Assessing the Efficacy of an External Insulation Fixed Kit in Maintaining Optimal Temperature for Hot Compress Therapy.

Background: Hot compress therapy is commonly used for various musculoskeletal conditions, aiming to alleviate pain and improve blood circulation. However, maintaining the desired temperature throughout the treatment session can be challenging. Objective: This study aims to investigate the impact of an external insulation fixed kit on maintaining the optimal temperature during hot compress therapy. Methods: A randomized controlled trial was conducted, and a total of 116 patients undergoing heat application were selected. The patients were divided into two groups: the control group (C Group, n=58), utilizing traditional external application methods, and the research group (R Group, n=58), employing the external insulation fixed kit. Parameters including the temperature of the external application material, displacement rate, dislodgement rate, and satisfaction with the heat application after 20 minutes of clinical use were compared between the two groups. Results: After 20 minutes of clinical application, the temperature in the R Group was [36.76 (35.60, 37.83)]°C, significantly higher than the C Group temperature of [26.26 (24.48, 27.90)]°C (P < .001). The incidence of displacement was 1.70%, and dislodgement was 0% in the R Group, while in the C Group, it was 8.60% and 5.20%, respectively. However, these differences were not statistically significant (P > .05). The satisfaction rate with hot packs was 91.38% in Group R and 74.14% in Group C, with significantly higher satisfaction in Group R (P < .05). Conclusion: The utilization of the external insulation fixed kit effectively maintained the optimal temperature during heat application treatment without increasing the rates of displacement and dislodgement.

[Pharmaceutical changes and countermeasures for transformation of traditional Chinese medicine preparations in medical institutions into new drugs based on human use experience].

Traditional Chinese medicine(TCM) preparations in medical institutions, as a unique and important form of preparations in China, have a long history of human use and serve as a bridge between clinical experience prescriptions and new Chinese medicine preparations. The state encourages medical institutions to transform their preparations into new traditional Chinese medicines, emphasizing their role as "incubators". Since the proposal of the traditional Chinese medicine registration and evaluation evidence system with the integration of TCM theory, human use experience(HUE), and clinical experience, the idea of transforming preparations used in medical institutions into new drugs based on HUE has been increasingly valued by drug research and development organizations. In the transformation process, pharmaceutical changes should be concerned from multiple aspects. This paper discusses the pharmaceutical changes and countermeasures based on the transformation of traditional Chinese medicine preparations in medical institutions into new drugs based on HUE from the aspects of excipients, dosage forms, production technology, production scale, packaging materials and containers, production sites, and registration standards. It is emphasized that scientific decisions should be made according to the characteristics and clinical needs of drugs to ensure the stability of drug quality. The impacts of pharmaceutical changes on drug quality should be objectively assessed based on appropriate evaluation indexes and detection methods. The layout should be carried out in advance, and the key pharmaceutical information of the preparations should be kept stable, so as to underpin the transformation of traditional Chinese medicine preparations in medical institutions into new drugs based on HUE.

[Research and development strategy of new traditional Chinese medicine drugs for syndromes based on human use experience].

Chinese drug registration laws and regulations have always reserved a place for the new traditional Chinese medicine(TCM) drugs for syndromes, but so far no such new drugs have been approved for registration. This paper expounded on the relevant policies, regulations, and technologies of new TCM drugs for syndromes in China and pointed out that the application of the animal model of TCM syndromes to carry out pharmacodynamics research and clinical efficacy evaluation criteria of TCM syndromes were the main technical difficulties in the research and development of new TCM drugs for syndromes. Not all syndromes are suitable for developing new drugs, and the indications for new TCM drugs should be constant syndromes. Among the three research and development models of simple syndrome, syndrome-unified disease, and combined disease and syndrome, the research and development model of combined disease and syndrome is recommended. Clinical positioning is the key to new TCM drugs for syndromes. It is encouraged to conduct high-quality human use experience studies to determine the clinical positioning of new TCM drugs for syndromes, as well as the target population, dose, course of treatment, and initial therapeutic and safety, and apply for exemption from non-clinical effectiveness studies. Clinical trials of new TCM drugs for syndromes should take the target symptoms or signs as the main efficacy index and the efficacy of TCM syndromes as the secondary efficacy index. Clinical research program design should implement the "patient-centered" concept and introduce clinical outcome evaluation indicators. In the clinical safety evaluation, special conditions such as characteristic syndromes and changes should be considered. With the construction of the human use experience technology system and the promotion of the TCM registration and evaluation evidence system featuring the "combination of TCM theory, human use experience, and clinical trials", it is believed that many high-quality new TCM drugs for syndromes will be developed in the future.

