American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

AAV-glycine receptor α3 alleviates CFA-induced inflammatory pain by downregulating ERK phosphorylation and proinflammatory cytokine expression in SD rats.

BACKGROUND: Glycine receptors (GlyRs) play key roles in the processing of inflammatory pain. The use of adeno-associated virus (AAV) vectors for gene therapy in human clinical trials has shown promise, as AAV generally causes a very mild immune response and long-term gene transfer, and there have been no reports of disease. Therefore, we used AAV for GlyRα1/3 gene transfer in F11 neuron cells and into Sprague-Dawley (SD) rats to investigate the effects and roles of AAV-GlyRα1/3 on cell cytotoxicity and inflammatory response. METHODS: In vitro experiments were performed using plasmid adeno-associated virus (pAAV)-GlyRα1/3-transfected F11 neurons to investigate the effects of pAAV-GlyRα1/3 on cell cytotoxicity and the prostaglandin E2 (PGE2)-mediated inflammatory response. In vivo experiment, the association between GlyRα3 and inflammatory pain was analyzed in normal rats after AAV-GlyRα3 intrathecal injection and after complete Freund's adjuvant (CFA) intraplantar administration. Intrathecal AAV-GlyRα3 delivery into SD rats was evaluated in terms of its potential for alleviating CFA-induced inflammatory pain. RESULTS: The activation of mitogen-activated protein kinase (MAPK) inflammatory signaling and neuronal injury marker activating transcription factor 3 (ATF-3) were evaluated by western blotting and immunofluorescence; the level of cytokine expression was measured by ELISA. The results showed that pAAV/pAAV-GlyRα1/3 transfection into F11 cells did not significantly reduce cell viability or induce extracellular signal-regulated kinase (ERK) phosphorylation or ATF-3 activation. PGE2-induced ERK phosphorylation in F11 cells was repressed by the expression of pAAV-GlyRα3 and administration of an EP2 inhibitor, GlyRαs antagonist (strychnine), and a protein kinase C inhibitor. Additionally, intrathecal AAV-GlyRα3 administration to SD rats significantly decreased CFA-induced inflammatory pain and suppressed CFA-induced ERK phosphorylation, did not induce obvious histopathological injury but increased ATF-3 activation in dorsal root ganglion (DRGs). CONCLUSIONS: Antagonists of the prostaglandin EP2 receptor, PKC, and glycine receptor can inhibit PGE2-induced ERK phosphorylation. Intrathecal AAV-GlyRα3 administration to SD rats significantly decreased CFA-induced inflammatory pain and suppressed CFA-induced ERK phosphorylation, did not significantly induce gross histopathological injury but elicited ATF-3 activation. We suggest that PGE2-induced ERK phosphorylation can be modulated by GlyRα3, and AAV-GlyRα3 significantly downregulated CFA-induced cytokine activation.

Mechanism Study on Chinese Medicine in Treatment of Nodular Goiter.

Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.

Mechanism Study on Chinese Medicine in Treatment of Nodular Goiter / 中国结合医学杂志

Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.

Tubeimoside-1: A review of its antitumor effects, pharmacokinetics, toxicity, and targeting preparations.

Tubeimoside-1 (TBMS-1), a natural triterpenoid saponin found in traditional Chinese herbal medicine Bolbostemmatis Rhizoma, is present in numerous Chinese medicine preparations. This review aims to comprehensively describe the pharmacology, pharmacokinetics, toxicity and targeting preparations of TBMS-1, as well the therapeutic potential for cancer treatement. Information concerning TBMS-1 was systematically collected from the authoritative internet database of PubMed, Web of Science, and China National Knowledge Infrastructure applying a combination of keywords involving "tumor," "pharmacokinetics," "toxicology," and targeting preparations. New evidence shows that TBMS-1 possesses a remarkable inhibitory effect on the tumors of the respiratory system, digestive system, nervous system, genital system as well as other systems in vivo and in vitro. Pharmacokinetic studies reveal that TBMS-1 is extensively distributed in various tissues and prone to degradation by the gastrointestinal tract after oral administration, causing a decrease in bioavailability. Meanwhile, several lines of evidence have shown that TBMS-1 may cause adverse and toxic effects at high doses. The development of liver-targeting and lung-targeting preparations can reduce the toxic effect of TBMS-1 and increase its efficacy. In summary, TBMS-1 can effectively control tumor treatment. However, additional research is necessary to investigate in vivo antitumor effects and the pharmacokinetics of TBMS-1. In addition, to reduce the toxicity of TBMS-1, future research should aim to modify its structure, formulate targeting preparations or combinations with other drugs.

