Lupeol alleviates autoimmune myocarditis by suppressing macrophage pyroptosis and polarization via PPARα/LACC1/NF-κB signaling pathway.

BACKGROUND: Autoimmune myocarditis, with increasing incidence and limited therapeutic strategies, is in urgent need to explore its underlying mechanisms and effective drugs. Pyroptosis is a programmed cell death that may contribute to the pathogenesis of myocarditis. Nonetheless, no direct evidence validated the role of pyroptosis in autoimmune myocarditis. Lupeol (Lup), a pentacyclic triterpene, possesses various biological activities such as antidiabetic properties. However, the effects of Lup on autoimmune myocarditis and pyroptosis remain unelucidated. PURPOSE: This study aimed to reveal the role of pyroptosis in autoimmune myocarditis and explore the protective effects of Lup, and its engaged mechanisms. METHODS: The experimental autoimmune myocarditis (EAM) mouse model was established by immunization with a fragment of cardiac myosin in Balb/c mice. Lup and MCC950 were administered after EAM induction. The protective effects were assessed by inflammation score, cardiac injury, chronic fibrosis, and cardiac function. Mechanistically, the effects of Lup on the M1 polarization and pyroptosis of macrophages were evaluated. Transcriptome sequencing and molecular docking were subsequently employed, and the underlying mechanisms of Lup were further explored in vitro with small interfering RNA and adenovirus. RESULTS: Administration of Lup and MCC950 alleviated EAM progression. Western blotting and immunofluorescence staining identified macrophages as the primary cells undergoing pyroptosis. Lup inhibited the expression of pyroptosis-associated proteins in macrophages during EAM in a dose-dependent manner. Furthermore, Lup suppressed pyroptosis in both bone marrow-derived macrophages (BMDMs) and THP-1-derived macrophages in vitro. In addition, Lup inhibited the M1 polarization of macrophages both in vivo and in vitro. Mechanistically, the protective effects of Lup were demonstrated via the suppression of the nuclear factor-κΒ (NF-κB) signaling pathway. Transcriptome sequencing and molecular docking revealed the potential involvement of peroxisome proliferator-associated receptor α (PPARα). Subsequently, we demonstrated that Lup activated PPARα to reduce the expression level of LACC1, thereby inhibiting the NF-κB pathway and pyroptosis. CONCLUSION: Our findings indicated the crucial role of macrophage pyroptosis in the pathogenesis of EAM. Lup ameliorated EAM by inhibiting the M1 polarization and pyroptosis of macrophages through the PPARα/LACC1/NF-κB signaling pathway. Thus, our results provided a novel therapeutic target and agent for myocarditis.

Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1ß, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

MAT as a promising therapeutic strategy against triple-negative breast cancer via inhibiting PI3K/AKT pathway.

Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks effective treatment options. Sophora flavescens Aiton, a Chinese medicinal plant, is often used in traditional Chinese medicine to treat cancer. Matrine (MAT) is an alkaloid extracted from Sophora flavescens. It has good anticancer effects, and thus can be explored as a new therapeutic agent in TNBC research. We performed bioinformatics analysis to analyze the differentially expressed genes between normal breast tissues and TNBC tissues, and comprehensive network pharmacology analyses. The activity and invasion ability of TNBC cells treated with MAT were analyzed. Apoptosis and cell cycle progression were determined using cytometry. We used Monodansylcadaverine (MDC) staining to determine the condition of autophagosomes. Finally, the expression levels of the key target proteins of the PI3K/AKT pathway were determined using western blotting. The proliferation and invasion ability of MDA-MB-231 and MDA-MB-468 can be effectively inhibited by MAT. The results of flow cytometry indicated that MAT arrested the TNBC cell cycle and induced apoptosis. In addition, we confirmed that MAT inhibited the expression of BCL-2 while up-regulating the expression of cleaved caspase-3. Moreover, enhanced intensity of MDC staining and high LC3-II expression were observed, which confirmed that MAT induced autophagy in TNBC cells. Western blotting showed that MAT inhibited the PI3K/AKT pathway and downregulated the expressions of PI3K, AKT, p-AKT, and PGK1. This study provides feasible methods, which include bioinformatics analysis and in vitro experiments, for the identification of compounds with anti-TNBC properties. MAT inhibited the PI3K/AKT signaling pathway, arrested cell cycle, as well as promoted cell apoptosis and autophagy. These experiments provide evidence for the anti-TNBC effect of MAT and identified potential targets against TNBC.

