19,617 results
Search Results
2. Paper New Allele of HL6 Regulates Trichome Elongation in Rice.
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Fei, Shang, Wenbin, Mou, Hao, Wu, Furong, Xu, Chunyan, Xiang, and Jianfei, Wang
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RICE ,PHYTOPATHOGENIC microorganisms ,ALLELES ,CELLULAR signal transduction ,PLANT development - Abstract
Trichomes are specialized epidermal cells that play multiple roles in plant development. However, knowledge about the molecular mechanism of trichome development in rice is limited. In this study, a hairy leaf locus HL6
SWWR of rice variety Suwangwanger (SWWR) was identified by map-based cloning. Transgenic complementation and knock-out mutation demonstrated that HL6SWWR regulated trichomes on leaves and expression levels of HL6SWWR affected trichome elongation. Transgenic experiments of PROSWWR :HL6NIP and PRONIP :HL6SWWR indicated that the promoter and coding sequences of HL6SWWR were indispensable for trichome regulation. Sequencing alignment of the promoter and coding regions of HL6 in 22 varieties showed that some cis -binding elements in the promoter region may be related to trichome development, while no decisive variation was found in the coding sequence. Furthermore, RNA-sequencing analysis revealed that 1 415 differential expression genes (DEGs) were detected in hl6SWWR mutant vs wild type and that 1 010 DEGs were found in HL6SWWR complementary transgenic line vs wild type. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that most of the DEGs were involved in metabolite pathway, secondary metabolite biosynthesis, plant pathogen interaction and phytohormone signal transduction in both the two groups. The results indicated that these enhanced pathways are critical during trichome development in rice. Taken together, our results provided new views into the regulatory mechanism of trichome formation in rice. [ABSTRACT FROM AUTHOR]- Published
- 2020
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3. FoxO1 knockdown inhibits RANKL‐induced osteoclastogenesis by blocking NLRP3 inflammasome activation.
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Wang, Zhanqi, Luo, Wenxin, Zhang, Guorui, Li, Haiyun, Zhou, Feng, Wang, Dongyang, Feng, Xuan, Xiong, Yi, and Wu, Yingying
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NF-kappa B ,BIOLOGICAL models ,PAPER chromatography ,RESEARCH funding ,CARRIER proteins ,BONE growth ,POLYMERASE chain reaction ,ENZYME-linked immunosorbent assay ,TRANSCRIPTION factors ,CELLULAR signal transduction ,FLUORESCENT antibody technique ,MICE ,STATE-Trait Anxiety Inventory ,GENES ,OSTEOCLASTS ,ANIMAL experimentation ,WESTERN immunoblotting ,GENETIC techniques ,PERIODONTITIS ,SIGNAL peptides ,MEMBRANE proteins ,TUMOR necrosis factors ,SEQUENCE analysis ,PHENOTYPES - Abstract
Objectives: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. Materials and Methods: A conventional ligature‐induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA‐seq) was performed to explore the underlying mechanisms of FoxO1 knockdown‐mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme‐linked immunosorbent assay. Results: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation‐related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA‐seq revealed that the nuclear factor kappa B (NF‐κB) and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1‐knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. Conclusions: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF‐κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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4. Candidate genes for individual recognition in Polistes fuscatus paper wasps.
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Berens, A., Tibbetts, E., and Toth, A.
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POLISTES , *PAPER wasps , *CELLULAR signal transduction , *REVERSE transcriptase polymerase chain reaction , *GENE expression - Abstract
Few animals are known to individually recognize conspecifics, i.e. learn and recall unique individuals during subsequent encounters, and nearly all are social vertebrates. Remarkably, the social paper wasp Polistes fuscatus has recently been discovered to possess this ability, which is useful for remembering identities during competitive social interactions. We analyzed brain gene expression in staged encounters between pairs of individuals to explore potential mechanisms underlying wasps' ability to recall familiar individuals using real-time qRT-PCR. We identified four candidate genes ( IP3K, IP3R, Nckx30C and Su(var)2- 10) that were down-regulated in the presence of familiar individuals compared to single wasps and pairs of wasps meeting for the first time. These candidate genes are related to calcium signaling, therefore, we treated wasps with lithium chloride, a pharmacological agent that inhibits calcium signaling in neurons. This treatment decreased aggression in paper wasps, but did not affect expression of genes related to calcium signaling. The results suggest calcium signaling differences may be related to individual memory recall in wasps, and we present four promising candidate genes for future study. These data suggest genes associated with dominance behavior may be co-opted for individual recognition, but further work is needed to establish a causal association with the behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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5. Shaping up field-deployable nucleic acid testing using microfluidic paper-based analytical devices.
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Dong, Tianyu, Wang, Guan A., and Li, Feng
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NUCLEIC acids ,PREDICATE calculus ,POWER resources ,POINT-of-care testing ,CELLULAR signal transduction ,TEST interpretation - Abstract
Rapid, low-cost, and sensitive nucleic acid detection and quantification assays enabled by microfluidic paper-based analytical devices (μPADs) hold great promise for point-of-care disease diagnostics and field-based molecular tests. Through the capillary action in μPAD, flexible manipulation of nucleic acid samples can be achieved without the need for external pumps or power supplies, making it possible to fabricate highly integrated sample-to-answer devices that streamline the nucleic acid extraction, separation, concentration, amplification, and detection. To detect minute amounts of genetic materials from clinical and biological samples, it is also critical to develop sensitive signal readouts that generate physically detectable signals for in-device nucleic acid detection and/or quantification. In this review, we will focus on μPAD approaches for the facile manipulation of nucleic acids and emerging signal transduction strategies allowing sensitive and specific nucleic acid detection in μPAD. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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6. Visual Signals of Individual Quality in a European Solitary Founding Paper Wasp.
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Petrocelli, Iacopo, Ricciardi, Giulia, Rodrigues de Souza, André, Ermanni, Andrea, Ninu, Andrea, Turillazzi, Stefano, and Herberstein, M.
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VISUALIZATION , *CELLULAR signal transduction , *PAPER wasps , *EXTERNALITIES , *POLISTES - Abstract
Conventional signals are maintained via social costs and commonly used in the animal kingdom to assess conspecifics' agonistic ability during disputes over resources. In the last decade, some experimental studies reported the existence of visual conventional signals in several social wasp species, being good rank predictors in different social contexts. Females of the social wasp Polistes gallicus do not cooperate to start nests but they often try to usurp conspecific nests. Here, we showed that the reproductive females of this species have variable facial colour patterns that function as conventional signals. Wasps with larger black spots on their clypeus are more likely to successfully overwinter, are larger, and are better at fighting and at holding a nest. Furthermore, in field experiments, resident foundresses rely on facial pattern to assess usurpers' fighting abilities, modulating their defence reaction accordingly, so that rivals with larger black spot receive more aggression than rivals with smaller or no black spots on the clypeus. Our study reveals that visual recognition abilities are widespread among paper wasps that, regardless of their social biology, face similar selective pressures within competitive contexts. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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7. Studies from Temple University Reveal New Findings on Hypertension (Milestone Papers On Signal Transduction Mechanisms of Hypertension and Its Complications).
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CELLULAR signal transduction ,HYPERTENSION ,REGULATION of blood pressure ,VASCULAR smooth muscle ,ALZHEIMER'S disease - Abstract
A recent study from Temple University in Philadelphia, Pennsylvania, highlights milestone papers that have contributed to our understanding of the signaling mechanisms behind hypertension and associated cardiovascular disorders. The research covers topics such as the renin-angiotensin system, contractile and vasodilatory pathways, membrane channels, and noncanonical regulation of blood pressure and vascular function. The study was funded by the National Institutes of Health, the Alzheimer's Association, and the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. The research has been peer-reviewed and provides valuable insights for further investigation in this field. [Extracted from the article]
- Published
- 2024
8. Aggregation-induced emissive nanoparticles for fluorescence signaling in a low cost paper-based immunoassay.
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Engels, Jan F., Roose, Jesse, Zhai, Demi Shuang, Yip, Ka Man, Lee, Mei Suet, Tang, Ben Zhong, and Renneberg, Reinhard
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NANOMEDICINE , *FLUORESCENCE , *IMMUNOASSAY , *CELLULAR signal transduction , *SCANNING electron microscopy , *QUENCHING (Chemistry) - Abstract
Low cost paper based immunoassays are receiving interest due to their fast performance and small amounts of biomolecules needed for developing an immunoassay complex. In this work aggregation-induced emissive (AIE) nanoparticles, obtained from a diastereoisomeric mixture of 1,2-di-(4-hydroxyphenyl)-1,2-diphenylethene (TPEDH) in a one-step top-down method, are characterized through Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Zeta potential. By measuring the Zeta potential before and after labeling the nanoparticles with antibodies we demonstrate that the colloidal system is stable in a wide pH-range. The AIE-active nanoparticles are deposited on chitosan and glutaraldehyde modified paper pads overcoming the common aggregation-caused quenching (ACQ) effect. Analyte concentrations from 1000 ng and below are applied in a model immunocomplex using Goat anti-Rabbit IgG and Rabbit IgG. In the range of 7.81 ng–250 ng, linear trends with a high R 2 are observed, which leads to a strong increase of the blue fluorescence from the TPEDH nanoparticles. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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9. Development of a photothermal-sensing microfluidic paper-based analytical chip (PT-Chip) for sensitive quantification of diethylstilbestrol.
