New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study.

OBJECTIVE: ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake. RESEARCH DESIGN AND METHODS: Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables. RESULTS: Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients. CONCLUSIONS: PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

Danggui Shaoyao San ameliorates the lipid metabolism via the PPAR signaling pathway in a Danio rerio (zebrafish) model of hyperlipidemia.

The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.

Protective effect and possible mechanisms of resveratrol in animal models of osteoporosis: A preclinical systematic review and meta-analysis.

Resveratrol (RES) has extensively been utilized to treat osteoporosis (OP) in animal models. However, the anti-OP effects of RES have not been tested during clinical application due to the lack of evidence and poor knowledge of the underlying mechanisms. Moreover, there is little preclinical evidence to support the use of RES in the management of OP. In the present paper, we conducted a preclinical systematic review and meta-analysis to assess the efficacy of RES in animal OP models. The potential mechanisms underlying the efficacy of RES against OP were summarized. The online databases PubMed, CNKI, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature, Cochrane Library, and Chinese VIP were retrieved from inception to December 2021. The CAMARADES 10-item quality checklist was utilized to assess the risk of bias of the included studies. STATA 12.0 software was employed to analyze the data. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Thirteen studies containing 248 animals were included yielding a mean risk of bias score of 5.54 (range 4-7). The pooled estimates showed that the administration of RES could significantly elevate the bone mineral density (BMD) both at femur (SMD = 2.536; 95% CI = 1.950-3.122; p < 0.001) and lumbar spine (SMD = 1.363; 95% CI = 0894-1.832; p < 0.001), bone volume over total volume (BV/TV) (SMD = 2.543; 95% CI = 2.023-3.062; p < 0.001), trabecular linear density (Tb.N) (SMD = 2.724; 95% CI = 2.186-3.262; p < 0.001) and trabecular thickness (Tb.Th) (SMD = 1.745; 95% CI = 1.294-2.196; p < 0.001), while serum phosphorus (S-P) (SMD = -2.168; 95% CI = -2.753 to -1.583; p < 0.001) and trabecular separation (Tb.Sp) (SMD = -2.856; 95% CI = -4.218 to -1.494; p < 0.001) were significantly reduced in animal OP models. No significant change in serum calcium (S-Ca) (SMD = -2.448; 95% CI = -5.255-0.360; p = 0.087) was observed after RES treatment. Furthermore, RES could significantly improve the bone biomechanical indexes: bone maximum load (BML) (SMD = 2.563; 95% CI = 1.827-3.299; p < 0.001) and connectivity density (Conn.D) (SMD = 1.512; 95% CI = 0.909-2.116; p < 0.001) and decrease the structural model index (SMI) (SMD = -2.522; 95% CI = -3.243 to -1.801; p < 0.001). Overall, the present study revealed that RES has huge prospects as a medicine or dietary supplement for the clinical treatment of OP. High-quality studies with stringent designs and larger sample sizes are warranted to substantiate our conclusion.

Identification of antioxidant peptides after digestion and absorption of isinglass by serum peptidomics and cellular antioxidant activity analysis.

Isinglass, a dried product of the swim bladder, has been widely used in traditional Chinese medicine. This study attempts to identify natural antioxidant peptides after digestion and absorption of isinglass in vivo. The antioxidant effects of dietary isinglass were demonstrated by evaluating the activities of SOD, CAT and MDA contents in the mouse liver. Four novel antioxidant-related peptides (RLLWENGNLL, GSKAENPTNPGP, SPVPDLVPGSF and VPDLVPGSF) were screened based on serum peptidomics and amino acid composition. Furthermore, pretreating with four peptides significantly increased the cell viability, and SOD and CAT activities of AML12 cells with H2O2-mediated oxidative damage, meanwhile, significantly reduced the ROS level, MDA content and apoptosis rate and attenuated DNA damage. Therefore, it was concluded that pretreatment of the identified peptides had a protective effect on oxidatively damaged cells. This result can aid in the recognition of active peptides from isinglass consumption for potential application in nutraceuticals or functional ingredients in food.

A Comparative Phylogenetic Analysis on the Chloroplast Genome in Different Reynoutria japonica Populations.

