Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Research progress on natural medicines and active compounds in the treatment of heart failure / 药学实践杂志

Heart failure is the terminal stage of various cardiovascular diseases and a leading cause of death. For a long time, natural medicines have been used to treat heart failure（HF） with remarkable effects. In this paper, the Traditional Chinese Medicine compound patents in the national patent database were mined, common Traditional Chinese Medicines for the clinical treatment of HF were selected, and the single active ingredient contained in them was analyzed, which provided some valuable tips for the development of drugs for the treatment of heart failure.

Research progress of traditional Chinese medicine monomer and compound intervention on the Wnt signaling pathway in regulating bone metabolism / 中国药房

Bone metabolism refers to the decomposition and anabolism occurring during bone remodeling， and its balance is regulated by bone resorption and bone formation. A slight deviation of this balance causes various skeletal diseases， such as osteoporosis and renal osteodystrophy. Traditional Chinese medicine （TCM） monomers and compounds have certain advantages in treating bone metabolism diseases. The Wnt signaling pathway includes the canonical Wnt signaling pathway， dependent on β-catenin， and the non-canonical Wnt signaling pathway， independent of β-catenin. Both types of pathways can maintain bone metabolism balance by regulating bone formation and bone resorption and are essential for bone development， bone mass maintenance， and bone remodeling. A variety of TCM monomers （albiflorin， catalpol and icariin） and formulas （Zuogui pill， Yishen gugu prescription， Duzhong jiangu prescription， etc.） have been confirmed to promote differentiation of bone marrow mesenchymal stem cells， proliferation and differentiation of osteoblasts， bone injury repair， and osteoporosis improvement by activating the Wnt signaling pathway in recent years. Here， this article summarizes the research progress in the Wnt signaling pathway regulation of bone metabolism by TCM monomers and compounds to provide ideas for the clinical application of TCM and the research and development of new drugs for the prevention and treatment of bone metabolism diseases.

Effect of elastomeric urethane monomer on physicochemical properties and shrinkage stress of resin composites

Abstract This study aimed to evaluate the effect of an elastomeric urethane monomer (Exothane-24) in different concentrations on physicochemical properties, gap formation, and polymerization shrinkage stress of experimental resin composites. All experimental composites were prepared with 50 wt.% of Bis-GMA and 50 wt.% of TEGDMA, to which 0 wt.% (control), 10 wt.%, 20 wt.%, 30 wt.%, and 40 wt.% of Exothane-24 were added. Filler particles (65 wt.%) were then added to these resin matrixes. Ultimate tensile strength (UTS: n = 10), flexural strength (FS: n = 10), flexural modulus (FM: n = 10), hardness (H: n = 10), hardness reduction (HR: n = 10), degree of conversion (DC: n = 5), gap width (GW: n = 10), and polymerization shrinkage stress in Class I (SS-I: n = 10) and Class II (SS-II: n = 10) simulated configuration. All test data were analyzed using one-way ANOVA and Tukey's test (α = 0.05; β= 0.2). Exothane-24 in all concentrations decreased the H, HR, DC, GW, SS-I, and SS-II (p < 0.05) without affecting the UTS, and FS (p > 0.05). Reduction in FM was observed only in the Exothane 40% and 30% groups compared to the control (p < 0.05). Exothane-24 at concentrations 20% and 30% seems suitable since it reduced GW and polymerization SS without affecting the properties of the composite resins tested, except for H.