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Wang, Minglu, Wang, Ying, Li, Xiangyang, and Zhang, Hongyan
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DIETHYLSTILBESTROL , *GOLD nanoparticles , *DETECTION limit , *CELLULAR signal transduction , *FOOD safety - Abstract
• A novel PT-Chip was developed for DES detection in food samples. • Black phosphorus hybrid gold nanoparticles was used as photothermal-sensing probe. • The PT-Chip shows high selectivity and long-term stability. • The developed PT-Chip can be used as universal analysis platform. The continuous intake of diethylstilbestrol (DES) residue seriously threatens the health of consumers, so the rapid and sensitive detection of DES is helpful for timely food safety warning. In this study, a photothermal-sensing microfluidic paper-based analytical chip (PT-Chip) was developed for effectively screening of DES residue in foods. Competitive inhibition immunochromatography was introduced and the composite of black phosphorus nanosheets and gold nanoparticles (BP-Au) was used as signal indicators. Then, the test area was irradiated by an 808 nm laser and the photothermal transduction signal was recorded by a thermal imager to achieve sensitive photothermal detection. The amount of DES was obtained by analyzing the temperature change curve of test area. The PT-Chip can achieve accurate quantification of DES with a detection limit of 0.1 μg/L. And the successful determination of DES in different food samples indicating that the PT-Chip can be used as a promising detection device. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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10. A sensitive and rapid sensing platform for ochratoxin A detection based on triple-helix molecular switch and CMC-EDC/NHS covalent immobilized paper.
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Zhu, Mingzhen and Feng, Liang
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MOLECULAR switches , *OCHRATOXINS , *APTAMERS , *CHIMERIC proteins , *DETECTION limit , *CELLULAR signal transduction , *CARRIER proteins - Abstract
Ochratoxin A (OTA) is the most common mycotoxin contaminant that is widely distributed in food products. Herein, a sensitive and rapid sensing platform was constructed based on triple-helix molecular switch and CMC-EDC/NHS covalent immobilized paper. The aptamer-based triple-helix molecular switch (THMS) released signal transduction probe (STP) upon the addition of OTA, which was then enriched on the TR512-peptide functionalized paper modified with CMC-EDC/NHS chemistry. The sensing platform achieved a lower detection limit of 0.012 ng/mL with the linear range of 0.025–100 ng/mL. Notably, the sensing could be finished in less than 15.5 min without complex concentration process or expensive equipment. Additionally, the TR512-peptide based fusion protein was strongly-immobilized on the paper substrate via carbodiimide coupling, which prevented the fusion protein from leaching and enabled a large amount of solution molecules to bind with the fusion protein (up to 1 mL). Finally, a full-set of device was developed and applied in real samples with good accuracy. Taken together, the sensing platform integrating THMS with functionalized paper possesses practical application prospects in food samples and may offer a new protocol for the detection of multifarious target analytes by virtue of altering the aptamer sequence in THMS. [Display omitted] • The dexterous combination of the triple-helix molecular switch and CMC-EDC/NHS covalent immobilized paper. • Low time-consumption : less than 15.5 min without complex concentration process or expensive equipment usage. • A sensitive OTA determination platform: a detection limit of 0.012 ng/mL with the range of 0.025–100 ng/mL. • CMC-EDC/NHS covalent immobilized paper enabled a large amount of solution molecules to flow through (up to 1 mL). • General applicability : variable aptamer sequence in the loop without redesigning the triple-helix structure. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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11. Chemical signal amplification in two-dimensional paper networks
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Fu, Elain, Kauffman, Peter, Lutz, Barry, and Yager, Paul
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BIOCHEMICAL engineering , *CELLULAR signal transduction , *BIOLOGICAL assay , *COLLOIDAL gold , *CHEMICAL detectors , *COMPARATIVE studies - Abstract
Abstract: Two-dimensional paper networks (2DPNs) hold great potential for extending the utility of paper-based chemical and biochemical diagnostics at a cost and ease-of-use that are comparable to conventional lateral flow strips. 2DPNs enable the automated sequential delivery of multiple reagents to a detection region with a single user activation step, and therefore have the potential to extend the processing capabilities of inexpensive paper-based assays with comparable ease of use to conventional lateral flow tests. In this communication, we used a simple 3 inlet 2DPN to perform signal amplification of a colloidal gold label using a gold enhancement solution, thus demonstrating the capability of 2DPNs to perform processes that can improve limits of detection. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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12. Transcriptional regulation of the paper mulberry under cold stress as revealed by a comprehensive analysis of transcription factors.
- Author
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Xianjun Peng, Qingqing Wu, Linhong Teng, Feng Tang, Zhi Pi, and Shihua Shen
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PHYSIOLOGICAL effects of cold temperatures , *PLANT development , *TRANSCRIPTION factors , *GENOMES , *CELLULAR signal transduction - Abstract
Background: Several studies have focused on cold tolerance in multiple regulated levels. However, a genome-scale molecular analysis of the regulated network under the control of transcription factors (TFs) is still lacking, especially for trees. To comprehensively identify the TFs that regulate cold stress response in the paper mulberry and understand their regulatory interactions, transcriptomic data was used to assess changes in gene expression induced by exposure to cold. Results: Results indicated that 794 TFs, belonging to 47 families and comprising more than 59% of the total TFs of this plant, were involved in the cold stress response. They were clustered into three groups, namely early, intermediate and late responsive groups which contained 95, 550 and 149 TFs, respectively. Among of these differentially expressed TFs, one bHLH, two ERFs and three CAMTAs were considered to be the key TFs functioning in the primary signal transduction. After that, at the intermediate stage of cold stress, there were mainly two biological processes that were regulated by TFs, namely cold stress resistance (including 5 bHLH, 14 ERFs, one HSF, 4 MYBs, 3 NACs, 11 WRKYs and so on) and growth and development of lateral organ or apical meristem (including ARR-B, B3, 5 bHLHs, 2 C2H2, 4 CO-like, 2 ERF, 3 HD-ZIP, 3 YABBYs, G2-like, GATA, GRAS and TCP). In late responsive group, 3 ARR-B, C3H, 6 CO-like, 2 G2-like, 2 HSFs, 2 NACs and TCP. Most of them presented the up-regulated expression at 12 or 24 hours after cold stress implied their important roles for the new growth homeostasis under cold stress. Conclusions: Our study identified the key TFs that function in the regulatory cascades mediating the activation of downstream genes during cold tress tolerance in the paper mulberry. Based on the analysis, we found that the AP2/ERF, bHLH, MYB, NAC and WRKY families might play the central and significant roles during cold stress response in the paper mulberry just as in other species. Meanwhile, many other TF families previously reported as involving in regulation of growth and development, including ARF, DBB, G2-like, GRF, GRAS, LBD, WOX and YAABY exhibited their important potential function in growth regulation under cold stress. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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13. A Simple Paper-Based Lab-on-a-Chip for the Detection of a Highly Pathogenic Strain of Porcine Reproductive and Respiratory Syndrome Virus.
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Chaumpiuk, Piyasak and Suriyasomboon, Annop
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DIAGNOSTIC microbiology , *PATHOGENIC microorganisms , *GENE amplification , *DETECTION limit , *CELLULAR signal transduction , *LAMINATED plastics , *LABORATORY swine - Abstract
A paper-based laboratory-on-a-chip assay for the rapid detection of a highly pathogenic strain of porcine reproductive and respiratory syndrome virus (HP-PRRSV) was developed for the first time. The single-unit chip was simply fabricated using Whatman filter paper and plastic lamination. The chip measured 2.5 × 3.0 cm[sup 2] and was divided into two parts, one for nucleic acid amplification and the other for signal detection. The HP-PRRSV assay was performed by specific ORF I Nsp 2 gene amplification via an isothermal reverse transcription loop-mediated DNA amplification platform, whereas the cDNA signal detection was performed by visual observation of colorimetric changes in blue silver nanoplates (AgNPls). Positive results caused non-aggregation of the blue AgNPls on the detection pad, whereas negative results induced colorimetric changes in the AgNPls from blue to colourless on the pad. The assay had a limit of detection of 100 copies of the target Nsp 2 gene and high specificity for other types of infectious viruses. The assay required only one hour to complete. This work demonstrates a simple and rapid assay for viruses using a simple, low-cost, paper-based chip. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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14. INTERACTION NETWORK OF TaRHA2b OF WHEAT (TRITICUM AESTIVUM L.) BASED ON HIGH-THROUGHPUT YEAST TWO-HYBRID SCREENING.
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LI, D. B., LYU, G. Z., JIANG, Y. M., NIU, H. B., WANG, X., and YIN, J.
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YEAST ,FILTER paper ,CROP improvement ,ANTISENSE DNA ,CELLULAR signal transduction ,COLORS - Abstract
To explore the signal transduction pathway that TaRHA2b gene is involved in regulating, yeast two-hybrid system was used to screen and identify proteins interacting with TaRHA2b. The homogenized cDNA library was constructed from the embryo of mixed barley. The decoy protein vector pGBKT7- TaRHA2b was constructed and transformed into yeast AH109 cells for self-activation detection. Candidate positive clones were screened by one to one yeast co-transfection, SD/-Leu/-Trp and SD/-Leu/- Trp/-Ade/-His medium screening and β-galactosidase chromogenic reaction. The in vitro co-transfection and GST-pull down experiments were used for further verification. The homogenized cDNA library of the barley embryos with titer of 1.2 10
6 cfu/ml and storage capacity of 1.1 106 was successfully constructed. The inserted fragment size was between 1000-3000 bp. The plasmids of the cDNA library were extracted and sequenced on a large scale, and 5000 plasmids were obtained. The decoy vector without self-activation function was successfully constructed. The x-gal filter paper of eighty-four hybrid clones showed strong blue color and forty-nine pieces of effective sequence information were obtained. Eight of them were selected for co-transfection verification. YTH2450 was selected for GST-pull down verification. The results showed that they were positive hybrid clones. TaRHA2b interacted with YTH2450 and other proteins. The information of above genes could be used for genetic improvement of crops, further improving the adaptability of crops to the environment. [ABSTRACT FROM AUTHOR]- Published
- 2019
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15. Oxytocin—a social peptide? Deconstructing the evidence.