[Quality requirements of human use experience research on traditional Chinese medicine].

The human use experience of traditional Chinese medicine(TCM) is of great significance for the development of new traditional Chinese medicine. In 2023, the National Medical Products Administration(NMPA) issued the Special Regulations on Registration Management of Traditional Chinese Medicine, which explicitly encouraged the conduct of high-quality human use experience research on TCM clinical practice to obtain sufficient evidence for registration support. It also required that human use experience research should comply with relevant requirements and undergo registration verification. The quality of human use experience research on TCM directly determines the reliability of the evidence. This article discussed the quality requirements for human use experience research on TCM from the perspectives of basic requirements, organizational management, key pharmaceutical information, scientific research, risk management, ethical compliance, and study implementation and proposed differential treatment in quality requirements and registration verification focus based on different research purposes, stages, and types of studies. While ensuring the authenticity of data, retrospective studies should pay particular attention to the integrity of the data, and prospective studies should focus on the normativity of the data, which may affect the research conclusions. Human use experience research, as part of drug registration materials, falls within the scope of relevant regulatory oversight. Researchers should have a strong awareness of regulations to avoid serious quality issues. The standardized conduct of human use experience research on TCM requires joint efforts from regulatory authorities, applicants, research institutions, and researchers to establish a research quality management system based on the clinical characteristics of TCM.

[Construction of clinical efficacy evaluation system based on optimal clinical experience].

Evidence-based medicine plays an important role in promoting the scientific nature of clinical decision-making. Howe-ver, there is a problem where evidence derived from clinical research may not necessarily be applicable to individual patients. Evidence-based medicine has been introduced into the field of traditional Chinese medicine(TCM) for over 20 years, and although certain achievements have been made, the overall level of clinical research evidence based on the principles of evidence-based medicine in TCM is not high. The acceptance of TCM diagnosis and treatment guidelines developed based on evidence-based medicine methods is generally low. As revealed by the analysis of the problems in the application of evidence-based medicine in the field of TCM, it is found that there is a structural contradiction between clinical randomized controlled trial(RCT) of TCM and the characteristics of TCM clinical practice. They cannot comprehensively, objectively, and truthfully reflect the clinical efficacy and safety of TCM. Conducting clinical RCTs of TCM in pursuit of "evidence" actually means giving up the advantages of TCM in clinical treatment based on syndrome differentiation, prescription changes along with syndromes, and treatment in accordance with three categories of disease cause, which leads to sacrificing some clinical effectiveness of TCM. Based on the concept of evidence-based medicine, this article proposed the construction of "clinical syndrome-based medicine" based on the optimal clinical experience, which was suitable for the characteristics of TCM clinical practice. The key to clinical syndrome-based medicine is the optimal clinical experience, and the core elements of the optimal clinical experience are regularity and reproducibility. Real-world research methods are recommended as a reference for obtaining the optimal clinical experience. Clinical syndrome-based medicine, combining the characteristics of TCM clinical practice and incorporating the concept of evidence-based medicine, is the product of integrating TCM into evidence-based medicine. It is dedicated to improving the clinical efficacy of TCM along with evidence-based medicine.

[Technical points of human use experience of ethnic medicine].

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.

Role of IgE-FcεR1 in Pathological Cardiac Remodeling and Dysfunction.

BACKGROUND: Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure are unknown. METHODS: Serum IgE levels and cardiac FcεR1 expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone marrow transplantation. The roles of the IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes and cardiac fibroblasts (CFs). RNA sequencing and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1. RESULTS: Serum IgE levels were significantly elevated in patients with heart failure as well as in 2 mouse cardiac disease models induced by chronic pressure overload via transverse aortic constriction and chronic angiotensin II infusion. Interestingly, FcεR1 expression levels were also significantly upregulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated transverse aortic constriction- or angiotensin II-induced pathological cardiac remodeling or dysfunction. Anti-IgE antibodies (including the clinical drug omalizumab) also significantly alleviated angiotensin II-induced cardiac remodeling. Bone marrow transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non-bone marrow-derived cells. FcεR1 was found to be expressed in both cardiomyocytes and CFs. In cultured rat cardiomyocytes, IgE-induced cardiomyocyte hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA sequencing and signaling pathway analyses revealed that transforming growth factor-ß may be a critical mediator, and blocking transforming growth factor-ß indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro. CONCLUSIONS: Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in cardiomyocytes and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling.