Reynoutria japonica Houtt., a traditional medicine herb of the Polygonaceae family, has been used since ancient times in China due to its various pharmacological effects. Chloroplast genomes are conservative and play an essential role in population diversity analysis. However, there are few studies on the chloroplast genome of R. japonica. In this study, the complete chloroplast genomes of three R. japonica from different regions were performed by next-generation sequencing technology. The results revealed that the lengths of the three chloroplast genomes are between 163,371~163,372 bp, and they have a highly conserved structure with a pair of inverted repeat (IR) regions (31,121 bp), a large single-copy (LSC) region (87,571~87,572 bp), and a small single-copy (SSC) region (13,558 bp). In total, 132 genes were annotated, including 8 rRNA genes, 37 tRNA genes, and 87 protein-coding genes. The phylogenetic analysis strongly revealed that 13 populations of R. japonica form a monophyly, and Fallopia multiflora (Polygonaceae) is its closest species. The two species diverged at ~20.47 million years ago, and R. japonica in China could be further divided into two major groups based on genetic structure analysis. In addition, several potential loci with suitable polymorphism were identified as molecular markers. Our study provides important genetic resources for further development and utilization of R. japonica germplasm, as well as some new insights into the evolutionary characteristics of this medicinal plant.

Clinical efficacy of gouty tea on chronic gouty arthritis and its effects on serum vascular endothelial function and inflammatory cytokines.

To observe the efficacy of Gouty Tea on chronic gouty arthritis and its effect on vascular endothelial function and inflammatory factor levels. Totally 120 patients with chronic gouty arthritis were divided into control group (allopurinol orally, 100 mg/time, tid, for 12 weeks) and observation group (Gouty Tea, 1 bag/time, tid, for 12 weeks) randomly (n=60 per group). Compared with those before treatment, the TCM symptom scores, visual analogue score (VAS) and the levels of UA and XOD of the two groups were reduced, while the levels of NO, ET-1, VEGF, vWF, CRP, IL-1ß, TNF- α and NALP3 of the two groups improved, 6 and 12 weeks after treatment (P< 0.05). Nevertheless, after 6 weeks of treatment, there were no significantly difference of the level of VAS between the two groups. After 12 weeks of treatment, in the observation group, VAS was significantly lower compared to the control group. The TCM symptom scores and the levels of UA and XOD were significantly lower, while the levels of NO, ET-1, VEGF, vWF, CRP, IL-1ß TNF- α and NALP3 were significantly better in the observation group than those of the control group 12 weeks after treatment (P< 0.05). The total effective rate was significantly higher and the incidence of adverse reactions was significantly lower in the observation group compared to the control group (P< 0.05). Gouty Tea can effectively reduce the UA, XOD levels and VAS, effectively improve the vascular endothelial function and inhibit the inflammation of patients.

Serum proteomic analysis reveals possible mechanism underlying physiological hemostasis of swim bladder.

The hemostatic effect of isinglass (dried swim bladder) in traditional Chinese medicine is well known. But its mechanism of action remains unclear. Here, mice were gavaged with the dried swim bladder of the chu's croaker (Nibea coibor). The hemostatic effect of swim bladder was investigated, tandem mass tag (TMT)-based quantitative proteomics analysis was performed to screen differentially abundant proteins associated with hemostasis in mouse serum. Results indicated that isinglass significantly shorten bleeding time and promoted coagulation after acute trauma (cut out mouse tail). In total, 57 differentially expressed proteins were identified in the sera between control and swim bladder group, of which 31 were up-regulated and 26 were down-regulated in swim bladder group. KEGG pathway enrichment analysis further demonstrated that the Neutrophil extracellular trap formation pathway was significantly affected. Combined with RT-qPCR verification, our findings further suggested that five candidate proteins in the pathway may be involved in the onset of hemostasis after swim bladder gavage, indicating their important role during the hemostasis process promoting by swim bladder. SIGNIFICANCE: Serum proteomics after swim bladder gavage described differentially enriched proteins related to hemostasis, and enriched pathways were validated. This study revealed the possible pathways involved in the hemostatic effect of swim bladder, which may provide a new effector target for the development of new hemostatic drugs.

Transesophageal electrophysiology study in the diagnosis of dual atrioventricular nodal nonreentrant tachycardia.

"Double fire" is generally characterized by 1:2 atrioventricular conduction of sinus beats traveling down fast and slow pathways that result in double ventricular response. When this phenomenon repeats rapidly, dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) occurs. We report a case of an irregular tachycardia with a comprehensive record that includes an electrocardiogram, a transesophageal electrophysiology study, and an intracardiac electrophysiology study. This is the first report of transesophageal electrophysiology study in the diagnosis of DAVNNT. A diagnosis of DAVNNT was deduced, and the patient was successfully treated with radiofrequency ablation of the slow pathway.

Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage / 中国结合医学杂志

OBJECTIVE@#To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.@*METHODS@#The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.@*RESULTS@#MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01).@*CONCLUSION@#TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.

Influences of age-adjusted Charlson comorbidity index on prognosis of patients undergoing laparoscopic radical gastrectomy: a multicenter retrospective study / 中华消化外科杂志

Objective:To investigate the influences of age-adjusted Charlson comorbidity index (ACCI) on prognosis of patients undergoing laparoscopic radical gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 242 gastric cancer patients who underwent laparoscopic radical gastrectomy in 19 hospitals of the Chinese Laparoscopic Gastrointestinal Surgery Study Group-04 study, including 54 patients in Fujian Medical University Union Hospital, 32 patients in the First Hospital of Putian City, 32 patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 31 patients in Zhangzhou Affiliated Hospital of Fujian Medical University, 17 patients in Nanfang Hospital of Southern Medical University, 11 patients in the First Affiliated Hospital with Nanjing Medical University, 8 patients in Qinghai University Affiliated Hospital, 8 patients in Meizhou People′s Hospital, 7 patients in Fujian Provincial Hospital, 6 patients in Zhongshan Hospital of Fudan University, 6 patients in Longyan First Hospital, 5 patients in the First Affiliated Hospital of Xinjiang Medical University, 5 patients in the First Hospital Affiliated to Army Medical University, 4 patients in the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 4 patients in West China Hospital of Sichuan University, 4 patients in Beijing University Cancer Hospital, 3 patients in the First Affiliated Hospital of Xiamen University, 3 patients in Guangdong Provincial People′s Hospital, 2 patients in the First Affiliated Hospital of Xi′an Jiaotong University, from September 2016 to October 2017 were collected. There were 193 males and 49 females, aged 62(range, 23?74)years. Observation indicators: (1) age distribution, comorbidities and ACCI status of patients; (2) the grouping of ACCI and comparison of clinicopathological characteristics of patients in each group; (3) incidence of postoperative early complications and analysis of factors affecting postoperative early complications; (4) follow-up; (5) analysis of factors affecting the 3-year recurrence-free survival rate of patients. Follow-up was conducted using outpatient examination or telephone interview to detect postoperative survival of patients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametric rank sum test. The X-Tile software (version 3.6.1) was used to analyze the best ACCI grouping threshold. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-Rank test was used for survival analysis. The Logistic regression model was used to analyze the factors affecting postoperative early complications. The COX proportional hazard model was used for univariate and multivariate analyses of factors affecting the 3-year recurrence-free survival rate of patients. Multivariate analysis used stepwise regression to include variables with P<0.05 in univariate analysis and variables clinically closely related to prognosis. Results:(1) Age distribution, comor-bidities and ACCI status of patients. Of the 242 patients, there were 28 cases with age <50 years, 68 cases with age of 50 to 59 years, 113 cases with age of 60 to 69 years, 33 cases with age of 70 to 79 years. There was 1 patient combined with mild liver disease, 1 patient combined with diabetes of end-organ damage, 2 patients combined with peripheral vascular diseases, 2 patients combined with peptic ulcer, 6 patients combined with congestive heart failure, 8 patients combined with chronic pulmonary diseases, 9 patients with diabetes without end-organ damage. The ACCI of 242 patients was 2 (range, 0-4). (2) The grouping of ACCI and comparison of clinicopathological characteristics of patients in each group. Results of X-Tile software analysis showed that ACCI=3 was the best grouping threshold. Of the 242 patients, 194 cases with ACCI <3 were set as the low ACCI group and 48 cases with ACCI ≥3 were set as the high ACCI group, respectively. Age, body mass index, cases with preoperative comorbidities, cases of American Society of Anesthesiologists classification as stage Ⅰ, stage Ⅱ, stage