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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 HL6 SWWR regulated trichomes on leaves and expression levels of HL6 SWWR affected trichome elongation. Transgenic experiments of PRO SWWR :HL6 NIP and PRO NIP :HL6 SWWR indicated that the promoter and coding sequences of HL6 SWWR 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 hl6 SWWR mutant vs wild type and that 1 010 DEGs were found in HL6 SWWR 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]

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]

• 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]

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]

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]

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]

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]

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]

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]

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]

The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression modulated by periodontal pathogens in cells and animal models for atherosclerosis. Cochrane, PRISMA and AMSTAR2 guidelines for systematic reviews were followed. Data search was conducted in Pub-med, LILACS and Science Direct databases. Gene and protein expression data were collected from the included papers to perform an overrepresentation analysis using the Reactome Pathway Analysis tool and the KEGG database. Thirty-two papers were included in the review, they analyzed the effect of Fusobacterium nucleatum , Porphyromonas gingivalis , Streptococcus anginosus , Streptococcus sanguinis , Tannerella forsythia , and Treponema denticola or/and their virulent factors on gene and protein expression in human cells and animal models of atherosclerosis. Some of the modulated pathways include the immune system, programmed cell death, cellular responses to external stimuli, transport of small molecules, and signal transduction (p < 0.05). Those pathways are known to be involved in different stages of atherosclerosis progression. Based on the performed analysis, it is possible to state that periodontal pathogens have the potential to be a contributing factor for atherosclerosis even in absence of a high-fat diet or high shear stress. [ABSTRACT FROM AUTHOR]

Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4. A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT , ATRX , TERT , and/or TP53. The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2 , high expression of RAD18 , homozygous deletion of CDKN2A/B , amplification of PDGFRA , copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies. Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation. • Multiple molecular markers associated with survival in IDH-mutant astrocytoma patients. • RB and RTK-PI3K-mTOR signalling pathways are commonly affected. • Genomic stability and (epigenetic) gene regulation markers are often affected as well. • Few molecular markers have been validated in independent patient cohorts. • International collaborations should enforce more and uniform data collection. [ABSTRACT FROM AUTHOR]

In recent years, Chinese herbal medicine has gained more and more recognition in disease prevention and control due to its low toxicity and comprehensive treatment. C. morifolium (Chrysanthemum morifolium Ramat.), as the medicine food homology plant with the bioactivity of anti-oxidation, anti-inflammatory, neuroprotection and cardiovascular protection, has important therapeutic effects and health benefits for colds, inflammation, cardiovascular diseases and various chronic diseases. By reviewing the historical development, classification and distribution of germplasm resources, phytochemistry, pharmacology, and modern application of C. morifolium , the paper provides a reliable basis for the further research and application of chrysanthemum as therapeutic agents and functional additives. The literature and information about C. morifolium published in the last ten years were collected from various platforms, including Google Scholar, PubMed, ScienceDirect, Web of Science and China Knowledge Network. A comprehensive analysis confirmed that C. morifolium originated in China, and it went through the development process from food and tea to medicine for more than 3000 years. During this period, different cultivars emerged through several breeding techniques and were distributed throughout the world. Moreover, A variety of chemical components such as flavonoids, phenolic acids, volatile oils, and terpenes in chrysanthemum have been proven they possess various pharmacology of anti-inflammatory, anti-oxidant, and prevention of chronic diseases by regulating inflammatory cytokines, oxidative stress responses and signaling pathways, which are the essential conditions to play a role in TCM, nutraceuticals and diet. This paper provides a comprehensive review of historical development, classification, phytochemistry, pharmacology, and modern application of C. morifolium. However, future studies should continue to focus on the bioactive compounds and the synergistic mechanism of the "multi-component, multi-target, and multi-pathway" of chrysanthemum, and it is necessary to develop more innovative products with therapeutic effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is a widely studied plant that shows potential in treating urinary diseases. Previous studies have focused on its chemical composition, pharmacological effects, and clinical applications. This review aims to provide a comprehensive summary and evaluation of the existing literature on CS. It also suggests future research directions to increase our understanding of its medicinal value. 129 pieces of literature were selected from several databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Database, and Google Scholar, and were analyzed. Forty-five active compounds of CS have pharmacological effects such as lowering uric acid, anti-inflammation, anti-oxidation, and kidney protection. The potential mechanisms of these effects may be related to inhibiting transforming growth factor β1 (TGF-β1) activation, reducing inflammatory factors such as IL-8, IL-1β, TNF-α, PGE2, IFN-γ, and IL-6 levels, suppressing the activation of NF-κB, JAK/STAT pathway, enhancing the clearance of ROS, MDA DPPH·, and O 2 ̇ −, and regulating the expression of apoptosis-related pathways and proteins. This paper also discusses the quality control of CS and its efficacy and safety in treating urinary diseases. The study concludes that CS has a high potential for treating urinary diseases. Future studies should focus on observing the metabolic changes of CS active compounds in vivo and investigating the effects of CS on key signaling pathways. Additionally, more standardized and reasonable clinical studies and safety evaluation experiments should be conducted to obtain more clinical data. [Display omitted] • The mechanism of CS treatment in urinary disease was summarized. • Summarized the role of active constituents or sites of CS in underlying mechanisms. • It presents conclusions about the cytokine changes observed in patients after applying CS. • The assistant therapy action and side effect evaluation of CS were discussed in detail. [ABSTRACT FROM AUTHOR]

