The nervous system stands as the most intricate regulatory system network in living organisms, characterized by its multilayered structural organization and functional diversity, from fine-scale synaptic interactions among neurons to the overarching coordination of large-scale neural circuits. This complexity underpins the diversity of neurological diseases. The emergence of microfluidic chip technologies, featuring micron-scale channel architectures and highly precise fluid manipulation, has revolutionized experimental platforms for studying neural systems. These microfluidic devices allow for the integration of multiple cell types within three-dimensional (3D) cultures, enabling the investigation of complex physiological behaviors and pathological mechanisms in vitro. This review provides an overview of physiological models developed using Nerve-on-a-Chip (NoC) systems to study neural functions, and summarizes advances in disease modeling for conditions such as neurovascular, neurodegenerative, and neuroimmune disorders. We conclude with a discussion on the strengths and limitations of NoC platforms in nervous system research and outline their potential applications and future directions in personalized medicine.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, cartilage degradation, and bone erosion. The diseases also involves pathological changes in the surrounding fascial tissues that lead to persistent pain. Current clinical treatments rely primarily on non-steroidal anti-inflammatory drugs and analgesics, which often have limited efficacy and potential side effects. Manual acupuncture (MA), a traditional therapeutic modality, has shown promising effects in alleviating RA-related symptoms. However, the underlying mechanisms remain largely unclear. Fibroblasts, which are known for their mechanosensitivity and immunomodulatory functions, may play a crucial role in mediating the therapeutic effects of acupuncture. In this study, we demonstrated that MA significantly ameliorated pathological changes in joint-associated fascia in a murine model of adjuvant-induced arthritis with minimal impact on bone and cartilage morphology. Post-acupuncture analysis revealed the upregulation of extracellular matrix (ECM)-related genes and proteins, such as fibromodulin, collagen I, and hyaluronan synthase 2, along with increased expression of mechanosensitive molecules, including Piezo1, Ras homolog family member A (RhoA), and Yes-associated protein 1 (YAP1). Moreover, local changes were observed in the expression of fibroblast-associated markers including Fibroblast Growth Factor 2 (FGF-2), Fibroblast Growth Factor 7 (FGF-7), Fibroblast-Specific Protein 1 (FSP-1), Cannabinoid Receptor 2 (CB2), and Proliferating Cell Nuclear Antigen (PCNA). Notably, selective ablation of fibroblasts in the acupoint area via recombinant adeno-associated virus -mediated apoptosis significantly attenuated the analgesic effect of acupuncture, accompanied by reduced collagen fiber deposition, decreased mast cell degranulation, and downregulation of ECM components and regulatory molecules, such as Hyaluronan Binding Protein 2 (HABP2) and CB2. In conclusion, the study findings suggest that acupuncture alleviates RA-induced pathological and pain responses by activating fibroblasts in the fascial tissue. This mechanotransduction process likely involves the downstream modulation of cannabinoid receptors and ECM-related proteins, including hyaluronic acid and collagen.
