Ligustilide covalently binds to Cys703 in the pre-S1 helix of TRPA1, blocking the opening of channel and relieving pain in rats with acute soft tissue injury.

ETHNOPHARMACOLOGICAL RELEVANCE: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. AIM OF THE STUDY: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. METHODS: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. RESULTS: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. CONCLUSIONS: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.

Quality evaluation methods of chinese medicine based on scientific supervision: recent research progress and prospects.

Traditional Chinese medicine (TCM) is increasingly getting attention worldwide, as it has played a very satisfactory role in treating COVID-19 during these past 3 years, and the Chinese government highly supports the development of TCM. The therapeutical theory and efficacies of Chinese medicine (CM) involve the safety, effectiveness and quality evaluation of CM, which requires a standard sound system. Constructing a scientific and reasonable CM quality and safety evaluation system, and establishing high-quality standards are the key cores to promote the high-quality development of CM. Through the traditional quality control methods of CM, the progress of the Q-marker research and development system proposed in recent years, this paper integrated the research ideas and methods of CM quality control and identified effective quality parameters. In addition, we also applied these effective quality parameters to create a new and supervision model for the quality control of CM. In conclusion, this review summarizes the methods and standards of quality control research used in recent years, and provides references to the quality control of CM and how researchers conduct quality control experiments.

Flaxseed Supplementation in Chicken Feed Accelerates Salmonella enterica subsp. enterica Serovar Enteritidis Clearance, Modulates Cecum Microbiota, and Influences Ovarian Gene Expression in Laying Hens.

Salmonella is a foodborne pathogen that poses a serious threat to both human and animal health and food safety. Flaxseed is rich in unsaturated fatty acids; has anti-metabolic syndrome, anti-inflammatory, and neuroprotective properties; and may be a potential source of feed additives. To investigate the impact of flaxseed on Salmonella-infected laying hens, we administered Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) after adding flaxseed to the feed of laying hens (15% [750 mg/kg]). S. Enteritidis colonization was reduced and its clearance was accelerated from the laying hens. Furthermore, flaxseed supplementation mitigated the damage to the ileum caused by S. Enteritidis. We analyzed alterations in intestinal flora through 16S rRNA amplicon sequencing. S. Enteritidis infection increased the abundance of Akkermansia and triggered the host inflammatory response. Conversely, the addition of flaxseed to the feed increased the abundance of beneficial intestinal bacteria, such as Lactobacilli and Bacteroides. Ovarian health is important for egg production performance in laying hens and our findings indicate that S. Enteritidis can persist in the ovaries for an extended period. Therefore, we further performed transcriptome sequencing analysis of ovarian tissues on day seven after S. Enteritidis infection. S. Enteritidis infection leads to altered ovarian gene expression, including the downregulation of lipid metabolism and growth and development genes and the upregulation of host immune response genes in laying hens. The upregulation of genes associated with growth and development may have stimulated ovarian growth and development.

Ginsenoside CK targeting KEAP1-DGR/Kelch domain disrupts the binding between KEAP1 and NRF2-DLG motif to ameliorate oxidative stress damage.