Resumo Este estudo teve como objetivo avaliar o efeito de um monômero elastomérico de uretano (Exothane-24) em diferentes concentrações em propriedades físico-químicas, formação de fenda e tensão de contração de polimerização de resinas compostas experimentais. Todos os compósitos experimentais foram preparados com 50% em peso de Bis-GMA e 50% em peso de TEGDMA, nos quais 0% (controle), 10%, 20%, 30% e 40% em peso de Exothane-24 foram adicionados. Partículas de carga (65% em peso) foram então adicionadas as matrizes resinosas. Resistência coesiva (RC: n = 10), resistência à flexão (RF: n = 10), módulo de flexão (MF: n = 10), dureza (D: n = 10), redução de dureza (RD: n = 10), grau de conversão (GC: n = 5), largura de fenda (LF: n = 10) e tensão de contração de polimerização em simulações de cavidades Classe I (TC-I: n = 10) e Classe II (TC-II: n = 10). Todos os dados do teste foram analisados usando one-way ANOVA e teste de Tukey (α = 0,05; β = 0,2). O Exothane-24 em todas as concentrações diminuiu a D, RD, GC, LF, TC-I e TC-II (p < 0,05) sem afetar o RC e RF (p > 0,05). A redução da MF foi observada apenas nos grupos Exothane 40% e 30% em relação ao controle (p < 0,05). O Exothane-24 nas concentrações de 20% e 30% pareceu ser adequado, pois reduziu LF e TC de polimerização sem afetar as propriedades das resinas compostas testadas, exceto para D.

Research progress on the intervention of traditional Chinese medicine monomer and formula in the mTOR signaling pathway for the treatment of osteoporosis / 中国药房

Osteoporosis is an important cause of bone weakness and susceptibility to fractures. Anti-osteoporosis drugs of Western medicine cannot reverse its progression， and can only reduce the loss of bone density； long-term use of them is accompanied by certain adverse reactions. Traditional Chinese medicine focuses on syndrome differentiation and holistic approach， which can make up for the shortcomings of Western medicine’s treatment. The mammalian target of rapamycin （mTOR） signaling pathway is involved in the growth， proliferation， and differentiation of bone cells， and is closely related to the occurrence and development of osteoporosis. In recent years， various traditional Chinese medicine monomers （such as flavonoids， polysaccharides， alkaloids， etc.） and traditional Chinese medicine formulas （such as Bushen huoxue decoction， Liuwei dihuang pills， Erzhi pills， etc.） have been proven to promote bone formation， inhibit bone resorption， enhance bone cell autophagy， and delay the progression of osteoporosis by regulating the mTOR signaling pathway. Therefore， the article summarizes the traditional Chinese medicine monomer and formula that intervene in the mTOR signaling pathway for the treatment of osteoporosis， in order to provide medication ideas for the traditional Chinese medicine treatment of osteoporosis.

Research progress on the mechanism of promoting fracture healing by traditional Chinese medicine monomer components and compound formulas / 中国药房

Traditional Chinese medicine has the characteristics of multiple components， pathways， and targets in the treatment of fracture healing， and has good therapeutic advantages and potential for fractures with complex pathological mechanisms. Based on this， the author summarized the mechanism of promoting fracture healing by the monomer components and compound formulas of traditional Chinese medicine and found that visfatin A， puerarin， and others can activate the mitogen-activated protein kinase （MAPK） signaling pathway； Xugudan， Guben zenggu formula and others can activate bone morphogenetic protein （BMP） signaling pathway； baicalin， Achyranthes bidentata polysaccharides and others can activate Wnt/β -catenin signaling pathway； apigenin， notoginsenoside and others can activate receptor activator of nuclear factor-κB （NF-κB）/receptor activator of NF-κB ligand/osteoprotegerin （RANK/RANKL/OPG） signaling pathway； Compound huoxue jiegu capsule， Jiangu granule and others can inhibit phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway； icariin can activate Notch signaling pathway； Taohong siwu decoction， crocin and others can activate Hippo signaling pathway； jujuboside A and osthole can inhibit NF-κB signaling pathway， and thus promote fracture healing.

Prevention and Treatment of NAFLD with Traditional Chinese Medicine Monomers by Regulating AMPK Pathway： A Review / 中国实验方剂学杂志

