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Background: Hyperlipidemia (HLP) presents a significant challenge to global public health. Mounting evidence suggests that statins, the recommended first-line lipid-lowering agents, have significant adverse effects. Consequently, the quest for natural and efficacious alternative therapies is steadily emerging as a research priority for HLP prevention and treatment. Consumption of tea, which is rich in diverse biologically active compounds with the capacity to regulate lipid metabolism and combat obesity, has emerged as a promising alternative therapy. Sea buckthorn leaves are rich in a multitude of biologically active substances, have a hypolipidemic effect, and can be used as a raw material for tea because of their unique flavor. There is a suggestion that combining Aspergillus cristatus with tea could modify or boost the lipid-lowering active compounds present in tea, thereby increasing its efficacy in regulating lipid metabolism. Results: Sea Buckthorn Leaf Fu Tea (SBLFT) was obtained by fermentation when sea buckthorn leaves contained 42 % moisture, inoculated with Aspergillus cristatus 0.2 mL/g, and incubated for 8 d at constant temperature. Animal experiments demonstrated that SBLFT significantly inhibited body weight gain in HLP rats and reduced lipid content and serum oxidative stress. In addition, liver tissue sections and functional indices showed that SBLFT can improve liver morphology and function abnormalities. Reverse transcription-polymerase chain reaction results indicated that the expression of Liver kinase B1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acetyl CoA carboxylase 1 (ACC1), and sterol-regulatory element binding protein-1 (SREBP1c) gene related to lipid metabolism was altered. Conclusion: SBLFT improved HLP, specifically via promoting the expression of LKB1 in the liver of HLP rats, activating AMPK, and inhibiting ACC1 and SREBP1c expression, resulting in the inhibition of fatty acid and triglyceride synthesis-related enzymes at the transcriptional level.
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Objective: With increasing rates of anxiety and depression during COVID-19, exercise treatment has drawn attention for its effects on COVID-19 patients with anxiety and depression. This study set out to assess the impact of exercise therapy on COVID-19 patients' anxiety and depression. Methods: PubMed, EMBASE, Web of Science and Cochrane Library were used to search articles about exercise therapy as a means of treating anxiety and depression in COVID-19 patients from inception to April 30, 2023. The risk of bias was assessed by the Cochrane Collaboration bias risk tool. Data were pooled with the random effects model. RevMan version 5.4 was used for the statistical analyses. This work was registered in the PROSPERO database (registration number: CRD42023406439). Selection criteria: Randomized clinical trials (RCTs) of COVID-19 patients with anxiety and depression were included to assess the impact of physical exercise on COVID-19 patients with anxiety and depression. Results: 6 studies including a total of 461 COVID-19 patients were analyzed in this meta-analysis. Overall, the meta-analysis showed that compared with the control group, exercise could significantly improve anxiety (SMD = -0.76; 95%CI: -0.96, -0.55; p < 0.00001), depression level (SMD = -0.39; 95%CI: -0.70, -0.09; p = 0.01), the PHQ-9 score (MD = -1.82; 95%CI: -2.93, -0.71; p = 0.001) and the sleep quality (SMD = -0.73; 95%CI: -1.32, -0.14; p = 0.01) in COVID-19 patients. Conclusion: The research provided evidence that exercise therapy is able to help COVID-19 patients experience less anxiety and depression and have better-quality sleep. Systematic review registration: CRD42023406439.
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Ansiedade , COVID-19 , Depressão , Terapia por Exercício , Humanos , COVID-19/psicologia , Depressão/terapia , Ansiedade/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2RESUMO
Infection poses a significant barrier to effective wound repair, leading to increased inflammatory responses that ultimately result in incomplete and prolonged wound healing. To address this challenge, numerous antibacterial ingredients have been incorporated into dressings to inhibit wound infection. Our previous work demonstrated that lysozyme/silver nanoparticles (LYZ/AgNPs) complexes, prepared using an eco-friendly one-step aqueous method, exhibited excellent antibacterial efficacy with favorable biosafety. To further explore its potential application in advancing wound healing, calcium alginate (CA) with good porosity, water absorption, and water retention capacities was formulated with LYZ/AgNPs to prepare composite sponge (CA/LYZ/AgNPs). As expected, in vivo experiments involving full-thickness skin wound and scald wound healing experiments demonstrated that CA-LYZ-AgNPs composite sponges with excellent biocompatibility exhibited remarkable antibacterial activity against gram-positive bacteria, gram-negative bacteria and fungi, and outperformed the wound healing process efficacy of other commercially available AgNPs-loaded wound dressings. In summary, this work introduces a CA/LYZ/AgNPs sponge featuring exceptional antibacterial efficacy and biocompatibility, thus holding promising potential in wound care applications.
