Cell-penetrating peptide (CPP) is a kind of small molecular peptide which can pass through a variety of cell membranes. It can carry bioactive macromolecules into cells. Due to lacking of tissue-selecting and targeting behavior, the application of CPP in the field of tumor treatment is limited. Activatable cell- penetrating peptide (ACPP) has brought the dawn to the application of CPP. This review mainly introduces the applications of ACPP in the targeting antitumor drug delivery which was designed based on the differences between tumor microenvironment and normal tissues as well as the exogenous physical stimulation.
Cell-Penetrating Peptides ; pharmacology ; Drug Delivery Systems ; Humans ; Neoplasms ; drug therapy ; Tumor Microenvironment

Objective To compare the values of a screening methods by OC-Hemodia and chemical fecal occult blood test (COB) for colorectal cancer in elderly people. Methods The screening programme targeted colorectal cancer in old people was conducted on 1 100 participants aged 60-92 years (mean was 81.3 years). All subjects received OC-Hemodia and COB examinations. Positive subjects were examined by colonoscopy and/or barium enema. Out of 1 100 subjects 1 046 were followed up in the next five years. Results Among 1 100 subjects, 231 subjects (21.0%) were positive by OC-Hemodia test and 159 subjects (14.5%) were positive by COB. There was a significant difference in positive rate between OC-Hemodia test and COB (P

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.
Absorption, Physicochemical ; Adhesiveness ; Administration, Ophthalmic ; Animals ; Drug Carriers ; Eye ; metabolism ; Fluoresceins ; chemistry ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Wheat Germ Agglutinins ; administration & dosage ; chemistry ; pharmacokinetics

In chronic kidney disease (CKD), inflammatory responses during the progression of renal tissue and tissue injury related causes its progression to end-state renal disease. Among them, nuclear factor (nuclear factor, NF)-kappaB signaling pathway by regulating the corresponding nuclear expression of target gene transcription, as well as affecting the synthesis of inflammatory mediators, induction of inflammation lead to kidney damage and renal fibrosis. Some single herbs and their extracts (such as Astragali Radix, Scutellariae Radix, Ginkgo Folium) and some traditional Chinese medicine (such as Danggui Buxue decoction, Qilian decoction) can reduce the inflammatory damage induced by renal tissue NF-kappaB signaling pathway and delay the progression of CKD.
Animals ; Humans ; Kidney ; drug effects ; pathology ; Medicine, Chinese Traditional ; methods ; NF-kappa B ; metabolism ; Renal Insufficiency, Chronic ; drug therapy ; pathology ; Signal Transduction ; drug effects

OBJECTIVETo investigate the effects and mechanisms of cordycepin,an effective component of cordyceps militaris, on renal interstitial fibrosis (RIF) and its related eIF2α/TGF-β/Smad signaling pathway.

METHODFirstly, 15 C57BL/6 mice were randomly divided into 3 groups,the control group (Group A), the model group (Group B) and the cordycepin-treated group (Group C). After renal interstitial fibrotic model was successfully established by unilateral ureteral obstruction (UUO), the mice in Group C were intraperitoneally administrated with cordycepin(5 mg x kg(-1) d(-1)) and the ones in Group A and B were administrated with physiological saline for 5 days. At the end of the study, the obstructed kidneys were collected and detected for the pathological changes of RIF, and the mRNA expressions of collagen type I (Col I) and α-smooth muscle actin (α-SMA) in the kidney by Northern blot. Secondly, after renal tubular epithelial (NRK-52E) cells cultured in vitro were exposed to transforming growth factor (TGF) -β with or without cordycepin, the mRNA expressions of Col I and collagen type IV( Col IV) by Northern blot, and the protein expressions of eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α ( p-eIF2α), Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were tested by Western blot.

RESULTIn vivo, cordycepin alleviated RIF in model mice, including improving fibrotic pathological characteristics and mRNA expressions of Col I and α-SMA. In vitro, cordycepin induced the high expression of p-elF2α, and inhibited the expressions of p-Smad2/3, Col I and Col IV induced by TGF-β in NRK-52E cells.

CONCLUSIONCordycepin attenuates RIF in vivo and in vitro, probably by inducing the phosphorylation of eIF2α, suppressing the expression of p-Smad2/3, a key signaling molecule in TGF-β/Smad signaling pathway, and reducing the expressions of collagens and α-SMA in the kidney.

