ABSTRACT
It is a crucial role for enhancing the power conversion efficiency (PCE) of perovskite solar cells (PSCs) to prepare high-quality perovskite films, which can be achieved by delaying the crystallization of perovskite film. Hence, we designed difluoroacetic anhydride (DFA) as an additive to regulating crystallization process thus reducing defect formation during perovskite film formation. It was found DFA reacts with DMSO by forming two molecules, difluoroacetate thioether ester (DTE) and difluoroacetic acid (DA). The strong bonding DTEâ PbI2 and DAâ PbI2 retard perovskite crystallization process for high-quality film formation, which was monitored through in situ UV/Vis and PL tests. By using DFA additives, we prepared perovskite films with high-quality and low defects. Finally, a champion PCE of 25.28 % was achieved with excellent environmental stability, which retained 95.75 % of the initial PCE after 1152â h at 25 °C under 25 % RH.
ABSTRACT
BACKGROUND: Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5-10% of all cases of acute respiratory illnesses and 4-15% of pneumonia cases in children younger than five years old. Without treatment, severe ADV pneumonia could result in fatality rates of over 50% in cases of emerging strains or disseminated disease. This study aims to uncover the relationship of clinical indicators with primary ADV infection severity, regarding duration of hospitalization and liver injury. METHODS: In this retrospective study, we collected and analyzed the medical records of 1151 in-patients who met the inclusion and exclusion criteria. According to duration of hospitalization, all patients were divided into three groups. Then the difference and correlation of clinical indicators with ADV infection were analyzed, and the relationship among liver injury, immune cells and cytokines was evaluated. RESULTS: The study revealed that patients with a duration of hospitalization exceeding 14 days had the highest percentage of abnormalities across most indicators. This was in contrast to the patients with a hospitalization duration of either less than or equal to 7 days or between 7 and 14 days. Furthermore, correlation analysis indicated that a longer duration of body temperature of ≥ 39°C, bilateral lung lobes infiltration detected by X ray, abnormal levels of AST, PaO2, and SPO2, and a lower age were all predictive of longer hospital stays. Furthermore, an elevated AST level and reduced liver synthesis capacity were related with a longer hospital stay and higher ADV copy number. Additionally, AST/ALT was correlated positively with IFN-γ level and IFN-γ level was only correlated positively with CD4+ T cells. CONCLUSIONS: The study provided a set of predicting indicators for longer duration of hospitalization, which responded for primary severe ADV infection, and elucidated the possible reason for prolonged duration of hospitalization attributing to liver injury via higher ADV copy number, IFN-γ and CD4+ T cells, which suggested the importance of IFN-γ level and liver function monitoring for the patients with primary severe ADV infection.
Subject(s)
Length of Stay , Humans , Male , Female , Retrospective Studies , Child, Preschool , Infant , Length of Stay/statistics & numerical data , Severity of Illness Index , Hospitalization/statistics & numerical data , Adenovirus Infections, Human/virology , Child , Liver/pathology , Liver/virology , Adenoviridae InfectionsABSTRACT
Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.
Subject(s)
Body Temperature , Nociception , TRPV Cation Channels , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Animals , Mice , Allosteric Regulation/drug effects , Nociception/drug effects , Nociception/physiology , Body Temperature/drug effects , Analgesics/pharmacology , Male , Humans , Mice, Inbred C57BL , Mice, Knockout , Pain/metabolism , Pain/drug therapyABSTRACT
The physical blending of high-mobility conjugated polymers with ductile elastomers provides a simple way to realize high-performance stretchable films. However, how to control the morphology of the conjugated polymer and elastomer blend film and its response to mechanical fracture processes during stretching are not well understood. Herein, a sandwich structure is constructed in the blend film based on a conjugated polymer poly[(5-fluoro-2,1,3-benzothiadiazole-4,7-diyl)(4,4-dihexadecyl-4H-cyclopenta[2,1-b:3,4-bâ³]dithiophene-2,6-diyl)(6-fluoro-2,1,3-benzothiadiazole-4,7-diyl)(4,4-dihexadecyl-4H-cyclopenta[2,1-b:3,4-bâ³]dithiophene-2,6-diyl)] (PCDTFBT) and an elastomer polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS). The sandwich structure is composed of a PCDTFBT:SEBS mixed layer laminated with a PCDTFBT-rich layer at both the top and bottom surfaces. During stretching, the external strain energy can be effectively dissipated by the deformation of the crystalline PCDTFBT domains and amorphous SEBS phases and the recrystallization of the PCDTFBT chains. This endows the blend film with excellent ductility, with a large crack onset strain exceeding 1100%, and minimized the electrical degradation of the blend film at a large strain. This study indicates that the electrical and mechanical performance of conjugated polymer/elastomer blend films can be improved by manipulating their microstructure.