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Alginatos , Nanopartículas Metálicas , Alginatos/farmacologia , Prata/farmacologia , Muramidase , Antibacterianos/farmacologia , Cicatrização , Bandagens , ÁguaRESUMO
The skin secretion of Andrias davidianus (SSAD) is a novel biological adhesive raw material under development. This material exhibits robust adhesion while maintaining the flexibility of the wound. It also has the potential for large-scale production, making it promising for practical application explore. Hence, in-depth research on methods to fine-tune SSAD properties is of great importance to promote its practical applications. Herein, we aim to enhance the adhesive and healing properties of SSAD by incorporating functional components. To achieve this goal, we selected 3,4-dihydroxy-l-phenylalanine and vaccarin as the functional components and mixed them with SSAD, resulting in a new bioadhesive, namely, a formulation termed "enhanced SSAD" (ESSAD). We found that the ESSAD exhibited superior adhesive properties, and its adhesive strength was improved compared with the SSAD. Moreover, ESSAD demonstrated a remarkable ability to promote wound healing. This study presents an SSAD-based bioadhesive formulation with enhanced properties, affirming the feasibility of developing SSAD-based adhesive materials with excellent performance and providing new evidence for the application of SSAD. This study also aims to show that SSAD can be mixed with other substances, and addition of effective components to SSAD can be studied to further adjust or improve its performance.
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Adesivos Teciduais , Cicatrização , Humanos , Adesivos/farmacologia , Pele , Adesivos Teciduais/farmacologia , Aderências Teciduais , Muco , HidrogéisRESUMO
Lanmaoa macrocarpa is a boletoid mushroom from the family Boletaceae and was named after its relatively larger basidiocarp and bluish color change when bruised. At present, its mitochondrial genome and phylogenetic relationships with other boletes remain unexplored. In this study, we sequenced the mitochondrial genome of L. macrocarpa using next-generation sequencing technology and found that its mitochondrial genome, a circular DNA molecule of 38,139 bp, comprised 15 core protein-coding genes, 26 transfer RNA genes and two ribosomal RNA genes. The mitochondrial genome had a base composition of A (37.05%), C (12.08%), G (11.42%) and T (39.45%) with a GC content of 23.50%. A phylogenetic tree based on 20 mitochondrial genomes was constructed, which revealed the phylogenetic relationships of this species with related boletes for the first time.
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The abnormal accumulation of fused in sarcoma (FUS) is a pathological hallmark in a proportion of patients with frontotemporal dementia and amyotrophic lateral sclerosis. Therefore, the clearance of FUS aggregates is a possible therapeutic strategy for FUS-associated neurodegenerative diseases. This study reports that curcumin can strongly suppress FUS droplet formation and stress granule aggregation of FUS. Fluorescence spectra and isothermal titration calorimetry showed that curcumin can bind FUS through hydrophobic interactions, thereby reducing the ß-sheet content of FUS. Aggregated FUS sequesters pyruvate kinase, leading to reduced ATP levels. However, results from a metabolomics study revealed that curcumin changed the metabolism pattern and differentially expressed metabolites were enriched in glycolysis. Curcumin attenuated FUS aggregation-mediated sequestration of pyruvate kinase and restored cellular metabolism, consequently increasing ATP levels. These results indicate that curcumin is a potent inhibitor of FUS liquid-liquid phase separation and provide novel insights into the effect of curcumin in ameliorating abnormal metabolism.