BACKGROUND: Panax ginseng and Panax notoginseng as traditional Chinese medicines, are widely used in the treatment of qi deficiency, viral or bacterial infection, inflammation and cancer. Ginsenoside CK, an active metabolite of protopanoxadiol among the ginseng saponins, has been shown in previous studies to improve the organism's oxidative balance by regulating the KEAP1-NRF2/ARE pathway, thus slowing the progression of diseases. However, the specific targets and mechanisms of CK in improving oxidative stress remain unclear. PURPOSE: The aim of this study was to determine the potential therapeutic targets and molecular mechanisms of CK in improving oxidative stress injury both in vitro and in vivo. METHODS: LPS was used to induce oxidative damage in RAW 264.7 cells to evaluate the regulatory effects of CK on the KEAP1-NRF2/ARE pathway. Drug affinity responsive target stability technology (DARTS) combined with proteomics was employed to identify CK's potential target proteins. CK functional probe were designed to analyze the target protein using click chemistry. Furthermore, small molecule and protein interaction technologies were used to verify the mechanism, and computer dynamic simulation technology was used to analyze the interaction sites between CK and the target protein. The pharmacological effects and mechanism of CK in improving oxidative damage were verified in vivo by LPS-induced acute injury in mice and physical mechanical injury in rat soft tissues. RESULTS: KEAP1 was identified as the target protein that CK regulates to improve oxidative damage through the KEAP1-NRF2/ARE pathway. CK competitively binds to the DGR/Kelch domain of KEAP1, disrupting the binding between DLG peptide in NRF2 and KEAP1, thereby inhibiting the occurrence of oxidative damage induced by LPS or physical mechanical stress. CONCLUSIONS: CK functions as a natural KEAP1-NRF2 inhibitor, disrupting the binding between KEAP1 and NRF2-DLG motifs by targeting the DGR/Kelch domain of KEAP1, activating the antioxidant transcriptional program of NRF2, and reducing oxidative stress damage.

Study on basic and clinical application of Shufeng Jiedu Capsule in treating respiratory tract infection.

Shufeng Jiedu Capsule (SFJDC), composed of eight herbs, is a big brand traditional Chinese medicine (TCM) for the treatment of different respiratory tract infectious diseases with good clinical efficacy and few side effects. It is clinically applied to acute upper respiratory tract infection(URI), influenza, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community-acquired pneumonia(CAP) and other diseases, due to its antibacterial, antiviral, anti-inflammatory, immunoregulatory and antipyretic activities. In particular, it has shown good clinical effects for COVID-19, and was included in the fourth to tenth editions of the 'Diagnosis and Treatment Protocol for COVID-19 (Trial)' by the National Health Commission. In recent years, studies on the secondary development which focus on the basic and clinical application of SFJDC have been widely reported. In this paper, chemical components, pharmacodynamic material basis, mechanisms, compatibility rule and clinical application were systematically summarized, in order to provide theoretical and experimental basis for further research and clinical application of SFJDC.

Research on safety early warning of uranium tailings dam based on abnormal radioactive indexes of water leachate.

The radioactive index value of the leachate of the uranium tailings dam is affected by the internal damage of the dam. Therefore, a way of using the deviation of the radioactive index concentration in the leachate to warn the instability of the dam is innovatively proposed in this paper. Firstly, the SSA-BP algorithm is used to predict and analyze the five groups of parameters U, Ra, ∑ α, ∑ ß and Rn. Then, the deviation between the actual value and the predicted value is computed. Finally, an early warning is given based on the entropy weight extension decision-making model. The model is verified by the leachate environment monitoring data of a uranium tailings dam in southern China from 2016 to 2020, which shows that the model can effectively caution of the instability of the uranium tailings dam and provides a reference for the subsequent decommissioning management.

["Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation].

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Molecular mechanisms of anti-cancer bioactivities of seaweed polysaccharides.

Seaweed is a traditional Chinese medicine homologous to food, in which polysaccharides are responsible for anti-cancer by enhancing immunity, inducing cancer cell apoptosis, inhibiting cancer cell invasion and metastasis or directly scavenging oxidative free radicals that induce cancer cell changes. Among them, regulating immunity and promoting cancer cell apoptosis are intensively studied due to the important role in preventing cancer. Here we reviewed seaweed in the apoptosis-inducing signaling pathways including PI3K/AKT, ROS and JNK and discussed challenges in studying seaweed.

Analysis of differential gene expression profiles uncovers mechanisms of Xuesaitong injection against cerebral ischemia-reperfusion injury.