Subject(s)
Polymers , Thiadiazoles , Elastomers/chemistry , Polymers/chemistry , Polystyrenes , Thiadiazoles/chemistry , Thiophenes/chemistryABSTRACT
Conjugated polymer films are promising in wearable X-ray detection. However, achieving optimal film microstructure possessing good electrical and detection performance under large deformation via scalable printing remains challenging. Herein, we report bar-coated high-performance stretchable films based on a conjugated polymer P(TDPP-Se) and elastomer SEBS blend by optimizing the solution-processing conditions. The moderate preaggregation in solution and prolonged growth dynamics from a solvent mixture with limited dissolving capacity is critical to forming aligned P(TDPP-Se) chains/crystalline nanofibers in the SEBS phase with enhanced π-π stacking for charge transport and stress dissipation. The film shows a large elongation at break of >400% and high mobilities of 5.29 cm2 V-1 s-1 at 0% strain and 1.66 cm2 V-1 s-1 over 500 stretch-release cycles at 50% strain, enabling good X-ray imaging with a high sensitivity of 1501.52 µC Gyair-1 cm-2. Our work provides a morphology control strategy toward high-performance conjugated polymer film-based stretchable electronics.
ABSTRACT
Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr01&hk01 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.
Subject(s)
Intracellular Signaling Peptides and Proteins , Pneumococcal Infections , Streptococcus pneumoniae , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/pathogenicity , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , A549 Cells , Humans , Pneumococcal Infections/metabolism , Pneumococcal Infections/microbiology , Bacterial AdhesionABSTRACT
BACKGROUND: Psoriasis (PsO) is a T-cell-associated inflammatory autoimmune dermatitis. Leucine leucine-37 (LL-37) is upregulated in PsO patients and correlated with the area and severity of PsO. However, the exact relation between LL-37 and T cell-associated inflammation is not well understood. It is very important to clarify the relationship between LL-37 and inflammatory response for clinical diagnosis and treatment of PsO. This study investigated the serum levels of LL-37 and inflammatory cytokines, as well as correlations between them in PsO patients, which aimed to provide new ideas for the diagnosis and treatment of PsO. METHODS: PsO patients (n = 50) and healthy volunteers (n = 33) were recruited in this study. Skin specimens were stained with hematoxylin and eosin (H&E). The serum levels of LL-37, T-helper type 1 (Th1, IFN-γ), T-helper type 17 (Th17, IL-17), T-helper type 22 (Th22, IL-22), and T-helper type 2 cytokines (Th2, IL-4) were assessed by enzyme-linked immunosorbent assay. Some of the patients were re-recruited after treatment to evaluate LL-37 and cytokines levels. RESULTS: Pathological changes were observed in PsO skin lesions. LL-37, IFN-γ, IL-17, and IL-22 serum levels were much higher in PsO patients than those in healthy volunteers (p < .001), and posttreatment reduction was observed in five patients. However, no remarkable difference in IL-4 level (p > .05) was found. LL-37 level was positively correlated with IFN-γ, IL-17, and IL-22 levels (p < .001) in PsO patients. CONCLUSION: LL-37 expression was significantly associated with inflammatory response, which may provide us new ideas for diagnosing and monitoring disease activity of PsO.
Subject(s)
Cytokines , Psoriasis , Humans , Cytokines/metabolism , Interleukin-17 , Leucine , Interleukin-4 , Psoriasis/diagnosisABSTRACT
With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.