Serotonin, a monoamine neurotransmitter, participates in signal transduction in the nervous systems of organisms. It is essential in the coordination of movement and regulation of mood. As the production of serotonin via chemical synthesis and tissue extraction is limited, production by microorganisms has attracted considerable attention in recent years. Tryptophan is an essential precursor for serotonin biosynthesis; this amino acid can be converted to serotonin through hydroxylation and decarboxylation. In vivo , the tryptophan regulatory network and synthetic pathway are complex. This paper discusses existing methods of serotonin production and introduces the metabolic pathway of serotonin biosynthesis by microorganisms. Additionally, metabolic strategies for the efficient production of tryptophan in Escherichia coli are summarised. Strategies for serotonin synthesis by engineered E. coli are identified. Finally, suggestions for constructing additional efficient serotonin-producing strains are presented. • Demonstrating the metabolic pathway of de novo serotonin biosynthesis by microorganisms. • Summarizing metabolic strategies for the efficient production of tryptophan in E. coli. • Proposing strategies for efficient serotonin synthesis by engineered E. coli. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 18:2) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 18:2 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1β, IL-6, and TNF-α in the hippocampus, serum, and colon were reduced by M 18:2. Furthermore, M 18:2 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified , as well as increased genera Muribaculaceae_unclassified , Muribaculum , Alistipes , and Bacteroides , which may be the possible biomarkers of cognitive aging. In summary, M 18:2 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota. [Display omitted] • Macamides could stably bind to AChE. • M 18:2 ameliorated the cognitive deficit in scopolamine-induced mice. • M 18:2 inhibited the activities of AChE, BuChE, MAO in scopolamine-induced mice. • M 18:2 improved the synaptic plasticity in scopolamine-induced mice. • M 18:2 modulated the composition of gut microbiota. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a serious and disabling central nervous system injury. Its complex pathological mechanism can lead to sensory and motor dysfunction. It has been reported that signaling pathway plays a key role in the pathological process and neuronal recovery mechanism of SCI. Such as PI3K/Akt, MAPK, NF-κB, and Wnt/β-catenin signaling pathways. According to reports, various stimuli and cytokines activate these signaling pathways related to SCI pathology, thereby participating in the regulation of pathological processes such as inflammation response, cell apoptosis, oxidative stress, and glial scar formation after injury. Activation or inhibition of relevant pathways can delay inflammatory response, reduce neuronal apoptosis, prevent glial scar formation, improve the microenvironment after SCI, and promote neural function recovery. Based on the role of signaling pathways in SCI, they may be potential targets for the treatment of SCI. Therefore, understanding the signaling pathway and its inhibitors may be beneficial to the development of SCI therapeutic targets and new drugs. This paper mainly summarizes the pathophysiological process of SCI, the signaling pathways involved in SCI pathogenesis, and the potential role of specific inhibitors/activators in its treatment. In addition, this review also discusses the deficiencies and defects of signaling pathways in SCI research. It is hoped that this study can provide reference for future research on signaling pathways in the pathogenesis of SCI and provide theoretical basis for SCI biotherapy. [ABSTRACT FROM AUTHOR]

Abstract This work proposes a novel approach to investigate the behavior of single chamber microbial fuel cells (SCMFCs) based sensors by implementing fluid dynamic simulations to especially investigate the role of diffusion phenomena. When different flow rates are applied (i.e., 25 mL/h and 100 mL/h) the electrolyte flows differently into the cell, changing its speed and the drift-area (A drift) in which the fluid/electrolyte is directly pushed during the drift process. Asymmetric squared SCMFCs (a-SCMFCs) ensure optimal fluid motion thanks to their architecture that maximizes the drift-area. In this work a-SCMFCs are tested as acetate bio-sensors using carbon paper and carbon felt as anodes. Experimental results show that the behavior of a-SCMFCs-based sodium acetate biosensors is strongly influenced by the morphology of both carbon felt and carbon paper-based anodes. We used fluid dynamics simulations implementing both the drift and the diffusion processes to gain new information on the behavior of carbon paper and carbon felt anodes. We especially investigated the role of their porosity, in determining the actual fluid distribution and analyte concentration inside the device, at the surface of the porous material and into its volume. We demonstrate that less porous materials, as carbon paper, are more adequate to be used in single chamber MFC-based biosensors. Indeed they can favor an optimal fluid motion, especially favoring more uniform diffusion phenomena and interaction between biofilm and surface than corrugates surfaces, as those characterizing carbon felt, resulting in a more effective analyte conversion and signal transduction. Highlights • Fluid dynamics modelling is an effective tool to design MFC-based biosensors and investigate their behavior. • Morphology of materials selected as anodes in SCMFC-based sensors significantly affect the behavior of the systems. • The Biofilm/Electrode interface plays a dominant role in SCMFC-based biosensors. [ABSTRACT FROM AUTHOR]

Abstract Background Myriads of signaling pathways in a single cell function to achieve the highest spatio-temporal integration. Data are accumulating on the role of electromechanical soliton-like waves in signal transduction processes. Theoretical studies strongly suggest feasibility of both classical and quantum computing involving microtubules. Aim A theoretical study of the role of the complex composed of the plasma membrane and the microtubule-based cytoskeleton as a system that transmits, stores and processes information. Methods Theoretical analysis presented here refers to (i) the Penrose–Hameroff theory of consciousness (Orchestrated Objective Reduction; Orch OR), (ii) the description of the centrosome as a reference system for construction of the 3D map of the cell proposed by Regolini, (iii) the Heimburg–Jackson model of the nerve pulse propagation along axons' lipid bilayer as soliton-like electro-mechanical waves. Results and conclusion The ideas presented in this paper provide a qualitative model for the decision-making processes in a living cell undergoing a differentiation process. Outlook This paper paves the way for the real-time live-cell observation of information processing by microtubule-based cytoskeleton and cell fate decision making. [ABSTRACT FROM AUTHOR]

The endogenous and dietary agent, alpha lipoic acid (ALA), is evaluated for its capacity to induce a broad spectrum of adaptive responses via hormetic dose responses and their underlying mechanisms. ALA was shown to induce hormetic effects in a wide range of experimental models within in vitro and in vivo experimental settings which included direct exposure and pre- and post-conditioning experimental protocols. The hormetic effects occur in a broad range of organ systems, including the brain, heart, kidney and other tissues, with possible public health and clinical/therapeutic applications linked to reducing the onset and progression of neurogenerative diseases and also in the preservation of sperm health and functionality during cryopreservation. This paper provides the first integrated assessment of ALA-induced hormetic dose responses. Underlying mechanisms that mediated the occurrence of ALA-induced hormetic effects involved the induction of low levels of ROS that activate key cell signaling antioxidant (e.g. Nrf2) pathways. [Display omitted] • First paper assessing capacity of ALA to induce hormetic dose responses. • ALA was shown to induce hormetic effects in a wide range of experimental models. • Experiments included direct exposure and pre- and post-conditioning protocols. • ALA induced protective effects via hormesis in a broad range of tissues/cell types. • Mechanisms involving low levels of ROS activate key cell signaling pathways. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a potentially lethal disorder that can have serious consequences for a woman's health. Because early symptoms are typically only present in the middle to late stages of the disease, clinical diagnosis and treatment can be challenging. Traditional Chinese medicine (TCM) has been shown to have unique benefits in terms of alleviating cancer clinical symptoms, lowering the risk of recurrence after surgery, and reducing toxic side effects and medication resistance after radiation therapy. It has also been shown to improve the quality of life for patients. Because of its improved anti-tumor effectiveness and biosafety, it could be considered an alternative therapy option. This study examines how TCM causes apoptosis in CC cells via signal transduction, including the active components and medicinal tonics. It also intends to provide a reliable clinical basis and protocol selection for the TCM therapy of CC. The following search terms were employed in PubMed, Web of Science, Embase, CNKI, Wanfang, VIP, SinoMed, and other scientific databases to retrieve pertinent literature on "cervical cancer," "apoptosis," "signaling pathway," "traditional Chinese medicine," "herbal monomers," "herbal components," "herbal extracts," and "herbal formulas." It has been demonstrated that herbal medicines can induce apoptosis in cells of the cervix, a type of cancer, by influencing the signaling pathways involved. A comprehensive literature search was conducted, and 148 papers from the period between January 2017 and December 2023 were identified as eligible for inclusion. After a meticulous process of screening, elimination and summary, generalization, and analysis, it was found that TCM can regulate multiple intracellular signaling pathways and related molecular targets, such as STAT3, PI3K/AKT, Wnt/β-catenin, MAPK, NF-κB, p53, HIF-1α, Fas/FasL and so forth. This regulatory capacity was observed to induce apoptosis in cervical cancer cells. The study of the mechanism of TCM against cervical cancer and the screening of new drug targets is of great significance for future research in this field. The results of this study will provide ideas and references for the future development of Chinese medicine in the diagnosis and treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis. • Briefly describe the concept, basic mechanism and signaling pathway of ferroptosis. • Pointed out the relationship between ferroptosis and hypoxia. • The positive and negative regulation of HIF-1α and HIF-2α on ferroptosis in normal cells and tumor cells was explored. • Point out the important role of ferroptosis in hypoxic diseases. [ABSTRACT FROM AUTHOR]