Abstract Background The acupoint is the initial response site to acupuncture stimulation, and changes in the acupoint affect the subsequent therapeutic effects of acupuncture. However, the mechanism of acupuncture from this initial site has not yet been clarified. Based on an experimental model of acupuncture at Neiguan (PC6) for intervening in acute myocardial infarction (AMI), this study aimed to 1) investigate whether acupuncture-induced local muscle contraction at the PC6 acupoint mediates the therapeutic effect of acupuncture, and 2) explore the initiation mechanism of acupuncture’s effect from the perspective of transient receptor potential vanilloid 1 (TRPV1). Methods Sprague–Dawley (SD) rats were used to establish the AMI model via ligation of the left anterior descending coronary artery (LAD). 1.To identify the key tissue layer mediating acupuncture efficacy: SD rats were randomly divided into the Sham group, AMI group, AMI + acupuncture at muscle-layer (ACU-M) group, and AMI + acupuncture at subcutaneous-layer (ACU-S) group. Cardiac function was evaluated using a small animal ultrasound imaging system; myocardial ischemic area was measured via 2,3,5-triphenyltetrazolium chloride (TTC) staining, and serum norepinephrine (NE) levels were detected using an enzyme-linked immunosorbent assay (ELISA) kit. 2.To verify the role of muscle contraction: Another cohort of SD rats was randomly divided into the Sham + Vehicle (0.9% sodium chloride, NaCl) group, AMI + Vehicle group, AMI + Vehicle + acupuncture group and AMI + succinylcholine chloride (Scc, muscle relaxant) + acupuncture group. Acupuncture was performed post-AMI modeling, with the same efficacy indexes as above. Additionally, PC6 tissue and C5–T1 segmental dorsal root ganglia (DRG) were collected from each group. Immunofluorescence (IF) staining and western blot (WB) analysis were used to detect TRPV1 expression in the acupoint muscle layer and TRPV1-positive neuron activation in DRGs. 3. To clarify the role of TRPV1: a TRPV1 inhibitor was microinjected into the PC6 muscle layer before acupuncture; changes in TRPV1 (acupoint/DRGs), cardiac function, myocardial ischemic area, and serum NE were measured to evaluate the relationship between acupuncture effect and TRPV1. Results Both the acupuncture at muscle and subcutaneous layer improved cardiac function, reduced the area of myocardial ischemia, and lowered serum NE levels in AMI rats, however the modulatory effect of acupuncture at muscle layer was more pronounced in AMI rats. PC6 injection of Scc followed by acupuncture reversed the modulatory effect of acupuncture on AMI rats. WB and IF results both showed that compared with the AMI group, TRPV1-positive area of the muscle layer in the acupoint area, protein expression as well as activated TRPV1-positive neurons in the DRG were significantly increased, while with the use of Scc followed by acupuncture, TRPV1-positive expression in the muscle layer of the acupoint area as well as activated TRPV1-positive neurons in the DRG were significantly decreased. Muscle injection of TRPV1 inhibitors followed by acupuncture significantly reduced TRPV1-positive expression in the muscle layer of the acupoint area as well as activated TRPV1-positive neurons in the DRG compared with the muscle injection of vehicle group, and also suppressed the improvement of cardiac function and myocardial ischemic area in rats with AMI by acupuncture. Conclusion The muscle layer at the PC6 acupoint is the primary tissue mediating the therapeutic effect of acupuncture for AMI. Acupuncture-induced muscle contraction at the acupoint serves as a key link in this effect: it upregulates TRPV1 expression in the acupoint muscle layer and activates TRPV1 ion channels in C5–T1 DRGs. Microinjection of a TRPV1 inhibitor into the acupoint muscle layer reverses acupuncture’s cardioprotective effect in AMI rats, confirming that TRPV1 in the acupoint muscle layer is a critical mediator initiating the acupuncture effect.
Non-small cell lung cancer (NSCLC) is a common cause of cancer-related deaths worldwide, and its incidence has been increasing in recent years. While targeted therapies like osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, have brought about notable improvements in patient outcomes for advanced NSCLC, the challenge of acquired drug resistance persists. Here, we found that cellular mesenchymal-epithelial transition factor (c-Met) was highly expressed in osimertinib-resistant cells, and depletion of c-Met markedly inhibited the growth of osimertinib-resistant cells ex vivo and in vivo, suggesting that c-Met is a potential target to address osimertinib resistance. Through a screening process using a natural product compound library, we identified piperlongumine as a potent inhibitor to overcome osimertinib resistance. Furthermore, the combined treatment of piperlongumine and osimertinib exhibited robust antitumor effects in resistant cells, partially restoring their sensitivity to osimertinib. Additionally, we discovered that piperlongumine could enhance the interaction between E3 ligase RNF4 and Sp1, inhibit the phosphorylation of Sp1 at Thr739, facilitate the ubiquitination and degradation of Sp1, lead to c-Met destabilization, and trigger intrinsic apoptosis in resistant cells. In summary, our study sheds light on the potential of piperlongumine in overcoming osimertinib resistance, offering new strategies and perspectives for the clinical management of drug-resistant NSCLC.
