CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

[Research progress on structure, structure-activity relationship, and biological activity of Aconiti Lateralis Radix Praeparata polysaccharides].

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.

Different frequency of acupoint thread-embedding for overweight/obesity of spleen deficiency and dampness retention: a randomized controlled trial. / ä¸åŒé¢‘æ¬¡ç©´ä½åŸ‹çº¿æ²»ç–—è„¾è™šæ¹¿é˜»åž‹è¶ é‡/è‚¥èƒ–ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention. METHODS: A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups. RESULTS: After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment (P<0.001, P<0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group(P<0.05, P<0.01, P<0.001). CONCLUSIONS: The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.

[Physicochemical properties and anti-inflammatory and immunomodulatory effects of Shengfupian polysaccharides].

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 µg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 µg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 µg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1ß and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

Conditioned medium of human menstrual blood-derived endometrial stem cells protects against cell inflammation and apoptosis of Npc1KO N2a cells.

Niemann-Pick disease type C1 (NPC1) is a hereditary neurodegenerative disorder caused by a mutation in the NPC1 gene. This gene encodes a transmembrane protein found in lysosomes. This disease characterized by hepatosplenomegaly, neurological impairments and premature death. Recent preclinical studies have shown promising results in using mesenchymal stem cells (MSCs) to alleviate the symptoms of NPC1. One type of MSCs, known as human menstrual blood-derived endometrial stem cells (MenSCs), has attracted attention due to its accessibility, abundant supply, and strong proliferation and regeneration capabilities. However, it remains uncertain whether the conditioned medium of MenSCs (MenSCs-CM) can effectively relieve the symptoms of NPC1. To investigate this further, we employed the CRISPR-Cas9 technique to successfully create a Npc1 gene knockout N2a cell line (Npc1KO N2a). Sanger sequencing confirmed the occurrence of Npc1 gene mutation in these cells, while western blotting revealed a lack of NPC1 protein expression. Filipin staining provided visual evidence of unesterified cholesterol accumulation in Npc1KO N2a cells. Moreover, Npc1KO N2a cells exhibited significantly decreased viability, increased inflammation, and heightened cell apoptosis. Notably, our study demonstrated that the viability of Npc1KO N2a cells was most significantly improved after being cultured by 36 h-collected MenSCs-CM for 0.5 days. Additionally, MenSCs-CM exhibited the ability to effectively reduce inflammation, counteract cell apoptosis, and ameliorate unesterified cholesterol accumulation in Npc1KO N2a cells. This groundbreaking finding establishes, for the first time, the protective effect of MenSCs-CM on N2a cells with Npc1 gene deletion. These findings suggest that the potential of MenSCs-CM as a beneficial therapeutic approach for NPC1 and other neurodegenerative diseases.

Menstrual blood-derived endometrial stem cells inhibit neuroinflammation by regulating microglia through the TLR4/MyD88/NLRP3/Casp1 pathway.

Neuroinflammation is a common response in various neurological disorders. Mesenchymal stem cell-based treatment has become a promising therapy for neuroinflammation-associated diseases. However, the effects of mesenchymal stem cells are controversial, and the underlying mechanism is incompletely understood. In the present study, menstrual blood-derived endometrial stem cells were intravenously transplanted into a mouse model of neuroinflammation established by peripheral injection of lipopolysaccharide. Microglial cells challenged with lipopolysaccharide were cultured with conditioned medium from endometrial stem cells. The levels of cytokines were detected by enzyme-linked immunosorbent assay. Cell proliferation and death were detected by Cell Counting Kit 8 and flow cytometry, respectively. The expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (Casp1) were evaluated by western blotting. The results showed that intravenous transplantation of endometrial stem cells downregulated proinflammatory factors and upregulated anti-inflammatory factors in the brain of mice with neuroinflammation. Conditioned medium suppressed the inflammatory reaction and hyperactivation of microglial cells and protected microglial cells from cell death induced by lipopolysaccharide in vitro. The expression of TLR4, MyD88, NLRP3 and Casp1 in the brain of mice with neuroinflammation and in lipopolysaccharide-stimulated microglial cells was downregulated by endometrial stem cells and conditioned medium, respectively. These data suggested that menstrual blood-derived endometrial stem cells may suppress neuroinflammatory reactions partially by regulating microglia through the TLR4/MyD88/NLRP3/Casp1 signalling pathway. Our findings may be very useful for the development of an alternative stem cell-based therapy for neuroinflammation-associated disorders.

[Comparison of odor and quality of Galli Gigerii Endothelium Corneum derived from domestic chickens and broilers].