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Curcumina , Demência Frontotemporal , Sarcoma , Humanos , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Curcumina/farmacologia , Demência Frontotemporal/metabolismo , Trifosfato de Adenosina , Mutação , Proteína FUS de Ligação a RNA/química , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismoRESUMO
The biological effects of magnetic fields (MFs) have been a controversial issue. Fortunately, in recent years, there has been increasing evidence that MFs do affect biological systems. However, the physical mechanism remains unclear. Here, we show that MFs (16 T) reduce apoptosis in cell lines by inhibiting liquid-liquid phase separation (LLPS) of Tau-441, suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the "mysterious" magnetobiological effects. The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite. The phase-separated droplets of Tau-441 recruited hexokinase (HK), resulting in a decrease in the amount of free HK in the cytoplasm. In cells, HK and Bax compete to bind to the voltage-dependent anion channel (VDAC I) on the mitochondrial membrane. A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I, leading to increased Bax-mediated apoptosis. In the presence of a static MF, LLPS was marked inhibited and HK recruitment was reduced, resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I, thus reducing Bax-mediated apoptosis. Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS. In addition, these results show the potential applications of physical environments, such as MFs in this study, in the treatment of LLPS-related diseases.
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There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1â mg of protein is consumed in collecting a complete dataset.
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Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.
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COVID-19 , Doenças Neurodegenerativas , Humanos , Proteínas Amiloidogênicas , Peptídeos beta-Amiloides/química , Amiloide/metabolismoRESUMO
Staphylococcus aureus (S. aureus) infection, especially its drug-resistant bacterial infection, is a great challenge often faced by clinicians and patients, and it is also one of the most important threats to public health. Finding a safe and effective antibacterial agent is of great significance for the prevention and treatment of S. aureus infection. Lysozyme is known to have antibacterial effects against Gram-positive bacteria including S. aureus. Here, high-quality lysozyme with a purity of more than 99% and an activity of more than 60, 000 U/mg was prepared from egg white, which showed excellent antibacterial activity against three strains of S. aureus, especially against MRSA. Furthermore, an antibacterial cream loaded with lysozyme was prepared and tested in scald wound healing. The lysozyme-loaded cream exhibited the effect of preventing wound infection and promoting wound healing on scalds, and no toxicity was found in animal organs. Overall, lysozyme showed great application potential in the prevention and treatment of infections caused by S. aureus and scalded wound healing. The most remarkable discovery in this work is the unexpectedly powerful inhibitory effect of lysozyme on the drug-resistant bacterial, especially MRSA, which is usually very difficult to deal with using normal antibacterial drugs.
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Queimaduras , Fármacos Dermatológicos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Staphylococcus aureus , Testes de Sensibilidade Microbiana , Muramidase/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Cicatrização , Fármacos Dermatológicos/farmacologia , Queimaduras/tratamento farmacológicoRESUMO
BACKGROUND: In patients undergoing peritoneal dialysis (PD), catheter dysfunction is a common complication. A misplaced catheter is one of the reasons contributing to its dysfunction. The present study aimed to describe a case of misplaced PD catheter with an unusual location of the catheter tip. CASE SUMMARY: A 61-year-old man undergoing PD for 4 years was investigated for progressive nausea and fatigue of 3 mo. Dialysis adequacy studies indicated inefficient dialysis. Imaging discovered that the PD catheter tip was mispositioned in the pelvic cavity with its tip outside the peritoneal cavity. Despite the dialysate accumulating outside the peritoneal cavity, the patient had not developed perineal or scrotal edema. The patient had experienced a sustainable prolonged dialysis efficacy in this case until the renal function deteriorated further in view of the poor dialysis outcome and worsening health condition. The patient was subsequently transitioned to hemodialysis. CONCLUSION: Proper placement of the catheter in the peritoneal cavity should always be confirmed and re-checked when necessary in patients undergoing PD to ensure dialytic adequacy.
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A versatile hydrophilic and antifouling coating was designed and prepared based on catechol-modified four-arm polyethylene glycol. The dopamine (DA) molecules were grafted onto the end of the four-arm polyethylene glycol carboxyl (4A-PEG-COOH) through the amidation reaction, which was proven by 1H NMR and FTIR analysis, assisting the strong adhesion of PEG on the surface of various types of materials, including metallic, inorganic, and polymeric materials. The reduction of the water contact angle and the bacteria-repellent and protein-repellent effects indicated that the coating had good hydrophilicity and antifouling performance. Raman spectroscopy analysis demonstrated the affinity between the polymeric surface and water, which further confirmed the hydrophilicity of the coating. Finally, in vitro cytotoxicity assay demonstrated good biocompatibility of the coating layer.
