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The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC50 = 16.94 μg·mL-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.
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The immune system plays a pivotal role in the pathogenesis and progression of diseases. Lipid peroxidation, as a key effector molecule in the execution of ferroptosis, exerts critical effects on the functionality and survival of various immune cells and is involved in the pathological processes of multiple diseases. There is accumulating evidence suggesting the presence of ferroptosis in immune cells as well. Lipid peroxidation is closely associated with immune cell function. Accumulation of lipid peroxidation products in immune cells can lead to ferroptosis, directly impacting immune cell function. Non-immune cells, through lipid peroxidation-mediated cell death, release signaling molecules that regulate immune cell function. They jointly influence the body's homeostasis. This article provides a comprehensive review of the latest research progress on the regulatory role of lipid peroxidation in immune function. It analyzes the relationship between lipid peroxidation and immune cells, and provides a theoretical foundation for potential strategies targeting cellular lipid peroxidation and immunotherapy in the treatment of diseases.
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In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.
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The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.
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The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.
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Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.
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In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.
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In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.
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The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.
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In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.
Subject(s)
Animals , Mice , Capsules , Herpes Simplex , Herpesvirus 1, Human , Mice, Inbred BALB C , Psychological DistressABSTRACT
The biochemical integrity of the brain is necessary to maintain normal function. Oxidative damage is one of the mortal important reasons leading to the destruction of this integrity. The nervous system is enriched in phospholipid and polyunsaturated fatty acids (PUFAs). Due to the nature of high oxygen-consumption and rich lipids, brain is particularly vulnerable to oxidative damages. Phospholipid peroxidation is one of the results of imbalance in oxidation-antioxidant system. Once the antioxidant system is insufficient to resist oxidative damage, membrane phospholipids will be prone to free radical attack. Phospholipid peroxidation leads to a variety of toxic oxidation products, including membrane damage, mitochondrial dysfunction, rapid accumulation of amyloid, etc. Multiple proteins and nucleic acids can be covalently modified by peroxidation products, resulting in the loss of the protein functions, which eventually triggers programmed cell death and general neuroinflammation in brain, and ends up with an increased susceptibility to neurodegenerative diseases. Based on the knowledge of mechanisms of phospholipid peroxidation, this review focuses on the characteristics of phospholipid peroxidation as a key factor in the development of neurodegenerative diseases, in order to provide theoretical basis for targeted intervention of phospholipid peroxidation as a potential strategy to prevent neurodegenerative diseases.
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Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Yin-Yang balance is an essential concept in traditional Chinese medicine (TCM) theory. Yin represents stable and inhibitory factors, and Yang represents the active and aggressive factors. When the organism is exposed to stress, especially psychological stress caused by emotional stimulation, the Yin-Yang balance is disturbed and the virus can re-engage in productive replication, resulting in recurrent diseases. Therefore, a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1. Here we reviewed the recent advances in the studies of HSV-1 susceptibility, latency and reactivation. We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.
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Objective:To study the regulatory level of Dima decoction on adenovirus E1B 19 kD interacting protein 3（BNIP3） protein and to understand the mechanism in intervening mitophagy and controlling inflammation in ulcerative colitis. Method:The 60 SPF SD rats were randomly divided into normal control group, model control group, low, medium ang high dose Dima decoction（8.5，17.0，34.0 g·kg-1）group and mesalazine（3.0 g·kg-1） group，10 for each group. The model of UC rats was established by the method of environmental diet intervention +2,4,6-trinitro-Benzenesulfonicacid（TNBS）+ethanol，the administration group was administered for 14 days.Hematoxylin-eosin (HE) was used to detect pathological changes of colonic mucosal tissues in rats.Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the expressions of BNIP3 protein and mRNA in intestinal epithelial cells. Result:HE staining results showed that a large number of inflammatory cell infiltration and non-cheesy granulation tissue were observed in the colon of rats in the model group, while the rats in each drug group showed different degrees of fibrous repair. Compared with normal group, the expression of BNIP3 protein and mRNA in model group were significantly increased (P<0.05). Compared with model group, the expression of BNIP3 protein and mRNA in low, medium and high-dose Dima decoction group and mesalazine group were significantly increased (P<0.01). Compared with low-dose group, the expression of BNIP3 protein and mRNA in medium and high-dose groups and mesalazine group were significantly increased (P<0.05). Conclusion:Dima decoction can increase the expression of BNIP3 in the intestinal epithelium of UC active rats, which may be one of the mechanisms of promoting mitochondrial autophagy against UC inflammation.
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Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain)
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In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.
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OBJECTIVE: To evaluate the interrater and intrarater reliability of North Star Ambulatory Assessment(NSAA)used in the children with Duchenne muscular dystrophy(DMD)and explore the feasibility of evaluating motor function by videos. METHODS: The assessment data of 40 cases of DMD admitted from July 2017 to November 2017 to Peking University First Hospital were analyzed. Forty DMD boys aged 4.3 to 13.4 years were admitted. They were divided into three groups based on their age. Ten boys were younger than 5 years. Eighteen boys were aged 5 to 9 years. Twelve boys were older than 9 years.Three evaluators,A,B,and C,joined the study. In the interrater reliability study,evaluator A performed the evaluation with NSAA on the boys and video-taped their performance,then evaluators B and C scored the performance in the videos independently to examine interrater reliability. After one month,three evaluators rescored the performance according to the videos again to examine the intrarater reliability. The intra-group reliability was calculated according to the NSAA scores evaluated by the evaluators B and C twice for the same child. The consistency of the video score with the on-site score was calculated according to the NSAA score of the two assessments of the same child by evaluator A. Intraclass correlation coefficient(ICC)was calculated to examine the reliability. RESULTS: In the interrater reliability study,total ICC was 0.990,subgroups ICC was from 0.971 to 0.992. In the intrarater reliability study,total ICC was from 0.987 to 0.988. The video score and the on-site score wereconsistent withICCbeing 0.980. CONCLUSION: NSAA is a reliable and practical method to evaluate the motor development of children with DMD. The consistency between on-site scoring and video scores is high.