MK2206 attenuates atherosclerosis by inhibiting lipid accumulation, cell migration, proliferation, and inflammation.

Cardiovascular disease is a common comorbidity in patients with cancer, and the main leading cause of noncancer-related deaths in cancer survivors. Considering that current antitumor drugs usually induce cardiovascular injury, the quest for developing new antitumor drugs, especially those with cardiovascular protection, is crucial for improving cancer prognosis. MK2206 is a phase II clinical anticancer drug and the role of this drug in cardiovascular disease is still unclear. Here, we revealed that MK2206 significantly reduced vascular inflammation, atherosclerotic lesions, and inhibited proliferation of vascular smooth muscle cell in ApoE-/- mice in vivo. We demonstrated that MK2206 reduced lipid accumulation by promoting cholesterol efflux but did not affect lipid uptake and decreased inflammatory response by modulating inflammation-related mRNA stability in macrophages. In addition, we revealed that MK2206 suppressed migration, proliferation, and inflammation in vascular smooth muscle cells. Moreover, MK2206 inhibited proliferation and inflammation of endothelial cells. The present results suggest that MK2206, as a promising drug in clinical antitumor therapy, exhibits anti-inflammatory and antiatherosclerotic potential. This report provides a novel strategy for the prevention of cardiovascular comorbidities in cancer survivors.

[Types of clinical data and statistical methodology of human use experience in traditional Chinese medicine].

Application experience in humans, a summary of the clinical practice of traditional Chinese medicine(TCM), serves as an important data source for evaluating the safety, effectiveness, and clinical value of drugs in the development of new Chinese medicine. The collected data serving as the evaluation evidence through statistical analysis are critical to the research on the application experience in humans. This article summarized and analyzed the data characteristics and statistical methodology of application experience of Chinese medicine in humans, and concluded the data types, outcome evaluation, bias evaluation, confounding factors, and missing values. Furthermore, the article emphasized the importance of data analysis of application experience of Chinese medicine in humans for TCM evidence and put forward the current difficulties, such as low data quality and large internal bias, lack of individualized data processing methods, and lack of methods for "disease-syndrome combination" data. We believe that with the development of methodology, the application experience of Chinese medicine in humans can strongly support the development of new drugs in TCM.

[Expert consensus on human use experience research of traditional Chinese medicine].

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.

[Application of add-on-design in post-marketing evaluation of traditional Chinese medicine].

Post-marketing evaluation of traditional Chinese medicine(TCM) is an important research stage in the life cycle of a drug, and the add-on-design is a common method for its post-marketing evaluation. This article introduces the basic concept of add-on-design, and points out that it is suitable for use based on the principles of medical ethics when the standard treatment should not be interrupted. The post-marketing evaluation of TCM should be carried out based on human experience and in compliance with regulations and ethics. The clinical values of TCM, such as the therapeutic effect for disease, improvement of disease symptoms, improvement in quality of life, as well as the synergism and toxicity attenuation of combined use of TCM and chemical drugs, should be fully reflected through the clinical trials designed with add-on-design. The key points of add-on-design are accurate clinical positioning, scientific estimation of sample size, and rigorous standard treatment. Standard treatment should be a recognized one, consistent and stable; appropriate and recognized efficacy indicators and targeted safety indicators should be selected; the design and operation of clinical research scheme should meet the requirements of randomization and blind method, with special emphasis on the production of qualified placebo. The add-on-design has the advantages that the rights and interests of the subjects are adequately protected. Besides, the research conclusions are easily put into clinical application. But there are also many difficulties, such as the influence of confounding bias, the "ceiling" effect of clinical efficacy, and the difficulty of interpretation of adverse events. Therefore, a rigorous research quality assu-rance system should be established, and the quality control of evaluation consistency of researchers should be emphasized to ensure strict quality control in the research process.

[Application of real world study and human use experience in research and development of new traditional Chinese medicine drugs].

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.

[Data collection, quality and evidence formation for human use experience of traditional Chinese medicine].

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.

[Theoretical thinking on guiding research and development of new drugs of traditional Chinese medicine].

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.

[Development of clinical trial of new drugs of traditional Chinese medicines].