Subject(s)
Drugs, Chinese Herbal , Rats , Animals , Drugs, Chinese Herbal/pharmacology , Rats, Sprague-Dawley , Serotonin , Metabolomics , WaterABSTRACT
OBJECTIVES: To investigate the potential of dual-energy computed tomography (DECT) parameters in identifying metastatic cervical lymph nodes in oral squamous cell carcinoma (OSCC) patients and to explore the relationships between DECT and pathological features. METHODS: Clinical and DECT data were collected from patients who underwent radical resection of OSCC and cervical lymph node dissection between November 2019 and June 2021. Microvascular density was assessed using the Weidner counting method. The electron density (ED) and effective atomic number (Zeff) in non - contrast phase and iodine concentration (IC), normalized IC, slope of the energy spectrum curve (λHU), and dual-energy index (DEI) in parenchymal phase were compared between metastatic and non - metastatic lymph nodes. Student's t-test, Pearson's rank correlation, and receiver operating characteristic curves were performed. RESULTS: The inclusion criteria were met in 399 lymph nodes from 103 patients. Metastatic nodes (n = 158) displayed significantly decreased ED, IC, normalized IC, λHU, and DEI values compared with non-metastatic nodes (n = 241) (all p < 0.01). Strong correlations were found between IC (r = 0.776), normalized IC (r = 0.779), λHU (r = 0.738), DEI (r = 0.734), and microvascular density. Area under the curve (AUC) for normalized IC performed the highest (0.875) in diagnosing metastatic nodes. When combined with the width of nodes, AUC increased to 0.918. CONCLUSION: DECT parameters IC, normalized IC, λHU, and DEI reflect pathologic changes in lymph nodes to a certain extent, and aid for detection of metastatic cervical lymph nodes from OSCC. KEY POINTS: ⢠Electron density, iodine concentration, normalized iodine concentration, λHU, and dual-energy index values showed significant differences between metastatic and non-metastatic nodes. ⢠Strong correlations were found between iodine concentration, normalized iodine concentration, slope of the spectral Hounsfield unit curve, dual-energy index, and microvascular density. ⢠DECT qualitative parameters reflect the pathologic changes in lymph nodes to a certain extent, and aid for the detection of metastatic cervical lymph nodes from oral squamous cell carcinoma.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Iodine , Mouth Neoplasms , Humans , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Tomography, X-Ray Computed/methods , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Head and Neck Neoplasms/pathology , Retrospective StudiesABSTRACT
OBJECTIVE: To evaluate the curative efficacy by comparing perioperative characteristics and 1.5-year observational outcomes in 1-segment lumbar spondylolisthesis between traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and optimized Endoscopic TLIF techniques. METHODS: The study was a single-center, randomized controlled trial comparing two different treatment approaches for 1-segment lumbar spondylolisthesis. 102 patients treated by MIS-TLIF (48 cases) or Endo-TLIF (54 cases) were included from March 2018 to April 2019. Perioperative parameters and clinical outcomes were evaluated. Degree of slip were measured, and fusion rates were determined at 18 months after surgery. RESULTS: The Endo-TLIF group had similar return to work time and rate. Blood loss, left bed time, analgesic ratio were significantly less in Endo-TLIF group. The Endo-TLIF group had a significantly longer operative time. Significant postoperative reduction in %slip was showed in both groups. The VAS and ODI improved significantly in both groups after surgery. Significant decreases in low-back pain in Endo-TLIF group were found at postoperative day 1 and 3 months. The fusion rate in the two groups was similar. CONCLUSION: Endo-TLIF surgery with a C-shaped working tube and a visualization system may be regarded as an efficient alternative surgery for 1-segment lumbar spondylolisthesis. It is a safe and minimally invasive way to perform this surgery and has shown satisfactory clinical outcomes. TRIAL REGISTRATION: ChiCTR1800015197, 13 March 2018. TRIAL REGISTRY: Chinese Clinical Trial Registry. Registered 13 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25865.
