Expression and Potential Significance of miR-499 and IL-1ß in Serum of Dilated Cardiomyopathy Patients with Atrial Fibrillation.

Context: Dilated cardiomyopathy (DCM) is the terminal manifestation of many heart diseases, and atrial fibrillation (AF) is the most common type of arrhythmia in DCM. The mutual influence of DCM and AF can ultimately lead to a poor prognosis for patients. Objective: The study intended to investigate the risk factors for DCM complicated with AF as well as the expression and clinical value of miR-499 and IL-1ß, to provide more research targets for controlling the risk of AF in clinical practice. Design: The research team conducted a retrospective, observational, case-control study. Setting: The study took place at Huai'an First People's Hospital. Participants: Participants were 79 patients with DCM who had been admitted to the hospital between January 2018 and January 2023. Groups: The study included two groups: (1) 31 participants with atrial fibrillation (AF), the AF group and (2) 48 participants without AF, the non-AF group. Outcome Measures: The research team: (1) examined the baseline characteristics of the two groups and compared the groups using single factor analysis; (2) compared the group's serum indicators and echocardiographic parameters; (3) evaluated the expression and potential relationship of microRNA (miR-499) and interleukin-1 beta (IL-1ß) to AF, using reverse transcription-polymerase chain reaction (RT-PCR) and Pearson, and compared the group's expressions of miR-499 and IL-1ß; and (4) analyzed the potential relationship between participants' characteristics and the occurrence of AF, using binary logistic regression. Results: Compared to the non-AF group, the AF group's: (1) age (P = .000) and number of participants with a high pulmonary artery pressure (P = .004) were significantly greater; (2) LVEF was significantly lower (P = .030) and LVESD (P = .000), LAD (P = .018), uric acid (P = .000), and BNP (P = .000) were significantly higher; and (3) serum miR-499 (P = .020) and IL-1ß (P = .000) were significantly higher. Also, a significant positive correlation existed between miR-499 (P = .019) and IL-1ß (P = .022) and DCM with AF. In addition, the AF group's age (P = .001), disease duration (P = .032), serum triglyceride levels (P = .036), uric acid value (P = .001), left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), left atrial anteroposterior diameter, LAD, pulmonary hypertension were significant independent risk factors DCM with AF. Conclusions: A close relationship exists between the abnormal expression of serum miR-499 and IL-1ß and DCM complicated with AF, which will be of great importance in future research. In addition, the data of patients with DCM are related to the occurrence and development of AF, and clinicians should actively perform early drug interventions to reduce myocardial remodeling, so as to reduce the incidence of AF.

Comparison of Minimally Invasive Valve Surgery: Hemi-Sternotomy vs. Right Anterolateral Thoracotomy Incision.

Objective: This study aims to compare patient data from two different surgical approaches for minimally invasive valve surgery: hemi-sternotomy and right anterolateral thoracotomy. The primary objective is to determine the safety and efficacy of both surgical incisions. Methods: Between December 2019 and December 2022, a total of 90 patients underwent minimally invasive valve surgery at our center. Among them, 36 patients received the hemi-sternotomy incision with an average age of 45.86 ± 14.83, and 54 patients received the right anterolateral thoracotomy with an average age of 56.77 ± 14.83 years. In the hemi-sternotomy group, 21 patients underwent aortic valve surgery, and 15 had mitral valve surgery, while in the right anterolateral thoracotomy group, 30 patients underwent aortic valve surgery, and 15 patients had mitral valve surgery. Results: No deaths or significant bleeding occurred in the hemi-sternotomy group. However, in the right anterolateral thoracotomy group, one patient died from continuous low cardiac output syndrome after surgery, and one patient suffered a femoral artery dissection. All other patients were discharged without complications. The aortic clamp time and the cardiopulmonary bypass time were significantly lower in the hemi-sternotomy group compared to the right anterolateral thoracotomy group. Conversely, the two groups had no significant differences in intubation time, 24-hour drainage, hospitalization time, and blood transfusion. On the second day after surgery, serum c-TNT and NT-PROBNP levels significantly increased in both groups, but they were significantly higher in the right anterolateral thoracotomy group than in the hemi-sternotomy group. However, on the fifth day after surgery, serum c-TNT and NT-PROBNP levels decreased significantly in both groups, with no significant differences between them. Conclusions: Minimally invasive valve surgery, whether performed with right anterolateral thoracotomy or hemi-sternotomy, is safe and effective after the learning curve. Patients can benefit from these advances in minimally invasive cardiac surgery, and surgeons can easily master these techniques.

[Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy].

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

Mechanisms of Dangua Recipe in Improving Glycolipid Metabolic Disorders Based on Transcriptomics.

OBJECTIVE: To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics. METHODS: Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A1c (HbA1c), plasma total cholesterol and triglycerides were detected. RESULTS: Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA1c, triglyceride and total cholesterol levels in the diabetic rats (P<;0.05 or P<;0.01); while all the above-mentioned levels (except triglyceride) were decreased significantly by GEN-617 combined with DGR intervention (P<;0.05 or P<;0.01). CONCLUSION: Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.

[Spatial Distribution Characteristics of Phosphorus Fractions and Release Risk in Sediments of Honghu International Importance Wetland].

According to a spatial distribution analysis of phosphorus in sediments from Honghu Wetland, it was found that TP content in sediments at the mouth of Honghu Lake was 781.31-1955.84 mg·kg-1 and the average value was(1287.21±437.28)mg·kg-1. TP content in sediments in the open water area was 438.33-1554.04 mg·kg-1, with an average value of(718.10±238.15)mg·kg-1. The TP content of sediments in lake inlet was significantly higher than that of sediments in the open water area(P<0.05), and that in the enclosed aquaculture was higher than in the open water area, although no significant difference was observed (P>0.05). The TP content of sediments to the northwest and northeast of Honghu Lake was higher than that to the southwest of Honghu Lake, and the TP content of sediments in The Four-lake main canal was significantly higher than that of Luoshan main canal(P<0.05). The phosphorus input in the Four-lake main canal may be the main source of phosphorus in Honghu Lake sediments. The phosphorus fraction composition in sediments from different sampling sites were significantly different. Fe/Al-P and Ca-P were the main forms of phosphorus in sediments from the lake inlet, while OP and Ca-P were the main forms of phosphorus in sediments from the open water area. The variation in spatial phosphorus form composition was related to the influence of human activity and the distribution of aquatic plants. Fe/Al-P and OP contents were used to estimate the content of biological available phosphorus (BAP) in evaluated sediments, and the proportion of BAP in TP was used to estimate the risk of phosphorus release in Honghu sediments. BAP/TP was 39.8%-69%, with an average of(56.5±7.23)%, indicating a high risk of phosphorus release. OP and BAP were significantly correlated with TP in overlying water(P<0.01), and the correlation between BAP and phosphate in the overlying water was the highest. The results showed that phosphorus concentration in the overlying water may be related to the release of Fe/Al-P and OP into water bodies.

Combination of 3-Dimensional Virtual Reality and Hands-On Aromatherapy in Improving Institutionalized Older Adults' Psychological Health: Quasi-Experimental Study.

BACKGROUND: In Taiwan, which has one of the most rapidly aging populations in the world, it is becoming increasingly critical to promote successful aging strategies that are effective, easily usable, and acceptable to institutionalized older adults. Although many practitioners and professionals have explored aromatherapy and identified its psychological benefits, the effectiveness of combining 3-dimensional (3D) virtual reality and hands-on aromatherapy remains unknown. OBJECTIVE: A quasi-experimental trial was designed to evaluate the effectiveness of this combination in lowering perceived stress and promoting happiness, sleep quality, meditation experience, and life satisfaction among institutionalized older adults in Taiwan. METHODS: A total of 60 institutionalized elderly participants either received the combined intervention or were in a control group. Weekly 2-hour sessions were implemented over 9 weeks. The outcome variables were happiness, perceived stress, sleep quality, meditation experience, and life satisfaction, which were assessed at baseline and after the intervention. RESULTS: Generalized estimating equation (GEE) analyses indicated that the experimental group showed significant post-intervention improvements in terms of scores for happiness, perceived stress, sleep quality, meditation experience, and life satisfaction (n=48; all P<.001). Another GEE analysis showed that the significant improvements in the 5 outcome variables persisted in participants aged 80 years and older (n=35; all P<.001). CONCLUSIONS: This is the first trial to explore the effectiveness of a combination of 3D virtual reality and hands-on aromatherapy in improving older adults' psychological health. The results are promising for the promotion of psychological health in institutionalized older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324216; https://clinicaltrials.gov/ct2/show/NCT04324216.

Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63.

Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as ß-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 µg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 µM and 2.60 µM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 µM) and indigodole B (IC50 = 2.09 µM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.

Therapy to Obese Type 2 Diabetes Mellitus: How Far Will We Go Down the Wrong Road?

Traditional glucose-lowering chemical agents, including various types of insulin and insulin secretagogues, insulin sensitizers, gliptins, etc., are based on diabetic pathogenesis of insulin resistance (IR) and islet insufficiency. Numerous evidence-based medical studies have shown that these traditional hypoglycemic chemical agents do not provide cardiovascular benefit to patients with type 2 diabetes mellitus (T2DM) and may even increase the risk of all-cause mortality. Based on research evidence published to date, these studies show that overload of energy could increase the incidence and prevalence of T2DM, and reduction in the heat load can significantly reduce the incidence of T2DM. Therefore, the essence of T2DM is heat overload, meaning heat overload is the etiology of obese T2DM. At the same time, results of numerous studies show that heat overloading is the cause of IR. IR and islet dysfunction are protective factors in intervening with heat overload. These drugs, which are based on the mechanisms of IR and islet insufficiency, increase caloric reserve and cause or worsen obesity, which is equivalent to exacerbating the basic etiology and the cardiovascular risk factor of T2DM. Thus, a reasonable strategy for prevention and treatment of obese T2DM appears to promote the negative balance of calories and the elimination of caloric reserves. Chinese herbal medicines can promote negative balance of heat in many aspects, which can bring new hope for prevention and treatment of T2DM.

Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63.

Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia. Recently, a severe respiratory illness outbreak of HCoV-NL63 has been reported in a long-term care facility. Sambucus FormosanaNakai, a species of elderberry, is a traditional medicinal herb with anti-inflammatory and antiviral potential. The study investigated the antiviral activity of Sambucus FormosanaNakai stem ethanol extract and some phenolic acid constituents against HCoV-NL63. The extract was less cytotoxic and concentration-dependently increased anti-HCoV-NL63 activities, including cytopathicity, sub-G1 fraction, virus yield (IC50 = 1.17 µg/ml), plaque formation (IC50 = 4.67 µg/ml) and virus attachment (IC50 = 15.75 µg/ml). Among the phenolic acid constituents in Sambucus FormosanaNakai extract, caffeic acid, chlorogenic acid and gallic acid sustained the anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid (IC50 = 3.54 µM) > chlorogenic acid (IC50 = 43.45 µM) > coumaric acid (IC50 = 71.48 µM). Caffeic acid significantly inhibited the replication of HCoV-NL63 in a cell-type independent manner, and specifically blocked virus attachment (IC50 = 8.1 µM). Therefore, the results revealed that Sambucus Formosana Nakai stem ethanol extract displayed the strong anti-HCoV-NL63 potential; caffeic acid could be the vital component with anti-HCoV-NL63 activity. The finding could be helpful for developing antivirals against HCoV-NL63.

Luteolin: A Natural Flavonoid Enhances the Survival of HUVECs against Oxidative Stress by Modulating AMPK/PKC Pathway.