Microcomb-driven silicon photonic systems.

Microcombs have sparked a surge of applications over the past decade, ranging from optical communications to metrology1-4. Despite their diverse deployment, most microcomb-based systems rely on a large amount of bulky elements and equipment to fulfil their desired functions, which is complicated, expensive and power consuming. By contrast, foundry-based silicon photonics (SiPh) has had remarkable success in providing versatile functionality in a scalable and low-cost manner5-7, but its available chip-based light sources lack the capacity for parallelization, which limits the scope of SiPh applications. Here we combine these two technologies by using a power-efficient and operationally simple aluminium-gallium-arsenide-on-insulator microcomb source to drive complementary metal-oxide-semiconductor SiPh engines. We present two important chip-scale photonic systems for optical data transmission and microwave photonics, respectively. A microcomb-based integrated photonic data link is demonstrated, based on a pulse-amplitude four-level modulation scheme with a two-terabit-per-second aggregate rate, and a highly reconfigurable microwave photonic filter with a high level of integration is constructed using a time-stretch approach. Such synergy of a microcomb and SiPh integrated components is an essential step towards the next generation of fully integrated photonic systems.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier.

BACKGROUND: The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PURPOSE: The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. METHODS: The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. RESULTS: HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. CONCLUSIONS: These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.

Processing Methods and Quality Evaluation of Pinelliae Rhizoma： A Review / 中国实验方剂学杂志

In this paper， by consulting the historical herbs and medical classics coupled with related literature in modern research， the historical edition of Chinese Pharmacopoeia and local chronicles of traditional Chinese medicine （TCM） along with the ancient historical evolution of the processing methods of Pinelliae Rhizoma origin as well as the related processing methods of Pinelliae Rhizoma origin from 1959 to 2020 were systematically collated and summarized. It was found that the main processing methods of Pinelliae Rhizoma origin were peeling， decoction washing， lime wrapping and sun-drying. However， stacking， peeling， sun-drying or oven-drying are the primary methods in modern local chronicles of TCM. Meanwhile， washing， peeling， removing fibrous roots and sun-drying are the main methods in Chinese Pharmacopoeia. In addition， there were some changes in the quality evaluation of Pinelliae Rhizoma in different historical periods. Round and white were the best in the quality evaluation of Pinelliae Rhizoma in ancient times， while the evaluation indexes were further refined to size， color， texture， powder property， purity and evenness in modern herbal works. In modern studies， the quality of Pinelliae Rhizoma was mostly evaluated by the chemical components such as alkaloids， total organic acids， polysaccharides， nucleosides， fingerprint and pharmacodynamics. At present， the purification and drying stages of Pinelliae Rhizoma are in the transitional stage between the traditional manual peeling and natural drying methods as well as the modern mechanized and large-scale production. Therefore， a reasonable and feasible modern processing methods and guiding standards of Pinelliae Rhizoma are developed urgently to normalize the processing of Pinelliae Rhizoma and ensure the quality of medicinal materials.

Processing Methods and Quality Evaluation of Pinelliae Rhizoma： A Review / 中国实验方剂学杂志