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease with complex and diverse pathogenesis， and there is no effective treatment or specific drugs for its clinical treatment. In recent years， its incidence has been on the rise， and it has become the earnest expectation of medical researchers in China and abroad that related patients could be treated. AMP-activated protein kinase （AMPK） functions to regulate cellular energy homeostasis and mitochondrial homeostasis. When activated， it has a good intervention effect on NAFLD progression with lipid metabolism disorders and mitochondrial homeostasis disorders. For NAFLD， the activation of AMPK can inhibit the production of new lipogenesis in the liver， promote the oxidation of fatty acids in the liver， and enhance the mitochondrial function of adipose tissues. As a key target of metabolic diseases， AMPK can also improve apoptosis， liver fibrosis， autophagy， and inflammation. Traditional Chinese medicine （TCM） is good at treating diseases from multiple targets and multiple pathways and is also commonly used in the treatment of chronic liver disease in clinical practice. A large number of in vitro and in vivo experimental studies on NAFLD have shown that TCM monomers have good prospects for the treatment of NAFLD through the AMPK signaling pathway， including glycosides， phenols， alkaloids， flavonoids， quinones， terpenoids， and lignans， which are natural activators of AMPK. This study reviewed the research progress on TCM monomers in regulating the AMPK pathway to prevent and treat NAFLD， providing a broader perspective for TCM treatment of NAFLD.

Efficacy and Mechanism of Chinese Medicinal Compounds and Monomers from Chinese Medicinals against Colorectal Cancer： A Review / 中国实验方剂学杂志

Colorectal cancer （CRC） is one of the refractory malignant tumors of the digestive system worldwide. With limitations， the available clinical therapies are usually suspended or show unsatisfactory effect. Therefore， it is urgent to find and develop new candidate drugs specifically targeting the cancer with ideal efficacy， low toxicity， and low cost， and the solutions can be found in traditional Chinese medicine （TCM） which has a long history. In TCM， sovereign， ministry， assistant， and guiding medicinals are selected based on the syndrome differentiation， and it has shown remarkable efficacy on CRC in recent years. In particular， Chinese medicinal compounds and monomers from Chinese medicinals which have been applied in clinical settings are advantageous in the treatment of CRCs， as they improve the quality of life， alleviate clinical symptoms and toxic and side effects of chemotherapy， and prolong the survival of patients. Therefore， we retrieved the English and Chinese articles with "CRC"， "TCM"， "compound" and "monomer" as keywords， and summarized the progress in the treatment of CRC with Chinese medicinal compounds and monomers from Chinese medicinals from four aspects of "replenishing Qi and invigorating spleen"， "clearing heat and removing toxin"， "nourishing liver and kidney"， and "tonifying Qi and nourishing blood". However， Chinese medicine features multiple components， multiple targets， and multiple pathways， and in-depth research should be carried out on the application of Chinese medicinal compounds and monomers from Chinese medicinals in the treatment of CRC， in an attempt to minimize the pain and side effects and maximize the therapeutic effect. This study is expected to provide new insight into the treatment of CRC and a reference for further research on the efficacy and mechanism of Chinese medicine.

Research progress in the intervention of Chinese herb monomers on diabetic retinal neurodegeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)has been traditionally considered a purely microvascular disease in the retina. Currently, mainstream therapies focus only on advanced vascular complications and a single molecular target-vascular endothelial growth factor(VEGF). However, the research is shifting towards a more comprehensive view that DR is a neurovascular disease caused by neurovascular unit(NVU)injury. In the early stage of DR, diabetic retinal neurodegeneration(DRN)dominates and may precede the retinal microvascular abnormalities. Moreover, neuronal apoptosis can further lead to microvascular injury and blood-retinal barrier(BRB)disruption. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse DRN. However, no drug targeting DRN has been approved for clinical use. In recent years, it has become a trend to study the protective effect of traditional Chinese medicine on the retina. The primary research focuses on Chinese herb monomers. This article reviews the research status of representative monomers in DRN to provide references for the early treatment of DR and development of new drugs.

Effects of thermal cycling on bonding properties of novel low-shrinkage resin adhesive / 华西口腔医学杂志