The relevant laws and regulations of drug clinical trials were introduced in this paper. It is pointed out that with drug re-gulatory laws and technological advances, clinical trials have become an important link in the development of new drugs of traditional Chinese medicines(TCM). Clinical trials of new drugs of TCM must comply with the requirement of "Good Clinical Practice for Trial on Medicinal Products". In view of the particularities of clinical trials of new drugs of TCM, China has established an ethical review system for clinical research in TCM and carried out ethical review and certification of TCM research. In order to guide the development of clinical trials of new drugs of TCM, relevant departments have promulgated a series of guidelines for clinical trials of it, and established a new review system and technical requirements for clinical trials. Since 1983, the "national clinical pharmacology base" has been established. At present, there are 96 drug clinical trial institutions and 32 phase I clinical research wards in TCM hospitals, which can meet the development of clinical trials of new drugs of TCM. In the long-term practice, the technical team has continued to grow and develop, the research experience and technical strength have been significantly improved, and a large number of experts have become the backbone of clinical research in Chinese medicine. It is pointed out that we should attach importance to risk and benefit assessment, human experience, select scientific, objective and appropriate effectiveness indexes, evaluate the efficacy of TCM syndromes, and encourage the use of electronic methods in clinical research of new drugs of TCM. Based on the analysis of clinical trials of TCM in recent five years, it is pointed out that the active degree of clinical trials of new drugs of TCM is not high, the innovation ability of it is insufficient and the ability and enthusiasm of all aspects need to be improved. It is of great significance to carry out clinical trials of new traditional Chinese medicines to upgrade the TCM industry and produce high-level evidence-based medicine evidences. The high quality development of TCM can be promoted by strengthening clinical trials of new drugs of TCM.

Logic-signal-based multiplex detection of MiRNAs with high tension hybridization and multiple signal amplification.

MicroRNAs (miRNAs) are crucial regulators of gene expression. The abnormal expression of miRNA is often closely related to many diseases. However, the accurate clinical profiling of miRNA expression remains a great challenge due to the high similarity and wide variety of miRNA sequence structures. Here, we report a highly specific and sensitive multiplex miRNA detection scheme with high tension hybridization and dual signal amplification based on the recyclable autocatalytic DNAzyme and a light harvesting conjugated polymer. Multiple signals can be read out simultaneously by single excitation through the efficient multiple fluorescence resonance energy transfer (FRET) between the conjugated polymer and different small molecule dyes. In addition, different types of logic gates can also be operated by observing the emission intensities of the labeling dyes with miRNAs as inputs, thus giving rise to a new way for the specific detection of certain miRNAs according to the logic signals. Furthermore, we successfully applied the strategy for multiple miRNA detection in cell lysates and the results agree well with those of qRT-PCR. Thus, we believe that this platform holds great potential for miRNA detection in biological samples.

Anti-parasitic effect on Toxoplasma gondii induced by a spider peptide lycosin-I.

Toxoplasmosis is a widely distributed parasitic protozoan disease, caused by Toxoplasma gondii (T. gondii). High prevalence of toxoplasmosis and limitations of conventional treatments lead to a search for new therapeutic drugs. Lycosin-I is a linear peptide, derived from the venom of the spider Lycosa singoriensis. The aim of the present study was to determine the anti-parasitic effect of lycosin-Ι against T. gondii. In vitro, the anti-T. gondii activities of lycosin-Ι were evaluated by MTT assay, trypan blue exclusion assay, cell counting assay and plaque assay. Cytokines of IL-6 and IL-8 were measured by quantitative PCR. In addition, the structures of tachyzoites treated with lycosin-Ι were also observed by scanning and transmission electron microscopy. In vivo, mice were challenged with parasites treated by lycosin-I. The results revealed that lycosin-Ι had shown a significant ability to inhibit T. gondii invasion and proliferation. Cytokines of IL-6 and IL-8 were reduced by lycosin-Ι at transcription level in human foreskin fibroblast (HFF) cells infected with T. gondii tachyzoites, but they were increased compared to non-infected cells. For tachyzoites, lycosin-Ι induced their cell membrane alterations with formation of invaginations, some of them appeared to be vacuolated in their cytoplasm. Moreover, lycosin-Ι had prolonged the survival time of mice by controlling T. gondii proliferation. In conclusion, our present study provides the first evidence for anti-T. gondii by using the spider peptide lycosin-Ι. These findings suggest that lycosin-Ι is a potential alternative agent for the treatment of toxoplasmosis.