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Leng, Gareth, Leng, Rhodri I., and Ludwig, Mike
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OXYTOCIN ,PEPTIDES ,SCIENTIFIC literature ,INTRANASAL administration ,CELLULAR signal transduction - Abstract
In this paper, we analyse the claim that oxytocin is a 'social neuropeptide'. This claim originated from evidence that oxytocin was instrumental in the initiation of maternal behaviour and it was extended to become the claim that oxytocin has a key role in promoting social interactions between individuals. We begin by considering the structure of the scientific literature on this topic, identifying closely interconnected clusters of papers on particular themes. We then analyse this claim by considering evidence of four types as generated by these clusters: (i) mechanistic studies in animal models, designed to understand the pathways involved in the behavioural effects of centrally administered oxytocin; (ii) evidence from observational studies indicating an association between oxytocin signalling pathways and social behaviour; (iii) evidence from intervention studies, mainly involving intranasal oxytocin administration; and (iv) evidence from translational studies of patients with disorders of social behaviour. We then critically analyse the most highly cited papers in each segment of the evidence; we conclude that, if these represent the best evidence, then the evidence for the claim is weak. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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16. Cardioprotection by gene therapy: A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology.
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Madonna, Rosalinda, Cadeddu, Christian, Deidda, Martino, Giricz, Zoltán, Madeddu, Clelia, Mele, Donato, Monte, Ines, Novo, Giuseppina, Pagliaro, Pasquale, Pepe, Alessia, Spallarossa, Paolo, Tocchetti, Carlo Gabriele, Varga, Zoltán V., Zito, Concetta, Yong-Jian Geng, Mercuro, Giuseppe, and Ferdinandy, Peter
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GENE therapy , *TEAMS in the workplace , *CARDIOTOXICITY , *CORONARY heart disease treatment , *TREATMENT of reperfusion injuries , *CELLULAR signal transduction - Abstract
Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprotection. Genes critical for signaling pathways in cardioprotection include protectomiRs (e.g., microRNA 125b*), ZAC1 transcription factor, pro-inflammatory genes such as cycloxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), antioxidant enzymes such as hemoxygenase (HO)-1, extracellular and manganese superoxidase dismutases (ec-SOD and Mg-SOD), heat shock proteins (HSPs), growth factors such as insulin like growth factor (IGF)-1 and hepatocyte growth factor (HGF), antiapoptotic proteins such as Bcl-2 and Bcl-xL, pro-apoptotic proteins such as FasL, Bcl-2, Bax, caspase-3 and p53, and proangiogenic genes such as TGFbeta, sphingosine kinase 1 (SPK1), and PI3K-Akt. By identifying the gene expression profiles of IRI and ischemic conditioning, one may reveal potential gene targets responsible for cardioprotection. In this manuscript, we review the current state of the art of gene therapy in cardioprotection and propose that gene expression analysis facilitates the identification of individual genes associated with cardioprotection. We discuss signaling pathways associated with cardioprotection that can be targeted by gene therapy to achieve cardioprotection. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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17. Molecularly imprinted polymer-enhanced biomimetic paper-based analytical devices: A review.
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Li, Wang, Zhang, Xiaoyue, Li, Tingting, Ji, Yibing, and Li, Ruijun
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IMPRINTED polymers , *COMPLEX matrices , *CHEMICAL stability , *BIOMIMETIC materials , *CELLULAR signal transduction , *CHEMILUMINESCENCE , *PHOTOELECTROCHEMISTRY , *ELECTROCHEMILUMINESCENCE - Abstract
The popularization of paper-based analytical devices (PADs) in analytical science has fostered research on enhancing their analytical performance for accurate and sensitive assays. With their superb recognition capability and structural stability, molecularly imprinted polymers (MIPs) have been extensively employed as biomimetic receptors for capturing target analytes in various complex matrices. The integration of MIPs as recognition elements with PADs (MIP-PADs) has opened new opportunities for advanced analytical devices with elevated selectivity and sensitivity, as well as a shorter assay time and a lower cost. This review covers recent advances in MIP-PAD fabrication and engineering based on multifarious signal transduction systems such as colorimetry, fluorescence, electrochemistry, photoelectrochemistry, and chemiluminescence. The application of MIP-PADs in the fields of biomedical diagnostics, environmental analysis, and food safety monitoring is also reviewed. Further, the advantages, challenges, and perspectives of MIP-PADs are discussed. Image 1 • Recent advances on the biomimetic paper-based analytical devices. • Construction strategies of MIP-PADs based on different signal readout modes. • Enhanced analytical performance of MIP-PADs in chemo/bioanalysis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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18. Nanomaterial-mediated paper-based biosensors for colorimetric pathogen detection.
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Nguyen, Quynh Huong and Kim, Moon Il
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COVID-19 , *BIOSENSORS , *PATHOGENIC microorganisms , *CELLULAR signal transduction , *POINT-of-care testing - Abstract
The pervasive spread of infectious diseases and pandemics, such as the 2019 coronavirus disease (COVID-19), are becoming increasingly serious and urgent threats to human health. Preventing the spread of such diseases prioritizes the development of sensing devices that can rapidly, selectively, and reliably detect pathogens at minimal cost. Paper-based analytical devices (PADs) are promising tools that satisfy those criteria. Numerous paper-based biosensors have been established that rival conventional pathogen detection methods. Among them, colorimetric strategies are promising since results can be interpreted by eye, and are simple to operate, which is advantageous for point-of-care testing (POCT). Particularly, the application of nanomaterials on paper-based biosensors has become important as these materials are capable of converting signals from pathogens through unique mechanisms to yield an amplified colorimetric readout. To highlight the research progress on using nanomaterials in colorimetric paper-based biosensor for pathogen detection, we discuss the sensing mechanisms of how they work, structural and analytical characteristics of the devices, and representative recent applications. Current challenges and future directions of using PADs and nanomaterial-mediated strategies are also discussed. Image 1 • Recent developments in paper-based analytical devices for colorimetric detection of pathogens are reviewed in detail. • Three main types of point-of-care paper-based devices are exploited for robust performance in pathogen detection. • Colorimetric strategies are sensitive and offer fast response and convenience to end-users. • Diverse nanomaterials are deployed for both signal transduction and amplification to enhance sensitivity. • Sensing mechanisms fundamental to colorimetric pathogen detection are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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19. Paper del receptor CD40 en l'activació de les cèl·lules endotelials. Rellevància de la interacció CD40-CD40L en processos immunoinflamatoris
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Pluvinet Ortega, Raquel, Aran Perramon, Josep M., Albalat Rodríguez, Ricard, Universitat de Barcelona. Departament de Genètica, Aran Perramon, Josep Mª, and Albalat Rodriguez, Ricard
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Inflammation ,Cellular signal transduction ,Antígens CD ,Microarrays ,Transducció de senyal cel·lular ,Endoteli ,Inflamació ,Ciències Experimentals i Matemàtiques ,Patologia cel·lular ,Cellular immunity ,Cellular pathology ,Cèl·lules endotelials ,CD antigens ,Immunitat cel·lular ,Trasplantament ,SiRNA ,CD40 ,Endothelium - Abstract
CD40 (TNFRSF5) és una glicoproteïna de membrana que pertany a la família de receptors del factor de necrosi tumoral (TNF-R). La interacció amb el seu lligand fisiològic (CD40L o CD154) regula una àmplia varietat de funcions biològiques, des de l'activació del sistema immune, tant humoral com cel·lular, a diferents aspectes de la resposta inflamatòria. Els principals objectius d'aquesta tesi han estat 1) l'estudi a nivell molecular del paper de CD40 en l'activació de les cèl·lules endotelials, i 2) les conseqüències del bloqueig d'aquesta via de senyalització en la resposta immunoinflamatòria. S'ha obtingut un siRNA potent i específic capaç de reduir l'expressió del receptor CD40 humà en un 85%, tant a nivell de mRNA com a nivell de proteïna. Aquest siRNA expressat en forma de shRNA en un vector lentiviral permet assolir un silenciament gènic eficient i estable de CD40 al llarg del temps. S'ha validat l'activitat antiinflamatòria d'aquest siRNA analitzant les conseqüències funcionals del silenciament d'aquest receptor en cèl·lules endotelials. Aquest siRNA bloqueja l'activació endotelial via CD40L impedint la inducció de l'expressió de les molècules d'adhesió ICAM-1, VCAM-1 i E-selectina, i inhibint l'adhesió leucocitària en aquestes cèl·lules en un 87%. S'ha utilitzat el potencial antiinflamatori del siRNA dirigit contra CD40 humà per estudiar el paper d'aquest receptor en cèl·lules endotelials en inflamació. Utilitzant microarrays, s'ha realitzat una anàlisi comparativa del perfil global d'expressió gènica en cèl·lules endotelials humanes en les quals s'inactiva específicament aquesta via de senyalització mitjançant RNAi, en el context de la interacció cèl·lula endotelial i limfòcit T activat (CD40L+), com a primer pas en l'inici de la resposta immunoinflamatòria. Aquest estudi d'expressió gènica ha permès identificar nous gens i noves vies de senyalització implicades en la inducció de la resposta inflamatòria desencadenada per l'activació de CD40 en endoteli.Per altra banda, es volia avaluar l'eficàcia del silenciament gènic de CD40 per a la inducció de tolerància immunològica en un model experimental d'al·lotrasplantament renal. Amb aquesta finalitat s'ha obtingut un siRNA anti-CD40 de rata amb una potent eficiència silenciadora i s'ha optimitzat la transferència d'aquest siRNA en el ronyó a trasplantar mitjançant electroporació in vivo de l'òrgan. L'objectiu d'aquest estudi era silenciar temporalment l'expressió d'aquest receptor en les cèl·lules renals i bloquejar la interacció CD40-CD40L essencial per a la inducció de procés inflamatori que dóna lloc al rebuig del ronyó trasplantat. Resultats preliminars mostren que la teràpia gènica local amb siRNA redueix la resposta inflamatòria posttrasplantament. El siRNA anti-CD40 causa una reducció significativa de l'expressió del mRNA de CD40, disminuint l'aparició de rebuig agut humoral i allargant el temps mig de supervivència dels animals trasplantats amb els ronyons tractats amb siRNA en comparació amb els animals control., CD40 (TNFRSF5) belongs to the tumor necrosis factor receptor family (TNF-R). Its interaction with its physiological ligand (CD40L or CD154) regulates a wide variety of biological functions, from the activation of the immune system, to different aspects of the inflammatory response.The main goals of this work have been 1) the molecular study of the role of CD40 in the activation of the endothelial cells, and 2) the consequences of blocking this signaling in the immunoinflammatory response. We have obtained a powerful and specific siRNA able to reduce human CD40 expression by 85%. The anti-inflammatory activity of this siRNA has been validated by analyzing the functional consequences of CD40 silencing in endothelial cells activated via CD40L. This siRNA blocks the induction of ICAM-1, VCAM-1 and E-selectin expression, and inhibits leukocyte adhesion in these cells by 87%.We have used the anti-inflammatory potential of this siRNA directed against human CD40 to carry out a global gene expression profiling analysis in order to study the role of CD40 in endothelial cells during inflammation. Using microarrays, we have performed a comparative transcriptome analysis in human endothelial cells, in the context of the endotelial cell interaction with activated T lymphocyte (CD40L+), as the first step of the immunoinflammatory response. This study has allowed us to identify new genes and signaling pathways involved in the induction of the inflammatory response by CD40 activation in endothelium.On the other hand, we have obtained an siRNA against rat CD40 with a powerful silencing activity and we have optimized its transfer to the kidney through in vivo electroporation. The purpose of this study was to determine the CD40 gene silencing effectiveness in inducing immunological tolerance in an experimental model of renal allotransplantation. Preliminary results show that local gene therapy with siRNA reduces the inflammatory response post-transplantation. The anti-CD40 siRNA treatment causes a significant reduction of the incidence of acute humoral rejection and increases the survival half life of animals transplanted with kidneys treated with siRNA compared to control animals.