OBJECTIVES@#The current study aimed to investigate the bonding properties of a novel low-shrinkage resin adhesive containing expanding monomer and epoxy resin monomer after thermal cycling aging treatment.@*METHODS@#Expanding monomer of 3,9-diethyl-3,9-dimethylol-1,5,7,11-tetraoxaspiro-[5,5] undecane (DDTU) as an anti-shrinkage additive and unsaturated epoxy monomer of diallyl bisphenol A diglycidyl ether (DBDE) as a coupling agent were synthesized. A blend of DDTU and DBDE at a mass ratio of 1∶1, referred to as "UE", was added into the resin matrix at the mass fraction of 20% to prepare a novel low-shrinkage resin adhesive.Then, the methacrylate resin adhesive without UE was used as the blank control group, and a commercial resin adhesive system was selected as the commercial control group. Moreover, the resin-dentin bonding and micro-leakage testing specimens were prepared for the thermal cycling aging treatment. The bonding strength was tested, the fracture modes were calculated, the bonding fracture surface was observed by scanning electron microscope (SEM), and the dye penetration was used to evaluate the tooth-restoration marginal interface micro-leakage. All the data were analyzed statistically.@*RESULTS@#After aging, the dentin bonding strength of the experimental group was (19.20±1.03) MPa without a significant decrease (P>0.05), that of the blank control group was (11.22±1.48) MPa with a significant decrease (P<0.05) and that of the commercial control group was (19.16±1.68) MPa without a significant decrease (P>0.05). The interface fracture was observed as the main fracture mode in each group after thermal cycling by SEM. The fractured bonding surfaces of the experimental group often occurred on the top of the hybrid layer, whereas those of the blank and commercial control groups mostly occurred on the bottom of the hybrid layer. Micro-leakage rating counts of specimens before and after thermal cycling were as follows: the experimental group was primarily 0 grade, thereby indicating that a relatively ideal marginal sealing effect could be achieved (P>0.05); meanwhile, the blank control group was primarily 1 grade, and the penetration depth of dye significantly increased after thermal cycling (P<0.05); the commercial control group was primarily 0 grade without statistical difference before and after thermal cycling (P>0.05), while a significant difference was observed between the commercial control group and experimental group after thermal cycling (P<0.05).@*CONCLUSIONS@#The novel low-shrinkage resin adhesive containing 20%UE exhibited excellent bonding properties even after thermal cycling aging treatment, thereby showing a promising prospect for dental application.

Anti-colorectal Cancer Mechanism of Zuojinwan and Its Main Monomer Components： A Review / 中国实验方剂学杂志

Zuojinwan is a classic Chinese medicine prescription recorded in the Danxi's Experiential Therapy， with Coptidis Rhizoma and Euodiae Fructus in a ratio of 6 ∶ 1. It can treat symptoms such as liver fire hypochondriac pain， stomach duct pain， vomiting， and acid swallowing. There are many pharmacological studies on Zuojinwan in modern times， especially in the digestive tract， but the prescription also has its unique effect on digestive tract cancer， and its anti-tumor studies mainly focus on colorectal cancer and gastric cancer. Colorectal cancer is the third most common type of cancer in the world and the second deadliest malignancy. At present， a number of studies have shown that the basic pharmacological studies of anti-colorectal cancer by Zuojinwan include the proliferation， apoptosis， invasion， energy metabolism， epigenetics， and drug resistance of colorectal cancer. Alkaloids are the main active ingredients of Zuojinwan， such as berberine， evodiamine， coptisine， palmatine， and rutaecarpine. Compared with the effect of Zuojinwan on colorectal cancer， studies on the effect of berberine and evodiamine on tumor angiogenesis， tumor-promoting inflammation， and intestinal flora are carried out， except the studies on the resistance of berberine and the effect of evodiamine on energy metabolism. In addition， coptisine， palmatine， and rutaecarpine can regulate the proliferation， apoptosis， and metastasis of colorectal cancer cells， the proliferation and apoptosis of colorectal cancer cells， tumor-promoting inflammatory response， and the proliferation， migration， and invasion of colorectal cancer cells， respectively. Moreover， other studies have shown that the combination of berberine and evodiamine can have a synergistic effect on the growth， migration， and invasion of colorectal cancer cells and can reduce the cardiac toxicity induced by evodiamine. Therefore， this paper summarizes the studies on the anti-colorectal cancer mechanism of Zuojinwan and its main monomer components in recent years， so as to provide a theoretical basis for future clinical research and development of new high-efficiency and low-toxicity anti-colorectal cancer drugs and lay a solid foundation for clinical practice.

