ABSTRACT
Acne is a common and chronic skin condition characterized by high incidence, recurrent symptoms and difficult cure. Summarizing the clinical treatment experience, it was found that the powder for ascending and descending was effective in the treatment of acne. Our aim was to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of powder for ascending and descending against acne. First, the chemical components and target genes of PAD were sifted using the TCMSP and HERB database. The targets of acne were obtained simultaneously from the CTD, OMIM and GeneCards database. The obtained drug targets and disease targets were imported into the R language software to draw Venn diagrams. Then, the potential targets were imported into the String website to construct a protein interaction network diagram. And Cytoscape software was used for topological analysis to screen the core targets, and the core targets were analyzed by GO functional enrichment and KEGG pathway enrichment. Finally, molecular docking was used to verify the predictions of key genes' reliability. The core targets of the treatment of acne were TNF, GADPH, IL-6 and so on. The results of enrichment analysis showed that the treatment of acne with PAD may be related to TNF signaling pathway and AGE-RAGE signaling pathway. The molecular docking verification showed that the components were well bound to the core targets of acne, and the docking ability of stigmasterol and TNF (-12.73 kcal/mol) was particularly outstanding.
Subject(s)
Acne Vulgaris , Molecular Docking Simulation , Network Pharmacology , Acne Vulgaris/drug therapy , Humans , Network Pharmacology/methods , Protein Interaction Maps , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Signal Transduction/drug effects , Medicine, Chinese Traditional/methodsABSTRACT
BACKGROUND: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.
ABSTRACT
Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of heterogeneity and prognosis in HNSCC. Publicly available transcriptome and clinical data of HNSCC were obtained and analyzed using consensus clustering to identify molecular subtypes. A risk model based on LRGs was developed and evaluated, including its correlation with clinical features, immune infiltration, drug sensitivity, and response to immune therapy. Gene set enrichment analysis was conducted to explore relevant pathways, and a prognostic nomogram model for HNSCC was constructed and evaluated. In this study, we identified 542 LRGs that exhibited differential expression in HNSCC, with 116 of these being significantly associated with overall survival. Two LRGs-derived molecular subtypes were identified, which displayed significant differences in prognosis and immune cell infiltration. Additionally, a prognostic risk model was developed, which included 13 LRGs. This model successfully divided HNSCC into low-risk and high-risk groups with different prognoses and immune cell infiltrations. The LRGs-derived risk signature was associated with immune infiltration, clinical features, drug sensitivity and immunotherapy response. The good prognosis of the low-risk group was linked to the activation of immune response-related processes and the inhibition of pathways such as necroptosis and neutrophil extracellular trap formation. Patients in the low-risk group had better immune therapy response, while those in the high-risk group had higher drug sensitivity. Finally, our nomogram, which combines clinical N staging and LRG-derived model, demonstrated excellent prognostic evaluation performance as shown by decision curve analysis and calibration curve. The study provides a comprehensive analysis of the expression and prognostic significance of LRGs in HNSCC, leading to the identification of 2 distinct molecular subtypes and the development of a risk model based on LRGs.
Subject(s)
Head and Neck Neoplasms , Lysosomes , Humans , Prognosis , Squamous Cell Carcinoma of Head and Neck/genetics , Nomograms , Head and Neck Neoplasms/geneticsABSTRACT
Total glucosides of paeony (TGP), an active ingredient extracted from the root of Paeonia alba, has been reported to display an antiinflammatory effect. However, the effect of TGP on allergic rhinitis (AR) is still unknown. The present study aimed to assess the role of TGP in an AR mouse model. An AR mouse model was established using the ovalbumin method. The expression levels of Smad7/TGFß pathwayrelated prtoeins in nasal mucosa tissues were determined by immunofluorescence, immunohistochemistry and western blotting. The severity of nasal allergic symptoms was detected by recording the frequency of sneezing and nose rubbing motions in all mice for 20 min. The levels of IgE and inflammatory cytokines, including IL4, IL5, IL17 and IFNγ, in the serum were measured by conducting ELISAs. H&E staining, periodic acidSchiff staining and Masson staining were used to detected histopathological changes in mice. The concentrations of malondialdehyde and glutathione, and the activities of superoxide dismutase and catalase in tissue supernatant and serum were quantified using commercial assay kits. Apoptosis of nasal tissue cells was detected by performing TUNEL assays and western blotting. The expression of Smad7 was upregulated and that of TGFß was downregulated in the nasal tissue of AR mice. Additionally, TGP regulated the Smad7/TGFß pathway in the nasal tissue of AR mice. TGP alleviated serum IgE, nasal symptoms and histopathological changes in AR mice. Moreover, TGP ameliorated oxidative stress, cell apoptosis and inflammatory response. Smad7 small interfering RNA intervention aggravated the symptoms of AR mice via activation of the TGFß pathway and reversed the protective effect of TGP in AR mice. TGP ameliorated oxidative stress, apoptosis and inflammatory response via the Smad7/TGFß pathway in AR.
