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1.
Polymers (Basel) ; 16(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39125161

ABSTRACT

Polylactic acid (PLA) composite serve as widely used filaments in fused deposition modeling (FDM) 3D printing. This study investigates the enhancement of PLA composite's comprehensive mechanical properties and thermal stability through the incorporation of carbon fiber (CF). The influence of FDM process parameters on the mechanical properties of PLA composite is also analyzed. Results show that adding 5 wt.% CF significantly enhances the stiffness and comprehensive mechanical properties of PLA composite. The order of printing factors affecting the tensile strength of the PLA composite product is as follows: printing layer thickness, bottom plate temperature, printing speed, and nozzle temperature. Finally, optimal tensile strength is achieved under specific conditions: 0.1 mm layer thickness, 60 °C bottom plate temperature, 40 mm/s printing speed, and 215 °C nozzle temperature.

2.
Biosci Rep ; 44(6)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38393364

ABSTRACT

Psoriasis is a common chronic inflammatory skin disease characterized by aberrant proliferation of keratinocytes and infiltration of immune cells. We previously found that GPR15LG protein is highly expressed in psoriasis lesional skin and it positively regulates psoriatic keratinocyte proliferation. Our data also showed that GPR15LG could regulate the activity of NF-κB pathway, which is associated with psoriatic inflammation. In the present study, we demonstrated that Gpr15lg (ortholog of GPR15LG) knockdown attenuated the severity of imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Such an effect was achieved by down-regulating the expression of inflammatory cytokines interleukin (IL)-1α, IL-1ß, tumor necrosis factor (TNF)-α and S100A7. Consistently, GPR15LG knockdown in vitro significantly downgraded the expression of inflammatory factors in the cellular model of psoriasis. These results suggested that GPR15LG could be involved in the development of psoriasis by regulating inflammation.


Subject(s)
Imiquimod , Interleukin-1alpha , Keratinocytes , Psoriasis , Receptors, G-Protein-Coupled , Animals , Humans , Male , Mice , Disease Models, Animal , Down-Regulation , HaCaT Cells , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Interleukin-1alpha/metabolism , Interleukin-1alpha/genetics , Interleukin-1beta/metabolism , Interleukin-1beta/genetics , Keratinocytes/metabolism , Keratinocytes/pathology , Mice, Inbred BALB C , NF-kappa B/metabolism , Psoriasis/genetics , Psoriasis/metabolism , Psoriasis/pathology , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , S100 Calcium Binding Protein A7/metabolism , S100 Calcium Binding Protein A7/genetics , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics
3.
J Cancer ; 15(4): 1115-1123, 2024.
Article in English | MEDLINE | ID: mdl-38230211

ABSTRACT

Background: Melanoma is a highly malignant tumor, and it is characterized by high mortality. Growth differentiation factor 15 (GDF15) and PTEN/PI3K/AKT signaling pathway have been proved to be related with regulation of tumors. If GDF15 could regulate melanoma through targeting PTEN/PI3K/AKT signaling pathway remain unclear. Methods: EdU staining, wound healing, Transwell assay, and flow cytometry were performed to measure cell proliferation, migration, invasion, and apoptosis. GEPIA and TCGA data bases were applied to analyze the relationship between GDF15 and prognosis. Results: We found that high expression of GDF15 suggested lower survival of melanoma patients, and is positively linked with advanced stage through analysis with GEPIA and TCGA data bases. Knockdown of GDF15 greatly inhibited the migration, invasion and proliferation ability of both M14 and M21 cells, but promoted cell apoptosis. However, the influence of GDF15 on M14 and M21 cells were reversed by 740Y-P, the activator of PTEN/PI3K/AKT signaling pathway. In addition, 740Y-P significantly reversed the influence of sh-GDF15 on the epithelial-mesenchymal transition (EMT) related proteins expression in M14 and M21 cell lines. Significant higher expression of GDF15 in melanoma was observed. In addition, the inhibition of PTEN/PI3K/AKT signaling pathway by knocking down GDF15 was observed in both M14 and M21 cell lines. sh-GDF15 greatly decreased the resistance of M14 and M21 to chemotherapy drugs, docetaxel and doxorubicin. Conclusions: GDF15 regulated the cell proliferation, apoptosis, migration, invasion, and EMT process of M14 and M21 cell lines through targeting PTEN/PI3K/AKT signaling pathway. This research provides a novel prevention and treatment strategy for melanoma.