Study progress on traditional Chinese medicine monomer intervening in pancreatic cancer by regulating PI3K/Akt signaling pathway / 中国药房

Pancreatic cancer is one of the most destructive malignant tumors； the pathogenesis of this disease is complex and is closely related to genetic susceptibility， chronic pancreatitis， and gene mutations in signaling pathways. The phosphoinositide 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classical cancer signaling pathway that is aberrantly activated in pancreatic cancer cells. In recent years， it has been found that traditional Chinese medicine （TCM） monomers show special activity in the treatment of pancreatic cancer and can be potential drug for the treatment of pancreatic cancer. Based on PI3K/Akt signaling pathway， this paper summarizes the mechanism of TCM monomer intervening in pancreatic cancer and finds that TCM monomer of alkaloids （sinomenine， dictamnine， dauricine， etc.）， terpenoids （saikosaponin A， linderalactone， isoalantolactone， etc.）， phenols （6-gingerol， curcumin， pterostilbene， etc.）， flavonoids （fisetin， kaempferol， quercetin， etc.） and quinones （β-hydroxyisovaleryl shikonin， rhein， lucidone， etc.） can inhibit the proliferation， invasion and migration of pancreatic cancer cells， regulate autophagy and apoptosis， and then inhibit the pathological process of pancreatic cancer by inhibiting PI3K/Akt signaling pathway.

Active Components of Chinese Medicine Against Liver Fibrosis Based on PI3K/Akt Signaling Pathway： A Review / 中国实验方剂学杂志

Hepatic fibrosis is a pathological reparative response of the liver to chronic injury and a crucial step in the progression of chronic liver disease， characterized mainly by the activation of hepatic stellate cells and diffuse deposition of extracellular matrix. Currently， there is no ideal specific drug for the treatment of liver fibrosis in clinical practice. In recent years， with the development and progress of traditional Chinese medicine （TCM） in the treatment of liver fibrosis， TCM has been widely recognized for its significant therapeutic effect and fewer adverse reactions. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is an important pathway that affects the formation and development of liver fibrosis. It mainly plays a role in liver fibrosis by inhibiting the activation and proliferation of hepatic stellate cells， promoting their apoptosis， reducing oxidative stress in liver cells， decreasing the deposition of extracellular matrix， and enhancing liver cell autophagy. This article summarized the mechanisms by which Chinese medicinal monomers regulated the PI3K/Akt pathway to exert their effects on liver fibrosis and their synergistic effects with other signaling pathways， providing a theoretical basis and references for the development of new drugs for the treatment of liver fibrosis with TCM.

Research progress in mechanism of Chinese herbal compounds and monomers in delaying lumbar intervertebral disc degeneration / 中国中药杂志

Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/β-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.

Chinese Medicine Monomers Regulate Atherosclerosis Through NF-κB Pathway： A Review / 中国实验方剂学杂志

Cardiovascular diseases are the leading cause of death in the world today. Atherosclerosis （AS） is a chronic inflammatory disease characterized by thickening or functional degeneration of the arterial wall， and in the later stage of the disease， plaque ruptures to induce thrombosis， which in turn causes ischemia in tissues or organs. It is therefore the pathological basis for all types of cardiovascular diseases. Nuclear transcription factor kappa B （NF-κB）， an important nuclear transcription factor in the inflammatory response， is activated to mediate the transcription of inflammatory factors that can trigger or exacerbate the development of AS. Vascular endothelial cells are activated by inflammatory factors. NF-κB mediates related regulatory genes in endothelial cells to secrete adhesion molecules， chemokines， and coagulation factors， promotes selective aggregation of monocytes， up-regulates the expression of adhesion molecules to make adhesion molecules stick to the endothelium and move toward the intima， promotes the degradation of the extracellular matrix， and forms unstable plaques. In recent years， traditional Chinese medicine （TCM） has achieved certain results in the prevention and treatment of AS， and many Chinese medicines have been proved to be effective in resisting AS and can act on multiple targets in the human body， affecting the occurrence and development of AS in different links. This paper mainly introduced the NF-κB pathway and its relationship with AS， reviewed research progress on 75 components of different types in Chinese medicine monomers such as flavonoids， terpenoids， and alkaloids in AS resistance based on the NF-κB pathway， and found that Chinese medicine monomers mainly regulate cholesterol balance， inhibit the inflammatory response， reduce cell proliferation， inhibit intercellular adhesion， and suppress foam cell formation by regulating the NF-κB pathway to provide a reference for the prevention and treatment of AS.