In this paper， by consulting the historical herbs and medical classics coupled with related literature in modern research， the historical edition of Chinese Pharmacopoeia and local chronicles of traditional Chinese medicine （TCM） along with the ancient historical evolution of the processing methods of Pinelliae Rhizoma origin as well as the related processing methods of Pinelliae Rhizoma origin from 1959 to 2020 were systematically collated and summarized. It was found that the main processing methods of Pinelliae Rhizoma origin were peeling， decoction washing， lime wrapping and sun-drying. However， stacking， peeling， sun-drying or oven-drying are the primary methods in modern local chronicles of TCM. Meanwhile， washing， peeling， removing fibrous roots and sun-drying are the main methods in Chinese Pharmacopoeia. In addition， there were some changes in the quality evaluation of Pinelliae Rhizoma in different historical periods. Round and white were the best in the quality evaluation of Pinelliae Rhizoma in ancient times， while the evaluation indexes were further refined to size， color， texture， powder property， purity and evenness in modern herbal works. In modern studies， the quality of Pinelliae Rhizoma was mostly evaluated by the chemical components such as alkaloids， total organic acids， polysaccharides， nucleosides， fingerprint and pharmacodynamics. At present， the purification and drying stages of Pinelliae Rhizoma are in the transitional stage between the traditional manual peeling and natural drying methods as well as the modern mechanized and large-scale production. Therefore， a reasonable and feasible modern processing methods and guiding standards of Pinelliae Rhizoma are developed urgently to normalize the processing of Pinelliae Rhizoma and ensure the quality of medicinal materials.

[Research progress on Pheretima and earthworms with related origin].

Through literature analysis of Pheretima and its origin-related earthworm,this study summarized the progress on Pheretima in textual criticism of origin,origin identification,effective components,detection of harmful components,and pharmacological effects,which can lay a basis for further research on Pheretima. Through literature research,the authors found that Pheretima was first recorded in Secret Formulary for Traumatology and Fracture Taught by Immortal written by LIN Daoren in Tang Dynasty rather than the Taiping Holy Prescriptions for Universal Relief in Song Dynasty. The latest techniques for origin identification include microscopic trait identification,DNA barcoding,and HPLC. The main effective components of Pheretima are proteins,polypeptides,enzymes,nucleotides,amino acids,and trace elements. According to recent studies,Pheretima has anti-pulmonary and anti-renal interstitial fibrosis,respiratory syncytial virus-inhibiting,human hypertrophic scar fibroblast proliferation-suppressing,and mouse embryonic fibroblast proliferation-promoting effects. Moreover,Pheretima can prevent colitis-induced colon cancer by inhibiting the activation of COX-2/PGE2/ß-catenin signaling pathway. METHODS:: for detecting the harmful components and their residues( organic pollutant polychlorinated biphenyl,heavy metals) and bacteria in Pheretima,have been established. Pheretima,mainly derived from wild earthworms,has remarkable clinical efficacy. However,the wild resource is in short supply and artificial culture is expected to be a promising solution.

Laser soliton microcombs heterogeneously integrated on silicon.

Silicon photonics enables wafer-scale integration of optical functionalities on chip. Silicon-based laser frequency combs can provide integrated sources of mutually coherent laser lines for terabit-per-second transceivers, parallel coherent light detection and ranging, or photonics-assisted signal processing. We report heterogeneously integrated laser soliton microcombs combining both indium phospide/silicon (InP/Si) semiconductor lasers and ultralow-loss silicon nitride (Si3N4) microresonators on a monolithic silicon substrate. Thousands of devices can be produced from a single wafer by using complementary metal-oxide-semiconductor-compatible techniques. With on-chip electrical control of the laser-microresonator relative optical phase, these devices can output single-soliton microcombs with a 100-gigahertz repetition rate. Furthermore, we observe laser frequency noise reduction due to self-injection locking of the InP/Si laser to the Si3N4 microresonator. Our approach provides a route for large-volume, low-cost manufacturing of narrow-linewidth, chip-based frequency combs for next-generation high-capacity transceivers, data centers, space and mobile platforms.

[Moxibustion inhibits growth of tumor by down-regulating expression of FGFR1 and VEGFR2 in mice with sarcoma].