4.
Sensors (Basel) ; 23(20)2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37896583

ABSTRACT

The high correlation between rolling bearing composite faults and single fault samples is prone to misclassification. Therefore, this paper proposes a rolling bearing composite fault diagnosis method based on a deep graph convolutional network. First, the acquired raw vibration signals are pre-processed and divided into sub-samples. Secondly, a number of sub-samples in different health states are constructed as graph-structured data, divided into a training set and a test set. Finally, the training set is used as input to a deep graph convolutional neural network (DGCN) model, which is trained to determine the optimal structure and parameters of the network. A test set verifies the feasibility and effectiveness of the network. The experimental result shows that the DGCN can effectively identify compound faults in rolling bearings, which provides a new approach for the identification of compound faults in bearings.

5.
J Affect Disord ; 342: 33-44, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37689313

ABSTRACT

BACKGROUND: Evidence about effective psychoeducational interventions to improve prenatal attachment, anxiety and depression has been increasing, but it lacks a complete synthesis of the results. The aim of this study is to evaluate the effect of psychoeducational intervention on prenatal attachment and anxiety/depression in pregnant women and their partners. METHODS: Ten databases were systematically searched to identify randomized controlled trials (RCTs) on the effectiveness of psychoeducational interventions on prenatal attachment from inception to March 2023, then manually screened to include studies of anxiety or depression. Two researchers assessed the methodological quality of the included studies using the Cochrane risk-of-bias tool and meta-analysis was performed using RevMan 5.4 software. RESULTS: Ten RCTs with a total of 700 pregnant women and 399 partners were included. Prenatal attachment scores after the intervention (standardized mean difference = 1.10, 95 % CI 0.65 to 1.55, P <.00001) was significantly increased and anxiety scores (standardized mean difference = -0.99, 95 % CI -1.18 to -0.80, P <.00001) was significantly lower. The subgroup analysis showed that the different prenatal attachment assessment tools were the source of heterogeneity in the combined results. The sensitivity analysis results showed reliable pooled results except for the studies using the self-made anxiety scale. CONCLUSION: This review suggests that psychoeducational interventions can effectively enhance prenatal attachment, reduce anxiety and depression, providing reference for the promotion of evidence-based practice of psychoeducational interventions in perinatal pregnant women and their partners.


Subject(s)
Depression , Pregnant Women , Pregnancy , Female , Humans , Depression/therapy , Anxiety/therapy , Parturition , Anxiety Disorders
6.
J Inorg Biochem ; 246: 112284, 2023 09.
Article in English | MEDLINE | ID: mdl-37327592

ABSTRACT

Six terpyridine ligands(L1-L6) with chlorophenol or bromophenol moiety were obtained to prepare metal terpyridine derivatives complexes: [Ru(L1)(DMSO)Cl2] (1), [Ru(L2)(DMSO)Cl2] (2), [Ru(L3)(DMSO)Cl2] (3), [Cu(L4)Br2]·DMSO (4), Cu(L5)Br2 (5), and [Cu(L6)Br2]⋅CH3OH (6). The complexes were fully characterized. Ru complexes 1-3 showed low cytotoxicity against the tested cell lines. Cu complexes 4-6 exhibited higher cytotoxicity against several tested cancer cell lines compared to their ligands and cisplatin, and lower toxicity towards normal human cells. Copper(II) complexes 4-6 arrested T-24 cell cycle in G1 phase. The mechanism studies indicated that complexes 4-6 accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential, increase of the intracellular ROS levels and the release of Ca2+, and the activation of the Caspase cascade, finally inducing apoptosis. Animal studies showed that complex 6 obviously inhibited the tumor growth in a mouse xenograft model bearing T-24 tumor cells without significant toxicity.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Neoplasms , Animals , Mice , Humans , Antineoplastic Agents/pharmacology , Copper/pharmacology , Dimethyl Sulfoxide/pharmacology , Ligands , Coordination Complexes/pharmacology , Apoptosis , Drug Screening Assays, Antitumor , Cell Line, Tumor
7.
Arch Womens Ment Health ; 26(4): 423-439, 2023 08.
Article in English | MEDLINE | ID: mdl-37231116