Galli Gigerii Endothelium Corneum(GGEC) is commonly used for the clinical treatment of indigestion, vomiting, diarrhea, and infantile malnutrition with accumulation. In recent decades, omnivorous domestic chickens, the original source of GGEC, has been replaced by broilers, which may lead to significant changes in the quality of the yielding GGEC. Through subjective and objective sensory evaluation, biological evaluation, and chemical analysis, this study compared the odor and quality between GGEC derived from domestic chickens and that from broilers. The odor intensity between them was compared by odor profile analysis and it was found that the fishy odor of GGEC derived from domestic chickens was significantly weaker than that of GGEC from broilers. Headspace-solid phase microextraction-gas chromatography-triple quadrupole tandem mass spectrometry(HS-SPME/GC-QQQ-MS/MS) suggested that the overall odor-causing chemicals were consistent with the fishy odor-causing chemicals. According to the odor activity va-lue and the orthogonal partial least squares discriminant analysis(OPLS-DA) result, dimethyl trisulfide, 2-methoxy-3-isobutylpyrazine, and 2-methylisoborneol were responsible for the fishy odor(OAV≥1) and the content of fishy odor-causing chemicals in GGEC derived from broilers was 1.12-2.13 folds that in GGEC from domestic chickens. The average pepsin potency in GGEC derived from broilers was 15.679 U·mg~(-1), and the corresponding figure for the medicinal from domestic chickens was 26.529 U·mg~(-1). The results of pre-column derivatization reverse-phase high-performance liquid chromatography(RP-HPLC) assay showed that the content of total amino acids and digestion-promoting amino acids in domestic chickens-derived GGEC was 1.12 times and 1.15 times that in GGEC from broilers, and the bitter amino acid content was 1.21 times folds that of the latter. In conclusion, GGEC derived from domestic chickens had weaker fishy odor, stronger enzyme activity, higher content of digestion-promoting amino acids, and stronger bitter taste than GGEC from broilers. This study lays a scientific basis for studying the quality variation of GGEC and provides a method for identifying high-quality GGEC. Therefore, it is of great significance for the development and cultivation of GGEC as both food and medicine and breeding of corresponding varieties.

[Main spicy components, mechanism and masking technology for spicy flavor of Chinese medicine: a review].

Many Chinese medicinal materials, vegetable oils and extracts, and even Chinese patent medicines are spicy, which influences the medication compliance of patients, especially children. Different from the sour, sweet, bitter, salty, and umami tastes, it is a painful sensation formed when the spicy substances stimulate the nerve endings. At the moment, there are a few studies on the spicy components and mechanism and masking technology for the spicy flavor of Chinese medicine in the pharmaceutical industry, and the findings in food science are usually taken as a reference, which fail to guide the masking of the spicy flavor in Chinese medicine preparations. According to literature research, the exterior-releasing medicine, dampness-resolving medicine, and interior-warming medicine are spicy, especially some vegetable oils and extracts. Taking Zingiberis Rhizoma and prescriptions containing this medicinal as an example, the spicy components in Chinese medicine and the structure-activity characteristics were analyzed to reveal the mechanism for the spicy flavor: spicy components activate the transient receptor potential vanilloid subfamily member 1(TRPV1). The advantages and disadvantages of separation, neutralization with sugar, and inclusion for the masking of the spicy flavor were summarized and the applicability in Chinese medicine was analyzed. Moreover, the future development direction was put forward. This study is expected to promote the development of spicy masking technology for Chinese medicine prescriptions for children.

[Policy Analysis in Plastic Pollution Governance and Recommendations in China].

Plastic pollution is a global concern and an issue in environmental governance. Based on the updated "Plastic Prohibition/Restriction Order" issued recently in China, the present study systematically reviewed the implementation effectiveness of the "Plastic Prohibition/Restriction Order" since 2007. Furthermore, we summarized plastics in China and plastic waste management progress policies. Additionally, three deficiencies of the updated "Plastic Prohibition/Restriction Order" were discussed:policy formulation, implementation, and supervision. Some positive recommendations were provided based on the available reports, such as integrating plastic pollution into national basic laws and regulation systems, building a network platform for public attendance, and coordinating the publicity of the "Plastic prohibition/Restriction Order" with the public interest. Besides these measurements, some points about plastic waste management in the future were also highlighted, such as the "blind area" in small retail stores, the rational sharing of environmental protection responsibility, new materials and processes, and recycling and disposal systems for plastic wastes. Most importantly, the present study could provide ideas for policy-makers to address plastic pollution at its sources.