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- 2007
20. Research Paper. BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice.
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Li-Tao Yi, Jing Li, Bin-Bin Liu, Liu Luo, Qing Liu, and Di Geng
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ANTIDEPRESSANTS , *MENTAL depression , *ANALYSIS of variance , *ANIMAL experimentation , *CELLULAR signal transduction , *IMMUNOHISTOCHEMISTRY , *POLYMERASE chain reaction , *RATS , *RESEARCH funding , *STATISTICS , *PSYCHOLOGICAL stress , *TERPENES , *WESTERN immunoblotting , *DATA analysis , *DESCRIPTIVE statistics - Abstract
BACKGROUND: Although previous study has demonstrated that brain-derived neurotrophic factor (BDNF) is involved in the antidepressant-like effect of oleanolic acid, there is little information regarding the details of the molecular mechanism involved in this effect. METHODS: We used a chronic unpredictable mild stress (CUMS) model to test the antidepressant-like effect of oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic protein expression in the male mouse hippocampus. Furthermore, we explored the possible signalling pathways associated with miR-132 expression that mediate the effect of oleanolic acid on neuronal proliferation. RESULTS: The results demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid led to the BDNF-related phosphorylation and activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine monophosphate response element binding protein (CREB), which was associated with the upregulation of miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal proliferation and the postsynaptic density protein 95, but did not affect presynaptic protein synapsin I. LIMITATIONS: Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling. CONCLUSION: Our results show that oleanolic acid induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF-ERK-CREB signalling pathways. [ABSTRACT FROM AUTHOR]
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- 2014
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21. Research Paper. MicroRNA-137 regulates a glucocorticoid receptordependent signalling network: implications for the etiology of schizophrenia.
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Vallès, Astrid, Martens, Gerard J.M., Weerd, Peter De, Poelmans, Geert, and Aschrafi, Armaz
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RNA physiology , *ANIMAL experimentation , *BIOLOGICAL models , *CELLULAR signal transduction , *GLUCOCORTICOIDS , *MICE , *NEUROPLASTICITY , *RESEARCH funding , *SCHIZOPHRENIA - Abstract
BACKGROUND: Schizophrenia is a highly heritable neurodevelopmental disorder. A genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide association with schizophrenia, suggesting that this miRNA plays a key role in its etiology. Therefore, a molecular network of interacting miR-137 targets may provide insights into the biological processes underlying schizophrenia. METHODS: We first used bioinformatics tools to obtain and analyze predicted human and mouse miR-137 targets. We then determined miR-137 levels in rat barrel cortex after environmental enrichment (EE), a neuronal plasticity model that induces upregulation of several predicted miR-137 targets. Subsequently, expression changes of these predicted targets were examined through loss of miR-137 function experiments in rat cortical neurons. Finally, we conducted bioinformatics and literature analyses to examine the targets that were upregulated upon miR-137 downregulation. RESULTS: Predicted human and mouse miR-137 targets were enriched in neuronal processes, such as axon guidance, neuritogenesis and neurotransmission. The miR-137 levels were significantly downregulated after EE, and we identified 5 novel miR-137 targets through loss of miR-137 function experiments. These targets fit into a glucocorticoid receptor-dependent signalling network that also includes 3 known miR-137 targets with genome-wide significant association with schizophrenia. LIMITATIONS: The bioinformatics analyses involved predicted human and mouse miR-137 targets owing to lack of information on predicted rat miR-137 targets, whereas follow-up experiments were performed with rats. Furthermore, indirect effects in the loss of miR-137 function experiments cannot be excluded. CONCLUSION: We have identified a miR-137-regulated protein network that contributes to our understanding of the molecular basis of schizophrenia and provides clues for future research into psychopharmacological treatments for schizophrenia. [ABSTRACT FROM AUTHOR]
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- 2014
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22. Development of phosphocellulose paper-based screening of inhibitors of lipid kinases: Case study with PI3Kβ.
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Yanamandra, Mahesh, Kole, Labanyamoy, Giri, Archana, and Mitra, Sayan
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CELLULOSE , *LIPIDS , *KINASE inhibitors , *PHOSPHATIDYLINOSITOL 3-kinases , *CELLULAR signal transduction , *CELL growth , *CELL proliferation - Abstract
Abstract: The phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate the cellular signal transduction pathways involved in cell growth, proliferation, survival, apoptosis, and adhesion. Deregulation of these pathways are common in oncogenesis, and they are known to be altered in other metabolic disorders as well. Despite its huge potential as an attractive target in these diseases, there is an unmet need for the development of a successful inhibitor. Unlike protein kinase inhibitors, screening for lipid kinase inhibitors has been challenging. Here we report, for the first time, the development of a radioactive lipid kinase screening platform using a phosphocellulose plate that involves transfer of radiolabeled [γ-32P]ATP to phosphatidylinositol 4,5-phosphate forming phosphatidylinositol 3,4,5-phosphate, captured on the phosphocellulose plate. Enzyme kinetics and inhibitory properties were established in the plate format using standard inhibitors, such as LY294002, TGX-221, and wortmannin, having different potencies toward PI3K isoforms. ATP and lipid apparent K m for both were determined and IC50 values generated that matched the historical data. Here we report the use of a phosphocellulose plate for a lipid kinase assay (PI3Kβ as the target) as an excellent platform for the identification of novel chemical entities in PI3K drug discovery. [Copyright &y& Elsevier]
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- 2014
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23. Paper de la senyalització de la Reelina en la migració neuronal al Sistema Nerviós Central
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Simó Olivar, Sergi, Soriano García, Eduardo, and Universitat de Barcelona. Departament de Biologia Cel·lular
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Neurobiologia del desenvolupament ,Neurons ,Cellular signal transduction ,Sistema nerviós central ,Transducció de senyal cel·lular ,Proteins ,Neurones ,Migració neuronal ,Ciències Experimentals i Matemàtiques ,Fosforilació ,nervous system ,Central nervous system ,Reelina ,Sistema Nerviós Central (SNC) ,Developmental neurobiology ,Proteïnes - Abstract
Durant el període de formació del Sistema Nerviós Central (SNC) una multitud de factors participen en el desenvolupament de les diferents estructures cerebrals. Aquests factors controlen tant la migració cel·lular com el correcte posicionament de les diferents cèl·lules dins el SNC. La Reelina és un proteïna soluble de matriu extracel·lular expressada al llarg del desenvolupament i de l'edat adulta, encara que la seva funció principal s'hipotetitza durant el desenvolupment. La present tesi abarca tres funcions diferents de la Reelina en el control de la migració cel·lular durant el desenvolupament i l'edat adulta.En el primer apartat d'aquesta Tesi, hem demostrat que la Reelina pot controlar el nivell de fosforilació en mode I de la proteïna MAP1B durant la migració de les neurones que formen l'escorça cerebral. Aquesta fosforilació en mode I s'ha associat al control de l'estabilitat dels microtúbuls durant la migració cel·lular. L'estudi morfològic que hem desenvolupat en l'animal deficient per la proteïna MAP1B ens ha corraborat que existeix una relació entre la cascada de senyalització desencadenada per la Reelina i l'activitat de la proteïna MAP1B. Finalment també hem descrit que en resposta a la Reelina la quinasa GSK3-beta fosforila principalment MAP1B en mode I, encara que la participació, en menor grau, de la quinasa Cdk5/p35 no pot ser descartada.En el següent punt del nostre estudi, hem relacionat la via de senyalització MAPK/ERK amb la cascada activada per la Reelina. Hem comprovat que la Reelina pot induir la fosforilació d'mDab1 i la subseqüent activació de la proteïna PI3K, que a la seva vegada pot fosforilar a la proteïna Akt1/PKB. A partir d'aquest resultats, hem demostrat que l'activació de PI3K en reposta a la Reelina indueix l'activació de MEK1/2 i que aquesta activació desenvoca en la fosforilació de les proteïnes Erk1 i Erk2. També hem descrit que les formes fosforilades d'Erk1/2 en resposta a Reelina es transloquen a nucli en neurones corticals on indueixen