OBJECTIVE: To observe the effect of moxibustion on the growth of tumor and expression of fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial cell growth factor receptor 2 (VEGFR2) in mice with sarcoma, so as to explore its mechanisms underlying inhibiting sarcoma growth. METHODS: C57BL/6J mice (half male and half female) were inoculated with S180 sarcoma cells to form transplanted tumors, and divided into model control, medication and moxibustion groups, with 10 mice in each group. Moxibustion was applied to the transplanted tumor directly for 10 min, once a day for 14 days. After the treatment, Luminex liquid suspension chip was used to detect the contents of serum vascular endothelial growth factor (VEGF), FGFR1 and VEGFR2. The weight of the transplanted tumor was measured, and the expression of VEGF in the transplanted tumor was detected by immunohistochemistry, and the expression of FGFR1 and VEGFR2 mRNAs in the transplanted tumor was detected by fluorescence in situ hybridization. RESULTS: The tumor weight, VEGF immunoactivity, serum VEGF, VEGFR2 and FGFR1 contents, and expression levels of VEGFR2 and FGFR1 mRNAs in the transplanted tumor were significantly lower in the moxibustion group than in the model group (P<0.001, P<0.01, P<0.05). Compared with the model group, the tumor weight was remarkably lower in the medication group (P<0.001). Compared with the medication group, th VEGF immunoactivity and the contents of serum VEGF, VEGFR2 and FGFR1 were significantly lower in the moxibustion group （P<0.01, P<0.05）. H.E. staining showed a large number of red blood cells were observed in the microenvironment of the transplanted tumor in the moxibustion group rather than in the medication group. CONCLUSION: Moxibustion can inhibit the growth of tumor in mice with sarcoma, which may be related to its function in reducing the expression of FGFR1 and VEGFR2 to inhibit angiogenesis.

Effects of moxibustion on Treg cells in sarcoma microenvironment.

OBJECTIVE: To investigate the therapeutic effect of moxibustion on sarcomas from mesenchymal tissues, which have a low response rate to chemotherapy and radiotherapy. METHODS: S180 sarcoma cell line was inoculated in C57BL/6 mice to form transplanted tumor. Moxibustion therapy was directly applied at the transplanted tumor sites, at a distance of 3.0 cm, 10 min per session, till skin temperature reached 45 °C, once a day, for 14 consecutive days of intervention. After the mice were killed, serum was collected and used to detect concentrations of interleukin-10 (IL-10), transforming growth factor-ß1 (TGF-ß1), IL-4 and interferon-γ (IFN-γ) by Luminex liquid suspension chip. The numbers of Treg+ T cells and CD4+CD25+Forkhead Box P3 (Foxp3)+ T cells were detected by flow cytometry. Fluorescence in situ hybridization was used to analyze the changes of CD4, CD8, Foxp3 and TGF-ß1 in the tumor microenvironment (TME). RESULTS: Weight of S180 transplanted tumor in the control group was (2.03 ± 0.54) g, and that in the moxibustion group was (1.27 ± 0.29) g, which was statistically different (P = 0.023). The mean value of Foxp3+ T cells in the normal group was 2.01%, which increased to 3.63% after the formation of transplanted tumor, and decreased to 1.48% after moxibustion treatment. The moxibustion group also had reduced numbers of CD4+CD25+Foxp3+ T cells in the spleen of mice with transplanted tumor. The concentrations of IL-10, TGF-ß1 and IL-4 decreased in the serum of mice with transplanted tumor, while the concentration of IFN-γ increased. Moxibustion was associated with downregulation in expression of Foxp3, IL-10 and TGF-ß1 genes in the transplanted tumor, and increases in the gene expression of CD4+ T cells and CD8+ T cells in the TME. CONCLUSION: Moxibustion may have therapeutic effects on sarcomas by reducing the number of Treg cells in the blood and controlling the infiltration of Treg cells in the TME.

Effects of Huangqin Decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. OBJECTIVE: To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). METHODS: The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H-C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. RESULTS: The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H-C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. CONCLUSIONS: HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.