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Shanghuo(excessive internal heat) is a special organic state based on the concept of traditional Chinese medicine(TCM), commonly known as the abnormal heating syndrome of body in folks. With the acceleration of modern life rhythm and the increase of the social competition pressure, emotional stress has become an important cause for the spread of Shanghuo symptoms. What's more, Shanghuo can impact the body physiological functions to cause the onset, recurrence and progression of common diseases, harming the health of the body. According to the long-term research findings, the author found that Shanghuo referred to the imbalance of multiple physiological functions, such as nerve, immunity and metabolism, caused by emotional stress. "Shanghuo" is not a disease itself, but it can increase the susceptibility to a variety of diseases. This study reviewed the traditional medicine theory and the modern medical studies, and explored the relevance and correlation mechanisms between the Shanghuo symptoms and disease susceptibility, so as to provide a reference to improve the state of sub-health and prevent or treat modern diseases.
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The model of drug-induced liver injury (DILI) induced by acetaminophen (APAP) in mice was established to investigate the anti-oxidation and anti-ferroptosis mechanisms of Fuzheng Yanggan Mixture on DILI. C57BL/6 mice were randomly divided into five groups: control group, model group, positive group, and low and high-dose Fuzheng Yanggan Mixture groups (0.12, 0.24 g·kg⁻¹). Mice were intragastrically administration with Fuzheng Yanggan Mixture (0.12, 0.24 g·kg⁻¹) once per day for 21 consecutive days, and at the same time, mice were weighted every day. The mice were injected intraperitoneally with 600 mg·kg⁻¹ of APAP to establish a mouse model of acute DILI after 16 h from the last administration of Fuzheng Yanggan Mixture. After 6 h from APAP challenge, the experimental animals were weighted and sacrificed to collect blood and liver tissue samples. And then, the effect of Fuzheng Yanggan Mixture on liver weight and the liver weight ratio of mice were examined; the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and the level of malondialdehyde (MDA), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) in the liver tissue were measured. Prostaglandinendoperoxide synthase 2(ptgs2) mRNA level in liver tissues was detected by Q-PCR, and protein expression levels of SLC7A11 and GPX4 in liver tissues were detected by Western blot. Moreover, HE staining, immunohistochemical assay and TUNEL staining were used to observe pathological changes of the liver tissue sections. It is found that Fuzheng Yanggan Mixture could relieve APAP-induced liver enlargement and inhibit hepatic weight ratio increase. Compared with model group, the mice in Fuzheng Yanggan Mixture groups showed decreases in the content of ALT, AST and MDA, and increases in the content of GSH and NADPH. What is more, Fuzheng Yanggan Mixture could down-regulate ptgs2 mRNA level and up-regulate SLC7A11 and GPX4 protein levels. All of the results lead to a conclusion that Fuzheng Yanggan Mixture plays a protective effect on DILI in mice, which may be associated with the inhibition of ferroptosis.
Subject(s)
Animals , Mice , Acetaminophen , Alanine Transaminase , Aspartate Aminotransferases , Chemical and Drug Induced Liver Injury , Glutathione , Liver , Mice, Inbred C57BL , Oxidative StressABSTRACT
Ferroptosis is a novel type of cell death which induced by iron-dependent lipid peroxidation accumulation. This type of cell death is significantly different from other cell death in terms of morphology, genetics and biochemistry. It has been reported that ferroptosis is involved in a variety of human diseases, particularly in liver diseases. Therefore, screening and studying of inhibitors or activators of ferroptosis may provide novel strategies for prevention and treatment of liver diseases. This review provides the biological characteristics and regulatory signaling pathways of ferroptosis, as well as the relationship between ferroptosis and liver diseases, which will contribute to new insight into the pathogenesis of liver diseases.
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By retrieving the clinical research literature of treatment functional dyspepsia by traditional Chinese medicine (TCM) from January 2004 to December 2014 based on China National Knowledge Internet (CNKI), we would establish a TCM decoction database for treating functional dyspepsia in this study. One hundred and sixty-four literature were included, involving 159 prescriptions, 377 medicines, in a total of 1 990 herbs. These herbs can be divided into 18 categories according to the effectiveness; and qi-regulating herbs, blood circulation herbs, and antipyretic herbs ranked top three ones according to the frequency of usage of the herbs, whose medicine usage frequency accounted for 51.81%. Usage frequency of 16 herbs was over 30, and Atractylodes, Radix, Poriaranked top three according to the usage frequency. Medicinal properties were divided into 9 kinds according to the frequency statistics, and the top three were warm, flat, and cold. Taste frequency statistics were classifiedinto 9 kinds, and the top three were acrid, sweet, and bitter. In frequency statistics of the meridian tropism of herbs, it was classifiedinto 11 kinds, and the top three were spleen, stomach, lung. The analysis can provide a reference for treatment and study of TCM of functional dyspepsia.