ABSTRACT

Digital psychological interventions have been widely used clinically in recent years, but the methodological quality and quality of evidence of related studies are unclear, thus interfering with the translation of practice outcomes and the application of clinical decisions. We searched for meta-analyses of randomized controlled trials in the PubMed, Web of Science, Embase, Cochrane Library, JBI Database, CINAHL, and PsycINFO databases as well as some databases containing gray literature up to 27 April 2022 using a combination of keywords. After two researchers independently screened and extracted data from the literature, the methodological quality of the included literature was evaluated by the AMSTAR 2 scale, and the evidence quality of the outcome index was graded by the Grading of Recommendations, Assessment, Development, and Evaluation system. A total of 12 meta-analyses reporting the positive impact of digital psychological interventions in the prevention and/or treatment of depressive symptoms in perinatal women were included, but the methodological quality and evidence level of the included studies were low. Digital psychological interventions are effective in reducing perinatal depression, but the methodological quality and reliability of outcome indicators are mostly low. Improving study designs, using higher-quality clinical evidence, conducting systematic evaluation studies strictly following the procedures, and standardizing the reporting of study results are recommended.


Subject(s)
Depression , Depressive Disorder , Pregnancy , Humans , Female , Depression/therapy , Psychosocial Intervention , Reproducibility of Results
8.
Immunopharmacol Immunotoxicol ; 45(3): 328-333, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36326098

ABSTRACT

BACKGROUND: Psoriasis is a prevalent chronic inflammatory dermatosis, which can significantly impact life quality of patients. The treatment of psoriasis is no cure and novel therapeutic options are urgently needed. Hydroxytyrosol (HT) possesses multiple biological activities, such as anti-inflammatory and anti-proliferation properties, suggesting its potential to counteract hallmarks of psoriasis. However, its role in the regulation of psoriasis remains unknown. OBJECTIVE: In the current study, we explored the anti-proliferative activity and anti-inflammatory responses of HT in psoriatic keratinocytes in vitro. METHODS: We used M5 cytokines cocktail, which includes tumor necrosis factor (TNF)-α, oncostatin-M, interleukin (IL)-17A, IL-1α, and IL-22, to simulate HaCaT cells to establish the cell model of psoriasis and explore the effects of HT on psoriasis in vitro. RESULTS: This study showed that HT exerted potent anti-inflammatory effect via influencing the expression of IL-6, IL-8, and TNF-α in M5-induced cell model of psoriasis. Moreover, it suppressed the expression of antimicrobial proteins in psoriatic keratinocytes. Additionally, it inhibited cell proliferation in psoriasis cell model. CONCLUSIONS: Altogether, our results suggested that HT has anti-psoriasis effects in vitro and HT may be a promising therapeutic agent in psoriasis treatment.


Subject(s)
HaCaT Cells , Psoriasis , Humans , HaCaT Cells/metabolism , HaCaT Cells/pathology , Cell Line , Psoriasis/drug therapy , Keratinocytes , Inflammation/pathology , Tumor Necrosis Factor-alpha/metabolism , Anti-Inflammatory Agents/therapeutic use , Cell Proliferation
9.
J Inorg Biochem ; 240: 112093, 2023 03.
Article in English | MEDLINE | ID: mdl-36525715