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Incrustação Biológica , Polietilenoglicóis , Incrustação Biológica/prevenção & controle , Dopamina , Interações Hidrofóbicas e Hidrofílicas , Polietilenoglicóis/farmacologia , ÁguaRESUMO
Proteins are like miracle machines, playing important roles in living organisms. They perform vital biofunctions by further combining together and/or with other biomacromolecules to form assemblies or condensates such as membraneless organelles. Therefore, studying the self-assembly of biomacromolecules is of fundamental importance. In addition to their biological activities, protein assemblies also exhibit extra properties that enable them to achieve applications beyond their original functions. Herein, this study showed that in the presence of monosaccharides, ethylene glycols, and amino acids, ß-lactoglobulin (ß-LG) can form assemblies with specific structures, which were highly reproducible. The mechanism of the assembly process was studied through multi-scale observations and theoretical analysis, and it was found that the assembling all started from the formation of solute-rich liquid droplets via liquid-liquid phase separation (LLPS). These droplets then combined together to form condensates with elaborate structures, and the condensates finally evolved to form assemblies with various morphologies. Such a mechanism of the assembly is valuable for studying the assembly processes that frequently occur in living organisms. Detailed studies concerning the properties and applications of the obtained ß-LG assemblies showed that the assemblies exhibited significantly better performances than the protein itself in terms of autofluorescence, antioxidant activity, and metal ion absorption, which indicates broad applications of these assemblies in bioimaging, biodetection, biodiagnosis, health maintenance, and pollution treatment. This study revealed that biomacromolecules, especially proteins, can be assembled via LLPS, and some unexpected application potentials could be found beyond their original biological functions.
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Antioxidantes/metabolismo , Quelantes/metabolismo , Lactoglobulinas/metabolismo , Animais , Antioxidantes/química , Quelantes/química , Cobre/química , Ligação de Hidrogênio , Ferro/química , Lactoglobulinas/química , Chumbo/química , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Multimerização Proteica , Células RAW 264.7RESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor beta 1 (TGF-ß1)-induced epithelial mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-ß1. METHODS: Our study was performed at Ningbo University, Ningbo, Zhejiang, China between Mar 2017 and Jun 2018. HK-2 cells were initially treated with TGF-ß1, then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTS assay and flow cytometry were employed to detect the effect of TGF-ß1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 cells EMT. RESULTS: Overexpressing TGF-ß1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished. CONCLUSION: TGF-ß1 was a motivating factor of kidney cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-ß1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti- fibrosis.
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The self-assembly of biomacromolecules is an extremely important process. It is potentially useful in the fields of life science and materials science. To carry out the study on the self-assembly of proteins, it is necessary to find out the suitable self-assembly conditions, which have always been a challenging task in practice. Inspired by the screening technique in the field of protein crystallization, we proposed using the same screening technique for seeking suitable protein self-assembly conditions. Based on this consideration, we selected 5 proteins (ß-lactoglobulin, hemoglobin, pepsin, lysozyme, α-chymotrypsinogen (II) A) together with 5 screening kits (IndexTM, BML, Morpheus, JCSG, PEG/Ion ScreenTM) to investigate the performance of these crystallization screening techniques in order to discover new optimized conditions of protein self-assembly. The screens were all kept at 293 K for certain days, and were analyzed using optical microscope, scanning electron microscope, transmission electron microscope, atomic force microscope, fluorescence microscope, and atomic absorption spectroscope. The results demonstrated that the method of protein crystallization screening can be successfully applied in the screening of self-assembly conditions. This method is fast, high throughput, and easily implemented in an automated system, with a low protein consumption feature. These results suggested that such strategy can be applied to finding new conditions or forms in routine research of protein self-assembly. KEY POINTS: ⢠Protein crystallization screening method is successfully applied in the screening of self-assembly conditions. ⢠This screening method can be applied on various kinds of proteins and possess a feature of low protein consumption. ⢠This screening method is fast, high throughput, and easily implemented in an automated system.