Ⅲ, tumor diameter, cases with tumor histological type as signet ring cell or poorly differentiated adenocarcinoma and cases with tumor type as moderately or well differentiated adenocarcinoma, cases with tumor pathological T staging as stage T1, stage T2, stage T3, stage T4, chemotherapy cycles were (58±9)years, (22.6±2.9)kg/m 2, 31, 106, 85, 3, (4.0±1.9)cm, 104, 90, 16, 29, 72, 77, 6(4,6) in the low ACCI group, versus (70±4) years, (21.7±2.7)kg/m 2, 23, 14, 33, 1, (5.4±3.1)cm, 36, 12, 3, 4, 13, 28, 4(2,5) in the high ACCI group, showing significant differences in the above indicators between the two groups ( t=-14.37, 1.98, χ2=22.64, Z=-3.11, t=-2.91, χ2=7.22, Z=-2.21, -3.61, P<0.05). (3) Incidence of postoperative early complications and analysis of factors affecting postoperative early complications. Of the 242 patients, 33 cases had postoperative early complications, including 20 cases with local complications and 16 cases with systemic complica-tions. Some patients had multiple complications at the same time. Of the 20 patients with local complications, 12 cases had abdominal infection, 7 cases had anastomotic leakage, 2 cases had incision infection, 2 cases had abdominal hemorrhage, 2 cases had anastomotic hemorrhage and 1 case had lymphatic leakage. Of the 16 patients with systemic complications, 11 cases had pulmonary infection, 2 cases had arrhythmias, 2 cases had sepsis, 1 case had liver failure, 1 case had renal failure, 1 case had pulmonary embolism, 1 case had deep vein thrombosis, 1 case had urinary infection and 1 case had urine retention. Of the 33 cases with postoperative early complications, there were 3 cases with grade Ⅰ complications, 22 cases with grade Ⅱ complications, 5 cases with grade Ⅲa complications, 2 cases with grade Ⅲb complications and 1 case with grade Ⅳ complica-tions of Clavien-Dindo classification. Cases with postoperative early complications, cases with local complications, cases with systemic complications were 22, 13, 9 in the low ACCI group, versus 11, 7, 7 in the high ACCI group, respectively. There were significant differences in cases with postoperative early complications and cases with systemic complications between the two groups ( χ2=4.38, 4.66, P<0.05), and there was no significant difference in cases with local complications between the two groups ( χ2=2.20, P>0.05). Results of Logistic regression analysis showed that ACCI was a related factor for postoperative early complications of gastric cancer patients undergoing laparoscopic radical gastrectomy [ odds ratio=2.32, 95% confidence interval ( CI) as 1.04-5.21, P<0.05]. (4) Follow-up. All the 242 patients were followed up for 36(range,1?46)months. During the follow-up, 53 patients died and 13 patients survived with tumor. The 3-year recurrence-free survival rate of the 242 patients was 73.5%. The follow-up time, cases died and cases survived with tumor during follow-up, the 3-year recurrence-free survival rate were 36(range, 2-46)months, 29, 10, 80.0% for the low ACCI group, versus 35(range, 1-42)months, 24, 3, 47.4% for the high ACCI group. There was a significant difference in the 3-year recurrence-free survival rate between the two groups ( χ2=30.49, P<0.05). (5) Analysis of factors affecting the 3-year recurrence-free survival rate of patients. Results of univariate analysis showed that preoperative comorbidities, ACCI, tumor diameter, histological type, vascular invasion, lymphatic invasion, neural invasion, tumor pathological TNM staging, postoperative early complications were related factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy [ hazard ratio ( HR)=2.52, 3.64, 2.62, 0.47, 2.87, 1.90, 1.86, 21.77, 1.97, 95% CI as 1.52-4.17, 2.22-5.95, 1.54-4.46, 0.27-0.80, 1.76-4.70, 1.15-3.12, 1.10-3.14, 3.01-157.52, 1.11-3.50, P<0.05]. Results of multivariate analysis showed that ACCI, tumor pathological TNM staging, adjuvant chemotherapy were indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy ( HR=3.65, 11.00, 40.66, 0.39, 95% CI as 2.21-6.02, 1.40-86.73, 5.41-305.69, 0.22-0.68, P<0.05). Conclusions:ACCI is a related factor for post-operative early complications of gastric cancer patients undergoing laparos-copic radical gastrectomy. ACCI, tumor pathological TNM staging, adjuvant chemotherapy are indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy.

Dietary fucoidan extracted from macroalgae Saccharina japonica alleviate the hepatic lipid accumulation of black seabream (Acanthopagrus schlegelii).