Honokiol Inhibits the Inflammatory Response and Lipid Metabolism Disorder by Inhibiting p38α in Alcoholic Liver Disease.

Alcoholic liver disease is one of the leading causes of liver-related morbidity and mortality worldwide, but effective treatments are still lacking. Honokiol, a lignin-type natural compound isolated from the leaves and bark of Magnolia plants, has been widely studied for its beneficial effects on several chronic diseases. Accumulating studies have revealed that honokiol displays a potential therapeutic effect on alcoholic liver disease. In this study, the protective activity of honokiol on alcoholic liver disease was confirmed due to its significant inhibitory activity on the expression levels of inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1ß) in EtOH-fed mice and in EtOH-induced AML-12 cells. Meanwhile, the expression of the lipid metabolic parameter sterol regulatory element-binding protein-1c was also reduced. However, peroxisome proliferator-activated receptor α was increased in animal and cell experiments, which indicates that the activity of honokiol was related to its regulated activity on lipid metabolism. The result showed that honokiol significantly inhibited the expression level of p38α in vivo and in vitro. Blocking p38α inhibited the expression levels of tumor necrosis factor-alpha, interleukin-6, interleukin-1ß, and sterol regulatory element-binding protein-1c but promoted the expression level of peroxisome proliferator-activated receptor α compared with the honokiol-treated group. Moreover, the forced expression level of p38α further produced the opposite effect on inflammatory cytokines and lipid metabolism indicators. Furthermore, p38α has been related to the activation of the nuclear factor kappa B signaling pathway. In our study, honokiol significantly inhibited the activation of the nuclear factor kappa B signaling pathway mediated by p38α. In conclusion, the results suggest that honokiol might be an effective regulator of p38α by downregulating the nuclear factor kappa B signaling pathway, thereby reducing the inflammatory response and lipid metabolism disorder in alcoholic liver disease.

Correlation between Retinol Binding Protein 4 and CT Perfusion Imaging and Prognosis in Patients with Acute Ischemic Stroke Based on Cell Imaging Data Analysis.

Objective: In order to explore the correlation between the retinol binding protein 4 (RBP4) and prognosis of patients with acute ischemic stroke (AIS), CT perfusion imaging can be used to scan the brain tissue of patients, which can identify abnormal perfusion areas and ischemic penumbra brain tissue, so as to provide a basis for doctors to formulate a reasonable clinical treatment plan. Methods: 200 patients with first-episode acute ischemic stroke were selected from the Department of Neurology of our hospital, including 128 males and 72 females, aged between 32 and 85 years, with an average age of 45 ± 4.3 years. After admission, the patients were tested for xanthol binding protein 4 in time, the patient's demographic data and the basic clinical data were recorded, the degree of brain injury was evaluated, and the short-term outcome was evaluated after treatment. Results: A total of 200 AIS patients with different degrees of brain injury were included in this study, including 128 males and 78 females, aged between 32 and 85 years, with an average age of 45 ± 4.3 years. Among them, 100 patients used CT perfusion imaging for brain scanning as the observation group, 100 patients used traditional imaging methods as the reference group, and 100 healthy people were included as the blank group. At the same time, the contents of total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured by using an automatic biochemical analyzer. The patients were evaluated in the early stage of treatment and the effect of prognostic intervention was recorded. Conclusion: The application of CT perfusion imaging in the adjuvant treatment of AIS patients was helpful to identify the abnormal perfusion area and the brain tissue of ischemic penumbra, so as to provide a basis for doctors' follow-up treatment. At the same time, AIS patients with high serum RBP4 level had mild stroke severity, good short-term prognosis, and improved treatment effect, which improved patients' quality of life.

The Therapeutic Effect of Traditional Chinese Medicine on Inflammatory Diseases Caused by Virus, Especially on Those Caused by COVID-19.

Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and interleukin-1 ß (IL-1ß). IL-1ß was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1ß is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Monitoring the Whole Cycle Length Change of Cement Mortar Incorporated with SRA by CMOS Image Sensor.