Oxidative stress has been implicated in the pathogenesis of atherosclerotic cardiovascular diseases. Dietary supplementation of anti-oxidants has been reported to have beneficial effects on the prevention of atherogenic diseases. Luteolin (a natural flavonoid) has been shown to possess antimutagenic, antitumorigenic, anti-oxidant and anti-inflammatory properties. However, the effects and underlying molecular mechanisms of luteolin on cardiovascular systems are poorly explored. Therefore, the aim of the present study was to test whether luteolin could protect against oxidative stress-induced endothelial cell injury and explore the underlying mechanisms. In this study, human umbilical vein endothelial cells (HUVECs) were pre-treated with luteolin followed by hydrogen peroxide induction (H2O2). Our results showed that luteolin protected against H2O2-induced oxidative stress and ameliorated ROS and superoxide generation. In addition, we found that luteolin treatment inhibited the H2O2-induced membrane assembly of NADPH oxidase subunits, which was further confirmed by specifically inhibiting NADPH oxidase using DPI treatment. Furthermore, pAMPK protein expression was enhanced and p-PKC isoforms were significantly down-regulated by luteolin treatment in a dose-dependent manner, and a similar effect was observed upon DPI treatment. However, co-treatment with the specific inhibitor of AMPK (Compound C) restored p-PKC levels suggesting the role of AMPK signaling in regulating p-PKC expression under oxidative stress condition in HUVECs. Finally, we confirmed using siRNAs and specific inhibitor and/or activator of AMPK (AICAR) that luteolin treatment induced AMPK is a key player and regulator of activated expression of PKC isoforms and thereby confers protection against H2O2-induced oxidative stress in HUVECs.

Cis-3-O-p-hydroxycinnamoyl Ursolic Acid Induced ROS-Dependent p53-Mediated Mitochondrial Apoptosis in Oral Cancer Cells.

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 µM and 17.8 µM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.

Beneficial effect of Burdock complex on asymptomatic Helicobacter pylori-infected subjects: A randomized, double-blind placebo-controlled clinical trial.

BACKGROUND: Burdock complex (BC) constitutes of burdock (Arctium lappa), angelica (Angelica sinensis), gromwell (Lithospermum erythrorhizon), and sesame (Sesamum indicum) oil, which are commonly used in traditional Chinese medicine (TCM) for treating various disorders. This study intended to examine the anti-H. pylori activity of BC on AGS cell model as well as in asymptomatic H. pylori-infected subjects. MATERIALS AND METHODS: AGS cell incubated with H. pylori and treated with BC to evaluate the minimum inhibition concentration (MIC), cell viability (MTT) anti-adhesion activity, and inflammatory markers. In case of clinical trial, H. pylori-positive subjects (urea breath test [UBT] >10%, n = 36) were enrolled and requested to intake BC (n = 19) or placebo (n = 17) for 8 weeks. Antioxidant capacity, total phenol, UBT, inflammatory markers were analyzed at the initial, 4th, 8th, and 10th weeks. Moreover, the endoscopic examination was carried out on baseline and 10th week. RESULTS: In vitro studies showed that BC treatment significantly inhibited (P < .05) the inflammatory markers and adhesion of H. pylori to AGS cell. However, H. pylori-infected subject ingested with BC for 8 weeks significantly decreased (P < .05) the UBT value, inflammatory markers with improved antioxidant activity, and phenolic levels as compared to placebo. Also, consumption of BC considerably healed the ulcer wound. CONCLUSION: Overall, the BC could attenuate H. pylori infection by inhibiting H. pylori adhesion and subsequent inflammatory response on the gastric epithelial cell (AGS) as well as clinically ameliorated UBT, antioxidant capacity, and alleviated inflammation to display its anti-H. pylori activity.

Comparing the Effectiveness of Combined External Beam Radiation and Hyperthermia Versus External Beam Radiation Alone in Treating Patients With Painful Bony Metastases: A Phase 3 Prospective, Randomized, Controlled Trial.