The use of an artificial diet often leads to the increase of risk factors for the development of liver diseases, such as hepatic lipid accumulation (HLA) in commercially cultured fish species. Our previous study showed that dietary Saccharina japonica could effectively alleviate HLA in black seabream (Acanthopagrus schlegelii), which may be linked predominantly to S. japonica fucoidan. Thus, a 56d nutritional trial was designed to investigate the effects of dietary fucoidan (CTRL, 0 g kg-1; ASJ1, 0.75 g kg-1; ASJ2, 3.00 g kg-1) on growth performance, fillets nutritional values, and HLA of black seabream. Results showed that dietary fucoidan significantly improved the growth and the contents of n-3 polyunsaturated fatty acids (n-3PUFA) in fillets of black seabream. Moreover, dietary fucoidan improved HLA-related parameters, including reducing serum and liver lipid contents and the activity of aminotransferase. Meanwhile, histological analysis showed that dietary fucoidan reduced the area of hepatic lipid droplets in black seabream (P < 0.05). In addition, the transcriptomic analysis of differentially expressed gene (DEG) showed that all DEG in fatty acid metabolism, primary bile acid biosynthesis, and fatty acid biosynthesis were down-regulated, and all DEG in the regulation of autophagy were up-regulated in the ASJ1 group compared with CTRL group. Moreover, the metabolomic analysis of differentially expressed metabolite (DEM) found that lipid metabolism was the main type of KEGG pathway altered by fucoidan supplementation. Furthermore, the combined transcriptomic and metabolomic analysis found that dietary fucoidan mainly modified the lipid metabolic pathway of primary bile acid biosynthesis, glycerophospholipid metabolism, and arachidonic acid metabolism in the liver. In general, dietary fucoidan effectively alleviated HLA of black seabream, and the underlying mechanism may be ascribed to promoting the autophagy and inhibiting the synthesis of lipids and bile acids.

Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-ß1/Smads Signaling Pathway.

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-ß1 (TGF-ß1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-ß1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-ß1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-ß1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-ß1/Smads signaling pathway.

Relationship between miR-338-3p and Clinicopathological Parameters, Prognosis, and STAT3 mRNA Expression in Nasopharyngeal Carcinoma.

OBJECTIVE: To investigate the expression of miR-338-3p in nasopharyngeal carcinoma (NPC) and its relationship with STAT3 mRNA expression as well as their relationship with clinical pathological parameters and prognosis of patients. METHODS: From September 2016 to September 2018, 71 patients with NPC were selected as the NPC group, and 71 samples of NPC tissues were collected during the operation. A total of 23 patients who underwent biopsy due to chronic nasopharyngitis were selected as the control group and 23 nasopharyngeal mucosal tissues were collected. The expressions of miR-338-3p and STAT3 mRNA in nasopharyngeal tissue of two groups were detected by real-time quantitative PCR, and the relationship between the two was analyzed. To collect clinical data of NPC patients and analyze the relationship between the expressions of miR-338-3p and STAT3 in NPC tissues and clinical pathological parameters of the patients, we followed up the patients with nasopharyngeal carcinoma for three years to observe the relationship between miR-338-3p, STAT3, and the prognosis of the patients. RESULTS: The relative expression levels of miR-338-3p in nasopharyngeal tissues of the NPC group and the control group were 0.39 ± 0.05 and 1.01 ± 0.09, respectively (P < 0.05). The relative expression levels of STAT3 mRNA in nasopharyngeal tissues of the NPC group and the control group were 3.82 ± 0.21 and 1.04 ± 0.11, respectively (P > 0.05). miR-338-3p was negatively correlated with the relative expression of STAT3 mRNA in nasopharyngeal carcinoma (r = 0.038, P > 0.05). The expression of miR-338-3p was related to the age of the patient, clinical TNM stage, T stage, and distant metastasis (all P < 0.05). STAT3 expression was correlated with clinical TNM stage, T stage, and distant metastasis in our patient (P < 0.05). The expressions of miR-338-3p and STAT3 in nasopharyngeal carcinoma tissues from different gender, histological type, N stage, M stage, and degree of differentiation showed no statistical differences (P > 0.05). The survival rate of the group with low miR-338-3p expression was significantly lower than that of the group with high miR-338-3p expression (P > 0.05). The survival rate of patients with the high STAT3 expression group was significantly lower than that of patients with the low STAT3 expression group (P > 0.05). CONCLUSION: There is a negative correlation between the low expression of miR-338-3p and the high expression of STAT3 in NPC, which are all related to the TNM stage, T stage, and prognosis of the patient.

Development and validation of ultra-high performance supercritical fluid chromatography method for quantitative determination of six compounds in Guizhi Fuling capsule and tablet samples.