This paper introduces a new method to measure whole cycle length change non-destructively and continuously using a digital image analysis system. The macroscale length changes of mortars containing different shrinkage-reducing admixture (SRA) dosages (0%, 1%, 2% and 5% by cement weight) were first determined using a complementary metal oxide semiconductor (CMOS) image sensor under alternating dry and wet curing conditions. After that, the length change was calculated using developed digital image processing technology (DIPT) software. After that, several significant conclusions could be drawn by combining with the results of systematic tests of the macroscopic and microscale physical properties of the cement mortar using X-ray diffraction, scanning electron microscopy, mercury intrusion porosimetry (MIP) and nuclear magnetic resonance (NMR) methods. The test results indicated that SRAs exhibited significant effects on the shrinkage inhibition of cement mortars, whereas the shrinkage reduction behaviour was also affected by varying the curing conditions. The MIP and NMR analyses demonstrated that SRAs reduced the irreversible shrinkage of the cement mortars by decreasing the volume percentage of the 3-50 nm pores and promoting the conversion of calcium silicate hydrate gel from an oligomeric to a high polymerization state thereby improving the volume stability of cement mortars.

Saponins of Panax japonicus Confer Neuroprotection against Brain Aging through Mitochondrial Related Oxidative Stress and Autophagy in Rats.

BACKGROUND: Oxidative stress and mitochondrial dysfunction play a vital role in the pathogenesis of brain aging. Saponins from Panax japonicus (SPJ) have attracted much attention for their potential to attenuate age-related oxidative stress as the main ingredient in rhizomes of Panax japonicus. OBJECTIVE: This study aimed to investigate the neuroprotective effects of SPJ on natural aging rats as well as the underlying mechanisms regarding oxidative stress and mitochondrial pathway. METHODS: Sprague-Dawley rats were divided into control groups (3-, 9-, 15- and 24-month old groups) and SPJ-treated groups. For SPJ-treated groups, SPJ were orally administrated to 18-month old rats at doses of 10 mg/kg, 30 mg/kg and 60 mg/kg once daily. Control groups were given the same volume of saline. After the treatment with SPJ or saline for six months, the cortex and hippocampus were rapidly harvested and deposited at -80°C after the rats were decapitated under anesthesia. The neuroprotective effects of SPJ were estimated by histopathological observation, TUNEL detection, biochemical determination and western blotting. RESULTS: SPJ improved pathomorphological changes in neuronal cells and decreased apoptosis in the cortex and hippocampus of aging rats, increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na+/K+-ATPase, Ca2+-ATPase and Ca2+/Mg2+-ATPase whereas, decreased malondialdehyde (MDA) contents in the cortex of aging rats. Furthermore, the SPJ increased silent mating type information regulation 2 homolog-1 (SIRT1) protein expression, decreased acetylated level of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the cortex and hippocampus of aging rats, and reversed the aging-induced decline of Forkhead box O3 (Foxo3a), Superoxide Dismutase 2 (SOD2), microtubule-associated protein light chain 3 (LC3II) and Beclin1 levels in the cortex and hippocampus. CONCLUSION: Our data showed that SPJ conferred neuroprotection partly through the regulation of oxidative stress and mitochondria-related pathways in aging rats.

Association Between Copper, Zinc, Iron, and Selenium Intakes and TC/HDL-C Ratio in US Adults.

The trace minerals zinc, copper, iron, and selenium are essential micronutrients, and because of their antioxidant activity, they are hypothesized to improve cardiovascular health. However, their associations with different risk levels for cardiovascular diseases are less clear. Data from the National Health and Nutrition Examination Survey 2007-2014 were used. In this study, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was used as a risk marker for cardiovascular disease, and a ratio ≥ 5 was considered to indicate high risk. A total of 7597 adults (3673 men and 3924 women) were included, and 15.9% of the participants had a high risk of cardiovascular disease. Using quantile regression analysis, we found the negative correlation between zinc, copper, iron, and selenium intakes and TC/HDL-C. The effects of copper and zinc were enhanced with increasing quantiles of risk levels. In addition, the difference in the associations of the trace minerals was sex-dependent. The correlation between iron and cardiovascular risk in males was stronger than those in females, while that of copper was weaker than that in females. Moreover, a significant nonlinear relationship between selenium and the TC/HDL-C ratio was only found in females, and this relationship was U-shaped. Our findings suggest that among healthy adults in the US, zinc, copper, iron, and selenium intakes are inversely associated with cardiovascular disease risk, and the effect is enhanced with increasing quantiles of risk levels, with magnitudes differing by sex. Therefore, trace minerals may have the ability to prevent cardiovascular disease.