A cancer stem cell associated gene signature for predicting overall survival of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer characterized by high mortality and morbidity rate. The lack of effective treatments and the high frequency of recurrence lead to poor prognosis of patients with HCC. Therefore, it is important to develop robust prediction tools for predicting the prognosis of HCC. Recent studies have shown that cancer stem cells (CSC) participate in HCC progression. The aim of this study was to explore the prognostic value of CSC-related genes and establish a prediction model based on data from The Cancer Genome Atlas (TCGA) database. In this study, 475 CSC-related genes were obtained from the Molecular Signature Database and 160 differentially expressed CSC-related genes in HCC patients were identified using the limma R package in the TCGA database. A total of 79 CSC-related genes were found to be associated with overall survival (OS). Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions, a 3-gene signature (RAB10, TCOF1, and PSMD14) was constructed. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were constructed to test the prediction performance of the signature. Performance of the signature was validated using the International Cancer Genome Consortium (ICGC) dataset. In addition, immune feature and functional enrichment analyses were carried out to explore the underlying mechanisms. Moreover, a co-expression network was constructed using the weighted gene correlation network analysis (WGCNA) method to select genes significantly associated with risk scores in HCC in the TCGA dataset. The SGO2 gene was found to be significantly associated with risk scores of HCC. In vitro experiments revealed that it can promote HCC cell proliferation. Therefore, SGO2 may be a potential therapeutic target for HCC treatment. The constructed nomogram can help clinicians make decisions about HCC treatment.

Weather and Birth Weight: Different Roles of Maternal and Neonatal GPR61 Promoter Methylation.

Objectives: It is unclear whether G protein-coupled receptor 61 (GPR61) affecting body weight, plays a role in the association between birth weight and weather. This study aimed to assess the effects of prenatal weather and GPR61 on birth weight. Methods: A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during 2011-2012. We detected the maternal and neonatal GPR61 promoter methylation levels, and obtained meteorological and air pollution data. Results: A positive association was observed between maternal and neonatal GPR61 methylation levels, and both of them were affected by precipitation, relative humidity (RH) and daily temperature range (DTR). Birth weight was associated negatively with RH and positively with DTR ( P < 0.05). A significant association was observed between birth weight and neonatal GPR61 methylation. We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight ( P interaction < 0.10), while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight ( P < 0.05). Conclusions: Our findings revealed the significant associations among prenatal weather, GPR61 methylation and birth weight. Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions, while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.

[Challenges and strategies of high-quality development of Indigo Naturalis industry].

Traditional Chinese medicine( TCM) processing is a traditional pharmaceutical technology unique to China,which is an important means to ensure the safety and effectiveness of clinical medication. As China' s intangible cultural heritage,it contains a wealth of wisdom. With the evolution and optimization of processing methods,Indigo Naturalis,an ancient dye,has gradually become an effective medicine for the treatment of high fever in children,colitis,psoriasis,and leukemia. However,the quality of Indigo Naturalis pieces is difficult to be fundamentally improved due to the unique traditional processing method,complex technology,unclear principle,and outdated equipment. After spending 20 years in exploring the inheritance,innovation,and transformation of ancient lawtheory-principle-technology-equipment-quality control in Indigo Naturalis processing,our research group has basically expounded the processing principle and realized the modern expression and industrial transformation of traditional technology. As China enters a new era,the TCM industry has begun to undergo the high-quality transformation. It is urgent to carry out new excavations and improve the processing,quality,and clinical application of Indigo Naturalis pieces,to better inherit and innovate traditional processing technologies and meet people's demand for high-quality TCM health services.

[Microbial community structure and transformation of indoles in soaking and fermentation of Indigo Naturalis].

The soaking and fermentation of Baphicacanthus cusia( Nees),the important intermediate link of Indigo Naturalis processing,facilitates the synthesis of indigo and indirubin precursors and the dissolution of endogenous enzymes and other effective components,while the role of microorganisms in the fermentation is ignored. The present study investigated the changes of microbial community structure in Indigo Naturalis processing based on 16 S amplicon sequencing and bioinformatics. Meanwhile,the contents of indigo,indirubin,isatin,tryptanthrin,indole glycoside,etc. were determined to explore the correlation between the microorganisms and the alterations of the main components. As demonstrated by the results,the microbial diversity decreased gradually with the fermentation,which bottomed out after the addition of lime. Proteobacteria,Bacteroidetes,and Firmicutes were the main dominant communities in the fermentation. The relative abundance of Proteobacteria declined gradually with the prolongation of fermentation time,and to the lowest level after the addition of lime. The relative abundance of Firmicutes increased,and that of Bacteroidetes decreased first and then increased. The contents of effective substances in Indigo Naturalis also showed different variation tendencies. As fermentation went on,indole glycoside decreased gradually; indigo first increased and then decreased; indirubin and isatin first decreased and then increased; tryptanthrin gradually increased. Those changes were presumedly related to the roles of microorganisms in the synthesis of different components. This study preliminarily clarified the important role of microorganisms in the soaking and fermentation and provided a scientific basis for the control of Indigo Naturalis processing and the preparation of high-quality Indigo Naturalis.