Subject(s)
Arthroscopy , Lumbar Vertebrae/surgery , Outcome Assessment, Health Care , Spinal Fusion , Spondylolisthesis/surgery , Aged , Arthroscopy/methods , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Spinal Fusion/instrumentation , Spinal Fusion/methodsABSTRACT
PURPOSE: The experience of cancer could lead to positive psychological changes following the struggle with diagnosis and treatment. Understanding post-traumatic growth and its influencing factors in women affected by gynecological cancer is essential to enhance their possibility of achieving positive changes. The purpose of this study was to describe the post-traumatic growth level and explore the influencing factors of post-traumatic growth in Chinese women diagnosed with gynecological cancer. METHOD: A cross-sectional survey with a convenience sampling method was employed to collect data using the Post-traumatic Growth Inventory (PTGI), Distress Disclosure Index (DDI), Medical Coping Modes Questionnaire (MCMQ), and Multidimensional Scale of Perceived Social Support (MSPSS). The questionnaires were administered to 344 participants recruited from two hospitals in Hefei City, the capital of Anhui Province in China, between March 2018 and March 2019. All statistical analyses were performed using nonparametric tests. The Mann-Whitney U Test was used to distinguish the intergroup differences. Correlations were evaluated with Spearman rank correlation coefficients. RESULTS: Total score for PTGI was 56.5 (range 48.0-68.0). The subscale with the highest centesimal score in the PTGI was appreciation of life and the lowest was spiritual change. The top five items with the highest scores of PTGI belonged to appreciating life, personal strength, and relating to others. Self-disclosure, confrontation, avoidance, acceptance-resignation, perceived social support, education level, cancer type and the place they lived had significant influence on post-traumatic growth. CONCLUSIONS: The findings indicate that women who have high levels of perceived social support, confrontation, avoidance, self-disclosure and education level tend to experience more post-traumatic growth, while, conversely, high levels of acceptance-resignation have a negative influence on promoting post-traumatic growth. These meaningful findings propose new perspectives for promoting post-traumatic growth in Chinese women diagnosed with gynecological cancer.
Subject(s)
Genital Neoplasms, Female/psychology , Posttraumatic Growth, Psychological , Adaptation, Psychological , Adult , Aged , China , Cross-Sectional Studies , Female , Genital Neoplasms, Female/diagnosis , Humans , Middle Aged , Self Disclosure , Social Support , Surveys and Questionnaires , Young AdultABSTRACT
In this paper, we propose a novel hyper-Laplacian regularized multiview subspace clustering with low-rank tensor constraint method, which is referred as HLR-MSCLRT. In the HLR-MSCLRT model, the subspace representation matrices of different views are stacked as a tensor, and then the high order correlations among data can be captured. To reduce the redundancy information of the learned subspace representations, a low-rank constraint is adopted to the constructed tensor. Since data in the real world often reside in multiple nonlinear subspaces, the HLR-MSCLRT model utilizes the hyper-Laplacian graph regularization to preserve the local geometry structure embedded in a high-dimensional ambient space. An efficient algorithm is also presented to solve the optimization problem of the HLR-MSCLRT model. The experimental results on some data sets show that the proposed HLR-MSCLRT model outperforms many state-of-the-art multi-view clustering approaches.
Subject(s)
Algorithms , Cluster Analysis , Pattern Recognition, Automated/methods , HumansABSTRACT
BACKGROUND: Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. METHODS: Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC-MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. RESULTS: Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC-MS identified the 14-3-3 ε/γ protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding. CONCLUSIONS: The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.