An enhanced pH-stable and highly sensitive electrochemical biosensor for the simultaneous detection of Cd2+, Pb2+, Hg2+, and As3+ was developed using dopamine/aptamer modified screen-printed electrodes. The aptamers of the four metal ions were initially immobilized on the surface of the corresponding working electrodes, where the specific conformation of the aptamers was induced in the presence of the toxic metal ions. Subsequently, the aptamer conformations were stabilized through electropolymerisation of dopamine, forming imprinted polymers to improve pH stability. After eluting the toxic metal ions with EDTA, the cavities left in the imprinted polymers selectively bound to the corresponding metal ions. Under optimized conditions, the developed electrochemical biosensor exhibits excellent specificity due to the specific ion conformation of dopamine imprinted polymers. Furthermore, the dopamine/aptamer imprinted polymer electrochemical sensor exhibited significantly enhanced pH stability compared to the electrochemical aptasensor, owing to the stabilization of the aptamer conformation by the imprinted polymers. The limits of detection (LOD) for the toxic metal ions were as follows: Pb2+ (1.4 mu g L-1), Cd2+ (4.0 mu g L-1), Hg2+ (1.9 mu g L-1), and As3+ (6.6 mu g L-1). The recovery rates in shredded squid and shrimp paste samples ranged from 87.5% to 108.8%, demonstrating the assay's excellent potential for the quantitative analysis of toxic metal ions in aquatic creatures.
Leveraging microfluidic chip platforms, the organ-on-a-chip technology integrates methodologies of cell biology, biomaterials science, and engineering to construct in vitro three-dimensional models that simulate the physiological microenvironments of human tissues and organs. This approach effectively overcomes the limitations of two-dimensional cell culture and animal models in replicating complex human structure-function relationships and elucidating disease mechanisms. However, current research often focuses on phenotypic observation, with insufficient exploration of the molecular regulatory mechanisms governing phenomena like drug effects and disease pathogenesis. Multi-omics, by integrating multidimensional molecular information from genomics, transcriptomics, proteomics, and metabolomics, provides crucial technical support for systematically deciphering complex biological processes and demonstrates significant value in biomedical research. In recent years, the synergistic application of organ-on-a-chip and multi-omics enables a multi-dimensional shift from single functional simulation to systematic biological analysis. This review systematically summarizes the application of cutting-edge advances of multi-omics in the research on diverse organ-on-a-chips, analyzes the challenges in data management, technical standardization, and technical compatibility arising from their deep integration, and proposes potential solutions, aiming to provide a theoretical reference for constructing a new paradigm of life science research.
Extracellular vesicles (EVs) contain a wealth of biological information and hold great value for disease diagnosis. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency, reduce external interferences and enable continuous or real-time dynamic monitoring. However, developing a simple and accurate in vivo assay for EVs remains challenging. In this study, we constructed an allosteric aptamer-based flexible microneedle biosensor capable of measuring disease-associated EVs in vivo. Firstly, the aptamer binding to CD63 captures EVs and immobilizes it on the electrode, and then the aptamer binding to EGFR contacts the EVs, which results in a change in redox current, due to the proximity of the reporter molecule to the electrode surface decreases electron efficiency. Continuous monitoring of tumor-derived EVs revealed significant variations in EVs concentrations across different tumor stages, which exhibited a strong correlation with tumor volume. This flexible microneedle sensor offers the advantages of selectivity, biocompatibility, and analytical performance, presenting a promising approach for tumor monitoring in vivo.