Association of multiple mineral and vitamin B group intake with blood glucose using quantile regression analysis: NHANES 2007-2014.

BACKGROUND: Hyperglycaemia and diabetes have become major public health problems worldwide. There is increasing evidence that minerals and the vitamin B group might play specific roles in hyperglycaemia and the pathogenesis and progression of diabetes or metabolic complications. OBJECTIVES: The main aim of this study is to investigate the effect of mineral and vitamin B group supplementation on the blood glucose levels of different populations. DESIGN: This was a cross-sectional study. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used in this study. A total of 8,322 participants (4,169 men and 4,153 women) were included in the study. Quantile regression (QR) was performed to identify the influence of mineral and vitamin B group intake on the level of fasting plasma glucose (FPG) in individuals in different quantiles of FPG. RESULTS: After adjusting for age, income, education, race, smoking, and alcohol consumption, FPG had a negative association with folic acid in individuals with normal or high FPG, with calcium in individuals with normal FPG, and with magnesium in males. FPG was negatively associated with folic acid and calcium in individuals with normal FPG, and magnesium in most of the quantiles for females. DISCUSSION: Hyperglycaemia and diabetes are currently becoming popular research topics. However, little is known about how the whole continuum of blood glucose is associated with commonly researched nutrient supplementation in terms of hyperglycaemia and diabetes. CONCLUSIONS: The intake of calcium, folic acid and magnesium was negatively associated with blood glucose levels in individuals in different quantiles of FPG. Appropriate prevention and treatment strategies should be developed for people with different blood glucose levels.

Predictive value of unipolar and bipolar electrograms in idiopathic outflow tract ventricular arrhythmia mapping and ablation.

INTRODUCTION: Radiofrequency catheter ablation is an effective therapy for focal idiopathic outflow tract ventricular arrhythmia (OTVA). However, visual inspection of the unipolar electrogram (EGM) QS morphology is subjective with a poor specificity for predicting successful ablation sites. This study aims to evaluate the predictive value of unipolar and bipolar EGMs in OTVA mapping and ablation. METHODS AND RESULTS: Twenty-two patients scheduled for idiopathic OTVA ablation were prospectively enrolled. During the procedure, unipolar and bipolar EGMs were recorded simultaneously and visually inspected by the operator to identify their values for predicting arrhythmogenic sites. Quantitative features of the unipolar EGM including the ratio of amplitude of the first positive peak versus the nadir (R-ratio), the maximum descending slope (MaxSlope), and the time interval between the initial deflection point to the MaxSlope (D-Max) were calculated for each target site in offline analysis. EGMs from 100 sites were collected in 20 patients and analyzed. The bipolar reverse polarity characteristic was not as practical for identifying successful ablation site as the unipolar QS characteristic. Successful ablation sites demonstrated smaller R-ratio and shorter D-Max than unsuccessful sites, but no significant difference in MaxSlope. A unipolar EGM-derived quantitative criterion provided significantly better specificity (0.70) than visual inspection (0.37) without compromising on the sensitivity (0.83 vs. 0.89). CONCLUSION: The bipolar reverse polarity characteristic was not a practical method for identifying target in idiopathic OTVA ablation. The unipolar EGM-derived quantitative criteria have better predictive performance than visual inspection of the QS characteristic and are likely to reduce unnecessary ablation sites.

Effect of Qingfei Mixture () on pediatric mycoplasma pneumoniae pneumonia with phlegm heat obstructing Fei (Lung) syndrome.