Stimulated production of secondary phenolic metabolites and proline was studied by using cell cultures of artichoke [ Cynara cardunculus L. subsp. scolymus (L.) Hayek] submitted to nutritional stress. Artichoke cell cultures accumulated phenolic secondary metabolites in a pattern similar to that seen in artichoke leaves and heads (capitula). This paper shows that both callus and cell suspension cultures under nutritional stress accumulated phenolic compounds and proline, at the same time their biomass production was negatively affected by nutrient deficiency. The results obtained strongly suggest that plant tissues respond to nutrient deprivation by a defensive costly mechanism, which determines the establishment of a mechanism of trade-off between growth and adaptive response. Furthermore, the results of this research suggest that perception of abiotic stress and increased phenolic metabolites are linked by a sequence of biochemical processes that also involves the intracellular free proline and the oxidative pentose phosphate pathway. The main conclusion of this paper is that, once calli and cell suspension cultures respond to nutrient deficiency, in acclimated cells the establishment of a negative correlation between primary metabolism (growth) and secondary metabolism (defence compounds) is observed. [ABSTRACT FROM AUTHOR]

As a unique iron-dependent non-apoptotic cell death, Ferroptosis is involved in the pathogenesis and development of many human diseases and has become a research hotspot in recent years. However, the regulatory role of ferroptosis in the gut-liver-brain axis has not been elucidated. This paper summarizes the regulatory role of ferroptosis and provides theoretical basis for related research. We searched PubMed, CNKI and Wed of Science databases on ferroptosis mediated gut-liver-brain axis diseases, summarized the regulatory role of ferroptosis on organ axis, and explained the adverse effects of related regulatory effects on various diseases. According to our summary, the main way in which ferroptosis mediates the gut-liver-brain axis is oxidative stress, and the key cross-talk of ferroptosis affecting signaling pathway network is Nrf2/HO-1. However, there were no specific marker between different organ axes mediate by ferroptosis. Our study illustrates the main ways and key cross-talk of ferroptosis mediating the gut-liver-brain axis, providing a basis for future research. [Display omitted] • Clarifing the regulation and physiopathology of ferroptosis on gut-liver-brain axis. • Clarifing ferroptosis mediating the gut-liver-brain axis is oxidative stress. • Integrating signaling pathways of gut-liver-brain axis mediating ferroptosis. • The key cross-talk of ferroptosis affecting signaling pathway network is Nrf2/HO-1. • There was no differential marker in different ferroptosis-mediated organ axis. [ABSTRACT FROM AUTHOR]

PFOA is one of the most representative compounds in the family of perfluorinated organic compounds. Due to its varying toxicity, alternatives to PFOA are beginning to emerge. HFPO-TA is an alternative for PFOA. It is currently unclear whether HFPO-TA affects glucose and lipid metabolism. In this study, rats were used as an animal model to investigate the effects of HFPO-TA on liver glucose and lipid metabolism. We found that HFPO-TA can affect glucose tolerance. Through omics analysis and molecular detection, it was found that HFPO-TA mainly affects the PPAR signaling pathway in the liver of rats, inhibiting liver glycolysis while promoting glucose production. HFPO-TA not only promotes the synthesis of fatty acids in the liver, but also promotes the breakdown of fatty acids, which ultimately leads to the disruption of hepatic glucose and lipid metabolism. The effects of HFPO-TA on metabolism are discussed in this paper to provide a reference for the risk assessment of this PFOA substitute. [Display omitted] • HFPO-TA affects the genes, metabolites involved in glucose and lipid metabolism. • HFPO-TA inhibits glycolysis while promoting glucose synthesis. • HFPO-TA affects the PPAR signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Au NPs/PC ZIF-8 -ZnO was acted as sensing substrate for signal amplification. • An electrochemical/photoelectrochemical dual-mode aptasensor was constructed. • The dual-mode AFB 1 aptasensor had a wide linear range with a low LOD. • The aptasensor was successfully applied for AFB1 detection in peanut samples. Aflatoxin B1 (AFB 1), a hepatotoxic and carcinogenic food contaminant, is commonly found in agricultural food. Herein, Au NPs anchored ZIF-8-derived porous carbon-ZnO (Au NPs/PC ZIF-8 -ZnO) was firstly synthesized to act as the sensing substrate. Then, a ratiometric electrochemical (EC) and "off–on" photoelectrochemical (PEC) dual-mode paper-based aptasensor was presented for AFB 1 detection based on a distance-modulation sensing strategy. The independent signal transduction mechanisms and output mode not only broaden the dynamic detection range but also provide a self-verification to assay results, improving the sensitivity and reliability. The wide detection ranges of 0.1 pg/mL-100 ng/mL (EC mode) and 0.02 pg/mL-100 ng/mL (PEC mode) were obtained using dual-mode aptasensor, with detection limits of 36.7 and 9.3 fg/mL, respectively. The fabricated aptasensor exhibited excellent selectivity, reproducibility and stability. Furthermore, it exhibited good practicability for AFB 1 assays in real samples, demonstrating great potential applications for food safety evaluation. [ABSTRACT FROM AUTHOR]