A fast and simple ultra-high performance supercritical fluid chromatography method has been developed for the determination of six analytes, namely (paeonol, coumarin, cinnamic alcohol, cinnamic acid, paeoniflorin, and amygdalin) in Guizhi Fuling capsule and tablet samples. The influence of the key chromatographic parameters for the separation purposes was evaluated. The optimal column was Trefoil CEL1 column. The optimal mobile phase was a gradient mixture of carbon dioxide and methanol at flow rate of 1.0 mL/min. The back pressure of the system was set to 1.38 × 107  Pa and the temperature to 45°C. The six compounds were separated within 11 min by the proposed ultra-high performance supercritical fluid chromatography method with satisfactory resolution. Method validation confirmed that the procedure is accurate with the recovery rates from 87.04 to 104.30%, intraday precision values less than 4.81% and interday precision less than 5.22%, and linear with R2 higher than 0.9967. Therefore, this work provides a simple and novel method for the simultaneous analysis of six compounds in Guizhi Fuling capsule and tablet samples.

Ergosta-7,9(11),22-trien-3ß-ol Alleviates Intracerebral Hemorrhage-Induced Brain Injury and BV-2 Microglial Activation.

Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by an exacerbation of neuroinflammation and neuronal injury, for which few effective therapies are available at present. Inhibition of excessive neuroglial activation has been reported to alleviate ICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanism of ergosta-7,9(11),22-trien-3ß-ol (EK100), a bioactive ingredient from Asian medicinal herb Antrodia camphorate, were evaluated. Post-treatment of EK100 significantly attenuated neurobehavioral deficit and MRI-related brain lesion in the mice model of collagenase-induced ICH. Additionally, EK100 alleviated the inducible expression of cyclooxygenase (COX)-2 and the activity of matrix metalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100 concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4 activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuated by EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among several signaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-Jun N-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNK activation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exerted the inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9 activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employed as a potential therapeutic agent for ICH.

Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway.

Dendrobium mixture (DMix) is a Traditional Chinese Medicine widely used for preventing and treating diabetic nephropathy (DN). Autophagy contributes to DN development and progression. The present study aimed to investigate the mechanism underlying the protective effects of DMix on the kidneys of rats with DN and to determine whether this involves autophagy. Herein, a high­sugar and high­fat diet, combined with the intra­abdominal injection of low­dose streptozocin, was used to induce DN in 40 Sprague­Dawley male rats. In total, 10 additional rats were used as controls. The rats with DN were then randomly divided into three groups and treated with DMix, gliquidone or saline via gastric administration for 8 weeks. Body weight, kidney weight, kidney index, fasting blood glucose (FBG), blood lipid, hemoglobin A1c (HbA1c), insulin, blood urea nitrogen and serum creatinine levels, as well as the 24­h urinary albumin excretion rate (UAER) were measured. H&E, Periodic Acid­Schiff and Masson staining were used to examine the renal pathology. The mRNA and protein expression levels of LC3 and Beclin­1 in renal tissues were measured using reverse transcription­quantitative PCR and immunohistochemistry, respectively. Western blotting was conducted to measure the protein expression levels of PI3K, phosphorylated (p)­PI3K, Akt, p­Akt, mTOR, p­mTOR, LC3 and Beclin­1 in renal tissues. It was found that DMix significantly reduced the FBG, blood lipids, HbA1c and insulin levels, kidney weight, kidney index and UAER in rats with DN, as well as improved renal function. Rats with DN showed notable glomerular hypertrophy, an increase in mesangial matrix content and renal interstitial fibrosis. Moreover, DMix notably reduced kidney damage. The results demonstrated that DMix inhibited the phosphorylation of PI3K, Akt and mTOR in the kidney tissues of rats with DN, and increased the protein and mRNA expression levels of LC3 and Beclin­1. Therefore, it was suggested that DMix has protective effects on the kidney of rats with DN, which may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway and activation of renal autophagy by this traditional medicine.

NIR Light-Propelled Janus-Based Nanoplatform for Cytosolic-Fueled microRNA Imaging.