BACKGROUND: Xuesaitong injection (XST), a well-known traditional Chinese patent medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. The exact mechanisms of XST in ischemic stroke remain to be thoroughly elucidated. PURPOSE: This study aims to characterize the candidate differentially expressed genes (DEGs) and pathways of XST in ischemic stroke by bioinformatics analysis, and to explore new clues for the underlying mechanisms of XST. METHODS: A dataset (GSE61616) was performed to screen out DEGs for deep analysis. Series Test of Cluster analysis for DEGs was carried out. For all DEGs, Gene Ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for visualization. The screened hub gene expression characteristics were verified in middle cerebral artery occlusion (MCAO) rats. In vivo studies have demonstrated the mechanisms of XST against cerebral ischemia-reperfusion (CIR) injury. RESULTS: A total of 8066 DEGs were screened out and the expression of genes in profile 8 was suggested to have clinical significance. The MAPK signaling pathway was indicated as the most significantly enriched pathway in profile 8. Bdnf was identified as the most significant hub gene according to node degree. Animal experiments demonstrated that XST attenuated CIR injury. XST increased brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) levels in MCAO. Furthermore, the knockdown of BDNF by siRNA abolished the in vivo effects of XST on brain injury, neurodegeneration and apoptosis after CIR. CONCLUSION: The integrated strategy, based on bioinformatics analyses with experimental verification, provides a novel cellular mechanism by which XST alleviates CIR injury. The BDNF-TrkB pathway was highly thought to play a vital role in the neuroprotective effects of XST.

Studies on Quality Markers of Kaihoujian Spray for Anti-Inflammation Based on Gray Correlation Analysis Strategy.

Kaihoujian spray (KHJ) was originated from the classical prescription of Miao medicine, which was commonly used for acute and chronic pharyngitis. The prescription was composed of Sophorae Tonkinensis Radix, Ardisiae Radix, Cicadae Periostracum, and menthol. However, in previous literature, only clinical studies have been reported. The Quality Marker (Q-Markers) of KHJ on anti-inflammation has not been clearly elucidated. In this study, a gray correlation analysis strategy combined with network pharmacology analysis was established for the investigation of Q-Markers in KHJ. A total of 52 components were identified or tentatively characterized in KHJ, including alkaloids, saponins, bergenin, flavonoids, amino acids, and their derivatives. Furthermore, regularity of recipe composition and gray correlation analysis revealed that the correlation degree of all peaks was greater than 0.5. The ranking of correlation degree was peak 1 > 6>9 > 8>7 > 10>4 > 5>11 > 3>2. Among them, peaks 2, 4, 5, 6, 8, 9, and 11 were identified as anagyrine, matrine, sophocarpine, norbergenin, bengenin, 11-O-galloylbergenin, and trifolirhizin. The network pharmacology analysis revealed that EGFR, MMP9, MMP3, MMP1, and PTGS2 were the main targets of KHJ. Bergenin, matrine, sophocarpine, calycosin, and trifolirhizin were the main anti-inflammatory active ingredient in KHJ. These results proposed that bergenin, sophocarpidine, sophocarpine, and trifolirhizin could be the Q-Markers of KHJ on anti-inflammation. The process of discovering the Q-Markers would provide a promising method of quality control on KHJ.

Gentiopicroside attenuates collagen-induced arthritis in mice via modulating the CD147/p38/NF-κB pathway.

Gentiopicroside (GEN) is a secoiridoid glycosides isolated from a traditional Chinese medicine Gentiana macrophylla Pall.. It exhibits potential activities in the treatment of inflammatory diseases. Here, we investigated whether GEN had the anti-rheumatoid arthritic activities in a model of rheumatoid arthritis, and explored its molecular mechanism. In vivo, the male C57BL/6J mice were injected chicken type II collagen to induce the animal model (collagen-induced arthritis, CIA). In vitro, we performed the research in rheumatoid fibroblast-like synoviocytes (FLS). In our study, it was innovatively authenticated that GEN treatment could not only reduce synovitis and inhibit the proliferation of RA FLS, but also relieve cartilage damage in CIA modal. More importantly, we firstly demonstrated that GEN treatment lessened the pain behaviors of CIA mice. In vivo and in vitro experiments confirmed that CD147 was the main target of GEN in attenuating RA symptoms for the first time. Next, we identified the downstream signaling pathway of CD147, and proved that the anti-RA effects of GEN were mediated by down-regulating the expression of p38, IκBα and p65 in vivo and in vitro assays. In conclusion, the data of this manuscript suggested that GEN treatment attenuated synovitis and cartilage destruction in CIA mice; the inhibitory effects on MMP secretion and the anti-rheumatic effects of GEN might be regulated by the CD147/p38/ NF-κB pathway. Accordingly, we found that GEN has the potential therapeutic effects for RA.