ABSTRACT

Three new synthetic terpyridine copper(II) complexes were characterized. The copper(II) complexes induced apoptosis of three cancer cell lines and arrested T-24 cell cycle in G1 phase. The complexes were accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential. The complexes increased both intracellular ROS and Ca2+ levels and activated the caspase-3/9 expression. The apoptosis was further confirmed by Western Blotting analysis. Bcl-2 was down-regulated and Bax was upregulated after treatment with complexes 1-3. The in vivo studies showed that complexes 1-3 obviously inhibited the growth of tumor without significant toxicity to other organs.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Cell Line , Cell Line, Tumor , Coordination Complexes/pharmacology , Coordination Complexes/therapeutic use , Copper/pharmacology , Copper/therapeutic use , Ligands , Neoplasms/drug therapy
10.
J Oncol ; 2022: 9412050, 2022.
Article in English | MEDLINE | ID: mdl-35847367

ABSTRACT

Objective: To evaluate the efficacy and satisfaction of rapid rehabilitation nursing in patients with laparoscopic myomectomy. Methods: In this retrospective study, a total of 60 patients scheduled for a laparoscopic myomectomy in our hospital from January 2019 to February 2022 were enrolled and assigned at a ratio of 1 : 1 to receive either routine nursing (routine group) or rapid rehabilitation nursing (study group) according to different nursing methods. Outcome measures included nursing efficiency and nursing satisfaction. Results: Rapid rehabilitation nursing resulted in less intraoperative blood loss, shorter postoperative exhaust time and hospital stay, and a lower incidence of bladder irritation (123.56 ± 30.68, 22.54 ± 5.07, 5.70 ± 1.06, and 4.55%) versus the routine nursing (185.78 ± 32.78, 31.02 ± 5.28, 7.57 ± 2.19, 18.18%) (P < 0.05). Rapid rehabilitation nursing was associated with a lower incidence of complications (3.33%) versus routine nursing (20.00%) (P < 0.05). The eligible patients receiving rapid rehabilitation nursing showed a significantly higher satisfaction (96.67%) versus routine nursing (80.00%) (P < 0.05). Conclusion: Rapid rehabilitation nursing is effective in the nursing of patients after laparoscopic myomectomy by minimizing the physical and mental stress of patients, shortening the length of hospital stay, reducing the occurrence of related complications, and boosting the quality of life of patients, so it is worthy of clinical application.

11.
J Cell Physiol ; 237(1): 1044-1056, 2022 01.
Article in English | MEDLINE | ID: mdl-34553380

ABSTRACT

Kynureninase (KYNU) is a key enzyme in the tryptophan metabolism pathway with elevated expression in psoriatic lesions relative to normal skin. However, whether KYNU contributes to the pathogenesis of psoriasis remains unknown. We sought to investigate the role of KYNU in psoriasis and its possible regulation mechanism. In the results, KYNU is upregulated in psoriatic skin samples from patients or animal models compared with normal skin control which was assayed in psoriatic patient samples, IMQ-induced psoriasis-like skin inflammation in BABL/c mice and M5-stimulated keratinocyte cell lines by immunohistochemistry (IHC). KYNU knockdown had a trivial impact on keratinocyte proliferation, but significantly inhibited the production of inflammatory cytokines in HaCaT, HEKα, and HEKn cells by quantitative reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot analysis. The 3'-untranslated region of KYNU contains a conserved target site of a skin-specific microRNA (miRNA), miR-203a, as predicted by TargetScan software. Furthermore, miR-203a exhibited an inversed expression kinetics to KYNU during the development of IMQ-induced psoriasis-like skin inflammation in BABL/c mice. Overexpression of miR-203 subsequently leading to the inhibition of KYNU, could significantly reduce the production of M5-induced, psoriasis-related inflammatory factors in keratinocytes. Finally, KYNU inhibitors could alleviate the pathological phenotypes in IMQ-mice. Our study supported the contributive role of KYNU in the development of psoriasis and provided preliminary evidence for KYNU as a potential therapeutic target in psoriasis.