OBJECTIVE: To explore the effect and mechanism of Qingfei Mixture (), a Chinese medicine, in treating mycoplasma pneumonia (MP) in MP patients and rat model METHODS: A total of 46 MP children with phlegm heat obstructing Fei (Lung) syndrome were randomly assigned to two groups by the method of random number table, with 23 children in each group. The control group was treated with intravenous infusion of azithromycin; the treatment group received intravenous infusion of azithromycin and oral administration of Qingfei Mixture. The treatment course was 7 days. Major symptoms and minor symptoms were observed and scored before and after treatments. A rat model of MP was also established. A total of 120 wistar rats were randomly divided into 5 groups: a normal group, infection group, Qingfei Mixture treatment group, azithromycin treatment group, and Qingfei Mixture + azithromycin treatment group. Each group contained 24 rats, from which every 6 were euthanatized 1, 3, 7 and 14 days after infection. MP DNA in pulmonary tissue homogenates was detected using real-time fluorescence quantitative polymerase chain reaction. Pathology was assessed after hematoxylin (HE) staining and lung tissue pathology scores were determined in pulmonary tissue. Transmission electron microscopic detection and electronic image analysis were performed on lung tissue 3 days after infection. Interleukin (IL)-17 was detected in serum using enzymelinked immunosorbent assay (ELISA) 7 days after infection. RESULTS: In the clinical study, both control and the treatment group showed improved results on removing symptoms of phlegm heat syndrome compared to the control group (P<0.05). In animal experiments, On the 7th day after MP infection, as detected by electron microscopy, the pulmonary capillary basement membranes of the azithromycin + Qingfei Mixture treatment group were much thinner than those of the azithromycin or Qingfei mixture treatment groups (P<0.05). The level of serum IL-17 in the azithromycin + Qingfei Mixture treatment group was lower than that in the azithromycin or Qingfei Mixture groups (P<0.01). CONCLUSION: Both Qingfei Mixture and azithromycin have therapeutic effects on mycoplasma pneumoniae pneumonia, but the combination of both agents had the greatest effect.

Delayed efficacy of radiofrequency catheter ablation on ventricular arrhythmias originating from the left ventricular anterobasal wall.

BACKGROUND: Ventricular arrhythmias (VAs) originating from the left ventricular anterobasal wall (LV-ABW) may represent a therapeutic challenge. OBJECTIVE: The purpose of this study was to investigate the delayed efficacy of radiofrequency catheter (RFCA) ablation without an epicardial approach on VAs originating from the LV-ABW. METHODS: Eighty patients (mean age 46.9 ± 14.9 years; 47 male) with VAs originating from the LV-ABW were enrolled. After systematic mapping of the right ventricular outflow tract, aortic root, adjacent LV endocardium, and coronary venous system, 3-4 ablation attempts were made at the earliest activation sites and/or best pace-mapping sites. Delayed efficacy was evaluated in patients with acute failure. RESULTS: During mean follow-up of 23.8 ± 21.9 months (range 3-72 months), complete elimination of all VAs was achieved in 47 patients (59%) and partial success in 19 (24%), for an overall success rate of 83%. In 25 of 37 patients (68%) with acute failure, VAs were eliminated or significantly reduced (>80% VA burden) by the delayed effect of RFCA during follow-up. Logistic regression analysis revealed that response time to ablation was a predictor of occurrence of delayed efficacy. No complications occurred during follow-up. CONCLUSION: Instead of extensive ablation, waiting for delayed efficacy of RFCA may be a reasonable choice for patients with VAs arising from the LV-ABW.

Chikusetsusaponin V attenuates lipopolysaccharide-induced liver injury in mice.

Chikusetsusaponin V (CsV), a saponin from Panax japonicus, has been reported to inhibit inflammatory responses in lipopolysaccharide (LPS)-induced macrophage cells. However, whether CsV could alleviate LPS-induced liver injury in vivo and the potential mechanisms involved remain unclear. In the present study, we investigated the anti-inflammatory effects of CsV on LPS-induced acute liver injury in mice and further explored the potential mechanisms involved. Our results showed that CsV significantly attenuated elevation of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels and improved liver histopathological changes in LPS-induced mice. In addition, CsV decreased serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels and inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), TNF-α and IL-1ß in LPS challenged mice. Furthermore, CsV inhibited nuclear factor kappa B (NF-κB) activation by downregulating phosphorylated NF-κB, IκB-α, ERK, c-Jun N-terminal kinase (JNK) and p38 levels in the liver tissue, which ultimately decreased nucleus NF-κB protein level. In conclusion, our data suggested that CsV could be a promising drug for preventing LPS challenged liver injury since it attenuated LPS-induced inflammatory responses, partly via inhibiting NF-κB and MAPK signaling pathways.