[Analysis and prediction of quality markers of Lonicerae Japonicae Flos].

Lonicerae Japonicae Flos, as common Chinese medicine, has been used for thousands of years in the treatment of inflammation and infectious diseases with definite efficacies. The complex composition of Lonicerae Japonicae Flos results in its extensive pharmacological effects, so the assessment of its quality by only a few index components is not comprehensive. Guided by the quality marker(Q-marker), the present study comprehensively analyzed and predicted the quality connotation of Lonicerae Japonicae Flos based on the chemical composition and component transfer, the phylogenetic relationship, chemical composition effectiveness, measurability, and specificity. Chlorogenic acid, isochlorogenic acids A, B, and C, luteoloside, rutin, sweroside, and secoxyloganin were predicted as candidate Q-markers of Lonicerae Japonicae Flos.

[Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacology].

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-ß-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.

[Study on critical quality attributes of Qingjin Huatan Decoction based on serum pharmacochemistry].

Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 µL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.

Research progress on quality markers of traditional Chinese medicine.

The quality of traditional Chinese medicine (TCM) is the lifeline for the development of TCM industry, but research work on this topic is seriously fragmented due to the lack of systematic thinking. Quality markers (Q-markers) are a new concept in TCM quality control. According to the characteristics of TCM system, such as biological attributes, manufacturing process, and compatibility theory, these markers take into account the correlation among effectiveness, material basis, and quality control landmark components and create a new model of TCM quality research. This paper reviews the research pathway and practice on TCM Q-markers in recent years and reports selected examples of case studies. It discusses the application of Q-markers to TCM quality traceability system and industry supervision. Results will provide references for further in-depth research on Q-markers to improve the whole-process quality control level of TCM.

Screening of the active Ingredients in Huanglian Jiedu decoction through amide bond-Immobilized magnetic nanoparticle-assisted cell membrane chromatography.

Introduction: The Huanglian Jiedu decoction (HLJDD) is a Chinese herbal formula that exerts neuroprotective effects by alleviating oxidative stress injuries and may potentially be prescribed for treating Alzheimer's disease; however, its active ingredients have not yet been identified. Cell membrane chromatography is a high-throughput method for screening active ingredients, but traditional cell membrane chromatography requires multiple centrifugation steps, which affects its separation efficiency. Magnetic nanoparticles are unparalleled in solid-liquid separation and can overcome the shortcomings of traditional cell membrane chromatography. Methods: In this study, the neuroprotective effects of the components of HLJDD were screened through a novel magnetic nanoparticle-assisted cell membrane chromatography method. Magnetic nanoparticles and cell membranes were stably immobilized by amide bonds. Magnetic bead (MB)-immobilized cell membranes of HT-22 cells were incubated with the HLJDD extract to isolate specific binding components. The specific binding components were then identified by ultraperformance liquid chromatography (UPLC)-Orbitrap Fusion Tribrid MS after solid-phase extraction. The bioactivity of these components was analyzed in an HT-22 cellular model of glutamate-induced injury. Results and Discussion: The preparation method of the composite of cell membrane and MBs has the advantages of simple preparation and no introduction of toxic organic reagents. MBs not only provide support for cell membranes, but also greatly improve the separation efficiency compared with traditional cell membrane chromatography. Fifteen of these components were found to specifically bind to the cell membranes, and seven of them were confirmed to reduce varying degrees of glutamate-induced toxicity in HT-22 cells. In conclusion, our findings suggest that the amide bond-based immobilization of magnetic nanoparticles on cell membranes, along with solid-phase extraction and UPLC, is an effective method for isolating and discovering the bioactive components of traditional Chinese medicines.