At present, a number of studies have shown that acupuncture at Zusanli (ST 36) can relieve pain, but the changes of local microenvironment in the acupoint area after acupuncture have not been elucidated. As a temperature and pain receptor, TRPV1 plays an important role in pain perception and inflammation regulation. In this study, RT-PCR technique was used to screen the types of mechanically sensitive ion channels in the local response to acupuncture in the acupoint area, and western bolt technique was used to verify in gene knockout and antagonist injection mice. Immunofluorescence double labeling technique was used to further determine the key cell types of TRPV1-mediated acupuncture analgesia. Finally, through the combined analysis of proteomics and phosphorylated proteomics, the local signaling pathways of acupoints that can be activated by acupuncture were analyzed. This study systematically explored the analgesic effect of acupuncture on inflammatory pain in mice and its mechanism. The study found that acupuncture can significantly improve the thermal pain threshold and mechanical pain threshold in mice, showing a significant analgesic effect. Further analysis revealed that this analgesic effect was closely related to the up-regulation of local TRPV1 expression at ST36, and its deletion or functional inhibition would significantly weaken the analgesic effect of acupuncture. In addition, we also found that acupuncture in the deep muscle layer can more effectively promote the expression and activity of TRPV1 than in the superficial fascia layer, and muscle cells are the key cell types of TRPV1-mediated acupuncture analgesia. Finally, through the combined analysis of multi-omics, it was clear that acupuncture could activate the local signal pathway TRPV1/CaMKII/AMPK/PGC1α to exert analgesic effect. In conclusion, this study not only confirmed the analgesic effect of acupuncture on inflammatory pain in mice, but also revealed the core role of TRPV1 in the mechanism of acupuncture analgesia, especially the important contribution of TRPV1 expression and activity in the muscle layer of ST36 acupoint to the analgesic effect of acupuncture, which provided a new scientific basis and potential therapeutic target for acupuncture treatment of inflammatory pain.
Multienzymatic cascade system (MCS) strategies have been a topic of growing interest in the electrochemical biosensor research field owing to their many advantages. By combining two or more enzymes in an appropriate manner, MCS approaches can extend the range of detection for particular analytes while improving the overall efficiency of biocatalytic cascade reactions. Compared with mono-enzyme biosensors, the integration of MCS and electrochemical biosensor platforms is inherently more challenging owing to the increased complexity of the resultant system. In recent years, substantial progress in the development of MCS-based electrochemical biosensors with enhanced analytical performance has been made. This review provides an overview of the types of MCS strategies and their biosensor applications, together with a summary of synergistic optimization approaches that can help improve key parameters including sensitivity, selectivity, and stability when designing MCS-based electrochemical biosensors. These discussions include examples of published biosensor platforms (2016-2024) while also surveying key advances in associated research areas including redox mediators/enzyme co-immobilization, enzyme engineering, multienzyme spatial regulation, enzyme-nanozyme integration and others. Lastly, a brief overview of current challenges and future perspectives pertaining to MCS-based electrochemical biosensor design is provided.
Enzyme biosensors are indispensable tools in diagnostics and environmental analysis, yet enhancing their performance necessitates the synergistic integration of precise biorecognition with robust signal amplification. Traditional enzyme immobilization techniques often suffer from limitations such as irregular spatial orientation and diminished cascade efficiency, posing challenges for detecting low-abundance targets. Recently, the emergence of DNA-assembled architecture nanotechnology has introduced a transformative strategy for engineering multi-enzyme cascades with nanometer-scale spatial precision. From the perspective of technical principles, the core advantage of DNA-assembled architectures stems from programmable base-pairing interactions: they enable the precise immobilization of enzymes in a variety of specific configurations, including linear structures, two-dimensional-like structures, and three-dimensional structures. This precise positioning can effectively optimize substrate transfer pathways and enhance catalytic throughput, fundamentally addressing the issue of low enzyme activity efficiency in traditional technologies. This review conducts a comprehensive analysis focusing on the DNA-guided enzyme cascade construction strategy. On one hand, it systematically summarizes the latest research progress in this field (2020–2025), with emphasis on clarifying its design principles, spatial coordination rules, and pioneering applications in biosensing systems. On the other hand, it critically explores the practical challenges faced by this technology, including low feasibility of large-scale fabrication, immature manufacturing processes, insufficient adaptability for clinical translation, and vulnerability to signal interference in complex matrix environments. Future advances, driven by cross-disciplinary innovation, promise highly integrated and adaptive biosensors tailored for precision diagnosis in both Traditional Chinese Medicine and Western medicine, as well as for point-of-care testing of target substances.
