments revealed that snhg1 acted as a sponge for miR145a-3p to inhibit the expression of miR-145a-3p and that miR-145a-3p promoted the expression of Bcl2 by directly targeting the 3'-UTR of Bcl2. Functional recovery experiments showed that cryptococcus promoted the maturation and apoptosis and inhibited the proliferation of dendritic cells through the snhg1-Bcl2 pathway. CONCLUSIONS: This study lays a foundation for the further understanding of the pathogenic role of snhg1-miR-145a-3p-Bcl2 axis in cryptococcosis.
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Criptococose , Células Dendríticas , MicroRNAs , Humanos , Apoptose , Proliferação de Células , Criptococose/genética , Células Dendríticas/imunologia , Imunidade , MicroRNAs/genéticaRESUMO
Skin infections are common diseases for which patients seek inpatient and outpatient medical care. Globally, an increasing number of people are affected by skin infections that could lead to physical and psychological damage. Skin infections always have a broad spectrum of clinical presentations that require physicians to make an aggressive and accurate diagnosis for prescribing the proper symptomatic antimicrobials. In most instances, the treatment for skin infections mainly includes oral or topical anti-infective drugs. However, some of the classical anti-infective drugs have limitations, such as poor water solubility, low bioavailability, and poor targeting efficiency, which can lead to poor efficacy, adverse effects, and drug resistance. Therefore, research priorities should focus on the development of more effective drug delivery systems with new materials. Hydrogels are a highly multifunctional class of medical materials with potential applications in dermatology. Several hydrogel dressings with anti-infective functions have been formulated and demonstrated to improve the efficacy and tolerance of oral or topical classical anti-infective drugs to a certain degree. In this study, the medical applications of hydrogels for the treatment of various skin infections are systematically reviewed to provide an important theoretical reference for future research studies on the treatment options for skin infections.
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Cutaneous nocardiosis is a rare bacterial infection that can result in various dermatologic manifestations such as actinomycetoma, lymphocutaneous infection, superficial skin infection, and secondary infection due to hematogenous dissemination. We report on a Chinese patient with erythema nodosum-like exanthema, possibly secondary to nocardiosis. Our diagnosis for this patient was based on the clinical presentation, histopathological evidence, and microbiological findings. Given the protean manifestation of Nocardia, persistent reports on new presentations of the disease are important for early identification and treatment.
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Eritema Nodoso , Nocardiose , Nocardia , Dermatopatias Bacterianas , Humanos , Eritema Nodoso/complicações , Eritema Nodoso/patologia , Nocardiose/complicações , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Pele/patologia , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologiaRESUMO
Solar ultraviolet radiation (UVR) is the primary pathogenetic factor in skin photoaging. It can disrupt cellular homeostasis by damaging DNA, inducing an inflammatory cascade, immunosuppression, and extracellular matrix (ECM) remodeling, resulting in a variety of dermatologic conditions. The skin microbiome plays an important role in the homeostasis and maintenance of healthy skin. Emerging evidence has indicated that highly diverse gut microbiome may also have an impact on the skin health, referred to as the gut-skin axis (GSA). Oral and topical probiotics through modulating the skin microbiome and gut-skin microbial interactions could serve as potential management to prevent and treat the skin photoaging by multiple pathways including reducing oxidative stress, inhibiting ECM remodeling, inhibiting the inflammatory cascade reaction, and maintaining immune homeostasis. In this review, the effects of oral and topical probiotics in skin photoaging and related mechanisms are both described systematically and comprehensively.
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Based on the fact that very little was found in the literature on the question of potential molecules and mechanism for high risk of cancer in patients with psoriasis, this study was designed and performed based on bioinformatics analysis including WGCNA. The most striking result to emerge from the data is that BUB1B/hsa-miR-130a-3p axis, closely related to the development of psoriasis, also plays a remarkable role in multiple cancer development. The expression patterns of hsa-miR-130a-3p were found significantly changed in multiple tumors, which was also associated with prognosis. Additionally, hsa-miR-130a-3p was downregulated in lesion skin of psoriasis, but there was no difference in blood between psoriasis patients and normal controls. Circulating has-miR-130a-3p was found to have a higher level of blood in multiple tumor patients, suggesting that hsa-miR-130a-3p has the potential to be a blood biomarker for cancer risk assessment in patients with psoriasis.