l'expressió del factor de transcripció Egr-1. Un punt important d'aquest estudi es basa en el fet que hem pogut relacionar la cascada Reelin-MAPK/ERK en el procés de desadhesió de les cèl·lules de la zona subventricular (o SVZ) que participen en la via de la migració rostral (o RMS). A partir del fet que en presència de la Reelina, les cèl·lules que surten d'explants de SVZ no migren homofílicament sino que pateixen un proces de desadhesió migrant de forma individualitzada, hem descrit que si bloquegem farmacològicament o genèticament la via d'activació MAPK/ERK l'efecte de desadhesió induït per la Reelina queda inhibit. Amb aquest resultat podem concloure que en resposta a la Reelina les proteïnes Erk1/2 es fosforilen i que aquesta fosforilació és necessària per que la Reelina desenvolupi els seu paper en desadhesió dels neuroblasts que participen en la RMS.El tercer i darrer punt d'aquesta Tesi es basa en el control per part de la Reelina de la migració radial de les cèl·lules granulars del cerebel. En resposta a Reelina les cèl·lules granulars del cerebel inhibeixen la seva migració i aquesta resposta es induïda mitjançant l'activació de la via de les MAPK/ERK. El bloqueig farmacològic d'aquesta via inhibeix l'efecte de la Reelina. Amb aquestes dades podem concloure que l'activació, induïda per la Reelina, de la via de les MAPK/ERK no només és important en el control de la migració en el cerbell anterior sino que també és important en el cerebel, y que aquesta pot ser una cascada de senyalització que participa àmplimant en les funcions on s'hipotetitza la funcionalitat de la Reelina., "Role of Reelin signalling during neuronal migration in the Central Nervous System"During the development of the Central Nervous System (CNS) a multitude of factors work together to generate the different brain structures. Some of these factors control both cellular migration and cellular positioning inside the CNS. Reelin is a soluble protein of the extracellular matrix expressed during both development and adulthood, however its principal function is hypothesized to occur during development. This current Thesis addresses three different functions of Reelin on neuronal migration during embryonic and postnatal development.In the first chapter, we have shown that Reelin controls mode I phosphorylation of MAP1B protein during neuronal migration in the neocortex. Mode I phosphorylation has been related to the microtubule stability during cell migration. We developed morphological studies on map1b-deficient mice that corroborated the relationship between Reelin signalling cascade and MAP1B activity. Furthermore, we also described that this relation is done through the Reelin-dependent GSK3 activation, which phosphorylates MAP1B in mode I.In the second chapter, we addressed the relationship of Reelin signalling and the MAPK/ERK pathway. We showed that Reelin induces the phosphorylation of Dab1 and subsequent PI3K/Akt1 activation. Based on these results, we first described that Reelin-dependent PI3K activation induces MEK activation, which triggers Erk1 and Erk2 (Erk1/2) phosphorylation. We also showed that these active phospho-Erk1/2 proteins translocate into the nucleus inducing the expression of the Egr-1 transcription factor. Furthermore, we have demonstrated that this Reelin-induced pathway is activated during rostral migratory stream migration when neuroblasts face Reelin expressed in the olfactory bulb. The activation of ERK pathway in response to Reelin is crucial to change neuroblast migration from tangential chain migration to radial individual migration into the olfactory bulb.In the last chapter, we studied the role of Reelin in the control of radial migration of granule cells during the postnatal development of the mouse cerebellum. We shared that cerebellar granule cell migration is blocked by Reelin stimulation through MAPK/ERK activation. Furthermore, when ERK activation was pharmacologically block the Reelin effect on granule cells migration was inhibit.
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- 2006
24. Position paper: The membrane estrogen receptor GPER – Clues and questions
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Barton, Matthias
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ESTROGEN receptors , *G protein coupled receptors , *CELLULAR signal transduction , *XENOESTROGENS , *CANCER cells , *LIGANDS (Biochemistry) , *CELL membranes - Abstract
Abstract: Rapid signaling of estrogen involves membrane estrogen receptors (ERs), including membrane subpopulations of ERα and ERβ. In the mid-1990s, several laboratories independently reported the cloning of an orphan G protein-coupled receptor from vascular and cancer cells that was named GPR30. Research published between 2000 and 2005 provided evidence that GPR30 binds and signals via estrogen indicating that this intracellular receptor is involved in rapid, non-genomic estrogen signaling. The receptor has since been designated as the G protein-coupled estrogen receptor (GPER) by the International Union of Pharmacology. The availability of genetic tools such as different lines of GPER knock-out mice, as well as GPER-selective agonists and antagonists has advanced our understanding, but also added some confusion about the new function of this receptor. GPER not only binds estrogens but also other substances, including SERMs, SERDs, and environmental ER activators (endocrine disruptors; xenoestrogens) and also interacts with other proteins. This article represents a summary of a lecture given at the 7th International Meeting on Rapid Responses to Steroid Hormones in September 2011 in Axos, Crete, and reviews the current knowledge and questions about GPER-dependent signaling and function. Controversies that have complicated our understanding of GPER, including interactions with human ERα-36 and aldosterone as a potential ligand, will also be discussed. [Copyright &y& Elsevier]
- Published
- 2012
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25. Commentary on the Paper of Walther L. et al.: Phosphatidylethanol Is Superior to CDT and GGT as an Alcohol Marker and Is a Reliable Estimate of Alcohol Consumption Level.
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Weinmann, Wolfgang, Schröck, Alexandra, and Wurst, Friedrich M.
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ALCOHOLISM , *BIOMARKERS , *CELLULAR signal transduction , *ETHANOL , *PHOSPHOLIPIDS - Abstract
The article presents the authors' views on the previously published article "Phosphatidylethanol Is Superior to CDT and GGT as an Alcohol Marker and Is a Reliable Estimate of Alcohol Consumption Level," by Walther L. and colleagues.
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- 2016
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26. research paper Impairment of death-inducing signalling complex formation in CD95-resistant human primary lymphoma B cells.
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Lajmanovich, Alicia, Irisarri, Magdalena, Molens, Jean-Paul, Pasquier, Marie-Anne, Sotto, Jean-Jacques, Bensa, Jean-Claude, Leroux, Dominique, and Plumas, Joël
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CELLULAR signal transduction , *LYMPHOMAS , *CELL death , *B cells , *INTERLEUKIN-1 , *LYMPHOCYTES - Abstract
Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis. [ABSTRACT FROM AUTHOR]
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- 2004
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27. research paper Signalling molecules and cytokine production in T cells of multiple myeloma-increased abnormalities with advancing stage.
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Mozaffari, Fariba, Hansson, Lotta, Kiaii, Shahryar, Xiuli Ju, Shahryar, Rossmann, Eva D., Rabbani, Hodjattallah, Mellstedt, Håkan, and Öterborg, Anders
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T cells , *CELLULAR signal transduction , *CYTOKINES , *INTERLEUKIN-4 , *ENTEROTOXINS , *MOLECULES - Abstract
T-cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T-cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four-colour flow cytometry was applied to study the surface bound molecules TCR α β, CD28, CD152 and CD154 involved in T-cell signalling and the signal transduction molecules CD3 ζ, p56lck, p59fyn, ZAP-70 and phosphatidyl-inositol-3 kinase (PI3-k) as well as the intracellular cytokines interferon- γ (IFN- γ), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non-stimulated and superantigen-stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3 ζ, p56lck, ZAP-70 and PI3-k. The level of intracellular T-cell cytokines (IFN- γ, IL-2 and IL-4) was normal or increased in non-stimulated cells but activation-induced cytokine production was impaired. These results illustrated profound and multiple T-cell signalling defects, from the surface and down-stream, consistent with involvement of a master T-cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune-based therapeutic approaches and when applying new emerging technologies that aim to restore T-cell functions. [ABSTRACT FROM AUTHOR]
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- 2004
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28. Smartphone-assisted robust enzymes@MOFs-based paper biosensor for point-of-care detection.