Iron is an essential micronutrient for maintaining physiological activities, especially for highly active cardiomyocytes. Inappropriate iron overload or deficiency has a significant impact on the incidence and severity of cardiovascular diseases (CVD). Iron overload exerts potentially deleterious effects on doxorubicin (DOX) cardiomyopathy, atherosclerosis, and myocardial ischemia-reperfusion injury (MI/RI) by participating in lipid peroxides production. Notably, iron overload-associated cell death has been defined as a possible mechanism for ferroptosis. At present, some traditional herbal medicines and extracts have been included in the study of regulating iron overload and the subsequent therapeutic effect on CVD. To give an outline of iron metabolism and ferroptosis in cardiomyocytes and to focus on herbal medicines and extracts to prevent iron overload in CVD. Literature information was systematically collected from ScienceDirect, PubMed, Google Scholar, Web of Science, China National Knowledge Infrastructure, WanFang data, as well as classic books and clinical reports. After understanding the mechanism of iron overload on CVD, this paper reviews the therapeutic function of various herbal medicines in eliminating iron overload in CVD. These include Chinese herbal compound prescriptions (Salvia miltiorrhiza injection, Gegen Qinlian decoction, Tongxinluo, Banxia-Houpu decoction), plant extracts, phenylpropanoids, flavonoids, terpenoids, and polyphenols. Among them, flavonoids are considered to be the most promising compounds because of their prominent iron chelation. Mechanically, these herbal medicines act on the Nrf2 signaling pathway, AMPK signaling pathway, and KAT5/GPX4 signaling pathway, thereby attenuating iron overload and lipid peroxidation in CVD. Our review provides up-to-date information on herbal medicines that exert cardiovascular protective effects by modulating iron overload and ferroptosis. These herbal medicines hold promise as a template for preventing iron overload in CVD. [Display omitted] • Iron overload exerts potentially deleterious effects in cardiovascular diseases. • The protective effects of various herbal medicines on eliminating iron overload in cardiovascular diseases. • Flavonoids have prominent iron chelates and are considered to be the most promising compounds. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions. [Display omitted] • Sirtuins (SIRTs), as key regulatory factors in cellular processes, are deeply involved in many life processes. • SIRTs modulators have shown great potential in treating various diseases and maintaining physiological balance. • The field of SIRTs and its modulators is developing very rapidly. This paper fills the gap in the research summary of SIRTs modulators in time, and provides valuable insights into the challenges encountered in the research field. [ABSTRACT FROM AUTHOR]

[Display omitted] Adipose derived mesenchymal stem cells (ADMSCs) are a component of adipose tissue that in recent years has gained on importance. The progenitor cells serve as an essentially unlimited source of new adipocytes and therefore are considered to be an important determinant of the tissue's physiology. In this paper we investigated mature adipocytes differentiated from ADMSCs obtained from subcutaneous/visceral fat of patients with different metabolic status (lean, obese without and with metabolic syndrome). We focused our interests on the sphingolipid signaling pathway, i.e. a signal transduction system indispensable for cells functioning, but also implicated in the development of medical conditions associated with obesity. We observed that the cells derived from visceral tissue had significantly greater levels of almost all the examined sphingolipids (especially Cer, dhCer, SM). Moreover, obesity and metabolic syndrome present in donor patients was associated with an increased level of sphingosine kinase (SPHK) and the product of its reaction sphingosine-1-phosphate (S1P). Moreover, the condition appeared to display a tissue specific pattern. Namely, the adipocytes of subcutaneous provenance had an increased activation of ceramide de novo synthesis pathway when the donors of ADMSCs had metabolic syndrome. The above translated into greater accumulation of ceramide in the cells. To our knowledge this is the first study that demonstrated altered sphingolipid profile in the mature adipocytes differentiated from ADMSCs with respect to the stem cells tissue of origin and the donor patient metabolic status. [ABSTRACT FROM AUTHOR]

iRhom2 is a crucial cofactor involved in upregulation of TNF receptors (TNFRs) and the pro-inflammatory cytokine tumor necrosis factor (TNF-) from the cell surface by ADAM17. Tumor necrosis factor- α converting enzyme (TACE) is another name given to ADAM17. Many membrane attached biologically active molecules are cleaved by this enzyme which includes TNFRs and the pro-inflammatory cytokine tumor necrosis factor- α. The TNF receptors are of two types TNFR1 and TNFR2. iRhom2 belongs to the pseudo-protease class of rhomboid family, its abundance is observed in the immune cells. Biological activity of ADAM17 is affected in multiple levels by the iRhom2. ADAM17 is trafficked into the Golgi apparatus by the action of iRhom2, where it gets matured proteolytically and is stimulated to perform its function on the cell surface. This process of activation of ADAM17 results in the protection of the organism from the cascade of inflammatory reactions, as this activation blocks the TNF- α mediated secretion responsible for inflammatory responses produced. Present paper illustrates about the iRhom2-TNF-α-BAFF signaling pathway and its correlation with several autoimmune disorders such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hemophilia Arthropathy, Alzheimer's disease and Tylosis with esophageal cancer etc. [Display omitted] • iRhom2-TNF-α-BAFF signaling pathway are involved in maturation of ADAM 17, which by fragmenting various biological molecules plays a vital role in TNFα, IL-6, EGFR and Notch signaling. • iRhom 2 is involved in the regulation of the enzyme TACE which controls the shedding of TNF-α. • iRhom2-TNF-α-BAFF signaling pathway and its misregulation has provided us with a wide range of knowledge of targeting the exact cause of autoimmune disorders such as rheumatoid arthritis, tylosis esophageal cancer, Alzheimer's disease, hemophilic arthropathy and other metabolic disorders. • Targeting the iRhome2 receptor may be a prototype for prevention of various autoimmune disorders. [ABSTRACT FROM AUTHOR]

Cancer-associated cachexia (CAC) is a complex multiple organ syndrome that significantly contributes to reduced quality of life and increased mortality among many cancer patients. Its multifactorial nature makes its early diagnosis and effective therapeutic interventions challenging. Adipose tissue is particularly impacted by cachexia, typically through increased lipolysis, browning and thermogenesis, mainly at the onset of the disease. These processes lead to depletion of fat mass and contribute to the dysfunction of other organs. The β-adrenergic signalling pathways are classical players in the regulation of adipose tissue metabolism. They are activated upon sympathetic stimulation inducing lipolysis, browning and thermogenesis, therefore contributing to energy expenditure. Despite accumulating evidence suggesting that β3-adrenergic receptor stimulation may be crucial to the adipose tissue remodelling during cachexia, the literature remains controversial. Moreover, there is limited knowledge regarding sexual dimorphism of adipose tissue in the context of cachexia. This review paper aims to present the current knowledge regarding adipose tissue wasting during CAC, with a specific focus on the role of the β3-adrenergic receptor, placing it as a potential therapeutic target against cachexia. [ABSTRACT FROM AUTHOR]