Subject(s)
MicroRNAs , Psoriasis , Animals , Cell Proliferation/genetics , Humans , Hydrolases , Imiquimod/adverse effects , Inflammation/metabolism , Keratinocytes/metabolism , Mice , MicroRNAs/metabolism , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/genetics , Skin/metabolism
12.
Small Methods ; 5(3): e2001055, 2021 03.
Article in English | MEDLINE | ID: mdl-34927837

ABSTRACT

In this paper, three configurations of LC (inductor-capacitor) pressure sensors are developed, namely series LC pressure sensors, compact LC pressure sensors, and far-field LC pressure sensor tags. The modified silk protein films have been chosen as substrates due to their good biocompatibility and air/water permeability, which is suitable for continuously pasting such substrates on skin. For series LC pressure sensors, conducting wire is used to connect the flexible capacitor and spiral inductor. It exhibits good cycling stability and high sensitivities, suitable for electronic skin. For compact LC pressure sensors, the spiral coil functions as inductor, antenna, and capacitor electrode simultaneously, minimizing the space cost and is suitable for array integration, while the sensitivities remain the same. By tailoring the turn of the spiral coil, the resonate frequency can be regulated continuously. An annular array of compact LC sensors with ten distinct resonate frequencies ranged from 400 to 1000 MHz is developed to remotely monitor the press of number 0-9. Finally, far-field LC pressure sensor tags with elongated detection distances are developed in which each compact LC sensor acts as a filter. A wireless in-shoe plantar to detect the sole pressure distribution using the far-field LC sensor configuration is developed.


Subject(s)
Wearable Electronic Devices , Wireless Technology , Monitoring, Physiologic , Silk , Skin
13.
Nanotechnology ; 32(6): 065502, 2021 Feb 05.
Article in English | MEDLINE | ID: mdl-33086215

ABSTRACT

Catalytic and electrocatalytic applications of supported metal nanoparticles are hindered due to an aggregation of metal nanoparticles and catalytic leaching under harsh operations. Hence, stable and leaching free catalysts with high surface area are extremely desirable but also challenging. Here we report a gold nanoparticles-hosted mesoporous nitrogen doped carbon matrix, which is prepared using bovine serum albumin (BSA) through calcination. BSA plays three roles in this process as a reducing agent, capping agent and carbon precursor, hence the protocol exhibits economic and sustainable. Gold nanoparticles at N-doped BSA carbon (AuNPs@NBSAC)-modified three-electrode strip-based flexible sensor system has been developed, which displayed effective, sensitive and selective for simultaneous detection of uric acid (UA) and dopamine (DA). The AuNPs@NBSAC-modified sensor showed an excellent response toward DA with a linear response throughout the concentration range from 1 to 50 µM and a detection limit of 0.05 µM. It also exhibited an excellent response toward UA, with a wide detection range from 5 to 200 µM as well as a detection limit of 0.1 µM. The findings suggest that the AuNPs@NBSAC nanohybrid reveals promising applications and can be considered as potential electrode materials for development of electrochemical biosensors.

14.
J Cell Biochem ; 121(11): 4580-4589, 2020 11.
Article in English | MEDLINE | ID: mdl-32065443

ABSTRACT

Long non-coding RNAs (LncRNAs) play essential roles in the development of various diseases including hepatic carcinoma, melanoma, and psoriasis. Meanwhile, lncRNA-RP6-65G23.1 was upregulated in psoriasis. However, it is still unclear whether lncRNA-RP6-65G23.1 expression is upregulated and contributes to keratinocytes proliferation and apoptosis, and which mechanisms are responsible for these processes. The aims of this study are to address these issues. RP6-65G23.1 was significantly upregulated in M5-stimulated keratinocytes and stimulated the proliferation and inhibited the apoptosis of HaCaT cells. Knockdown of RP6-65G23.1 resulted in defects of growth and increased rates of apoptosis in HaCaT cells, while overexpression of RP6-65G23.1 manifested the opposite effects. Consistently, the expression of antiapoptotic proteins Bcl-xl and Bcl2 were decreased in RP6-65G23.1-knockdown cells but elevated in RP6-65G23.1 overexpression cells. In addition, RP6-65G23.1 depletion blunted the activity of extracellular regulated kinase 1/2 (ERK1/2) and AKT signaling pathways and induced G1 /S-growth arrest. By contrast, overexpression of RP6-65G23.1 activates the ERK1/2 and AKT signaling pathways and inhibits the expression of p21 and p27 in an AKT-dependent manner leading to promote the G1/S progression. Our results suggested that lncRNA-RP6-65G23.1 would contribute to the pathogenesis of psoriasis by regulating the proliferation and apoptosis of keratinocytes via the p-ERK1/2 and p-AKT pathways.