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Kou, Xiaoxue, Tong, Linjing, Shen, Yujian, Zhu, Wangshu, Yin, Li, Huang, Siming, Zhu, Fang, Chen, Guosheng, and Ouyang, Gangfeng
- Subjects
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BIOSENSORS , *BIOMIMETIC materials , *METAL-organic frameworks , *URIC acid , *MOBILE apps , *CELLULAR signal transduction , *BIOMOLECULES - Abstract
Portable devices featured with fast analysis and affordable methodologies for clinical diagnostics have stimulated the rapid development of point-of-care (POC) technologies, potentially lowering the mortality rate. Herein, we demonstrated a portable, robust, and user-friendly intelligent metal-organic frameworks (MOFs) paper device, called smartphone-assisted biomimetic MOFs nanoreactor colorimetric paper (SBMCP), for on-demand POC detection of endogenous biomolecules. The concept of this paper platform was analogous to the intracellular cascades signal transduction, wherein the single/multiple enzymes components trapped within a ZIF-8 exoskeleton allowed the sensitive and selective recognition of target analyte via the accessible micropores network of ZIF-8, and then transferred the recognition event to a visual color signal based on the cascade reaction. Meanwhile, the ZIF-8 exoskeleton also endowed the enzymes with significantly elevated stability. As a result, this robust and portable SBMCP sensor enabled the on-site analysis of different important disease-related biomolecules through modulating the enzyme cascades, combining with a custom-designed smartphone application for signal readout. In the SBMCP assay, no sophisticated instruments or professional skill of the user was required, only 5 μL sample volume was needed, and the whole analysis process could be achieved within a portable MOFs paper and pervasive smartphone, endowing this new assay with the merits of low-cost, time-saving and easy-to-use. We demonstrated this SBMCP sensor was capable of real-time colorimetric detection of glucose and uric acid in diabetes and gout events. It is believed that this portable biosensor platform proposed herein potentially represents promising alternatives for POC diagnosis, especially applicable in developing world and resource-limited settings. Image 1 • A smartphone-assisted biomimetic MOFs paper device for POC detection was reported. • The stability of paper biosensor was significantly elevated by armour-like ZIF-8 exoskeleton. • On-demand detection for different biomarkers were achieved by modulating the enzyme cascades. • Real-time and on-site POC monitoring of glucose and uric acid in diabetes and gout events was achieved. [ABSTRACT FROM AUTHOR]
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- 2020
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29. Estudi del paper de l'annexina 6 en el transport intracel.lular. Implicació en la transducció del senyal
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Pons Pons, Mónica, Enrich Bastús, Carles, and Universitat de Barcelona. Departament de Biologia Cel·lular i Anatomia Patològica
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Cellular signal transduction ,Espectrina ,Lisosomes ,Membrane proteins ,Proteïnes de membrana ,Transducció de senyal cel·lular ,RAF ,Biological transport ,Transport biològic ,Lysosomes ,Ciències de la Salut - Abstract
[cat] La localització de l'anx6 ha estat sempre descrita associada a fosfolípids de membrana però el tipus de membrana discerneix segons el tipus cel.luar que s'estudia i l'anticos utilizat. En aquest estudi s'ha emprat un anticòs policlonal de conill contra la forma d'anx6 aïllada d'endosomes de fetge de rata. Concretament, en la membrana plasmàtica han classificat a l'anx6 com a proteïna estructural, unint-se per un costat a la membrana i per l'altre al citoesquelet, i també com a proteïna implicada en la transducció del senyal. També s'ha localitzat en compartiments endocítics i exocítics, així com en autofagosomes tardans. El nostre laboratori va trobar que en els hepatòcits de rata l'anx6 colocalitzava amb un marcador d'endosomes primerencs (Radb5) al voltant del canalicle biliar.
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- 2001
30. Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.
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Hu, Lifang, Chen, Wei, Qian, Airong, and Li, Yi-Ping
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WNT signal transduction ,BONE growth ,HOMEOSTASIS ,WNT proteins ,CATENINS ,CELL receptors ,CELLULAR signal transduction ,ADULT development - Abstract
Wnts are secreted, lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways, which control various biological processes throughout embryonic development and adult life. Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses. In this review, we provide an update of Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and diseases. The Wnt proteins, receptors, activators, inhibitors, and the crosstalk of Wnt signaling pathways with other signaling pathways are summarized and discussed. We mainly review Wnt signaling functions in bone formation, homeostasis, and related diseases, and summarize mouse models carrying genetic modifications of Wnt signaling components. Moreover, the therapeutic strategies for treating bone diseases by targeting Wnt signaling, including the extracellular molecules, cytosol components, and nuclear components of Wnt signaling are reviewed. In summary, this paper reviews our current understanding of the mechanisms by which Wnt signaling regulates bone formation, homeostasis, and the efforts targeting Wnt signaling for treating bone diseases. Finally, the paper evaluates the important questions in Wnt signaling to be further explored based on the progress of new biological analytical technologies. [ABSTRACT FROM AUTHOR]
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- 2024
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31. The research landscape of ferroptosis in neurodegenerative disease: a bibliometric analysis.
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Yun Liu, Dan Feng, Ling Shui, Yu-jie Wang, Li Yu, Yu-qi Liu, and Jin-yong Tian
- Subjects
SERIAL publications ,RESEARCH funding ,APOPTOSIS ,NEURODEGENERATION ,CELLULAR signal transduction ,DESCRIPTIVE statistics ,CHI-squared test ,CITATION analysis ,MEDICAL research ,BIBLIOMETRICS ,DATA analysis software - Abstract
Background: Ferroptosis, a newly proposed concept of programmed cell death, has garnered significant attention in research across different diseases in the last decade. Despite thorough citation analyses in neuroscience, there is a scarcity of information on ferroptosis research specifically related to neurodegenerative diseases. Method: The Web of Science Core Collection database retrieved relevant articles and reviews. Data on publications, countries, institutions, authors, journals, citations, and keywords in the included studies were systematically analyzed using Microsoft Excel 2019 and CiteSpace 6.2.R7 software. Result: A comprehensive analysis and visualization of 563 research papers on ferroptosis in neurodegenerative diseases from 2014 to 2023 revealed emerging research hotspots and trends. The number of annual publications in this field of study has displayed a pattern of stabilization in the early years of the decade, followed by a notable increase in the later years and peaking in 2023 with 196 publications. Regarding publication volume and total citations, notable research contributions were observed from countries, institutions, and authors in North America, Western Europe, and China. Current research endeavors primarily focus on understanding the intervention mechanisms of neurodegenerative diseases through the ferroptosis pathway and exploring and identifying potential therapeutic targets. Conclusion: The study highlights key areas of interest and emerging trends in ferroptosis research on neurodegenerative diseases, offering valuable insights for further exploration and potential directions for diagnosing and treating such conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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32. Agile Modelling of Cellular Signalling (Invited Paper).
- Author
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Danos, Vincent
- Subjects
CELLULAR signal transduction ,BIOLOGICAL models ,MODIFICATIONS ,PROTEIN-protein interactions ,BIOINFORMATICS - Abstract
Abstract: We illustrate with a simple example how using a rule-based approach to the modelling of protein interaction networks allows for quickly putting together models (ease of expression), and quickly modifying them (ease of variation). [Copyright &y& Elsevier]
- Published
- 2009
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33. Researchers at Semmelweis University Have Reported New Data on Gene Therapy (Cardioprotection by gene therapy A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology)
- Subjects
Genetic research ,Gene therapy ,Cardiology ,Genes ,Cellular signal transduction ,Health - Abstract
2015 JUL 9 (NewsRx) -- By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Current study results on Biotechnology have been published. According to news reporting originating from [...]
- Published
- 2015
34. Paper and Other Fibrous Materials—A Complete Platform for Biosensing Applications.
- Author
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Flores-Hernandez, Domingo R., Santamaria-Garcia, Vivian J., Melchor-Martínez, Elda M., Sosa-Hernández, Juan Eduardo, Parra-Saldívar, Roberto, and Bonilla-Rios, Jaime
- Subjects
THERAPEUTIC immobilization ,FOOD supply ,CELLULAR signal transduction ,FOOD quality ,QUALITY control - Abstract
Paper-based analytical devices (PADs) and Electrospun Fiber-Based Biosensors (EFBs) have aroused the interest of the academy and industry due to their affordability, sensitivity, ease of use, robustness, being equipment-free, and deliverability to end-users. These features make them suitable to face the need for point-of-care (POC) diagnostics, monitoring, environmental, and quality food control applications. Our work introduces new and experienced researchers in the field to a practical guide for fibrous-based biosensors fabrication with insight into the chemical and physical interaction of fibrous materials with a wide variety of materials for functionalization and biofunctionalization purposes. This research also allows readers to compare classical and novel materials, fabrication techniques, immobilization methods, signal transduction, and readout. Moreover, the examined classical and alternative mathematical models provide a powerful tool for bioanalytical device designing for the multiple steps required in biosensing platforms. Finally, we aimed this research to comprise the current state of PADs and EFBs research and their future direction to offer the reader a full insight on this topic. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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35. p-Coumaric-Acid-Containing Adenostemma lavenia Ameliorates Acute Lung Injury by Activating AMPK/Nrf2/HO-1 Signaling and Improving the Anti-oxidant Response.