A systematic mechanistic review was performed to determine mechanistic evidence for curcumin on pro-inflammatory matrix metalloproteinases and Osteoarthritis to understand the underlying pathophysiology, and to evaluate available human intervention evidence to inform clinical decision making. The systematic literature search was performed in 3 tranches (reviews, mechanistic, intervention studies) using PubMed, with no date limitations and using specific search terms. 65 out of 393 screened papers were accepted based on detailed inclusion and exclusion criteria. The mechanistic search was divided into three searches and the intervention searches were subdivided into four searches. Curcumin demonstrated significant inhibition of matrix metalloproteinases linked to cartilage degradation in Osteoarthritis through reduced activation of the nuclear factor kappa-B signaling pathway via suppressing phosphorylation of Iκβa and p65 nuclear translocation. Mechanistic evidence implicated matrix metalloproteinases in Osteoarthritis by decreasing Type II collagen, leading to cartilage damage. As a potential nutritional intervention for Osteoarthritis, curcumin could reduce inflammatory markers and improve pain and function scores. The evidence indicates most formulations of turmeric extract and curcumin extract, bio-enhanced and non-bio-enhanced, are effective at improving inflammatory markers and pain and function to a greater or lesser extent. Due to the high heterogeneity of the formulations, dosage, and duration of the studies, further research is needed to fully understand curcumin's potential as a promising non-pharmaceutical intervention for Osteoarthritis. This mechanism review identifies a gap in current research for the mechanism by which Type II collagen is mediated. [Display omitted] • NFkB is a key inflammatory mediator in the development and progression of Osteoarthritis. • MMPs interact with type II collagen and proteoglycans leading to cartilage damage. • Curcumin inhibits matrix metalloproteinases linked to cartilage degradation by modulating NFkB. • Curcumin demonstrates significant improvements in inflammation, pain and function scores. • All formulations of turmeric extract and curcumin extract demonstrated similar improvements. [ABSTRACT FROM AUTHOR]

Sanguinarine is a quaternary ammonium benzophenanthine alkaloid found in traditional herbs such as Chelidonium , Corydalis , Sanguinarum , and Borovula. It has been proven to possess broad-spectrum biological activities, such as antitumor, anti-inflammatory, antiosteoporosis, neuroprotective, and antipathogenic microorganism activities. In this paper, recent progress on the biological activity and mechanism of action of sanguinarine and its derivatives over the past ten years is reviewed. The results showed that the biological activities of hematarginine and its derivatives are related mainly to the JAK/STAT, PI3K/Akt/mTOR, NF-κB, TGF-β, MAPK and Wnt/β-catenin signaling pathways. The limitations of using sanguinarine in clinical application are also discussed, and the research prospects of this subject are outlined. In general, sanguinarine, a natural medicine, has many pharmacological effects, but its toxicity and safety in clinical application still need to be further studied. This review provides useful information for the development of sanguinarine-based bioactive agents. [Display omitted] • Multiple pharmacological activities of sanguinarine and its derivatives were concluded. • Mechanism of action of sanguinarine and its derivatives were detailly reviewed. • Outlooks about sanguinarine-related research were presented and discussed. [ABSTRACT FROM AUTHOR]

E-cadherin plays a critical role in preserving cell-cell adhesion and tissue integrity, and its reduced expression is a hallmark feature of the epithelial-mesenchymal transition (EMT) associated with cancer metastasis. This paper explores signaling pathways, including Snail family transcriptional repressor (Snail), Mitogen-activated protein kinase (MAPK), Store-operated calcium entry (SOCE), Transforming growth factor (TGF-β), Janus kinase/signal transducers and activators of transcription (JAK/STAT), Wingless-related integration site (Wnt), and Renin angiotensin system (RAS), elucidating their functions in regulating E-cadherin levels and controlling cell migration and proliferation. Also, regulation of E-cadherin signaling pathways by various dietary components is explored. This comprehensive review presents the critical role of E-cadherin and its associated pathways in various diseases, particularly cancer and cardiovascular conditions. Additionally, the article discusses the influence of dietary components like antioxidants, polyphenols, and herbs on E-cadherin pathways, offering potential pathways for modulating cell migration and proliferation in chronic diseases. It emphasizes the potential for therapeutic interventions targeting these pathways and suggests the significance of considering dietary factors in disease prevention and treatment strategies. • Loss of E-cadherin is an essential element of invasion and metastasis. • E-cadherin and related pathways including Snail, MAPK, SOCE, TGF-β, JAK/STAT, Wnt, and RAS regulate migration and proliferation. • Dietary components influence the E-cadherin pathways and interaction. [ABSTRACT FROM AUTHOR]

As an indispensable component of the extracellular matrix, perlecan (Pln) plays an essential role in cartilaginous tissue function. Although there exist studies suggesting that Pln expressed by cartilaginous tissues is critical for chondrogenesis, few papers have discussed the potential impact Pln may have on cartilage regeneration. In this review, we delineate Pln structure, biomechanical properties, and interactive ligands—which together contribute to the effect Pln has on cartilaginous tissue development. We also review how the signaling pathways of Pln affect cartilage development and scrutinize the potential application of Pln to divisions of cartilage regeneration, spanning vascularization, stem cell differentiation, and biomaterial improvement. The aim of this review is to deepen our understanding of the spatial and temporal interactions that occur between Pln and cartilaginous tissue and ultimately apply Pln in scaffold design to improve cell-based cartilage engineering and regeneration. As a key component of the basement membrane, Pln plays a critical role in tissue development and repair. Recent findings suggest that Pln existing in the pericellular matrix surrounding mature chondrocytes is actively involved in cartilage regeneration and functionality. We propose that Pln is essential to developing an in vitro matrix niche within biological scaffolds for cartilage tissue engineering. Perlecan's potential application in cartilage regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Estrogens are known to stimulate the growth of breast cancer but they are also an effective treatment for this disease (this has been termed the 'estrogen paradox'). The fact that estrogens can be an effective treatment for breast cancer is something that has almost been forgotten, whereas the fear for estrogens remains. This paper reviews the use of estrogens for the treatment of breast cancer and identifies possible applications. The data summarised in this review demonstrate that high-dose estrogens are effective for the treatment of advanced breast cancer, both as first-line treatment as well as for treatment after occurrence of endocrine resistance to TAM and AIs. Essential for efficacy is an extended period of estrogen deprivation before the tumour is subject to estrogen treatment (the gap hypothesis). Research on the mechanism of action has shown that apoptosis induced by estrogens is regulated via the estrogen receptor and growth factor signalling pathways. High-dose estrogens have a negative safety image, especially in terms of side-effects and increased rates of cardiovascular disease, but the safety data reviewed in this paper do not give rise to major concerns. Taking into account their side-effect profile together with their observed clinical efficacy, high-dose estrogens should be considered a valuable alternative to chemotherapy in selected patients. [ABSTRACT FROM AUTHOR]