[Modern research progress of traditional Chinese medicine Paeoniae Radix Alba and prediction of its Q-markers].

Paeoniae Radix Alba is the dried root of Paeonia lactiflora, which was first recorded in the Shennong's Classic of Materia Medica and listed as the top grade. It is a common blood-tonifying herb, and its chemical components are mainly monoterpenes and their glycosides, triterpenes, flavonoids and so on. Modern research has demonstrated that Paeoniae Radix Alba has the activities of anti-inflammation, pain easing, liver protection, and anti-oxidation, and thus it is widely used in clinical practice and has broad development prospects. In this paper, the research progress on the chemical composition, pharmacological effects, and quality control of Paeoniae Radix Alba were summarized. On this basis, the Q-markers of Paeoniae Radix Alba were predicted from the aspects of mass transfer and traceability, chemical composition specificity, and availability and measurability of chemical components, which will provide a scientific basis for the quality evaluation of Paeoniae Radix Alba.

STUDY ON THE INFLUENCE OF DRY DENSITY AND PARTICLE SIZE FRACTAL DISTRIBUTION ON THE RADON CONTROL PERFORMANCE OF OVERLYING SOIL IN URANIUM TAILINGS POND.

In order to explore the influence of dry density and particle size fractal distribution on the radon control performance of overlying soil in uranium tailings pond, overlying soil samples with different particle size fractal dimension and dry density were prepared for radon exhalation experiments. According to the principle of radon generation and diffusion, a set of radon measuring device was designed independently. In addition, the radon concentration on the surface of different overlying soil layers was measured by local static method, and the radon exhalation rate was further calculated. The relationship between radon exhalation law, dry density and fractal dimension of overlying soil was studied by correlation analysis method. Furthermore, a piecewise linear function between radon exhalation rate, dry density and fractal dimension was constructed. Then, the average value of the experimental data was compared with the calculated results. Results show that: at the same dry density and different fractal dimension, the radon exhalation rate decreased with the increase of fractal dimension. When the fractal dimension increased to a certain value, the radon exhalation rate tended to be stable. At the same fractal dimension and different dry density, the radon exhalation rate decreased with the increase of dry density. The calculated results of piecewise linear function were relatively close to the experimental data, which verified the practicability of the formula.

Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs.

Neuroprotection of Chikusetsu saponin V on transient focal cerebral ischemia/reperfusion and the underlying mechanism.

BACKGROUND: Oxidative stress and frequently unwanted alterations in mitochondrial structure and function are key aspects of the pathological cascade in transient focal cerebral ischemia. Chikusetsu saponin V (CHS V), a major component of saponins from Panax japonicas, can attenuate H2O2-induced oxidative stress in SH-SY5Y cells. PURPOSE: The aim of the present study was to investigate the neuroprotective effects and the possible underlying mechanism of CHS V on transient focal cerebral ischemia/reperfusion. METHODS: Mice with middle cerebral artery occlusion (MCAO) and cultured cortical neurons exposed to oxygen glucose deprivation (OGD) were used as in vivo and in vitro models of cerebral ischemia, respectively. The neurobehavioral scores, infarction volumes, H&E staining and some antioxidant levels in the brain were evaluated. The occurrence of neuronal death was estimated. Total and mitochondrial reactive oxygen species (ROS) levels, as well as mitochondrial potential were measured using flow cytometry analysis. Mitochondrial structure and respiratory activity were also examined. Protein levels were investigated by western blotting and immunohistochemistry. RESULTS: CHS V effectively attenuated cerebral ischemia/reperfusion (CI/R) injury, including improving neurological deficits, shrinking infarct volume and reducing the number of apoptotic cells. Furthermore, CHS V treatment remarkably increased antioxidant levels and reduced ROS levels and mitochondrial damage by enhancing the expression and deacetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by activating AMPK and SIRT-1, respectively. CONCLUSION: Our data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1α with AMPK and SIRT-1.