Subject(s)
Gene Expression Regulation , Keratinocytes/pathology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Psoriasis/pathology , RNA, Long Noncoding/genetics , Apoptosis , Cell Proliferation , Cells, Cultured , Humans , Keratinocytes/metabolism , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 3/genetics , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Psoriasis/genetics , Psoriasis/metabolism
15.
Trials ; 20(1): 66, 2019 Jan 18.
Article in English | MEDLINE | ID: mdl-30658660

ABSTRACT

BACKGROUND: People with allergic rhinitis (AR) often seek help from Chinese medicine due to dissatisfaction with conventional treatments. Lung-spleen qi deficiency syndrome (LSQDS) is the most common type of AR, and the Chinese herbal medicine formula bi min fang (BMF) is commonly prescribed for AR patients with LSQDS. However, direct evidence supporting its efficacy and safety is not available, and its potential mechanism of action remains unclear. METHODS/DESIGN: This paper presents a double-blind, double-dummy, randomized controlled trial. After a 2-week run-in period, 80 AR patients with LSQDS will be recruited and randomly allocated to the BMF group or the control group in a 1:1 ratio. The patients in the BMF group will receive BMF and the placebo for levocetirizine hydrochloride orally, while the control group participants will receive levocetirizine hydrochloride and the placebo for BMF orally. All participants will receive 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is a change in the Total Nasal Symptom Score (TNSS). Secondary outcomes include changes in scores for the standard version of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), and visual analog scale (VAS); changes in serum levels of the cytokines interleukin-4, interferon-γ, transforming growth factor ß-1, and interleukin-17; and changes in the gut microbiota composition in the stool. The TNSS, RQLQ(S), and VAS will be recorded at the beginning of, middle of and after the treatment period and at the end of each month in the 3-month follow-up period. Blood and stool samples will be collected at baseline and the end of the treatment. The aforementioned four cytokines will be detected in the serum using enzyme-linked immunosorbent assays, and the stool gut microbiota will be detected using 16S ribosomal ribonucleic acid sequencing. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide consolidated evidence of the effect of BMF on AR and the potential mechanism by which BMF acts. This study will be the first to explore the mechanism of action of Chinese herbal medicine on the gut microbiota in AR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-17010970 . Registered on 23 March 2017.


Subject(s)
Anti-Allergic Agents/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Rhinitis, Allergic/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Anti-Allergic Agents/adverse effects , China , Cytokines/blood , Double-Blind Method , Drug Administration Schedule , Drugs, Chinese Herbal/adverse effects , Female , Gastrointestinal Microbiome/drug effects , Humans , Male , Middle Aged , Quality of Life , Randomized Controlled Trials as Topic , Rhinitis, Allergic/blood , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/microbiology , Time Factors , Treatment Outcome , Young Adult
16.
J Invest Dermatol ; 139(1): 71-80, 2019 01.
Article in English | MEDLINE | ID: mdl-30009832