PURPOSE: To compare the response, duration of pain relief, and time to achieve complete pain relief after radiation therapy (RT) with or without hyperthermia (HT) in patients with painful bony metastases. METHODS AND MATERIALS: Cancer patients with bony metastases and pain score ≥4 on the Brief Pain Inventory (BPI) were randomized to RT of 30 Gy in 10 fractions combined with HT (RT + HT) versus RT alone. Hyperthermia was performed by the Thermotron RF-8, with maintenance of the target temperature for 40 minutes per treatment within 2 hours after RT, twice weekly for 2 weeks. Patients were stratified by lesion number (solitary or multiple), BPI score (4-6 vs 7-10), and primary site. The primary endpoint was complete response (CR) (BPI = 0 with no increase of analgesics) within 3 months after treatment. This study was registered with ClinicalTrials.gov. RESULTS: The study was terminated early after an interim analysis of 57 patients, 3 years after the first enrollment (November 2013 to November 2016): 29 patients in the RT + HT group and 28 patients in the RT-alone group. The CR rate at 3 months after treatment was 37.9% in the RT + HT group versus 7.1% in the RT-alone group (P=.006). The accumulated CR rate within 3 months after treatment was 58.6% in the RT + HT group versus 32.1% in the RT-alone group (P=.045). Median time to pain progression was 55 days in patients with CR (n=9) in the RT-alone group, whereas the endpoint was not reached during the 24-week follow-up in the RT + HT group (P<.01). CONCLUSIONS: The addition of HT to RT significantly increases the pain control rate and extends response duration compared with RT alone for painful bony metastases.

Evaluation of LPS-Induced Acute Lung Injury Attenuation in Rats by Aminothiazole-Paeonol Derivatives.

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol (4) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents.

Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus.

Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 5'- and 3'- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. Genetic instability of JEV genome cDNA in the pBR322 plasmid was associated with the prokaryotic promoter at 5' end of the JEV genome that triggers the expression of the structural proteins in E. coli. JEV structural proteins were toxic E. coli, thus the encoding region for structural proteins was replaced by a reporter gene (enhanced green fluorescent protein, EGFP) that was in-frame fused with the first eight amino acids of the C protein at N-terminus and the foot-and-mouth disease virus (FMDV) 2A peptide at C-terminus in a pBR322-based JEV-EGFP replicon. JEV-EGFP SRIPs generated from JEV-EGFP replicon-transfected packaging cells displayed the infectivity with cytopathic effect induction, self-replication of viral genomes, and the expression of EGFP and viral proteins. Moreover, the combination of JEV-EGFP SRIP plus flow cytometry was used to determine the half maximal inhibitory concentration (IC50) values of antiviral agents according to fluorescent intensity and positivity of SRIP-infected packaging cells post treatment. MJ-47, a quinazolinone derivative, significantly inhibited JEV-induced cytopathic effect, reducing the replication and expression of JEV-EGFP replicon in vitro. The IC50 value of 6.28 µM for MJ-47 against JEV was determined by the assay of JEV-EGFP SRIP infection in packaging cells plus flow cytometry that was more sensitive, effective, and efficient compared to the traditional plaque assay. Therefore, the system of JEV-EGFP SRIPs plus flow cytometry was a rapid and reliable platform for screening antiviral agents and evaluating antiviral potency.

[Effect of Dangua Recipe on Hepatic Adiponectin Receptor 2 Expression in Diabetic Apolipoprotein E Knockout Mice].

Objective To observe the effect of Dangua Recipe (DR) on adiponectin receptor 2 (AdipoR2) expression in liver of apolipoprotein E knockout (ApoE⁻¹â») diabetic mice. Methods Eight- week-old ApoE⁻¹â» mice were randomly divided into the model control group, the DR group, the pioglitazone group, and the combined treatment group. Besides, a C57 group was set up consisting of same age C57BL/ 6J mice. Streptozotocin (STZ) was injected to ApoE⁻¹â» mice in the four groups to induce diabetic model, and they were intervened by corresponding drugs. After 12 weeks the effect of DF on glucose-lipid metabolism was observed. mRNA and protein expressions of AdipoR2 in liver were detected. Histomorphological changes of the liver were observed by hematoxylineosin ( HE) staining, red Ο fat dyeing, and Masson staining, respectively. Results Contents of fasting blood glucose (FBG) , total cholesterol (TC) , and low-density lipoprotein cholesterol (LDL-C) were reduced more significantly in the DR group than in the model group. DR could promote liver expression of AdipoR2 mRNA and protein expressions in ApoE⁻¹â» mice, which was significantly higher than that of the model group (P <0. 01) , and better than that of pioglitazone (P <0. 05, P <0. 01). DR could improve ectopic fat deposition and fibrosis of liver cells in diabet- ic ApoE⁻¹â» mice significantly, which was better than that of the pioglitazone group and the combined treatment group. Conclusion DR could significantly improve liver lipid metabolism , and reduce liver fat deposition and fibrosis, which might possibly be associated with promoting AdipoR2 expression in liver.