Subject(s)
Chemokine CXCL12/blood , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/diagnostic imaging , Absorptiometry, Photon , Aged , Aged, 80 and over , Bone Density , Collagen Type I/blood , Disability Evaluation , Female , Femur Neck/diagnostic imaging , Hip/diagnostic imaging , Humans , Middle Aged , Pain Measurement , Spinal Fractures/blood , Spinal Fractures/diagnostic imaging , Spine/diagnostic imaging , Tumor Necrosis Factor-alpha/bloodABSTRACT
Nickel (Ni) is a silver-white transition metal that is widely used in the production field due to its unique physical and chemical properties. As a toxicant, long-term exposure to Ni can cause rhinitis, pneumonia and other respiratory inflammation. In the present study, we investigated the effect of particles extracted from Ni-refining fumes on cell viability, inflammation-related proteins and mitochondrial damage in human lung epithelial Beas-2B cells. The cells were exposed to Ni-refining fume particles for 24â¯hâ¯at concentrations of 0, 6.25, 12.50 and 25.00⯵g/mL. The expression levels of the NACHT-LRR-PYD domains-containing protein 3 (NLRP3), caspase-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α protein in Beas-2B cells exposed to Ni-refining fume particles increased significantly. Downregulation of NLRP3 expression by siRNA decreased the content of IL-1ß. During activation of NLRP3, the mitochondrial membrane potential (MMP) decreased, the opening rate of mitochondrial permeability transition pore (MPTP) increased, and the content of reactive oxygen species (ROS) increased. Using lipopolysaccharide (LPS) intervention as the positive control group, N-acetylcysteine (NAC, an effective ROS remover) acted as an inhibitor. After NAC reduced the level of ROS, activation of the NLRP3 inflammasome was significantly inhibited. Ni-refining fumes caused significant cytotoxicity, inflammation and mitochondrial damage in Beas-2B cells. The present study thus provides experimental support for the hypothesis that Ni-refining fumes cause inflammation by inducing ROS production in Beas-2B cells.
Subject(s)
Mitochondria/drug effects , Mitochondria/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Nickel/toxicity , Reactive Oxygen Species/metabolism , Cell Line , Cytokines/metabolism , Dose-Response Relationship, Drug , Humans , Mitochondria/metabolism , Nickel/chemistryABSTRACT
Platelet counts have been reported to be closely related to distant metastasis of many malignant tumors. Our previous study showed that elevated peripheral blood platelet counts may be an adverse prognostic factor of anaplastic thyroid carcinoma (ATC) patients, indicating that platelets may promote ATC progression. In the present study, we aimed to identify the role of platelets in ATC cell invasion and migration and to explore the underlying mechanisms. We found that platelets can promote the invasive and migratory of ATC cells, which may be related to the interaction between activated platelet-secreted chemokine (C-C motif) ligand 3 (CCL3) and its receptor CCR5. The interaction was shown to induce the upregulation of matrix metalloproteinase (MMP)-1 via NF-κB pathway. These findings could provide a new idea for the research of targeted platelets to inhibit tumor metastasis.
Subject(s)
Blood Platelets/metabolism , Chemokine CCL3/metabolism , Matrix Metalloproteinase 1/metabolism , Receptors, CCR5/metabolism , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Neoplasms/metabolism , Blood Platelets/pathology , Cell Line, Tumor , Cell Movement , HEK293 Cells , Humans , NF-kappa B/metabolism , Platelet Activation , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/pathologyABSTRACT
Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, yet the global functions of H2Bub1 remain poorly understood. Ferroptosis is a form of non-apoptotic cell death characterized by the iron-dependent overproduction of lipid hydroperoxides, which can be inhibited by the antioxidant activity of the solute carrier family member 11 (SLC7A11/xCT), a component of the cystine/glutamate antiporter. Whether nuclear events participate in the regulation of ferroptosis is largely unknown. Here, we show that the levels of H2Bub1 are decreased during erastin-induced ferroptosis and that loss of H2Bub1 increases the cellular sensitivity to ferroptosis. H2Bub1 epigenetically activates the expression of SLC7A11. Additionally, we show that the tumor suppressor p53 negatively regulates H2Bub1 levels independently of p53's transcription factor activity by promoting the nuclear translocation of the deubiquitinase USP7. Moreover, our studies reveal that p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. These data not only suggest a noncanonical role of p53 in chromatin regulation but also link p53 to ferroptosis via an H2Bub1-mediated epigenetic pathway. Overall, our work uncovers a previously unappreciated epigenetic mechanism for the regulation of ferroptosis.