ABSTRACT Cd(II) and Hg(II) are well‐known toxic heavy metal elements that are difficult to degrade by microorganisms in the environment. Limits for Cd(II) and Hg(II) in food have been established by the Chinese Government and other authorities. Aptamer‐based electrochemical sensor detection is a promising method for rapidly and sensitively detecting heavy metals. However, aptamer configurations are easily affected by the environment and their stability needs to be improved. In this study, an ultra‐sensitive electrochemical sensor was successfully constructed based on aptamer/dopamine molecularly imprinted polymer composite material, to explore the simultaneous detection of Cd(II) and Hg(II). Graphdiyne nanomaterial was used to increase the load of aptamer on the electrode surface. The aptamer of Cd(II) and Hg(II) was captured by AuNPs on a modified electrode through Au‐S bonds. Dopamine was used as a functional monomer for self‐polymerization to form an imprinted layer, stabilizing the aptamer conformation and enhancing its environmental tolerance. Under optimal conditions, the limits of detection (LOD) for Cd(II) and Hg(II) were 7.6 and 6.0 ng/mL, respectively. Six days of good stability in the sensor response were attained. The satisfactory recovery obtained in both crab and ribbonfish samples demonstrates this sensor's potential for multi‐species food analysis.
Mechanical forces are crucial in regulating fibroblast behavior, yet the underlying mechanisms remain unclear. This study aims to elucidate the role of the Piezo1 ion channel in fibroblast responses to mechanical stimulation. A mechanical stimulation culture platform was developed using a polydimethylsiloxane (PDMS)-based stretchable membrane and the Cell Tank uniaxial cell stretching system. Fibroblasts subjected to uniaxial cyclic stretching were analyzed using proteomic profiling, Western blotting, and confocal laser scanning microscopy to assess cytoskeletal changes and activation markers. Immunofluorescence staining was performed to evaluate the expression of Piezo1, YAP1, and Ki67 proteins. Cell viability and migration capacity were assessed using Calcein-AM/PI double staining and a migration assay. Mechanical stretch-induced fibroblast activation is characterized by morphological changes, increased proliferation, and enhanced migration. The cytoskeletal reorganization was observed, with elevated F-actin expression. Modulating Piezo1 activity altered fibroblast activation, indicating its essential role in mechanotransduction. These findings demonstrate that mechanical stretch upregulates Piezo1 expression, promoting fibroblast activation through the YAP pathway. This study provides new insights into the mechanotransduction mechanisms in fibroblasts and highlights the critical role of Piezo1 in mediating responses to mechanical stimuli, which may have implications for understanding tissue remodeling and fibrosis.
