Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

Leflunomide increased the renal exposure of acyclovir by inhibiting OAT1/3 and MRP2

Rheumatoid arthritis patients can be prescribed a combination of immunosuppressive drug leflunomide(LEF)and the antiviral drug acyclovir to reduce the high risk of infection.Acyclovir is a substrate of organic anion transporter(OAT)1/3 and multidrug resistance-associated protein(MRP)2.Considering the extraordinarily long half-life of LEF’s active metabolite teriflunomide(TER)and the kidney injury risk of acyclovir,it is necessary to elucidate the potential impact of LEF on the disposition of acyclovir.Here we used a specific MRP inhibitor MK571 and probenecid(OAT1/3 and MRP2 inhibitor)to assess the effects of MRP2 and OAT1/3 on the pharmacokinetics and tissue distribution of acyclovir in rats.We showed that LEF and probenecid,but not MK571 significantly increased the plasma concentration of acyclovir.However,kidney and liver exposures of acyclovir were increased when coadministered with LEF,probenecid or MK571.The kidney/plasma ratio of acyclovir was increased to approximately 2-fold by LEF or probenecid,whereas it was increased to as much as 14.5-fold by MK571.Consistently,these drugs markedly decreased the urinary excretion of acyclovir.TER(0.5−100μmol/L)dose-dependently increased the accumulation of acyclovir in MRP2-MDCK cells with an IC50 value of 4.91μmol/L.TER(5μmol/L)significantly inhibited the uptake of acyclovir in hOAT1/3-HEK293 cells.These results suggest that LEF/TER increased the kidney accumulation of acyclovir by inhibiting the efflux transporter MRP2,which increased its kidney/plasma ratio and renal injury risk.However,the inhibitory effects of LEF/TER on OAT1/3 reduced the tubular cells’uptake of acyclovir and increased the plasma concentration.     

Chemical Stimulation of Renal Tissue Induces Sympathetic Activation and a Pressor Response via the Paraventricular Nucleus in Rats

Sympathetic activation and the kidney play critical roles in hypertension and chronic heart failure.The role of the kidney in sympathetic activation is still not well known.In this study,we revealed an excitatory renal reflex(ERR)in rats induced by chemical stimulation of the kidney that regulated sympathetic activity and blood pressure.The ERR was induced by renal infusion of capsaicin,and evaluated by the changes in renal sympathetic outflow,blood pressure,and heart rate.Renal infusion of capsaicin dose-dependently increased the contralateral renal sympathetic nerve activity,mean arterial pressure,and heart rate.Capsaicin in the corticomedullary border had greater effects than in the cortex or medulla.Intravenous infusion of capsaicin had no significant effects.The effects of renal infusion of capsaicin were abolished by ipsilateral renal denervation,but were not affected by bilateral sinoaortic denervation.Renal infusion of capsaicin increased the ipsilateral renal afferent activity.The ERR was also induced by renal infusion of bradykinin,adenosine,and angiotensin II,but not by ATP.Renal infusion of capsaicin increased c-Fos expression in the paraventricular nucleus(PVN)of hypothalamus.Lesion of neurons in the PVN with kainic acid abolished the capsaicin-induced ERR.These findings indicate that chemical stimulation of kidney causes an excitatory reflex,leading to sympathetic activation,pressor response,and accelerated heart rate.The PVN is an important central nucleus in the pathway of the ERR.     

Effects of traditional Chinese herbal medicine San-HuangXie-Xin-Tang on gastrointestinal motility in mice

AIM: To investigate the effects of San-Huang-Xie-XinTang(SHXXT), a herbal product used in traditional Chinese medicine, on gastrointestinal(GI) motility in mice.METHODS: The in vivo effects of SHXXT on GI motility were investigated by measuring the intestinal transit rates(ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction(GMD).RESULTS: In normal ICR mice, ITRs were significantly and dose-dependently increased by SHXXT(0.1-1 g/kg). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. The ITRs of GMD mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by SHXXT(0.1-1 g/kg).CONCLUSION: These results suggest that SHXXT is a novel candidate for the development of a prokinetic agent that may prevent or alleviate GMD.     

Simultaneous Determination of Six Compounds in Rat Plasma by Ultra‑Performance Liquid Chromatography with Tandem Mass Spectrometry: Application in the Pharmacokinetic Study of Qing Gan‑Shu Yu‑Fang

A rapid and high selective ultra?performance liquid chromatography (UPLC) with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin, paeoniflorin, picroside I, picroside II, saikosaponin A, and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard. One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.4 mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the Mobile phase A and B. Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components. Calibration curves showed good linearity (R2 > 0.9908) over a wide concentration range for all compounds. The intra- and interday precision (relative standard deviation) ranged 2.4%–7.0% and 2.6%–8.0%, respectively. The accuracy (relative error) was from ?13.0% to 13.2% at all quality control levels. The recovery ranged from 81.1% to 92.5%. The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan?Shu Yu?Fang. The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.     