[Key to Indigo Naturalis' oral effectiveness: in vivo and in vitro verification of bile action].

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

[Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation].

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1ßand TNF-αin serum and IL-1ßand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1ßlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota.

Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC. Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing. Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1ß,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics. Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.

Fever and Antipyretic Supported by Traditional Chinese Medicine: A Multi-Pathway Regulation.

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19.

[Analysis of transcriptome differences in two leaf-type cultivars of Aconitum carmichaelii].

According to the major differences of agricultural characters among various Aconitum carmichaelii cultivars, the lateral roots of Ai-leaf and Dahua-leaf A.carmichaelii plants were selected as the research objects. And the Illumina Hiseq high-throughput platform was used for transcriptome sequencing, assembly and annotation. We mostly focused the activity differential transcripts, metabolism pathways and enrichment functions. The results showed that a total of 52.23 Gb nucleotide bases were obtained from 6 A.carmichaelii transcriptome databases, with 52 471 unigenes and 28 765 matched annotation. There were 1 052 transcripts of the two kinds of A.carmichaelii with a difference of more than 2 times, 808 of which were annotated. Through GO and COG analysis, they were found to mainly concentrate in metabolic processes, cell processes, catalytic processes and transport processes, connections and other functions. KEGG analysis showed that 262 DEGs were enriched in 78 metabolic pathways, such as starch and sucrose metabolism, plant hormone signaling, carbon compounded transport etc. It was implied that many genes in Dahua-leaf A.carmichaelii regulated the conversion of starch to small molecules such as sucrose, glucose and maltose, while some other genes regulated the accumulation of amino acids, which may be the important biological principles for the formation of the differences between the quality and disease resistance of two leaf types of A.carmichaelii. This study will provide reference datas for A.carmichaelii breeding research.

[Study advances of microwave processing technology in traditional Chinese medicine].

The iterative innovation of processing technology is one of the important tasks in studies on processing of traditional Chinese medicine(TCM). It is also the prerequisite for modern, refined, automatic and intelligent manufacturing of TCM pieces. Microwave processing is a new fire processing technique developed in the recent 30 years, with a unique thermodynamic form, and energy transfer and transformation laws. Moreover, it owns the advantages of a high processing efficiency, good product properties and low production energy consumption, with great application prospects. This paper introduced the study overview of microwave expansion technology in the food industry, reviewed the origin of microwave processing technology of TCM, and expounded the basic concept, principle and main purpose of microwave processing technology used in TCM. Then, the impacts of drug factors and microwave factors on the microwave processing effect were summarized, the industrial equipment that could be used for microwave processing was listed, and the impacts of microwave heating on starch, polysaccharide, protein and other components in Chinese herbal medicines were analyzed. Furthermore, the study advance of microwave processing of 14 herbs was investigated, including Aconiti Lateralis Radix Praeparaia, Galli Gigerii Endothelium Corneum and Asini Corii Colla; and the appearance and components of herbs processed by traditional processing method and microwave processing method were compared, so as to reveal the opportunities and challenges of microwave processing technology in the industrial transformation. We hoped that the systematic study of microwave processing technology could provide new ideas and techniques for the high-quality and high-level development of the TCM pieces industry in the new era, and promote its inheritance, innovation and transformation.

Rynchopeterine F, unique heterodimer of phenethanol-phenylacetyl linking with lactic acid from the medicinal insect Blaps rynchopetera.

A new heterodimer, rynchopeterine F (1), a new natural product, rynchopeterine G (2), and eleven known phenolics were isolated from Blap rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi and Bai Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS) along with calculated electronic circular dichroism method. Rynchopeterine F was a unusual heterodimer of a 3,4-dihudroxy phenylethanol unit fused to a 3,4-dihudroxy phenylacetyl group through two ester bonds with lactic acid, and rynchopeterine G was a 3,4-dihudroxy phenylethanyl monoester succinate. Attributed to the adjacent dihydroxyl grops, compounds 1 and 2 exhibited significant anti-radical activity with an IC50 value of 3.52 and 7.83 µg/mL for DPPH radical-scavenging, similar with that of the positive controls, vitamin C, 6.92 µg/mL and rutin, 8.28 µg/mL.