Various nanoplatforms have been developed to visualize intracellular microRNAs (miRNAs) because of their clinical significance in tumor progression and diagnosis. However, the diffusion-limited motion of the nanoplatforms penalizes the miRNA imaging efficiency in cells. Herein, we fabricated a near-infrared (NIR) light-propelled Janus-based nanoplatform to advance the imaging response. The Janus nanomotor covered with an Au half-shell was loaded by the endocytosis adjuvant of the MnO2 nanosheet for delivering a miRNA-responsive hQN (hairpin DNA quadrangular nanostructure) probe with a catalyzed hairpin assembly (CHA). Once the nanoplatform entered into cells, the MnO2 nanosheet was degraded to Mn2+ by endogenous fuels (such as glutathione) to release the hQN probe. The NIR light irradiation of the nanoplatform generated a heat gradient and thus propelled motion of the nanoplatform. This process accelerated the intracellular reaction of the hQN probe with miRNAs to trigger the cascade CHA amplification with an enhanced fluorescence readout.

A drug-tunable Flt23k gene therapy for controlled intervention in retinal neovascularization.

Gene therapies that chronically suppress vascular endothelial growth factor (VEGF) represent a new approach for managing retinal vascular leakage and neovascularization. However, constitutive suppression of VEGF in the eye may have deleterious side effects. Here, we developed a novel strategy to introduce Flt23k, a decoy receptor that binds intracellular VEGF, fused to the destabilizing domain (DD) of Escherichia coli dihydrofolate reductase (DHFR) into the retina. The expressed DHFR(DD)-Flt23k fusion protein is degraded unless "switched on" by administering a stabilizer; in this case, the antibiotic trimethoprim (TMP). Cells transfected with the DHFR(DD)-Flt23k construct expressed the fusion protein at levels correlated with the TMP dose. Stabilization of the DHFR(DD)-Flt23k fusion protein by TMP was able to inhibit intracellular VEGF in hypoxic cells. Intravitreal injection of self-complementary adeno-associated viral vector (scAAV)-DHFR(DD)-Flt23k and subsequent administration of TMP resulted in tunable suppression of ischemia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy (OIR). Hence, our study suggests a promising novel approach for the treatment of retinal neovascularization. Schematic diagram of the tunable system utilizing the DHFR(DD)-Flt23k approach to reduce VEGF secretion. a The schematic shows normal VEGF secretion. b Without the ligand TMP, the DHFR(DD)-Flt23k protein is destabilized and degraded by the proteasome. c In the presence of the ligand TMP, DHFR(DD)-Flt23k is stabilized and sequestered in the ER, thereby conditionally inhibiting VEGF. Green lines indicate the intracellular and extracellular distributions of VEGF. Blue lines indicate proteasomal degradation of the DHFR(DD)-Flt23k protein. Orange lines indicate the uptake of cell-permeable TMP. TMP, trimethoprim; VEGF, vascular endothelial growth factor; ER, endoplasmic reticulum.

Research progress of acupuncture effect measured on transcranial doppler ultrasound technology / 国际中医中药杂志

Transcranial doppler (TCD) is an important ultrasound technology for non-invasive cerebrovascular dynamic monitoring. It has been widely used in the evaluation of acupuncture efficacy and the mechanism studies of acupuncture effect. Based on the TCD measuring participants in the physiological or pathological conditions, acupuncture at different single points or groups of points, or different acupuncture methods, can cause overall benign regulatory effectoncerebral hemodynamics. The TCD can provide visual basis for clinical acupuncture scheme optimization. However, there are still some deficiencies in the setting of cerebral blood flow parameters, clinical design, and technical operation. We should start with the intereted diseases, conduct large sample RCT, pay attention to cross contrast with other cerebral blood flow detection technologies, and carry out standardized research on the influencing factors of Acupuncture manipulation, acupuncture Deqi, and stimulation parameters.

Two new pyranonaphthoquinones from Mansoa alliacea / 中国中药杂志

Mansoa alliacea,commonly known as garlic vine,is native to the tropical rain forests of South America and widely cultivated in South China. As a popular folk medicine with various biological activities,however,this plant remains to be fully elucidated in terms of its phytochemical constituents. In this study,two new pyranonaphthoquinones were isolated from the 95% ethanol extract of the leaves and twigs of M. alliacea by various chromatographic approaches including silica gel,octadecyl silica( ODS),Sephadex LH-20,and preparative high-performance liquid chromatography( PHPLC). Their structures were determined to be 8,9-dimethoxy-α-lapachone( 1) and 7-hydroxy-8,9-dimethoxy-α-lapachone( 2) by comprehensive spectroscopic analyses and therefore respectively named as mansonin A( 1) and mansonin B( 2).