Eccentric exercise training is effective for increasing muscle mass and strength, and improving insulin sensitivity and blood lipid profiles. However, potential muscle damage symptoms such as prolonged loss of muscle function and delayed onset of muscle soreness may restrict the use of eccentric exercise, especially in clinical populations. Therefore, strategies to reduce eccentric exercise-induced muscle damage (EIMD) are necessary, and an extensive number of scientific studies have tried to identify potential intervention modalities to perform eccentric exercises without adverse effects. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which an ischemic preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an intermittent application of short-time non-lethal ischemia to an extremity (e.g. using a tourniquet) followed by reperfusion and was discovered in clinical settings in an attempt to minimize inflammatory responses induced by ischemia and ischemia-reperfusion-injury (I/R-Injury) during surgery. The present hypothesis is based on morphological and biochemical similarities in the pathophysiology of skeletal muscle damage during clinical surgery and EIMD. Even though the primary origin of stress differs between I/R-Injury and EIMD, subsequent cellular alterations characterized by an intracellular accumulation of Ca2+, an increased production of reactive oxygen species or increased apoptotic signaling are essential elements for both. Moreover, the incipient immune response appears to be similar in I/R-Injury and EIMD, which is indicated by an infiltration of leukocytes into the damaged soft-tissue. Thus far, IPC is considered as a potential intervention strategy in the area of cardiovascular or orthopedic surgery and provides significant impact on soft-tissue protection and downregulation of undesired excessive inflammation induced by I/R-Injury. Based on the known major impact of IPC on skeletal muscle physiology and immunology, the present paper aims to illustrate the potential protective effects of IPC on EIMD by discussing possible underlying mechanisms. [ABSTRACT FROM AUTHOR]

As one of the important traditional Chinese medicines, Alpinia oxyphylla could warm and tonify the kidney and spleen. It has been used as anti-salivation, anti-diarrhea in various diseases. In recent years, many studies have reported the significant effect of Alpinia oxyphylla on improving cognitive ability, anti oxidative stress and protecting neurons. In this paper, we studied whether AE and its main active components could improve M1 and M2 polarization, inhibit neuroinflammation through triggering receptor expressed on myeloid cells 2 (TREM2), and exert anti-inflammatory effects. In this paper, the concentrations of inflammatory cytokines such as NO, TNF-α, IL-10 were assessed using detection kits respectively. Arg-1 and Iba-1, as polarized markers of M1 and M2, were detected by Immunofluorescence staining. CD86 and CD206 were tested by flow cytometry as surface markers of M1 and M2. Furthermore, RT-PCR was performed to determinate TNF-α, IL-10, Arg-1, and Iba-1. Western blot was used to test the activation of PI3K/AKT/GSK3β and BDNF/TrkB/TLR4 signaling pathways. TREM2 siRNA treatment further verified the action target of Chrysin, the main active ingredient of Alpinia oxyphylla. Molecular docking study was performed to investigate the binding mode between Chrysin and the human TREM2. We found that AE could promote the phenotypic transformation of microglia from M1 to M2, and similar effects of Chrysin were observed. Furthermore, downregulation of TREM2 blocked the anti-neuroinflammation of Chrysin, and inhibited the shift of M1 phenotype to M2 phenotype. Additionally, TREM2-siRNA suppressed the effects of Chrysin on PI3K/AKT/GSK3β and BDNF/TrkB/TLR4 signaling pathways. Our findings indicated that AE could improve the polarization response of microglia. TREM2 plays a vital role in the microglial repolarization effects of Chrysin through PI3K/AKT/GSK3β and BDNF/TrkB/TLR4 signaling pathways regulated by neuroinflammation. [Display omitted] • Alpinae Oxyphyllae Fructus could regulate the phenotypic transformation of LPS-induced BV2 cells. • Chrysin is the key component of Alpinae Oxyphyllae Fructus to exert anti-inflammatory activity. • TREM2 plays a vital role in promoting M2 phenotype polarization. [ABSTRACT FROM AUTHOR]

Sophora flavescens Ait.- Angelica sinensis (Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1β were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1β, making them ideal agents for the treatment of eczema. SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1β, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway. [Display omitted] • Application of SG in the treatment of acute eczema. • Study on the mechanism of SG in the treatment of acute eczema for the first time. • The experiments were carried out in vivo. • The results showed that SG could reduce the expression of IL-1β and TNF-α. • The anti-inflammation effect of SG is mediated by TLR4/MyD88/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

LncRNA(long non-coding RNA)-protein interaction (LPI) has effects on chromosome structure and gene transcription, participating in key cellular processes such as signal transduction, chromosome replication, material transport, and mitosis. Accurate identification of LPIs will provide scientific basis for understanding the molecular mechanisms of LncRNA-related diseases, thereby promoting the progress of disease diagnosis technologies and the development of therapeutic procedures to a certain extent. How to comprehensively mine feature information reflecting functional attributes from LncRNAs and proteins, apply deep learning to extract advanced features from the original input features of proteins and LncRNAs, and effectively fuse them have been important research challenges in this field. Aiming at the limitations of existing methods, based on deep learning techniques such as bi-directional long short-term memory (BiLSTM), attention mechanism, and an improved residual network, an LPI prediction model called LPI-LSTM-ResNet is constructed in this paper. Firstly, the sequence and structural information of LncRNAs and proteins are extracted from different perspectives. Then, the deep interaction fused features between LncRNAs and proteins are obtained by BiLSTM and attention mechanism. Finally, the fused features are input into an improved residual network with LSTM as the residual element to preserve long-distance dependencies between sequences. The 5-fold cross-validation results indicate that the feature combination strategy, feature fusion strategy, and the improved residual network consistently improve the LPI prediction performance. Compared with existing methods on the same plant datasets, LPI-LSTM-ResNet exhibits superior performance. • Sequence and structural information of LncRNAs and proteins are extracted. • Deep interaction fused features are obtained by BiLSTM and attention mechanism. • An improved residual network is proposed to preserve long-distance dependencies. • Compared with existing methods, LPI-LSTM-ResNet exhibits superior performance. [ABSTRACT FROM AUTHOR]

Programmed cell death (PCD), also known as regulatory cell death (RCD), is a process that occurs in all organisms and is closely linked to both normal physiological processes and disease states. Various signaling pathways, such as TP53, KRAS, NOTCH, hypoxia, and metabolic reprogramming, have been found to regulate RCD. Polysaccharides, which are essential natural products, have been the subject of extensive research in the fields of food, nutrition, and medicine due to their wide range of pharmacological effects. Studies have shown that polysaccharides have biological activities and the potential to target signal transduction pathways for the treatment of diseases. This paper provides a review of the mechanisms through which polysaccharides exert their therapeutic effects at different levels and explores the relationship between different types of RCD and human diseases. The aim of this review is to provide a theoretical basis for the further clinical use and application of polysaccharide bioactivities. [ABSTRACT FROM AUTHOR]