Depression is a severe heterogeneous mental illness that is highly co-morbid with other mental and somatic disorders. It poses a significant healthcare burden on both individuals and society. Currently, the use of single-target antidepressants exhibits suboptimal efficacy with significant adverse effects. Acupuncture has been advocated as a practical and effective treatment for depression, due to its low adverse effects rate compared to antidepressant medication. Currently, several studies have shown that acupuncture treatment for depression primarily involves multiple therapeutic mechanisms, including the regulation of specific gene expression, neuropeptide and neurotransmitter release, increasing the expression of neurotrophic factors, suppressing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, attenuating inflammatory responses, and restoring gut microbiota balance. These therapeutic effects involve the regulation of critical signaling pathways, including the cAMP-responsive element binding protein (CREB) signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, mechanistic target of rapamycin (mTOR) signaling pathway, and toll-like receptors (TLR) signaling pathway. Notably, depression-associated molecular mechanisms and signaling pathway dysregulations are closely linked to impaired neural and synaptic plasticity. Acupuncture synergistically modulates the neuro-immune-microbiome multidimensional network and integrates crosstalk among key pathways such as CREB, thereby systemically restoring synaptic plasticity. This multi-dimensional integrative mechanism likely underlies its therapeutic superiority over single-target antidepressants. This review aims to elucidate how acupuncture restores cerebral synaptic plasticity by rectifying depression-related systemic dysfunctions and signaling pathway abnormalities, which will advance our understanding of its regulatory potential in depression treatment and inform the development of precision therapeutic strategies.
Plants play a crucial role in improving the environment by regulating the temperature, preventing soil erosion, and reducing wind speed. By yielding edible resources such as food crops, vegetables, and fruits, plants also provide essential nutrients for human beings. Consequently, the real-time monitoring of plant growth and surrounding environment has been the primary focus of researchers. Traditional plant monitoring relies on manual inspection, which is both subjective and discontinuous. In recent years, ongoing advancements in wearable sensors have enabled their application in various areas of plant monitoring such as plant growth assessment, environmental monitoring, nutritional detection, water management, and pest warning. These wearable sensors can be directly fixed to plant organs to deliver real-time data on plant growth and environmental conditions via wireless connections with smart devices. This facilitates user management and monitoring, which can contribute to the development of intelligent agriculture with high planting efficiency and sustainability. This review summarizes the design principles, manufacturing methods, characteristics, and feasibility of plant-wearable sensors based on their functions, including plant-phenotype sensors (e.g., hormones and nutrients), plant-growth-environment sensors (e.g., surrounding humidity), and plant stress sensors (e.g., pesticides, volatile organic compounds, and environmental stress). It also explores the challenges and development prospects in this field, providing valuable insights into the future application of wearable sensors to effectively optimize the plant growth status for crop yield and quality.
Introduction:Clostridium perfringens ε toxin (ETX), a category B biological weapon, causes fatal enterotoxemia in livestock. Vaccination is an effective way to prevent ETX intoxication. Methods:A cell membrane-encapsulated nanoparticle vaccine was prepared that adsorbed ASP-ETX (Ov-ASP-1 and epsilon toxin fusion protein) with a targeting effect on B cells and was loaded with the ETXY196E mutant protein (MNP-ASP-ETX). The antigen presentation efficiency of the nanoparticle vaccine was monitored through in vitro cell experiments and in vivo animal experiments, and the biological safety and overall efficacy of the nanoparticle vaccine were evaluated. Results:The ETX nanoparticle vaccine showed superior biosafety both in vivo and in vitro, favorable encapsulation efficiency, and a particle size that was easily taken up by antigen-presenting cells. The ETX nanoparticle vaccine released antigens more steadily and exhibited greater lymph node drainage capacity than the traditional aluminum adjuvanted group (ETXY196E + Al). MNP-ASP-ETX elicited antibody titers comparable to the ETXY196E + Al group and induced Th1 and Th2 immune responses. However, the protective effect of the ETX nanoparticle vaccine was slightly weaker than that of ETXY196E + Al. We therefore analyzed immune cell production in the spleen. Although MNP-ASP-ETX increased B-cell levels, indicating that ASP-ETX facilitates the ETX nanoparticle vaccine to target B cells, the effect was not statistically significant, likely owing to the less adsorption of ASP-ETX. The antibody titer and protective effect significantly increased after 2 months, with the magnitude of change surpassing that of ETXY196E + Al and indicating the strong potential of ETX nanoparticle vaccine for providing long-term immunity. Discussion:These findings demonstrate that MNP-ASP-ETX can be considered a novel vaccine for the prevention of ETX intoxication and provide new strategies for designing and developing toxin vaccines.