[Effects of the Saponins from Panax japonicus on Intestinal Epithelial Tight Junction Proteins in Aging Rats].

Objective: To investigate the moderating effects of total saponins of Panax japonicus on intestinal epithelial tight junction proteins in aging rats,and to explore the potential mechanism. Methods: SD rats were divided into adult group( 6 months),old model group( 24 months),and different doses( 10,30 and 60 mg / kg) of total saponins of Panax japonicus treatment groups. Levels of tight junction proteins( Occludin and ZO-1),anti-oxidative pathway proteins( Nrf2、HO-1 and NQO-1),mitochondrial biogenesis related proteins( Sirt1 and PGC-1α) and p-AMPK in the ileum were determined by immunohistochemistry staining. Results: Compared with adult group,the expressions of Occludin,ZO-1,Nrf2,HO-1,NQO-1,Sirt1 and PGC-1α of aging rats were obviously decreased( P < 0. 01),and p-AMPK was inhibited in the ileum of aging rats. Compared with aging model rats,total saponins of Panax japonicus increased the expressions of Occludin,ZO-1,Nrf2,HO-1,NQO-1,Sirt1 and PGC-1α( P < 0. 05 or P < 0. 01),and activated p-AMPK in the ileum of aging rats. Conclusion: The decreased level of intestinal tight junction proteins in the ileum of aging rats may be related to oxidative stress. Total saponins of Panax japonicus can up-regulate the level of intestinal tight junction proteins to improve the intestinal mucosal barrier dysfunction in the ileum of aging rat via reducing the levels of oxidative stress.

Impact of Alcohol Consumption on Substrate Remodeling and Ablation Outcome of Paroxysmal Atrial Fibrillation.

BACKGROUND: The effect of alcohol consumption on substrate remodeling and ablation outcome of paroxysmal atrial fibrillation (PAF) remains unknown. METHODS AND RESULTS: We performed circumferential pulmonary vein isolation (CPVI) and voltage mapping of left atrium (LA) during sinus rhythm in 122 consecutive patients with symptomatic PAF (age, 55.4±9.4 years; 73.8% men). Low-voltage zones (LVZs) were semiquantitatively estimated and presented as low-voltage index (LVI). Each patient's daily alcohol consumption history was recorded at baseline and classified into alcohol abstainers, moderate drinkers, and heavy drinkers based on the National Institute on Alcohol Abuse and Alcoholism definition. Follow-up was ≥12 months for AF recurrence. Alcohol abstainers and moderate and heavy drinkers were 70 (57.4%), 13 (10.6%), and 39 (32.0%), respectively. In total, LVZs were observed in 44 patients (36.1%). Daily alcohol consumption independently predicted presence of LVZs (odds ratio [OR], 1.097; 95% confidence interval [CI], 1.001-1.203; P=0.047). During mean follow-up of 20.9±5.9 months, 40 patients (35.1%) experienced AF recurrence. Success rate was 81.3%, 69.2%, and 35.1% in alcohol abstainers, moderate drinkers, and heavy drinkers, respectively (overall log rank, P<0.001). Multivariate analysis showed that both alcohol consumption and LVI were independent predictors of AF recurrence (hazard ratio [HR], 1.579; 95% CI, 1.085-2.298; P=0.017; HR, 2.188; 95% CI, 1.582-3.026; P<0.001, respectively). Furthermore, mediation analysis revealed that LVZs acted as a partial mediator in effect of alcohol consumption on AF ablation outcomes. CONCLUSIONS: Daily alcohol consumption was associated with atrial remodelling, and heavy drinkers have substantial risk for AF recurrence after CPVI.

Housefly maggot-treated composting as sustainable option for pig manure management.