区分良性和恶性孤立性肺部实性病灶:体素内不相干运动成像和扩散峰度成像是否优于传统的扩散加权成像

正摘要目的定量比较单指数和双指数扩散加权成像(DWI)和扩散峰度成像(DKI)在鉴别良性和恶性孤立性肺部病灶(SPL)中各种扩散参数的诊断价值。方法采用3 T MRI     

Inhibition of microRNA-29b suppresses oxidative stress and reduces apoptosis in ischemic stroke

MicroRNAs(miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. Micro RNA-29 b(mi R-29 b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of mi R-29 b in animal and cell models by inhibiting mi R-29 b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg mi R-29 b antagomir was injected via the tail vein. Mi R-29 b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of mi R-29 b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of mi R-29 b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the mi R-29 antagomir for 48 hours. The results revealed that mi R-29 b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of mi R-29 b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University(approval No. 201709276 S) on September 27, 2017.     

Impact of 1, 25-(OH)2D3 on Left Ventricular Hypertrophy in Type 2 Diabetic Rats

Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats.
Methods Type 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups:untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later.
Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased (all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group (P<0.05), whereas the other parameters were significantly decreased (all P<0.05).
Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.     

Analysis of the relationship between deep venous catheter-related infection and post-operative complications in patients receiving minimally invasive esophagectomy

Objective The aim of the study was to evaluate catheter-related infection rate(CRIR)for patients receiving minimally invasive esophagectomy(MIE),to identify the optimal catheterization approach and relationship between CRIR and post-operative complications.Methods In total,168 patients with esophageal carcinoma and undergoing MIE combined with preoperative deep venous catheterization(DVC)were analyzed in our institution(Qingdao Municipal Hospital,China),from 2014 to 2018.After completing DVC,catheter-tips together with intraductal venous blood samples were sent to the microbiology lab for bacterial strain culture.CRIR was statistically evaluated for the following clinical variables:gender,age,smoking status,drinking status,past history,tumor location,histologic grade,pathological T,N,and M category,anastomotic location,anastomotic leakage,anastomotic stricture,chylothorax,pneumonia,recurrent laryngeal nerve(RLN)injury,reflux esophagitis,catheterization site,and catheter-locking days.Results Among the 144 patients recruited in our study,105 catheters were inserted into the jugular vein and 39 catheters into the subclavian vein.The median age of these patients was 63 years(range:42–79 years),and the median catheter-locking period was seven days(range:4–21 days).Four catheters were identified with three types of strain colonizations,including Staphylococcus epidermidis,Staphylococcus aureus and Blastomyces albicans.Statistical data showed that patients diagnosed with catheter-related infection were likely to incur anastomotic leakage(66.67%,P<0.001)and pneumonia(27.27%,P<0.001);features such as tumors located in the upper esophagus(13.6%,P=0.003),and over seven catheterlocking days(10.00%,P<0.001)were attributed to a high CRIR.Conclusion Although both jugular and subclavian veins can be catheterized for patients with MIE,DVC is associated with more than seven catheter-locking days and upper esophagectomy,due to high CRIR.Furthermore,catheter-related infection is related to anastomotic leakage and pneumonia.     

Bronchogenic cyst of the stomach:A case report

BACKGROUND Gastric bronchogenic cysts(BCs)are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period.Gastric bronchial cysts are rare lesions first reported in 1956;as of 2019,only 37 cases are available in the MEDLINE/PubMed online databases.BCs usually have no clinical symptoms in the early stage,and their imaging findings also lack specificity.Therefore,they are difficult to diagnose before histopathological examination.CASE SUMMARY A 55-year-old woman presented at our hospital with intermittent epigastric pain.She had a slightly high level of serum carbohydrate antigen 72-4(CA 72-4).Endoscopic ultrasound found that a cystic mass originated from the submucosa of the posterior gastric wall near the cardia,indicating a diagnosis of cystic hygroma of the stomach.Furthermore,a computed tomography scan demonstrated a quasi-circular cystic mass closely related to the lesser curvature of the gastric fundus with a low density.Because the imaging examinations did not suggest a malignancy and the patient required complete resection,she underwent laparoscopic surgery.As an intraoperative finding,this cystic lesion was located in the posterior wall of the fundus and contained some yellow viscous liquid.Finally,the pathologists verified that the cyst in the fundus was a gastric BC.The patient recovered well with normal CA 72-4 levels,and her course was uneventful at 10 mo.CONCLUSION This is a valuable report as it describes an extremely rare case of gastric BC.Moreover,this is the first case of BC to present with elevated CA 72-4 levels.