Connarus semidecandrus Jack (Family: connaraceae) is a medicinal plant known for its wide distribution throughout Southeast Asia. Renowned for its diverse therapeutic properties, it has been traditionally used for treating fever, skin irritation, and colic. Numerous individuals suffer from skin issues, including wrinkles, hyperpigmentation, and inflammation, due to environmental factors. Although many drugs are available to treat skin problems, chemical drugs have many shortcomings and side effects. Therefore, natural products are attractive potential medicines for alleviating skin troubles. We recently showed that Connarus semidecandrus Jack ethanol extract (Cs-EE) has anti-alopecia potential. This paper aims to explore the potential skin-protective effects and underlying molecular mechanisms of Connarus semidecandrus Jack in UVB-induced human keratinocytes (HaCaT). Before utilization, Cs-EE was dissolved in dimethyl sulfoxide (DMSO) and was preserved at a temperature of −20 °C. The phytochemical constituents of Cs-EE were detected by gas chromatography–mass spectrometry analysis (GC-MS). Sequentially, HaCaT cells were exposed to varying concentrations of Cs-EE prior to ultraviolet B (UVB) irradiation. Evaluations of cellular responses in HaCaT cells, including assessments of cell viability, deoxyribonucleic acid (DNA) damage, and gene and protein expressions, were carried out. To explore the specific signaling pathway involved, we conducted a luciferase assay in addition to validating these pathways using Western blot analysis. Nitric oxide (NO) and intracellular reactive oxygen species were decreased. Melanin production through the activation of melanocytes by α-melanocyte-stimulating hormone (MSH) was also inhibited by Cs-EE. Furthermore, the mRNA expression levels of key factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), MMP-1, MMP-3, and MMP-9 exhibited a remarkable decrease. In addition, the phosphorylation of TAK1 within the signaling cascade exhibited a decline, and the activities of the transcription factor AP-1 were decreased according to a luciferase reporter assay. Taken together, these findings suggest that the anti-inflammatory, anti-aging, and anti-apoptotic effects of Cs-EE indicate the compound's potential usefulness as a natural component in pharmaceutical and cosmetic products. [Display omitted] • Connarus semidecandrus Jack ethanol extract (Cs-EE) shows radical scavenging activity. • Cs-EE reduces UVB-induced cell death and apoptosis. • Cs-EE reduces the expression of genes involved in UVB-induced inflammatory response and wrinkle formation. • Cs-EE downregulates α-MSH-induced melanogenic responses of melanocyte. • Cs-EE inhibits AP-1 activity via suppression of TAK1/MKK3/6/p38 pathway. [ABSTRACT FROM AUTHOR]

Aging is a gradual process of natural change that occurs after reaching sexual maturity. It is also a known risk factor for many chronic diseases. Recent research has shown that senolytics can extend the lifespans and health spans of model organisms, and they have also been demonstrated effective in treating age-related diseases. In this study, we conducted a high-throughput screening of 156 drugs that targeted the PI3K/AKT/mTOR pathway to identify potential senolytic medications. Among these drugs, PF-04691502 was selected for further investigation to understand its molecular mechanism of action. Our findings indicate that PF-04691502, a dual inhibitor of PI3K/AKT and mTOR, specifically eliminates senescent cells. It reduces the expression levels of key markers of cellular senescence, such as SA-β-Gal, senescence-associated secretory phenotypes (SASPs) and p16INK4a. Additionally, PF-04691502 inhibits the phosphorylation of S6K and AKT, leading to the apoptosis of senescent cells. These results suggest that PF-04691502 holds promise as a new senolytic drug. This paper provides important insights into the potential application of PF-04691502 in the study of cell senescence. • PF-04691502, a dual inhibitor of PI3K/AKT and mTOR, specifically eliminates senescent cells. • PF-04691502 reduces the expression levels of key markers of cellular senescence. • PF-04691502 inhibites the phosphorylation of S6K and AKT, leading to the apoptosis of senescent cells. • PF-04691502 holds promise as a new senolytic drug. [ABSTRACT FROM AUTHOR]

Fibrosis is a process of tissue repair that results in the slow creation of scar tissue to replace healthy tissue and can affect any tissue or organ. Its primary feature is the massive deposition of extracellular matrix (mainly collagen), eventually leading to tissue dysfunction and organ failure. The progression of fibrotic diseases has put a significant strain on global health and the economy, and as a result, there is an urgent need to find some new therapies. Previous studies have identified that inflammation, oxidative stress, some cytokines, and remodeling play a crucial role in fibrotic diseases and are essential avenues for treating fibrotic diseases. Among them, matrix metalloproteinases (MMPs) are considered the main targets for the treatment of fibrotic diseases since they are the primary driver involved in ECM degradation, and tissue inhibitors of metalloproteinases (TIMPs) are natural endogenous inhibitors of MMPs. Through previous studies, we found that MMP-9 is an essential target for treating fibrotic diseases. However, it is worth noting that MMP-9 plays a bidirectional regulatory role in different fibrotic diseases or different stages of the same fibrotic disease. Previously identified MMP-9 inhibitors, such as pirfenidone and nintedanib, suffer from some rather pronounced side effects, and therefore, there is an urgent need to investigate new drugs. In this review, we explore the mechanism of action and signaling pathways of MMP-9 in different tissues and organs, hoping to provide some ideas for developing safer and more effective biologics. [Display omitted] • Fibrosis is a process of tissue repair, scar tissue formation, and replacement of normal tissue. • Overgrowth of tissue leads to massive deposition of extracellular matrix, resulting in a chronic inflammatory response and organ failure. • MMPs can degrade the extracellular matrix and are potential targets for treating fibrotic diseases. • MMP9 is an essential target for fibrosis treatment and acts as a bidirectional regulator in fibrotic diseases. • This paper first summarizes the mechanism of action and signaling pathways of mMMP9 in treating different fibrotic diseases. [ABSTRACT FROM AUTHOR]