Study on antiviral and antipyretic mechanism of Phillyrin in vitro and in vivo / 中国药理学通报

Aim To study the antiviral anrl antipyretic mechanism of Phillvrin in vitro and in vivo.Methods By respiratory virus infection cell model, SI index and antiviral activity of forsythia glycosides virus activity in vitro were detected.A mouse model of influenza virus infection was established, and hemagglutination titer, lung index, lung histopathology pathology were detec¬ted.Hemagglutination titer, lung index, lung histopa¬thology pathology were observed and in vivo anti-influ¬enza virus and pneumonia effects were investigated.Dry yeast induced rat fever model was established, temperature and plasma and hypothalamus thermoregu¬lation and inflammation of the related factors were test¬ed , and its antipyretic mechanism was investigated.By AutoDock Vina software for molecular docking, the docking results were plotted with PyMol software.Re¬sults Phillyrin had certain inhibitory effects on H3N2, RSV, E71 , ADV-3, HSV-1 and HSV-2 (SI >2).Phillyrin could reduce hemagglutination titer of infected lung tissue, decrease lung index, and alleviate lung lesions, especially interstitial pneumonia.Phill- vrin could also significantly reduce the body tempera¬ture of rats with fever, and its antipyretic mechanism might he related to the decrease of PGE2 and IL-ip levels in plasma and hypothalamus of rats.Molecular docking results showed that the binding energies of Phillyrin with a-MSH, IL-lp, PEG2, A VP, cAMP and other proteins were all less than - 5 kcal • mol 1.Conclusions Phillyrin has obvious antiviral, antipy-retic and improvement of pulmonary inflammatory le¬sions, and it is speculated that it can play an anti-in¬fluenza effect through "treating both symptoms and root causes".

Research progress on therapeutic strategies for improving pulmonary vascular remodeling in pulmonary hypertension / 中国药理学通报

Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure. All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death. The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues. These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor. Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH. In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of "lung distension";(4)research into monomers of traditional Chinese medicine; and(5)research into new targets.

The effect of cooling procedures on monomer elution from heat-cured polymethyl methacrylate denture base materials

Abstract Objective To evaluate the amount of methyl methacrylate (MMA) released in water from heat-cured polymethyl methacrylate (PMMA) denture base materials subjected to different cooling procedures. Methodology Disk-shaped specimens (Ø:17 mm, h:2 mm) were fabricated from Paladon 65 (PA), ProBase Hot (PB), Stellon QC-20 (QC) and Vertex Rapid Simplified (VE) denture materials using five different cooling procedures (n=3/procedure): A) Bench-cooling for 10 min and then under running water for 15 min; B) Cooling in water-bath until room temperature; C) Cooling under running water for 15 min; D) Bench-cooling, and E) Bench-cooling for 30 min and under running water for 15 min. A, B, D, E procedures were proposed by the manufacturers, while the C was selected as the fastest one. Control specimens (n=3/material) were fabricated using a long polymerization cycle and bench-cooling. After deflasking, the specimens were ground, polished and stored in individual containers with 10 ml of distilled water for seven days (37oC). The amount of water-eluted MMA was measured per container using isocratic ultra-fast liquid chromatography (UFLC). Data were analyzed using Student's and Welch's t-test (α=0.05). Results MMA values below the lower quantification limit (LoQ=5.9 ppm) were registered in B, C, E (PA); E (PB) and B, D, E (QC) procedures, whereas values below the detection limit (LoD=1.96 ppm) were registered in A, D (PA); A, B, C, D (PB); C, D, E (VE) and in all specimens of the control group. A, B (VE) and A, C (QC) procedures yielded values ranging from 6.4 to 13.2 ppm with insignificant differences in material and procedure factors (p>0.05). Conclusions The cooling procedures may affect the monomer elution from denture base materials. The Ε procedure may be considered a universal cooling procedure compared to the ones proposed by the manufacturers, with the lowest residual monomer elution in water.