Subject(s)
Apoptosis/drug effects , Glucosides/pharmacology , Oxidative Stress/drug effects , Paeonia/chemistry , Plant Extracts/pharmacology , Smad7 Protein/metabolism , Transforming Growth Factor beta/metabolism , Animals , Biomarkers , Cytokines/metabolism , Disease Models, Animal , Glucosides/chemistry , Immunoglobulin E/immunology , Immunohistochemistry , Male , Mice , Plant Extracts/chemistry , Rhinitis, Allergic/etiology , Rhinitis, Allergic/metabolism , Rhinitis, Allergic/pathology , Signal TransductionABSTRACT
Allergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.
ABSTRACT
OBJECTIVE: To determine an approach enriching cancer stem cells from laryngeal cancer cell line. To investigate whether laryngeal cancer stem cells in chemoradiotherapy have the characteristic of resistance. METHOD: CD133+ cells and CD133- cells was detected and isolated from Hep-2 cell line by fluorescence activated cell sorting technology. The cytotoxicities of cisplatin and radiation were investigated by cell counting kit-8(CCK-8) assay. The apoptosis and cell cycle was analyzed with flow cytometry. RESULT: CD133+ cells accounted for a fraction of (2.43 +/- 0.77)% in Hep-2 cell line. CD133+ cells have a more obvious characteristics of cancer stem cells. Different cisplatin and radiation concentrations of for two cell have inhibition, in a certain concentration range and the dosage dependence. Cisplatin and radiation had synergistic inhibitory effects with CD133- cells on the growth of two cell. Moreover, cell cycle arrest at G0/G1 phase and more apoptosis was induced by synergistic combination. Different concentrations of cetuximab for Hep-2 cells have inhibition, in a certain concentration range and time and the dosage dependence. The half maxial inhibitory concentration (IC50) of cetuximab to Hep-2 cells on 24 h was 1 036.84 microg/L. Cisplatin and radiation had synergistic inhibitory effects with cetuximab on the growth of Hep-2 cell line. Moreover, cell cycle arrest at G0/G1 phase and more apoptosis was induced by synergistic combination. CONCLUSION: Compared with CD133- cells, CD133+ cells subpopulation exhibited extraordinary cancer stem.
Subject(s)
Chemoradiotherapy , Drug Resistance, Neoplasm , Laryngeal Neoplasms/therapy , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/radiation effects , Radiation Tolerance , AC133 Antigen , Antibodies, Monoclonal, Humanized/pharmacology , Antigens, CD/analysis , Antineoplastic Agents/pharmacology , Apoptosis , Cell Cycle , Cell Line, Tumor , Cetuximab , Cisplatin/pharmacology , Flow Cytometry , Glycoproteins/analysis , Humans , Peptides/analysisABSTRACT
OBJECTIVE: To evaluate the function of Th17 cells in allergic rhinitis,through comparing the symptoms, pathology and and the quantity of Th1, Th2 and Th17 cytokine in normal mice, allergic rhinitis mice and allergic rhinitis mice with IL-17 antibody application. METHOD: Thirty BALB/c mice were randomly divided into three groups, control group, allergic rhinitis group, and therapy group. The allergic rhinitis model was induced by classical method with ovalbumin. The therapy group was treated with IL-17 antibody. The concentration of IL-17, IL-4 and IFN-gamma in serum was measured by enzyme-linked immunosorbent assay (ELISA). Nasal mucosal inflammation was evaluated by HE staining. The expression of RORgammat mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The expression level of IL-17, IL-4 and RORgammat mRNA in allergic rhinitis group were significantly higher than those of control group and IL-17 antibody treated group (P < 0.05). While the expression level of IFN-gamma in allergic rhinitis group were significantly was lower than those of control group and IL-17 antibody treated group (P < 0.05). The inflammation reaction in therapy group abated with nasal mucosal HE staining. CONCLUSION: The large quantity of Th2, Th17 cells were found in allergic rhinitis. It might be associated with the pathogenesis of allergic rhinitis. The control of Th17 cells expression may be an effective way to treat allergic rhinitis.