- Author
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Chen, Jian-Jung, Deng, Jeng-Shyan, Huang, Chung-Chun, Li, Pei-Ying, Liang, Yu-Chia, Chou, Che-Yi, and Huang, Guan-Jhong
- Subjects
ANIMAL experimentation ,ANTI-inflammatory agents ,ANTIOXIDANTS ,BIOLOGICAL assay ,BIOLOGICAL models ,CELL culture ,CELLULAR signal transduction ,ANALYTICAL chemistry techniques ,HIGH performance liquid chromatography ,LUNG injuries ,MEDICINAL plants ,MICE ,PAPER chromatography ,PEPTIDES ,RESEARCH funding ,WESTERN immunoblotting ,PLANT extracts ,ACUTE diseases ,LIPOPOLYSACCHARIDES ,CELL survival ,IN vitro studies - Abstract
Adenostemma lavenia is a perennial herb belonging to the Compositae family and is widely distributed in the tropical parts of Asia. It has been widely used as medicine in Taiwan with the whole plant used to treat pulmonary congestion, pneumonia, bacterial infections of the respiratory tract, edema, and inflammation. This study sought to investigate the anti-inflammatory effects of A. lavenia in vitro and in animal models. The anti-inflammatory effects of ethyl acetate fractions of A. lavenia (EAAL) were stimulated with lipopolysaccharide (LPS) murine macrophages (RAW 264.7) and lung injury in mice. EAAL reduced proinflammatory cytokine responses. Preoral EAAL alleviated LPS-induced histological alterations in lung tissue and inhibited the infiltration of inflammatory cells and protein concentrations in bronchoalveolar lavage fluid (BALF). EAAL prevented protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2); phosphorylation of I κ B- α , MAPKs, and AMP-activated protein kinase (AMPK); and activated anti-oxidant enzymes (catalase, SOD, and GPx), heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) in LPS-stimulated cells and lung tissues. Fingerprinting of EAAL was performed with HPLC to control its quality, and p -coumaric acid was found to be a major constituent. This study suggests that EAAL is a potential therapeutic agent to treat inflammatory disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
36. Retraction: Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down-regulation of PI3K/AKT signaling pathway.
- Subjects
PI3K/AKT pathway ,POLYSACCHARIDES ,CELLULAR signal transduction ,HEMANGIOMAS ,APOPTOSIS ,ENDOTHELIAL cells - Abstract
The article titled "Retraction: Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down-regulation of PI3K/AKT signaling pathway" has been retracted from Bioscience Reports due to concerns raised by a reader regarding the appearance of Western blots and flow cytometry plots in the paper. The Western blots showed concerning features and the flow cytometry scatter plots were similar to those found in other papers by different authors. Additionally, some images in the paper appeared in papers by different authors. The authors have not responded to the concerns raised, and the Editorial Board has decided to retract the article. [Extracted from the article]
- Published
- 2024
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- View/download PDF
37. Association Between Atopic Dermatitis and Aging: Clinical Observations and Underlying Mechanisms.
- Author
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Chen, Peng-Yu, Shen, Minxue, Cai, Sui-Qing, and Tang, Zhen-Wei
- Subjects
ATOPIC dermatitis ,AGING ,OLDER people ,OLDER patients ,CELLULAR signal transduction ,PRESBYCUSIS - Abstract
As one of the most prevalent chronic inflammatory skin diseases, atopic dermatitis (AD) increasingly affects the aging population. Amid the ongoing global aging trend, it's essential to recognize the intricate relationship between AD and aging. This paper reviews existing knowledge, summarizing clinical observations of associations between AD and aging-related diseases in various systems, including endocrine, cardiovascular, and neurological. Additionally, it discusses major theories explaining the correlation, encompassing skin-mucosal barriers, systemic inflammation and stress, genes, signal transduction, and environmental and behavioral factors. The association between AD and aging holds significant importance, both in population and basic perspectives. While further research is warranted, this paper aims to inspire deeper exploration of inflammation/allergy-aging dynamics and the timely management of elderly patients with AD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Ianus Bifrons : The Two Faces of Metformin.
- Author
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Goglia, Umberto, Hasballa, Iderina, Teti, Claudia, Boschetti, Mara, Ferone, Diego, and Albertelli, Manuela
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THERAPEUTIC use of antineoplastic agents ,METFORMIN ,ADIPOSE tissues ,GLYCEMIC control ,CELLULAR signal transduction ,INSULIN resistance ,BLOOD sugar ,MOLECULAR structure ,CELL survival ,TUMORS ,DIABETES ,OBESITY ,PHARMACODYNAMICS - Abstract
Simple Summary: Metformin is one of the most widely used drugs in the world, since its first use in the second part of the 1950s in France (Aron, 1957) and in the United Kingdom (Rona, 1958), and is on the World Health Organization's List of Essential Medicines. Traditionally, metformin is used in diabetes mellitus, mainly in overweight and obese subjects, but also in other conditions of impaired glucose metabolism, such as insulin resistance. In recent years, in vitro and in vivo data on this molecule as an antiproliferative modulator have suggested a series of clinical trials in several tumors that—at the moment—have not confirmed the expected positive results. The aim of this paper is to offer a double vision of this molecule, with a very light side about the metabolic aspects and a darker side concerning its antineoplastic activity, focusing on molecular and subcellular pathways involved in both fields and discussing the contrast between preliminary cellular data and real clinical outcomes in different neoplasms. The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open? [ABSTRACT FROM AUTHOR]
- Published
- 2024
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39. Detecting Glucose Levels in Blood Plasma and Artificial Tear by Au(I) Complex on the Carbopol Polymer: A Microfluidic Paper-Based Method.
- Author
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Luo, Jong-Jheng, Pan, Sheng-Wei, Yang, Jia-Hui, Chang, Tian-Lin, Lin, Peng-Yi, Wu, Chen-Liang, Liu, Wei-Fang, Huang, Xin-Ru, Koshevoy, Igor O., Chou, Pi-Tai, and Ho, Mei-Lin
- Subjects
- *
BLOOD plasma , *FLUORESCENCE , *MICROFLUIDICS , *PHOSPHORESCENCE , *CELLULAR signal transduction , *DIAGNOSIS of diabetes - Abstract
We report on a selective paper-based method and a microfluidic paper-based analytical device (μPAD) for the detection of human plasma glucose and tear glucose using carbopol polymer-encapsulated Au(I) complex (AuC2C6H4OMe)2(Ph2P(C6H4)3PPh2), (B5). To the best of our knowledge, this demonstrates for the first time the glucose sensing based on dual emission, i.e., fluorescence and phosphorescence, of a single type molecule on the carbopol polymer. Upon addition of human blood treated with anticoagulants to μPADs, plasma is separated from the blood and flows into the response region of the μPADs to react with carbopol polymer-encapsulated B5, in which the ratiometric luminescence is analyzed. The plasma glucose concentration can be quantitively detected at 1.0–50.0 mM on paper, and tear glucose can be detected at 0.1–4.0 mM on μPADs. Owing to the structural design, this device has superior ratiometric changes of dual emission over other Au(I) complexes for signal transduction. The encapsulation of carbopol polymer also offers long-term storage stability. In tear measurement, carbopol polymer is not only used to encapsulate enzyme to remain the enzyme's activity, but also played as a glue (or media) to connect microfluidic channel and response region. This further improves the sensitivity and limit of detection for glucose. Moreover, this sensor provides a faster response time, a wider range for glucose sensing than reported previously, and no statistical difference of the data from a commercial glucometer, allowing for practical diagnosis of diabetes and healthy individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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40. Priority paper Partially deglycosylated human choriogonadotropin, stabilized by intersubunit disulfide bonds, shows full bioactivity.
- Author
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Heikoop, Judith C., van den Boogaart, Paul, de Leeuw, Renato, Rose, Ursula M., Mulders, John W. M., and Grootenhuis, Peter D. J.
- Subjects
- *
CHORIONIC gonadotropins , *OLIGOSACCHARIDES , *CELLULAR signal transduction - Abstract
Several studies indicate that in human choriogonadotropin the N-linked oligosaccharide at position 52 of the α-subunit is important for bioactivity. We have generated choriogonadotropin mutants in which the α52 glycosylation site is removed and the α and β subunits are covalently linked by intersubunit disulfide bonds. These mutants display wild-type receptor binding and bioactivity. Furthermore, we show that removal of the α52 sugar leads to instability of heterodimeric choriogonadotropin. Therefore, we conclude that the α52 oligosaccharide of choriogonadotropin is not involved in signal transduction, but in the stability of the heterodimer. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
41. Special Issue: "Inflammatory Signaling Pathways Involved in Gastrointestinal Diseases".
- Author
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Lauricella, Marianna and Di Liberto, Diana
- Subjects
GASTROINTESTINAL diseases ,CELLULAR signal transduction ,INFLAMMATORY bowel diseases ,CROHN'S disease ,THERAPEUTICS ,HISTAMINE receptors - Abstract
This document is a special issue of the International Journal of Molecular Sciences titled "Inflammatory Signaling Pathways Involved in Gastrointestinal Diseases." It contains six papers, including two research articles and four reviews, that explore the role of inflammation in gastrointestinal diseases and potential therapeutic strategies. The papers discuss topics such as chronic inflammation in Inflammatory Bowel Disease (IBD), the role of heat shock proteins and histamine in IBD, the use of polyphenols as anti-inflammatory agents, the potential of miR-369-3p as a therapeutic approach for IBD, the relationship between gut disorders and immune system deregulation, and the pathogenesis of Barrett's esophagus. The authors express gratitude to the contributors and declare no conflicts of interest. [Extracted from the article]
- Published
- 2024
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- View/download PDF
42. Mechanosensitive receptors in migraine: a systematic review.
- Author
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Della Pietra, Adriana, Gómez Dabó, Laura, Mikulenka, Petr, Espinoza-Vinces, Christian, Vuralli, Doga, Baytekin, Isil, Martelletti, Paolo, and Giniatullin, Rashid
- Subjects
MEDICAL databases ,NEUROBIOLOGY ,MIGRAINE ,SYSTEMATIC reviews ,CELLULAR signal transduction ,TRANSCRIPTION factors ,MEDLINE ,DRUG development ,NOCICEPTIVE pain - Abstract
Background: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. Methods: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. Results: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. Conclusions: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. [Retracted] ATP‑binding cassette transporter A7 accelerates epithelial‑to‑mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor‑β signaling pathway.