Effects of moxibustion on Treg cells in sarcoma microenvironment / 中西医结合学报

OBJECTIVE@#To investigate the therapeutic effect of moxibustion on sarcomas from mesenchymal tissues, which have a low response rate to chemotherapy and radiotherapy.@*METHODS@#S180 sarcoma cell line was inoculated in C57BL/6 mice to form transplanted tumor. Moxibustion therapy was directly applied at the transplanted tumor sites, at a distance of 3.0 cm, 10 min per session, till skin temperature reached 45 °C, once a day, for 14 consecutive days of intervention. After the mice were killed, serum was collected and used to detect concentrations of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), IL-4 and interferon-γ (IFN-γ) by Luminex liquid suspension chip. The numbers of Treg@*RESULTS@#Weight of S180 transplanted tumor in the control group was (2.03 ± 0.54) g, and that in the moxibustion group was (1.27 ± 0.29) g, which was statistically different (P = 0.023). The mean value of Foxp3@*CONCLUSION@#Moxibustion may have therapeutic effects on sarcomas by reducing the number of Treg cells in the blood and controlling the infiltration of Treg cells in the TME.

[Study on mechanisms of anti-Alzheimer's disease action of absorbed components of Gardeniae Fructus based on network pharmacology].

Gardeniae Fructus has the traditional effects of promoting intelligence and inducing resuscitation, but its mechanism is unclear. In this study, the relationship between Gardeniae Fructus's traditional effect of promoting intelligence and inducing resuscitation and anti-Alzheimer's disease effect was taken as the starting point to investigate the anti-Alzheimer's disease mechanism of the major absorbed components in Gardeniae Fructus by the network pharmacology method. The network pharmacology research model of "absorbed composition-target-pathway-disease" was adopted. In this study, the active components screening and target prediction technology were used to determine the active components and targets of Gardeniae Fructus in treatment of Alzheimer's disease. The enrichment pathway and biological process of Gardeniae Fructus were studied by using the bioinformatics annotation database(DAVID), and the results of molecular docking validation network analysis were used to elaborate the mechanism of Gardeniae Fructus in treatment of Alzheimer's disease. It was found that 35 absorbed components of Gardeniae Fructus not only regulated 48 targets such as cholines-terase(BCHE) and carbonic anhydrase 2(CA2), but also affected 11 biological processes(e.g. transcription factor activity, nuclear receptor activity, steroid hormone receptor activity, amide binding and peptide binding) and 7 metabolic pathways(MAPK signaling pathway, Alzheimer disease and estrogen signaling pathway, etc.). Molecular docking results showed that more than 60% of the active components could be well docked with key targets, and the relevant literature also showed that the active components could inhibit the MAPK1 expression of key targets, indicating a high reliability of results. These results indicated that Gardeniae Fructus may play its anti-Alzheimer's disease action via a "multi-ingredients-multi-targets and multi-pathways" mode, providing a scientific basis for further drug research and development.

[Effects of light intensity on physio-biochemical characteristics of Chrysanthemum indicum].

By analyzing the effects of light intensity on the growth, physiological and biochemical characteristics of Chrysanthemum indicum, the light intensity suitable for the growth of Ch. indicum was revealed, which provided a reference for the planting of Ch. indicum. There were five treatment groups of Ch. indicum, which was planted under 100%, 80%, 60%, 40% and 20% all natural light intensity conditions, respectively. In the meantime, these indicators of photosynthetic physiology, such as relative growth, photosynthetic pigment content, photosynthetic parameters, and chlorophyll fluorescence parameters etc. were measured in the peak period of growth of Ch. indicum as well as related indicators of the protective enzyme system, and the ultrastructure of chloroplast was observed with the use of transmission electron microscope technique. In our study, the results showed that the leaves of Ch. indicum occurred yellow phenomenon in different degrees when Ch. indicum was placed at more than 80% of the total natural light intensity condition, the height and stem diameter of plant reached the maximum at 60% of the total natural light intensity. More importantly, the number of branches of Ch. indicum was significantly increased under the total natural light intensity of more than 60%. Both the content of photosynthetic pigment and net photosynthetic rate were negatively correlated with light intensity, while photosynthetic parameters and chlorophyll fluorescence parameters showed a trend of rising first and then decreasing with the decrease of light intensity. The physiological indexes of Ch.indicum including stomatal conductivity, intracellular CO_2 concentration, transpiration rate, water use efficiency and actual photochemical quantum yield of PS Ⅱ had been determined, and the results showed that all of them were at the highest level under 60% total natural light intensity condition. The chloroplast structure of Ch. indicum was not obviously abnormal under 60% and 80% total natural light intensity treatments, but the stroma lamella was broken under 100% total natural light intensity, and not only the number of chloroplast, but also the number and volume of starch grains were decreased significantly under 20% and 40% total natural light intensity. With the decrease of light intensity, the enzymes activities of SOD and CAT decreased, the activity of POD increased in the early stage and decreased in the later stage, and the content of MDA showed a decreasing trend. The analysis of results indicated that the Ch. indicum can grow under 20%-100% total natural light intensity, but the best growth condition was under 60% total natural light intensity.