Study Progress of Effect of Traditional Chinese Medicine Monomer in Intervening Ovarian Cancer by Regulating PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

Ovarian cancer is a kind of malignant tumor in female reproductive system with a high incidence. This disease is insidious at its early stage and the symptoms are not typical. Most of the patients have reached advanced stage by the time of diagnosis， seriously threating women's life and health. Many signaling pathways are involved in the formation and development of ovarian cancer， among which the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway is one of the key regulatory pathways. In recent years， traditional Chinese medicine （TCM） has obtained wide attention in treatment of tumors due to its advantages of high safety and less adverse reactions， and more and more attention has been paid to the study of TCM monomers. Molecular biology studies have shown that TCM monomers can play a role against tumor by regulating multiple targets. By reviewing the literature and searching several databases， we found that TCM monomer can play an important role in the growth， proliferation， invasion and migration， apoptosis， autophagy and reversal of drug resistance of ovarian cancer cells by regulating PI3K/Akt signaling pathway. According to the existing studies， TCM monomers have a certain effect on ovarian cancer， but there are still many problems. Although the mechanisms of some TCM monomers have been clarified in the treatment of ovarian cancer， such TCM monomers are only limited to the tumor-bearing nude mice in vivo and experimental studies on in vitro cells， and further studies are needed in the future. In addition， in the future researches， ovarian cancer syndrome differentiation and targeted therapy can be linked to the TCM flavors， efficacy and indications to further develop the advantages of TCM. Based on the current research situation at home and abroad， this paper summarized the research progress of targeted intervention of TCM monomers in ovarian cancer by regulating PI3K/Akt signaling pathway， in order to provide reference for further research of TCM monomers， and provide important ideas for the development of targeted treatment of ovarian cancer with TCM.

Role of Autophagy in Rotavirus Enteritis and Intervention with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Rotavirus enteritis （RVE）， a common infectious disease of the digestive system， is commonly found in infants and young children. Its incidence is high， posing great threats to human health. At present， no specific drugs are available in western medicine and the symptomatic treatments like fluid infusion， anti-diarrhea， correction of electrolyte disorder， protection of gastrointestinal mucosa， and regulation of intestinal microecology have been employed. In addition to the poor therapeutic efficacy， they do not perform well in preventing the onset of RVE and shortening the course of disease. Traditional Chinese medicine （TCM） exerts the therapeutic effect against RVE via multiple targets， without inducing obvious adverse reactions and the cost is low. The specific mechanism of action has yet to be fully explained. Although there are some studies exploring the role of Chinese medicinal monomers in the pathogenesis of RVE， the types involved are still not enough. The effects of Chinese medicinal monomers on autophagy-related pathways fail to be uncovered， which is attributed to the lack of large-scale experimental data and clinical evidence. There are also many problems that cannot be ignored in the related research of Chinese medicinal compounds， taking the superficial exploration and limited scope for instance. Autophagy is a highly conserved biological phenomenon that involves a variety of signaling pathways. Its dysfunction is related to multiple pathological processes. Studies have shown that autophagy plays an important role in the pathogenesis of RVE， especially in the early stage of viral infection. Autophagy induces intestinal mucosal barrier damage， intestinal nerve dysfunction， and immune abnormality， resulting in the occurrence and development of RVE. In recent years， a large number of experimental studies have confirmed that TCM fights against circulatory， respiratory， digestive， and immune system diseases as well as tumors by intervening in autophagy. At the same time， a handful of studies have suggested that Chinese medicinal monomers and compounds regulate autophagy and interfere with viral replication by affecting related signaling pathways， thus playing a positive role in reversing the progression of RVE. However， at present， there are few studies on the regulation of autophagy by TCM in the treatment of RVE， and no systematic elaboration is available. This review aimed to summarize the role of autophagy in the pathogenesis of RVE and its intervention with TCM， in order to provide more theoretical and clinical evidence for the treatment of RVE with TCM.