Adiponectin, a cytokine associated with adipose tissue, is a recently defined adipocytokine involved in insulin, glucose, and adipocyte metabolism. Reduced adiponectin levels can increase the risk of developing metabolic syndrome (MS). Adiponectin is considered an important target for the treatment of type 2 diabetes mellitus (T2DM) and MS due to its anti-atherosclerotic and insulin-sensitizing effects. Therefore, the accurate determination of adiponectin concentrations in human plasma is necessary for the management of both T2DM and MS. A variety of biosensors have been developed for the detection of biomarkers such as adiponectin. This paper reviews the applications of electrochemical sensors, surface-enhanced Raman scattering sensors, and microfluidic chip-based chemiluminescence sensors in the detection of adiponectin and the recent research progress in the sensors for the detection of adiponectin, aiming to provide a reference for the research and application of sensors for adiponectin in the medical field.
Purpose:Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods:We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results:We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion:These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.
Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary infections and mortality. Acupuncture is a potential alternative treatment for sepsis. In this comprehensive literature review, we found that acupuncture is beneficial in treating immune disorders associated with sepsis. Acupuncture can improve immune disorders associated with sepsis and regulate the functions of innate and adaptive immune cells. Specifically, acupuncture can reduce the number of neutrophils in sepsis, promote the polarization of macrophages towards M2-like macrophages, and alleviate inflammation by reducing the activation of microglia and astrocytes. Furthermore, acupuncture can increase the percentage of T cells and modulate the balance between T cell subsets. The immunomodulatory mechanism of acupuncture in sepsis may be attributed to the balance of the autonomic nervous system, including activation of the sympathetic-adrenal axis, vagal-cholinergic pathway, and vagal-adrenal axis. In addition, acupuncture can inhibit inflammation by preserving the integrity of the intestinal barrier and regulating the composition of the intestinal microbiota. Clinical studies have also demonstrated that acupuncture can enhance the number of peripheral natural killer (NK) cells and T cell subsets, as well as the expression of human leukocyte antigen DR (HLA-DR). Moreover, acupuncture can decrease the ratio of white blood cells to neutrophils and reduce the levels of inflammatory factors. Therefore, acupuncture has the potential to improve immune function in sepsis. Further investigation of its mechanism is expected to provide a scientific and reliable foundation for the application of acupuncture in sepsis treatment.
Lung cancer remains a major driver of global morbidity and mortality, and diagnosing lung tumors early in their development is vital to maximizing treatment efficacy and patient survival. Several biomarkers, including CYFRA 21-1, NSE, ProGRP, CEA, and miRNA, have been identified as reliable indicators for early lung cancer detection and monitoring treatment progress. However, the minute changes in the levels of these biomarkers during the early stages of disease necessitate advanced detection platforms. In this space, electrochemical biosensors have currently emerged as robust tools for early lung cancer screening and diagnosis owing to their low costs, rapid responses, and superior sensitivity and selectivity. This review provides an up-to-date overview of the application of electrochemiluminescence, photoelectrochemical, and other electrochemical analytical strategies for detecting lung cancer-associated protein biomarkers, and miRNA. This review compares these techniques to provide a concise overview of the principles underlying these electrochemical analytical methods, the preparation of their components, and the performance of the resulting biosensors. Lastly, a discussion of the challenges and opportunities associated with electrochemical biosensors detection of lung cancer-associated biomarkers are provided.
Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I. On the other hand, acupuncture exerts analgesic effects by promoting the production of adenosine, enhancing the expression of downstream adenosine A1 and A2A receptors, and regulating downstream inflammatory factors or synaptic plasticity. Together, this systematic overview of the field provides a sound, evidence-based foundation for future research focused on the application of acupuncture as a means of relieving pain.