The peptide lycosin-I attenuates TNF-α-induced inflammation in human umbilical vein endothelial cells via IκB/NF-κB signaling pathway.

OBJECTIVE: The peptide lycosin-I has anti-bacterial and anti-cancer capacities. However, the anti-inflammatory activity of lycosin-I remains unknown. We investigated whether lycosin-I could attenuate inflammation. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with lycosin-I before exposure to tumor necrosis factor-α (TNF-α). The expression of intercellular cell adhesion molecule-1 (ICAM-1), nuclear transcription factor-kappa B (NF-κB) p65 and inhibitory subunit of NF-κB alpha (IκBα) was evaluated by western blot. The expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) was detected by quantitative RT-PCR or ELISA. Immunofluorescence analysis was used to determine the impact of lycosin-I on NF-κB pathway. C57BL/6 mice were pretreated with lycosin-I before exposure with lipopolysaccharide (LPS). RESULTS: Lycosin-I significantly reduced the TNF-α-enhanced expression of IL-6, IL-8 and ICAM-1. Lycosin-I also inhibited the human monocyte cells adhesion to HUVECs. We further demonstrated that lycosin-I could effectively suppress the reaction of endothelial cells to TNF-α by inhibiting IκBα degradation. Subsequently, the phosphorylation and translocation of NF-κB p65 could also be attenuated. Furthermore, lycosin-I exhibited a significant protection of C57BL/6 mice against LPS-induced death. CONCLUSIONS: Our results suggested that the anti-inflammatory activity of lycosin-I was associated with NF-κB activation and lycosin-I had potential to be a novel therapeutic candidate for inflammatory diseases.

Integrative Multi-omics Analysis to Characterize Herpes Virus Infection Increases the Risk of Alzheimer's Disease.

Evidence suggests that herpes virus infection is associated with an increased risk of Alzheimer's disease (AD), and innate and adaptive immunity plays an important role in the association. Although there have been many studies, the mechanism of the association is still unclear. This study aims to reveal the underlying molecular and immune regulatory network through multi-omics data and provide support for the study of the mechanism of infection and AD in the future. Here, we found that the herpes virus infection significantly increased the risk of AD. Genes associated with the occurrence and development of AD and genetically regulated by herpes virus infection are mainly enrichment in immune-related pathways. The 22 key regulatory genes identified by machine learning are mainly immune genes. They are also significantly related to the infiltration changes of 3 immune cell in AD. Furthermore, many of these genes have previously been reported to be linked, or potentially linked, to the pathological mechanisms of both herpes virus infection and AD. In conclusion, this study contributes to the study of the mechanisms related to herpes virus infection and AD, and indicates that the regulation of innate and adaptive immunity may be an effective strategy for preventing and treating herpes virus infection and AD. Additionally, the identified key regulatory genes, whether previously studied or newly discovered, may serve as valuable targets for prevention and treatment strategies.

Recent progress in biomaterials-driven ferroptosis for cancer therapy.

Ferroptosis, first suggested in 2012, is a type of non-apoptotic programmed cell death caused by the buildup of lipid peroxidation and marked by an overabundance of oxidized poly unsaturated fatty acids. During the last decade, researchers have uncovered the formation of ferroptosis and created multiple drugs aimed at it, but due to poor selectivity and pharmacokinetics, clinical application has been hindered. In recent years, biomedical discoveries and developments in nanotechnology have spurred the investigation of ferroptosis nanomaterials, providing new opportunities for the ferroptosis driven tumours treatment. Additionally, hydrogels have been widely studied in ferroptosis because of their unique 3D structure and excellent controllability. By using these biomaterials, it is possible to achieve controlled release and targeted delivery of drugs, thus increasing the potency of the drugs and minimizing adverse effects. Therefore, summarizing the biomedical nanomaterials, including hydrogels, used in ferroptosis for cancer therapy is a must. This article provides an overview of ferroptosis, detailing its properties and underlying mechanisms. It also categorizes and reviews the use of various nanomaterials in ferroptosis, along with relevant explanations and illustrations. In addition, we discuss the opportunities and challenges facing the application of nanomaterials in ferroptosis. Finally, the development prospects of this field are prospected. This review is intended to provide a foundation for the development and application of biomedical nanomaterials in ferroptosis.