- Author
-
Liu, Xia, Li, Qing, Zhou, Jing, and Zhang, Su
- Subjects
EPITHELIAL-mesenchymal transition ,ATP-binding cassette transporters ,OVARIAN cancer ,CELLULAR signal transduction ,CANCER cells ,CANCER cell proliferation - Abstract
This article, published in Oncology Letters, discusses the role of ATP-binding cassette transporter A7 (ABCA7) in promoting epithelial-to-mesenchymal transition (EMT) in ovarian cancer cells by upregulating the transforming growth factor-β (TGF-β) signaling pathway. However, the paper has been retracted due to concerns raised by a reader regarding the similarity of certain data in Figure 4C to data published in another article by different authors. The authors were asked for an explanation but did not respond. The Editor has decided to retract the paper and apologizes for any inconvenience caused. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
44. Network pharmacology-based mechanism analysis of dauricine on the alleviating Aβ-induced neurotoxicity in Caenorhabditis elegans.
- Author
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Zhang, Ranran, Huang, Xiaoyan, Zhou, Chunling, Zhang, Qian, Jia, Dongsheng, Xie, Xiaoliang, and Zhang, Ju
- Subjects
SYNDROMES ,COMPUTER-assisted molecular modeling ,PROTEINS ,ALZHEIMER'S disease ,ALKALOIDS ,NEUROTOXICOLOGY ,AUTOPHAGY ,RESEARCH funding ,PHARMACEUTICAL chemistry ,NEMATODES ,IN vivo studies ,DESCRIPTIVE statistics ,CELLULAR signal transduction ,PLANT extracts ,GENE expression ,EXPERIMENTAL design ,PHENOLS ,ANIMAL experimentation ,METABOLISM ,ISOQUINOLINE ,AMYLOID beta-protein precursor - Abstract
Background: Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer's disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. Methods: Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. Results: There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of "compound-target-biological process-pathway network". Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aβ aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T(Th-T)staining experiment revealed that DAU decreased Aβ accumulation in AD nematodes. Further experiments also confirmed DAU's protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. Conclusion: Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aβ aggregation and the restoration of protein homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Mitochondria: a new intervention target for tumor invasion and metastasis.
- Author
-
Zhou, Quanling, Cao, Tingping, Li, Fujun, Zhang, Ming, Li, Xiaohui, Zhao, Hailong, and Zhou, Ya
- Subjects
- *
MITOCHONDRIAL DNA , *PHENOMENOLOGICAL biology , *METASTASIS , *CELLULAR signal transduction , *BIOLOGY - Abstract
Mitochondria, responsible for cellular energy synthesis and signal transduction, intricately regulate diverse metabolic processes, mediating fundamental biological phenomena such as cell growth, aging, and apoptosis. Tumor invasion and metastasis, key characteristics of malignancies, significantly impact patient prognosis. Tumor cells frequently exhibit metabolic abnormalities in mitochondria, including alterations in metabolic dynamics and changes in the expression of relevant metabolic genes and associated signal transduction pathways. Recent investigations unveil further insights into mitochondrial metabolic abnormalities, revealing their active involvement in tumor cell proliferation, resistance to chemotherapy, and a crucial role in tumor cell invasion and metastasis. This paper comprehensively outlines the latest research advancements in mitochondrial structure and metabolic function. Emphasis is placed on summarizing the role of mitochondrial metabolic abnormalities in tumor invasion and metastasis, including alterations in the mitochondrial genome (mutations), activation of mitochondrial-to-nuclear signaling, and dynamics within the mitochondria, all intricately linked to the processes of tumor invasion and metastasis. In conclusion, the paper discusses unresolved scientific questions in this field, aiming to provide a theoretical foundation and novel perspectives for developing innovative strategies targeting tumor invasion and metastasis based on mitochondrial biology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Autophagy regulates apoptosis of colorectal cancer cells based on signaling pathways.
- Author
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Yan, Yuwei, Yu, Wenyan, Guo, Min, Zhu, Naicheng, Chen, Xiudan, Li, Nanxin, Zhong, Chen, and Wang, Guojuan
- Subjects
COLORECTAL cancer ,CANCER cells ,CELL communication ,CELLULAR signal transduction ,CARCINOGENESIS - Abstract
Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.
- Author
-
Banglu Wang, Fan Zhang, Xiaoyu Wu, and Mei Ji
- Subjects
TYPE I interferons ,CANCER invasiveness ,NATURAL immunity ,IMMUNE response ,CELLULAR signal transduction - Abstract
TANK-binding kinase 1 (TBK1) is a member of the IKK family and plays a crucial role in the activation of non-canonical NF-kB signaling and type I interferon responses. The aberrant activation of TBK1 contributes to the proliferation and survival of various types of tumor cells, particularly in specific mutational or tumorous contexts. Inhibitors targeting TBK1 are under development and application in both in vivo and in vitro settings, yet their clinical efficacy remains limited. Numerous literatures have shown that TBK1 can exhibit both tumor promoting and tumor inhibiting effects. TBK1 acts as a pivotal node within the innate immune pathway, mediating anti-tumor immunity through the activation of innate immune responses. Facilitating interferon-I (IFN-I) production represents a critical mechanism through which TBK1 bridges these processes. IFN has been shown to exert both beneficial and detrimental effects on tumor progression. Hence, the paradoxical role of TBK1 in tumor development may necessitate acknowledgment in light of its downstream IFNI signaling cascade. In this paper, we review the signaling pathways mediated by TBK1 in various tumor contexts and summarize the dual roles of TBK1 and the TBK1-IFN pathways in both promoting and inhibiting tumor progression. Additionally, we highlight the significance of the TBK1-IFN pathway in clinical therapy, particularly in the context of immune response. We anticipate further advancements in the development of TBK1 inhibitors as part of novel cancer treatment strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
48. Wnt signaling pathway in spinal cord injury: from mechanisms to potential applications.
- Author
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Kai Li, Zanzhi Chen, Xuejing Chang, Ruiyang Xue, Huaibo Wang, and Weitao Guo
- Subjects
WNT signal transduction ,NEURAL transmission ,CELLULAR signal transduction ,SPINAL cord injuries ,NEURONAL differentiation - Abstract
Spinal cord injury (SCI) denotes damage to both the structure and function of the spinal cord, primarily manifesting as sensory and motor deficits caused by disruptions in neural transmission pathways, potentially culminating in irreversible paralysis. Its pathophysiological processes are complex, with numerous molecules and signaling pathways intricately involved. Notably, the pronounced upregulation of the Wnt signaling pathway post-SCI holds promise for neural regeneration and repair. Activation of the Wnt pathway plays a crucial role in neuronal differentiation, axonal regeneration, local neuroinflammatory responses, and cell apoptosis, highlighting its potential as a therapeutic target for treating SCI. However, excessive activation of the Wnt pathway can also lead to negative effects, highlighting the need for further investigation into its applicability and significance in SCI. This paper provides an overview of the latest research advancements in the Wnt signaling pathway in SCI, summarizing the recent progress in treatment strategies associated with the Wnt pathway and analyzing their advantages and disadvantages. Additionally, we offer insights into the clinical application of the Wnt signaling pathway in SCI, along with prospective avenues for future research direction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.
- Author
-
Liu, Qi, Wang, Senyan, Fu, Jing, Chen, Yao, Xu, Jing, Wei, Wenjuan, Song, Hao, Zhao, Xiaofang, and Wang, Hongyang
- Subjects
LIVER regeneration ,STEM cell transplantation ,LIVER cells ,CELLULAR signal transduction ,HUMAN body - Abstract
The liver possesses a distinctive capacity for regeneration within the human body. Under normal circumstances, liver cells replicate themselves to maintain liver function. Compensatory replication of healthy hepatocytes is sufficient for the regeneration after acute liver injuries. In the late stage of chronic liver damage, a large number of hepatocytes die and hepatocyte replication is blocked. Liver regeneration has more complex mechanisms, such as the transdifferentiation between cell types or hepatic progenitor cells mediated. Dysregulation of liver regeneration causes severe chronic liver disease. Gaining a more comprehensive understanding of liver regeneration mechanisms would facilitate the advancement of efficient therapeutic approaches. This review provides an overview of the signalling pathways linked to different aspects of liver regeneration in various liver diseases. Moreover, new knowledge on cellular interactions during the regenerative process is also presented. Finally, this paper explores the potential applications of new technologies, such as nanotechnology, stem cell transplantation and organoids, in liver regeneration after injury, offering fresh perspectives on treating liver disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. The roles of AIM2 in neurodegenerative diseases: insights and therapeutic implications.
- Author
-
Kai Yang, Xi Wang, Hanyu Pan, Xinqing Wang, Yunhan Hu, Yihe Yao, Xinyue Zhao, and Taolei Sun
- Subjects
PARKINSON'S disease ,ALZHEIMER'S disease ,NEURODEGENERATION ,DISEASE progression ,CELLULAR signal transduction - Abstract
AIM2, a cytosolic innate immune receptor, has the capability to recognize doublestranded DNA (dsDNA). This paper delineates the structural features of AIM2 and its mechanisms of activation, emphasizing its capacity to detect cytosolic DNA and initiate inflammasome assembly. Additionally, we explore the diverse functions of AIM2 in different cells. Insights into AIM2-mediated neuroinflammation provide a foundation for investigating novel therapeutic strategies targeting AIM2 signaling pathways. Furthermore, we present a comprehensive review of the roles of AIM2 in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Finally, we discuss its therapeutic implications. In conclusion, a profound understanding of AIM2 in neurodegenerative diseases may facilitate the development of effective interventions to mitigate neuronal damage and slow disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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