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Photoaging is characterized by a chronic inflammatory response to UV light. One of the most prominent features of cutaneous photoaging is wrinkling, which is due primarily to a loss of collagen fibers and deposits of abnormal degenerative elastotic material within the dermis (actinic elastosis). These changes are thought to be mediated by inflammation, with subsequent upregulation of extracellular matrix-degrading proteases and down-regulation of collagen synthesis. Autophagy is a vital homeostatic cellular process of either clearing surplus or damaged cell components notably lipids and proteins or recycling the content of the cells' cytoplasm to promote cell survival and adaptive responses during starvation and other oxidative and/or genotoxic stress conditions. Autophagy may also become a means of supplying nutrients to maintain a high cellular proliferation rate when needed. It has been suggested that loss of autophagy leads to both photodamage and the initiation of photoaging in UV exposed skin. Moreover, UV radiation of sunlight is capable of regulating a number of autophagy-linked genes. This review will focus on the protective effect of autophagy in the skin cells damaged by UV radiation. We hope to draw attention to the significance of autophagy regulation in the prevention and treatment of skin photoaging.
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Background: Chronic cutaneous lupus erythematosus (CCLE) and subacute cutaneous lupus erythematosus (SCLE) are both common variants of cutaneous lupus erythematosus (CLE) that mainly involve the skin and mucous membrane. Oral mucosal involvement is frequently observed in patients of CLE. Despite that they have different clinicopathological features, whether there is a significant difference in pathogenesis between them remains unclear. Herein, we investigated specific genes and pathways of SCLE and CCLE via bioinformatics analysis. Methods: Microarray expression datasets of GSE109248 and GSE112943 were both retrieved from the GEO database. Differentially expressed genes (DEGs) between CCLE or SCLE skin tissues and health controls were selected by GEO2R. Common DEGs were picked out via the Venn diagram software. Then, functional enrichment and PPI network analysis were conducted, and the top 10 key genes were identified via Cytohubba. Results: Totally, 176 DEGs of SCLE and 287 DEGs of CCLE were identified. The GO enrichment and KEGG analysis of DEGs of SCLE is significantly enriched in the response to virus, defense response to virus, response to IFN-gamma, cellular response to IFN-γ, type I IFN signaling pathway, chemokine activity, chemokine receptor binding, NOD-like receptor signaling pathway, etc. The GO enrichment and KEGG analysis of DEGs of CCLE is significantly enriched in the response to virus, regulation of multiorganism process, negative regulation of viral process, regulation of lymphocyte activation, chemokine receptor binding, CCR chemokine receptor binding, NOD-like receptor signaling pathway, etc. The top 10 hub genes of SCLE and CCLE, respectively, include STAT1, CXCL10, IRF7, ISG15, and RSAD2 and CXCL10, IRF7, IFIT3, CTLA4, and ISG15. Conclusion: Our finding suggests that SCLE and CCLE have the similar potential key genes and pathways and majority of them belong to IFN signatures and IFN signaling pathway. Besides, the NOD-like receptor signaling pathway might also have an essential role in the pathogenesis of SCLE and CCLE. Together, the identified genes and signaling pathways have enhanced our understanding of the mechanism underlying the occurrence and development of both SCLE and CCLE.
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Doença Enxerto-Hospedeiro , Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Discoide , Antígeno CTLA-4 , Quimiocinas , Biologia Computacional , Humanos , Lúpus Eritematoso Cutâneo/genética , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Discoide/genética , Lúpus Eritematoso Discoide/patologia , Proteínas NLR , Receptores de QuimiocinasRESUMO
Background: Over the last several decades, our understanding of hidradenitis suppurativa (HS) has improved considerably, thereby enhancing our ability to clinically diagnose and treat the disease. Objective: The purpose of this study was to identify and analyze the top 100 most-cited publications related to HS to update bibliometric information on HS. Materials and methods: We used the Web of Science database to identify reports on hidradenitis suppurativa. Data from the 100 most-cited publications were extracted and analyzed. Results: The citation number of the top 100 most-cited articles was 89-532 (mean, 153.51), with the most productive periods being from years 2007 to 2016. Most publications originated from the British Journal of Dermatology and the Journal of the American Academy of Dermatology. The 100 articles originated from 18 countries, with Denmark being the most productive country, followed by the United States (17), England (14), and Germany (12). Jemec GB, from the University of Copenhagen, had 32 citations and was the most frequently identified author. The 100 articles encompassed several fields of research as follows: pathogenesis (18%), pathophysiology (7%), epidemiology (14%), clinical diagnosis and features (16%), treatment (25%), comorbidity (10%), and others (10%). In total, 11 reviews, three guidelines, and 86 original articles (nine randomized clinical trials) were included. Conclusion: Through this bibliometric analysis, we aimed to indicate a series of intellectual landmark publications that offer us critical reviews, guidelines, and original articles, which highlight the immense level of progress achieved in the field of HS.