In traditional composting, large amounts of bulking agents must be added to reduce the moisture of pig manure, which increases the cost of composting and dilutes the N, P and K content in organic fertilizers. In this study, maggot treatment was used in composting instead of bulking agents. In experiment of selecting an optimal inoculum level for composting, the treatment of 0.5% maggot inoculum resulted in the maximum yield of late instar maggots, 11.6% (maggots weight/manure weight). The manure residue became noticeably granular by day 6 and its moisture content was below 60%, which was suitable for further composting without bulking agents. Moreover, in composting experiment with a natural compost without maggot inoculum and maggot-treated compost at 0.5% inoculum level, there were no significant differences in nutrient content between the two organic fertilizers from the two treatments (paired Student's t15=1.0032, P=0.3317). Therefore, maggot culturing did not affect the characteristics of the organic fertilizer. The content of TNPK (total nitrogen+total phosphorus+total potassium) in organic fertilizer from maggot treatment was 10.72% (dry weight), which was far more than that of organic fertilizer made by conventional composting with bulking agents (about 8.0%). Dried maggots as feed meet the national standard (GB/T19164-2003) for commercial fish meal in China, which contained 55.32 ± 1.09% protein; 1.34 ± 0.02% methionine; 4.15 ± 0.10% lysine. This study highlights housefly maggot-treated composting can be considered sustainable alternatives for pig manure management to achieve high-quality organic fertilizer and maggots as feed without bulking agents.

Electroanatomical mapping of the right atrium during atrial tachycardia originating from right superior pulmonary vein: additional insights on differential diagnosis.

BACKGROUND: Atrial tachycardia (AT) from the right superior pulmonary vein (RSPV) may mimic right atrial (RA)-AT due to its proximity to the superior vena cava (SVC) and the preferential connections between the left atrium and right atrium. OBJECTIVE: RA electroanatomical mapping was performed and analyzed during RSPV-AT to differentiate it from RA-AT. METHODS: Electroanatomical mapping of the RA was performed in 16 consecutive patients with RSPV-AT and eight consecutive patients with SVC-AT served as control group. RESULTS: RA mapping revealed single breakthrough in six patients and double breakthroughs in 10 patients in the RSPV-AT group. The initial 10-ms atrial depolarization area averaged 4.3 ± 1.5 cm(2). None of the SVC-ATs exhibited double breakthrough sites with an initial 10-ms atrial depolarization area of 2.0 ± 0.6 cm(2) (P = 0.001). A cutoff value of activation area of initial 10 ms > 3.15 cm(2) was able to predict RSPV-AT with a sensitivity of 87.5% and a specificity of 100%. Preceding far-field RSPV potentials could be documented in the RA in six patients during RSPV-AT. CONCLUSIONS: During RSPV-AT, diffused initial depolarization and one or two separated breakthrough sites consistent with the preferential connections as revealed by RA mapping could help rule out RA-AT and avoid unnecessary ablation at the RA.

Treatment of Refractory Rheumatoid Arthritis by Huayu Tongbi Recipe Combined Methotrexate / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of Huayu Tongbi Recipe (HTR) combined methotrexate (MTX) in treating refractory rheumatoid arthritis (RRA).</p><p><b>METHODS</b>Totally 167 RRA patients were assigned to the treatment group (73 cases) and the control group (94 cases) according to different therapeutic methods. Patients in the treatment group were treated with HTR combined MTX, while those in the control group were treated with leflunomide (LEF) combined MTX. Clinical signs and symptoms, RF, CRP, ESR, disease activity score 28 (DAS28), and safety indicators were compared between the two groups before treatment, at week 12 and 24 after treatment. The efficacy and safety indices were also evaluated.</p><p><b>RESULTS</b>At week 12 after treatment the total effective rate was 82.2% (60/73 cases) in the treatment group and 79.8% (75/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). At week 24 after treatment the total effective rate was 78.1% (57/73 cases) in the treatment group and 755% (71/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). There was statistical difference in the total effective rate between week 24 and week 12 in the control group (chi2 = 0.49, P < 0.05). Clinical signs and symptoms, RF, CRP, ESR, and DAS28 were significantly improved in the two groups after 12- and 24-week treatment (P < 0.01). There was no statistical difference in the improvement at week 12 after treatment between the two groups (P > 0.05). There was statistical difference in time of morning stiffness, tender joint numbers, swollen joint numbers, patient global assessment, RF, CRP, and DAS28 at week 24 after treatment between the two groups (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.01).</p><p><b>CONCLUSION</b>The efficacy of HTR combined MTX was equivalent to that of LEF (10 mg per day) combined MTX, but with more stable therapeutic effects and less adverse reactions.</p>