Plant-mediated synthesis of dual-functional Eggshell/Ag nanocomposites towards catalysis and antibacterial applications.

Advances in nanotechnology provide plenty of exciting solutions to environmental issues affecting air, soil as well as water. To solve the water pollution problem caused by organics and microorganisms, development of a simple, environment-friendly, and cheap method for the synthesis of nanomaterials is of paramount importance. Herein, we prepared a novel nanocomposite (named Eggshell/Ag) using waste eggshell as a support and Cacumen platycladi extract as reducing and stabilizing agents in aqueous solutions at room temperature. Biogenic-stabilized Ag nanoparticles (Ag NPs) with an average diameter of 60 nm were well-dispersed on the surface of eggshells, exhibiting dual-functional properties of organics catalytic degradation and bacterial growth inhibition. Through five repeated assays, it was established that the reduction efficiency of the nanocomposite for 4-nitrophenol (4-NP) was high. The reduction could be completed rapidly at room temperature. Moreover, significant inhibition zones were observed for Staphylococcus aureus (S. aureus) agar plates and Escherichia coli (E. coli). Meanwhile, the minimum inhibition concentrations (MIC) were determined to be 0.08 and 0.04 mg mL-1, respectively, while the minimum bactericidal concentration (MBC) was measured as 0.64 mg mL-1. The biogenic Eggshell/Ag nanocomposites are promising candidates for a series of applications in the fields of biomedicine, environment as well as energy.

Cyclodextrin Prevents Abdominal Aortic Aneurysm via Activation of Vascular Smooth Muscle Cell Transcription Factor EB.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a severe aortic disease with a high mortality rate in the event of rupture. Pharmacological therapy is needed to inhibit AAA expansion and prevent aneurysm rupture. Transcription factor EB (TFEB), a master regulator of autophagy and lysosome biogenesis, is critical to maintain cell homeostasis. In this study, we aim to investigate the role of vascular smooth muscle cell (VSMC) TFEB in the development of AAA and establish TFEB as a novel target to treat AAA. METHODS: The expression of TFEB was measured in human and mouse aortic aneurysm samples. We used loss/gain-of-function approaches to understand the role of TFEB in VSMC survival and explored the underlying mechanisms through transcriptome and functional studies. Using VSMC-selective Tfeb knockout mice and different mouse AAA models, we determined the role of VSMC TFEB and a TFEB activator in AAA in vivo. RESULTS: We found that TFEB is downregulated in both human and mouse aortic aneurysm lesions. TFEB potently inhibits apoptosis in VSMCs, and transcriptome analysis revealed that TFEB regulates apoptotic signaling pathways, especially apoptosis inhibitor B-cell lymphoma 2. B-cell lymphoma 2 is significantly upregulated by TFEB and is required for TFEB to inhibit VSMC apoptosis. We consistently observed that TFEB deficiency increases VSMC apoptosis and promotes AAA formation in different mouse AAA models. Furthermore, we demonstrated that 2-hydroxypropyl-ß-cyclodextrin, a clinical agent used to enhance the solubility of drugs, activates TFEB and inhibits AAA formation and progression in mice. Last, we found that 2-hydroxypropyl-ß-cyclodextrin inhibits AAA in a VSMC TFEB-dependent manner in mouse models. CONCLUSIONS: Our study demonstrated that TFEB protects against VSMC apoptosis and AAA. TFEB activation by 2-hydroxypropyl-ß-cyclodextrin may be a promising therapeutic strategy for the prevention and treatment of AAA.