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Ultraviolet radiation (UVR) is a known carcinogen participated for the development of skin cancers. Solar UVR exposure, particularly ultraviolet B (UVB), is the mostly significant environmental risk factor for the occurrence and progress of basal cell carcinoma(BCC). Both cumulative and intermittent high-grade UVR exposure could promote the uncontrolled replication of skin cells. There are also exsiting other contributing environmental factors that combine with the UVR exposure to promote the development of BCC. DNA damage in formation of skin cancers is considered to be a result of UVR toxicity. It is UVR that could activate a series of oncogenes simultaneously inactivating tumor suppressor genes and aberrant proliferation and survival of keratinocytes that repair these damages. Furthermore, mounting evidence demonstrates that inflammatory responses of immune cells in the tumor microenvironment plays crucial role in the skin tumorigenesis as well. In this chapter, we will follow the function of UVR in the onset and development of BCC. We describe the factors that influence BCC induced by UVR, and also review the recent advances of pathogenesis of BCC induced by UVR from the genetic and inflammatory aspects.
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Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/epidemiologia , Humanos , Pele , Neoplasias Cutâneas/epidemiologia , Luz Solar , Microambiente Tumoral , Raios Ultravioleta/efeitos adversosRESUMO
Objective To explore the mechanism of mannose-capped lipoarabinomannan (ManLAM) lipopolysaccharide of mycobacterium tuberculosis (MTB) inducing exosomes of mast cells to recruit macrophages and influence macrophage polarization for immune evasion. Methods H37Rv MTB was cultured and ManLAM extracted and identified. The extracted ManLAM was used to treat mast cells, and the exosomes secreted by mast cells were collected. The protein components of the exosomes were analyzed and identified by proteomic analysis and Western blotting. The collected exosomes were co-cultured with macrophages differentiated from THP-1 cells. The chemotaxis of exosomes released by mast cells on macrophages was detected by TranswellTM assay. The macrophage polarization induced by ManLAM was detected by flow cytometry and real-time quantitative PCR. Results ManLAM was successfully extracted and purified, and the ratio of mannose to arabinose was about 12.6:9.4 identified by gas chromatography. ManLAM bound to Toll-like receptor 2 of mast cells, the exosomes produced by those mast cells had a high levels of CCL2, IL-4, and IL-13. ManLAM-induced mast cell exosomes recruited macrophages and promoted high expression of M2 polarization of macrophages molecular markers: arginase-1, IL-10, and FIZZ-1. Conclusions ManLAM stimulates mast cells to secrete exosomes and indirectly induces M2 polarization of macrophages, which makes MTB evade immune clearance.
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Exossomos , Lipopolissacarídeos , Lipopolissacarídeos/farmacologia , Macrófagos , Manose , Mastócitos , Proteômica , Receptor 2 Toll-Like/genéticaRESUMO
Psoriasis is a common chronic, immune-mediated, inflammatory skin disorder, with a reported prevalence of 0.0-2.1% among children and 0.91-8.50% among adults, worldwide. Psoriasis is induced by several environmental factors, including infection, alcohol consumption, drugs, trauma, acute withdrawal of systemic or potent topical corticosteroids, body mass index and endocrine disorders. Increasing evidence suggest that a variety of microorganisms play key roles in the induction and exacerbation of psoriasis. Pathogens, such as streptococci and staphylococci are considered causal factors, presumably via superantigen activation of skin-seeking T cells. In addition, fungal pathogens, such as Candida and Malassezia, and viral agents, such as human immunodeficiency virus, hepatitis C virus infection and human papillomavirus, are also closely associated with psoriasis. Recently, several types of pathogens, such as Helicobacter pylori infection, Zika virus and scabies, have been reported to potentially trigger psoriasis. The present review discusses the underlying molecular mechanisms by which these infections influence psoriasis to provide a better understanding of the pathogenesis of psoriasis.
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Chiral sulfones extensively exist in drugs, agricultural chemicals, chiral organic intermediates, and functional materials. Their importance causes the rapid development of their synthetic methods in recent years. Many transition metal complex catalysts with chiral ligands and chiral organocatalysts are adopted in synthesis of chiral sulfones. Most of the methods to construct chiral sulfones are based on the reduction of unsaturated sulfones and the introduction of sulfone groups into unsaturated hydrocarbons. This review describes all classes of asymmetric reactions for synthesis of chiral sulfones.