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Proteínas , CristalizaçãoRESUMO
A sample delivery system is one of the key parts of serial crystallography. It is the main limiting factor affecting the application of serial crystallography. At present, although a variety of useful sample delivery systems have been developed for serial crystallography, it still remains the focus of the field to further improve the performance and efficiency of sample delivery. In existing sample delivery technologies, samples are usually delivered in linear motion. Here we show that the samples can also be delivered using circular motion, which is a novel motion mode never tested before. In this paper, we report a microfluidic rotating-target sample delivery device, which is characterized by the circular motion of the samples, and verify the performance of the device at a synchrotron radiation facility. The microfluidic rotating-target sample delivery device consists of two parts: a microfluidic sample plate and a motion control system. Sample delivery is realized by rotating the microfluidic sample plate containing in situ grown crystals. This device offers significant advantages, including a very wide adjustable range of delivery speed, low background noise, and low sample consumption. Using the microfluidic rotating-target device, we carried out in situ serial crystallography experiments with lysozyme and proteinase K as model samples at the Shanghai Synchrotron Radiation Facility, and performed structural determination based on the serial crystallographic data. The results showed that the designed device is fully compatible with the synchrotron radiation facility, and the structure determination of proteins is successful using the serial crystallographic data obtained with the device.
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Dispositivos Lab-On-A-Chip , Síncrotrons , China , Cristalografia por Raios X , MicrofluídicaRESUMO
Interleukin-1ß (IL-1ß) is a pivotal proinflammatory cytokine that plays important roles in regulating immune responses and in inducing a series of inflammatory reactions in response to infection. Recently, increasing attention has focused on the regulatory mechanisms of IL-1ß activity in teleosts. In this regard, IL-1 receptor type 1 plays a crucial role in immune responses, whereas IL-1 receptor type 2 is a decoy receptor that functions as an IL-1ß signaling inhibitor. However, the interactions of these three proteins with respect to fish immunity have rarely been studied. In the present study, cDNAs of the il1b, il1r1, and il1r2 genes of the barbel steed (Hemibarbus labeo) were cloned and sequenced. Amino acid sequence analysis revealed that the IL-1ß protein and its two receptors identified in barbel steed are conserved in most teleosts, whereas phylogenetic tree analysis indicated that these three proteins are closely related to those of cyprinids. In response to lipopolysaccharide treatment, expression of the genes encoding IL-1ß and its two receptors was significantly upregulated in the immune-related tissues of barbel steed. Furthermore, expression of the il1r1 and il1r2 genes was induced in monocytes/macrophages in response to stimulation with recombinant IL-1ß.
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Cyprinidae/metabolismo , Proteínas de Peixes/metabolismo , Interleucina-1beta/metabolismo , Receptores de Interleucina-1/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Cyprinidae/genética , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Interleucina-1beta/genética , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Filogenia , Receptores de Interleucina-1/genética , Homologia de SequênciaRESUMO
Professor CHU Hao-ran successively followed famous doctors of acupuncture and spleen-stomach disease, such as ZHOU Mei-sheng, inherited their academic thoughts and clinical experience, and studied the classics to summarize and propose the clinical academic proposition regulating spleen-stomach, differentiating meridians-collaterals. In clinical practice, professor CHU focuses on individual differences of patients, carefully examines syndrome and refines acupoint selection; he pays attention to regulating spleen-stomach, and actively uses Zusanli (ST 36); he simultaneously uses acupuncture-moxibustion and acupoints with efficacy; he inherits traditional reinforcing and reducing methods, and extends the scope of acupoint diagnosis and treatment, while he emphasizes keeping spirit and treating spirit, and the combination of mind and qi, in order to improve clinical diagnosis and treatment effect.
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Terapia por Acupuntura , Meridianos , Moxibustão , Pontos de Acupuntura , Humanos , Masculino , Baço , EstômagoRESUMO
A new phenolic derivative (1) and a new dihydrophenanthrene (2) were isolated from the aerial part of Dendrobium hainanense rofe, along with 12 known compounds. The structures of the new compounds were elucidated by spectroscopic analysisï¼and the relative configuration of compound 1 was determined by J-based configuration analysis (JBCA) method. Bioassay result indicated that compound 1 exhibited weak antibacterial activity against Canidia albicans and Ralstonia solanaceanum.
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Dendrobium/química , Fenantrenos/química , Fenóis/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Estrutura Molecular , Fenóis/química , Componentes Aéreos da Planta/químicaRESUMO
As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the Wnt/ß-catenin signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, Wnt/ß-catenin signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated Wnt/ß-catenin signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway. Besides, si-ß-catenin was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the Wnt/ß-catenin signaling pathway in human PTC.