Subject(s)
Epigenesis, Genetic , Ferroptosis , Histones/metabolism , Tumor Suppressor Protein p53/metabolism , Ubiquitination , Active Transport, Cell Nucleus , Amino Acid Transport System y+/genetics , Amino Acid Transport System y+/metabolism , Cell Line, Tumor , Cell Nucleus , HEK293 Cells , HumansABSTRACT
Cimicifuga dahurica (Turcz.) Maxim. exerts significant antioxidative due to its high phenolic constituent content. In this study, the extraction condition of the phenolic constituents and antioxidant effect was optimized by the Box-Behnken design and response surface methodology. Eleven main bioactive analytes of Cimicifuga dahurica (Turcz.) Maxim. were simultaneously quantified by high-performance capillary electrophoresis with diode-array detector to assess the effect of extraction technology. The optimal extraction parameters were determined as: the concentration of ethanol 56.21%, liquid/solid ratio 14.65:1, and extraction time 1.64 h for 2.67 times. According to the results, a maximal value of total phenolic acids (3.67 mg/g) was obtained. Meanwhile, the influence of different extraction technology on antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonate), ferric reducing antioxidant power and hydroxyl radical scavenging method. The results presented here showed that the content of phenolic acid and antioxidant effect was much higher than the European Pharmacopoeia. Altogether, this method successfully applied response surface methodology to optimize the Cimicifuga dahurica (Turcz.) Maxim. extract with high antioxidant activities.
Subject(s)
Cimicifuga/chemistry , Phenols/isolation & purification , Plant Extracts/isolation & purification , Molecular Conformation , Phenols/chemistry , Plant Extracts/chemistry , Stereoisomerism , Surface PropertiesABSTRACT
AIM: To investigate if the serum CC motif ligand 4 (CCL4) levels are linked to disease severity in patients with postmenopausal osteoporosis (PMOP). PATIENTS & METHODS: We enrolled 66 PMOP females, 68 postmenopausal nonosteoporotic women and 67 healthy women of childbearing age. Bone mineral densities were assessed with dual x-ray absorptiometry scans. The Oswestry disability index and the visual analog scale were employed to quantify functional ability and severity of symptoms. Serum CCL4 levels were examined with a quantitative sandwich enzyme-linked immunosorbent assay. RESULTS: We observed a significant negative correlation of CCL4 serum levels with bone mineral density. Furthermore, serum CCL4 concentrations were significantly related to the visual analog scale and Oswestry Disability Index scores. CONCLUSION: Serum CCL4 is a potential biomarker to evaluate disease severity in PMOP females.
Subject(s)
Biomarkers/blood , Chemokine CCL4/blood , Osteoporosis, Postmenopausal/diagnosis , Severity of Illness Index , Bone Density , Case-Control Studies , Female , Follow-Up Studies , Humans , Middle Aged , Osteoporosis, Postmenopausal/blood , PrognosisABSTRACT
An increasing volume of data indicates that disrupting the interaction between CXC motif chemokine receptor 4 (CXCR4) and its specific ligand, CXC motif chemokine 12 (CXCL12), may reduce tumor growth and metastasis. However, the translation from bench to bedside must be performed with extreme caution, as the CXCR4/CXCL12 axis is crucial for the normal development and maintenance of tissues and organs. In the present study, Cell Counting Kit-8 and Transwell migration assays were used to detect in vitro proliferation and chemotaxis of CXCR4-expressing A549 cells, a cell strain originating from human non-small-cell lung cancer (NSCLC), with or without the presence of AMD3100, a small-molecule inhibitor specific to CXCR4 signaling. In a xenograft model established by injecting nude mice with A549 cells, tumor growth, CXCR4 expression and microvessel density (MVD) in the tumor mass were determined through tumor size measurements and immunohistochemical staining following intraperitoneal administration of AMD3100 or vehicle. The results demonstrated that CXCR4 blockade inhibited the proliferation of A549 cells and their migration towards CXCL12 in vitro. Tumor growth, CXCR4 expression and MVD were markedly reduced in nude mice treated with AMD3100 compared with mice treated with the vehicle. In conclusion, the present data demonstrated that CXCR4 targeting impaired NSCLC cell growth, angiogenesis and metastatic spread, indicating that it may represent a novel treatment strategy for NSCLC.