ABSTRACT

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. CRNN is a major component of the cornified cell envelope and implicated in several epithelial malignancies. Here, we show that CRNN expression was increased in the lesioned epidermis from the patients with psoriasis vulgaris and skin lesions from the imiquimod (IMQ)-treated mice. Expression of CRNN in cultured keratinocytes (HEKa and HaCaT) was also induced by M5, a mixture of five pro-inflammatory cytokines (i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α). Lentiviral expression of CRNN increased cell proliferation by inducing cyclin D1. Conversely, knockdown of CRNN by small interfering RNA suppressed G1/S transition and attenuated the M5-induced proliferation. In addition, CRNN overexpression increased the phosphorylation and activation of phosphoinositide 3-kinase and Akt. Inactivation of the phosphoinositide 3-kinase and Akt pathways using small interfering RNA or selective inhibitors (LY294002 and MK2206) reduced the proliferative effects of CRNN. Furthermore, topical use of anti-psoriatic calcipotriol effectively decreased expression of CRNN, inhibited the Akt activation and improved the IMQ-stimulated psoriasis-like pathologies. Taken together, these results suggest that induced expression of CRNN may contribute to the pathogenesis of psoriasis.


Subject(s)
Gene Expression Regulation , Membrane Proteins/genetics , Neoplasm Proteins/genetics , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Psoriasis/genetics , RNA/genetics , Skin/physiopathology , Animals , Blotting, Western , Cell Proliferation , Cells, Cultured , Cytokines/metabolism , Disease Models, Animal , Humans , Imiquimod/toxicity , Keratinocytes/metabolism , Keratinocytes/pathology , Membrane Proteins/biosynthesis , Mice , Mice, Inbred BALB C , Neoplasm Proteins/biosynthesis , Psoriasis/metabolism , Psoriasis/pathology , Signal Transduction , Skin/metabolism
17.
Sci Rep ; 8(1): 8590, 2018 06 05.
Article in English | MEDLINE | ID: mdl-29872130

ABSTRACT

Psoriasis is a chronic, relapsing inflammatory skin disease. The pathogenesis of psoriasis is complex and has not been fully understood. C10orf99 was a recently identified human antimicrobial peptide whose mRNA expression is elevated in psoriatic human skin samples. In this study, we investigated the functional roles of C10orf99 in epidermal proliferation under inflammatory condition. We showed that C10orf99 protein was significantly up-regulated in psoriatic skin samples from patients and the ortholog gene expression levels were up-regulated in imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Using M5-stimulated HaCaT cell line model of inflammation and a combinational approach of knockdown and overexpression of C10orf99, we demonstrated that C10orf99 could promote keratinocyte proliferation by facilitating the G1/S transition, and the pro-proliferation effect of C10orf99 was associated with the activation of the ERK1/2 and NF-κB but not the AKT pathways. Local depletion of C10orf99 by lentiviral vectors expressing C10orf99 shRNA effectively ameliorated IMQ-induced dermatitis. Taken together, these results indicate that C10orf99 plays a contributive role in psoriasis pathogenesis and may serve as a new target for psoriasis treatment.


Subject(s)
Antimicrobial Cationic Peptides/genetics , Cell Proliferation/genetics , DNA-Binding Proteins/genetics , Keratinocytes/metabolism , Psoriasis/genetics , Skin/metabolism , Adolescent , Adult , Animals , Antimicrobial Cationic Peptides/metabolism , Cell Line , Cell Proliferation/drug effects , Child , DNA-Binding Proteins/metabolism , Disease Models, Animal , Female , G1 Phase Cell Cycle Checkpoints/drug effects , G1 Phase Cell Cycle Checkpoints/genetics , Gene Expression/drug effects , Humans , Imiquimod/pharmacology , Keratinocytes/drug effects , Keratinocytes/pathology , Male , Mice, Inbred BALB C , Middle Aged , Psoriasis/metabolism , RNA Interference , Signal Transduction/drug effects , Signal Transduction/genetics , Skin/drug effects , Skin/pathology , Young Adult
18.
Exp Ther Med ; 14(1): 499-506, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28672959