As a "silent killer" that threatens women's lives and health, ovarian cancer (OC) has the clinical characteristics of being difficult to detect, difficult to treat, and high recurrence. Traditional Chinese medicine (TCM) can be utilized as a long-term complementary and alternative therapy since it has shown benefits in alleviating clinical symptoms of OC, decreasing toxic side effects of radiation and chemotherapy, as well as enhancing patients' quality of life. This paper reviews how TCM contributes to the apoptosis of OC cells through signaling pathways, including active constituents, extracts, and herbal formulas, with the aim of providing a basis for the development and clinical application of therapeutic strategies for TCM in OC. The search was conducted from scientific databases PubMed, Embase, Web of Science, CNKI, Wanfang, VIP, and SinoMed databases aiming to elucidate the apoptosis signaling pathways in OC cells by TCM. The articles were searched by the keywords "ovarian cancer", "apoptosis", "signaling pathway", "traditional Chinese medicine", "Chinese herbal monomer", "Chinese herbal extract", and "herbal formula". The search was conducted from January 2013 to June 2023. A total of 97 potentially relevant articles were included, including 93 articles on Chinese medicine active constituents or extracts and 4 articles on Chinese herbal compound prescriptions. TCM can induce apoptosis in OC cells by regulating signaling pathways with obvious advantages, including STAT3, PI3K/AKT, Wnt/β-catenin, MAPK, NF-κB, Nrf2, HIF-1α, Fas/Fas L signaling pathway, etc. Chinese medicine can induce apoptosis in OC cells through multiple pathways, targets, and routes. TCM has special advantages for treating OC, providing more reasonable evidence for the research and development of new apoptosis inducers. [Display omitted] [ABSTRACT FROM AUTHOR]

Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) can be used for both medicinal and tea and has lipid-lowering properties. Modern research has shown that its main bioactive components are flavonoids and saponins. It has many beneficial effects such as hypolipidemic, anti-cancer, cardioprotective, hepatoprotective, neuroprotective, anti-diabetic and anti-inflammatory. This review aimed to summarize its anti-glycolipid metabolic models and mechanisms are reviewed to facilitate a deeper understanding of the mechanism in lowering lipids. Information related to lipid lowering in G. pentaphyllum was collated by reviewing the relevant literature in the PubMed database from 1985 to 2023. Only 101 G. pentaphyllum compounds have been initially explored for their hypolipidemic activity. There are cell models, animal models and human subjects for lipid-lowering of it. It reduced triglyceride level via PPAR/UCP-1/PGC-1α/PRDM16 and (SREBP-1c)-ACC/FAS-CPT1 signal pathways. Cholesterol-lowering effects via (SREBP-2)-HMGCR, PCSK9-LDLR and bile acid biosynthetic pathways. Activation of adenosine 5′-monophosphate-activated protein kinase (AMPK) is a key factor in the regulation of glycolipid metabolism in G. pentaphyllum. Other pathways of action of G. pentaphyllum in regulating glucolipid metabolism are also discussed in this paper. To date, more than 328 saponins have been isolated and identified in Gynostemma. Further studies on these components, including molecular mechanisms and in vivo metabolic regulation, need to be further confirmed. G. pentaphyllum has the potential to be developed into drugs or functional foods, but further research is needed. [Display omitted] • The compounds of Gynostemma pentaphyllum that have been studied for lipid reduction are summarized. • The model for studying lipid metabolism of G. pentaphyllum was summarized. • The mechanism of G. pentaphyllum to reduce lipid was summarized. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa , an increasingly common competitive and biofilm organism in healthcare infection with sophisticated, interlinked and hierarchic quorum systems (Las , Rhl , PQS , and IQS), creates the greatest threats to the medical industry and has rendered prevailing chemotherapy medications ineffective. The rise of multidrug resistance has evolved into a concerning and potentially fatal occurrence for human life. P. aeruginosa biofilm development is assisted by exopolysaccharides, extracellular DNA, proteins, macromolecules, cellular signaling and interaction. Quorum sensing is a communication process between cells that involves autonomous inducers and regulators. Quorum-induced infectious agent biofilms and the synthesis of virulence factors have increased disease transmission, medication resistance, infection episodes, hospitalizations and mortality. Hence, quorum sensing may be a potential therapeutical target for bacterial illness, and developing quorum inhibitors as an anti-virulent tool could be a promising treatment strategy for existing antibiotics. Quorum quenching is a prevalent technique for treating infections caused by microbes because it diminishes microbial pathogenesis and increases microbe biofilm sensitivity to antibiotics, making it a potential candidate for drug development. This paper examines P. aeruginosa quorum sensing, the hierarchy of quorum sensing mechanism, quorum sensing inhibition and quorum sensing inhibitory agents as a drug development strategy to supplement traditional antibiotic strategies. [ABSTRACT FROM AUTHOR]

Breast cancer remains a leading cause of death for women worldwide, and new treatment strategies are needed. There are innumerable anomalous genes that are responsible for the multi-factorial carcinogenesis pathway. Although several disease-causing mutations have been detected, therapy frequently focuses on attenuating the manifestation of the disease rather than harmonizing the mutation in the target area. The advent of CRISPR-Cas9 technology has revolutionized genome editing, allowing for precise and efficient manipulation of gene expression. The purpose of this review paper is to summarize recent progress in the use of CRISPR-based approaches to target key signaling pathways associated with breast cancer progression. The first section introduces basic concepts of CRISPR technology, focusing on its application in genome editing and transcriptional regulation followed by an overview of aspects involving complex signaling pathways in breast cancer such as P13K/AKT/mTOR, EPK/MAPK and Wnt/β catenin. An extensive literature search using PubMed and Google Scholar is performed for information retrieval. Further, the role of CRISPR-based interventions in regulating gene expression revealed, altered pathway activity and potential therapeutic consequences are discussed. This review will be a valuable addition to providing comprehensive knowledge of CRISPR-Cas-mediated therapeutic targeting in breast cancer. [ABSTRACT FROM AUTHOR]

Cancer is a multifaceted, complex disease characterized by unchecked cell growth, genetic mutations, and dysregulated signalling pathways. These factors eventually cause evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, which makes it difficult for targeted therapeutic interventions to be effective. MicroRNAs (miRNAs) are essential gene expression regulators linked to several biological processes, including cancer and inflammation. The NF-κB signalling pathway, a critical regulator of inflammatory reactions and oncogenesis, has identified miR-155 as a significant participant in its modulation. An intricate network of transcription factors known as the NF-κB pathway regulates the expression of genes related to inflammation, cell survival, and immunological responses. The NF-κB pathway's dysregulation contributes to many cancer types' development, progression, and therapeutic resistance. In numerous cancer models, the well-studied miRNA miR-155 has been identified as a crucial regulator of NF-κB signalling. The p65 subunit and regulatory molecules like IκB are among the primary targets that miR-155 directly targets to alter NF-κB activity. The molecular processes by which miR-155 affects the NF-κB pathway are discussed in this paper. It also emphasizes the miR-155's direct and indirect interactions with important NF-κB cascade elements to control the expression of NF-κB subunits. We also investigate how miR-155 affects NF-κB downstream effectors in cancer, including inflammatory cytokines and anti-apoptotic proteins. [ABSTRACT FROM AUTHOR]