Flavonoids from Pronephrium megacuspe.

A chemical investigation of the whole plant of Pronephrium megacuspe (Bak.) Holtt. led to the isolation of four flavonoids, pronephrones A-D (1-4), which were firstly reported. The chemical structures of four compounds were established using spectroscopic methods. These isolates were further evaluated for cytotoxicity to ovarian cells of Spodoptera litura Fabricius.

Paradox of using intensive lowering of blood glucose in diabetics and strategies to overcome it and decrease cardiovascular risks.

Hyperglycemia significantly increases the risk of cardiovascular disease (CVD) in diabetics. However, it has been shown by a series of large scale international studies that intensive lowering of blood glucose levels not only has very limited benefits against cardiovascular problems in patients, but may even be harmful to patients at a high risk for CVD and/or poor long-term control of blood glucose levels. Therefore, Western medicine is faced with a paradox. One way to solve this may be administration of Chinese herbal medicines that not only regulate blood glucose, blood fat levels and blood pressure, but also act on multiple targets. These medicines can eliminate cytotoxicity of high glucose through anti-inflammatory and anti-oxidant methods, regulation of cytokines and multiple signaling molecules, and maintenance of cell vitality and the cell cycle, etc. This allows hyperglycemic conditions to exist in a healthy manner, which is called "harmless hyperglycemia" Furthermore, these cardiovascular benefits go beyond lowering blood glucose levels. The mechanisms of action not only avoid cardiovascular injury caused by intensive lowering of blood glucose levels, but also decrease the cardiovascular dangers posed by hyperglycemia.

ISMAC: An Intelligent System for Customized Clinical Case Management and Analysis.

Clinical cases are primary and vital evidence for Traditional Chinese Medicine (TCM) clinical research. A great deal of medical knowledge is hidden in the clinical cases of the highly experienced TCM practitioner. With a deep Chinese culture background and years of clinical experience, an experienced TCM specialist usually has his or her unique clinical pattern and diagnosis idea. Preserving huge clinical cases of experienced TCM practitioners as well as exploring the inherent knowledge is then an important but arduous task. The novel system ISMAC (Intelligent System for Management and Analysis of Clinical Cases in TCM) is designed and implemented for customized management and intelligent analysis of TCM clinical data. Customized templates with standard and expert-standard symptoms, diseases, syndromes, and Chinese Medince Formula (CMF) are constructed in ISMAC, according to the clinical diagnosis and treatment characteristic of each TCM specialist. With these templates, clinical cases are archived in order to maintain their original characteristics. Varying data analysis and mining methods, grouped as Basic Analysis, Association Rule, Feature Reduction, Cluster, Pattern Classification, and Pattern Prediction, are implemented in the system. With a flexible dataset retrieval mechanism, ISMAC is a powerful and convenient system for clinical case analysis and clinical knowledge discovery.

Dan-gua fang improves glycolipid metabolic disorders by promoting hepatic adenosine 5'-monophosphate activated protein kinase expression in diabetic Goto-Kakizaki rats.

OBJECTIVE: To investigate the effect of Dan-gua Fang on adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism. METHODS: Forty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPKα mRNA was assessed by real-time PCR. AMPKα and phospho-AMPKα protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded. RESULTS: Similar AMPKα mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups (P<0.05). AMPKα protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPKα (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group (P<0.05), respectively. However, phosphor-AMPKα/AMPKα ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly. CONCLUSION: Dan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.