ABSTRACT

Antimicrobial peptide LL-37 serves a function in the host defense against microbial invasion, and also regulates cell proliferation, immune activity and angiogenesis. Previous studies have reported that LL-37 participates in the development of numerous tumour types, such as ovarian cancer, lung cancer, melanoma and breast cancer. However, the function of LL-37 in the development of skin squamous cell carcinoma (SCC) has not yet been fully elucidated. The aim of the current study was to investigate how LL-37 promotes the expression of Y-box binding protein 1 (YB-1) in SCC. Short interfering RNA (siRNA) was used to inhibit the expression of YB-1, and in vitro MTT and Transwell migration assays were used to evaluate the effect of reduced YB-1 on the viability and invasion of A431 cells. A431 cells were stimulated with LL-37, and quantitative polymerase chain reaction, immunofluorescence and western blot analyses were used to detect changes in YB-1 expression. Mitogen-activated protein kinase kinase, mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathway inhibitors were also used to evaluate the mechanism of LL-37-induced YB-1 protein expression. It was found that YB-1 expression was increased in SCC tissue compared with normal tissue. Inhibiting YB-1 expression using siRNA significantly reduced the viability and suppressed the invasion of tumour cells (P<0.05 for both). LL-37 treatment at 0.05 µg/ml for 24 or 48 h significantly promoted YB-1 protein expression (P<0.05), and this was dependent on the NF-κB signaling pathway. In conclusion, the current study demonstrated that by upregulating the expression of YB-1, LL-37 can promote the occurrence and development of SCC, and this process involves the NF-κB signaling pathway.

19.
Oncol Lett ; 12(3): 1745-1752, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27588122

ABSTRACT

The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-κB inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-κB signalling pathway.

20.
Int J Clin Exp Pathol ; 8(7): 8367-75, 2015.
Article in English | MEDLINE | ID: mdl-26339406

ABSTRACT

PURPOSE: The aim of this study was to identify the correlations of IFN-γ-inducible protein-10 (IP-10) with the risk of chronic hepatitis B (CHB) and the efficacy of interferon therapy in Asians. METHOD: Serum IP-10 levels were assayed using enzyme linked immunosorbent assay (ELISA) in both CHB and control group. CHB group received interferon-α2b treatment to compare the pre-treatment and post-treatment serum IP-10 levels. Relevant studies met predefined inclusion and exclusion criteria were enrolled into further meta-analysis. Stata 12.0 software was applied for data analysis. RESULT: Our case-control study demonstrated that CHB group had evaluated serum IP-10 levels compared with control group (285.7 ± 41.6 pg/mL vs. 79.1 ± 33.8 pg/mL, t = 21.85, P < 0.001. After treatment for 12 weeks, CHB group had remarkably decreased post-treatment serum IP-10 levels than pre-treatment (78.5 ± 20.4 pg/mL vs. 285.7 ± 41.6 pg/mL, t = 33.76, P < 0.001). No significance was observed on post-treatment serum IP-10 levels between CHB and control group (78.5 ± 20.4 pg/mL vs. 78.1 ± 33.8 pg/mL, t = 0.07, P = 0.947). Meta-analysis results demonstrated that serum IP-10 levels in CHB group were obviously higher than healthy controls (SMD = 2.21, 95% CI = 1.55~2.87, P < 0.001). A subgroup based on the HBeAg states revealed that serum IP-10 levels in both HBeAg-positive and HBeAg-negative CHB patients were notably higher than healthy controls (HBeAg-positive: SMD = 2.00, 95% CI = 1.13-2.87, P < 0.001; HBeAg-negative: SMD = 1.34, 95% CI = 0.97-1.72, P < 0.001). CONCLUSION: Serum IP-10 may be correlated with the risk of CHB and the efficiency of interferon therapy, thus IP-10 may be a good biomarker for the diagnosis and treatment of CHB.


Subject(s)
Antiviral Agents/therapeutic use , Asian People , Chemokine CXCL10/blood , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Adult , Biomarkers/blood , Case-Control Studies , China , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/ethnology , Humans , Interferon alpha-2 , Male , Middle Aged , Recombinant Proteins/therapeutic use , Time Factors , Treatment Outcome
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