Actins ; analysis ; Animals ; Deoxyadenosines ; pharmacology ; Fibrosis ; Kidney ; drug effects ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Protein-Serine-Threonine Kinases ; physiology ; Signal Transduction ; drug effects ; Smad Proteins ; physiology ; Transforming Growth Factor beta ; antagonists & inhibitors ; physiology

OBJECTIVETo explore the effects and molecular mechanisms of rhein on reducing starvation-induced autophagic protein expression in renal tubular epithelial ( NRK-52E) cells.

METHODHank's balanced salt solution (HBSS) was used to induce NRK-52E cells to be in the state of starvation. After the intervention of HBSS for 0, 0.5,1, 2 and 6 hours, firstly, the protein expression of microtubule-associated protein 1 light chain 3(LC3 I/II), which is a key protein in autophagy, was detected. Secondly, the protein expressions of mammalian target of rapamycin (mTOR) and phosphorylated-mTOR Ser2448 (p-mTOR S2448) were examined. And then, after the co-treatment of rhein (5 mg x L(-1)) and HBSS (1 mL) without or with mTOR inhibitor, rapamycin (100 nmol x L(-1)), the protein expressions of LC3 I/II, mTOR and p-mTOR S2448 were tested, respectively.

RESULTHBSS could induce the up-regulation of LC3 II and the down-regulation of p-mTOR S2448 at protein expression level in NRK-52E cells. The co-treatment of rhein and HBSS could reversely regulate the protein expressions of LC3 II and p-mTOR S2448 in NRK-52E cells significantly. The co-treatment of rapamycin, rhein and HBSS could recover the level of LC3 II protein expression in HBSS-intervened NRK-52E cells.

CONCLUSIONHBSS induces autophagy in renal tubular epithelial cells by inhibiting mTOR signaling pathway activation. Rhein reduces the autophagic protein expression in renal tubular epithelial cells through regulating mTOR signaling pathway activation, which is the possible effects and molecular mechanisms.

Animals ; Anthraquinones ; pharmacology ; Autophagy ; drug effects ; Cells, Cultured ; Epithelial Cells ; drug effects ; metabolism ; Isotonic Solutions ; pharmacology ; Kidney Tubules ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; genetics ; physiology

OBJECTIVETo demonstrate the effects and mechanisms of Qifu decoction( QFD) on renal interstitial fibrosis (RIF) in model rats with yang-deficiency syndrome.

METHODThe rats were randomly divided into 3 groups, the Sham group (Group A), the Model group (Group B), the Qifu decoction group (Group C) and the Enalapril group (Group D). The RIF model was established by adenine administrated and unilateral ureteral obstruction (UUO) of the left ureter. After the model was successfully established, the rats in Group C and D were administrated with QFD or the Enalapril suspension,while the rats in Group A and B were administrated with distilled water. All rats were administrated for 3 weeks. Before administration and at the end of week 1, 2 and 3, the rats were weighted, and 24 h urinary protein excretion (Upro), urinary β2-microglobulin (Uβ2-MG) and urinary N-acetyl-D-glucosaminidase (NAG) were examined, respectively. All rats were killed after administration for 3 weeks. Blood and renal tissues were collected, renal morphology and tubulointerstitial morphology were evaluated, respectively. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), blood urea nitrogen (BUN), serum creatinine (Scr) and uric acid (UA) were detected, respectively. The protein expressions of E-cadherin, α-smooth muscle actin(α-SMA), transforming growth factor-β1 (TGF-β1), onnective tissue growth factor (CTGF) extracellular signal-regulated protein kinase 1/2(ERK1/2) and phosphorylated-ERK1/2 (p-ERK1/2) in kidney were evaluated, respectively.

RESULTQFD ameliorated serum cAMP level and the rate of cAMP/cGMP, attenuated urinary β2-MG level, NAG level and renal tubulointerstitial fibrosis, increased E-cadherin protein expression, and reduced α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions in the kidney. However, QFD had no influence on renal function in vivo. In addition, these effects were better than those of the model rats treated by Enalapril.

CONCLUSIONQFD could alleviate yang-deficiency parameters, as well as urinary β2-MG level and NAG level in model rats induced by adenine administration and UUO. Moreover, QFD could improve EMT and RIF by up-regulating E-cadherin protein expression, and down-regulating α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions, the key molecular in ERK1/2 signaling pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; Fibrosis ; Kidney ; drug effects ; pathology ; Kidney Diseases ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications ; Yang Deficiency ; complications

Objective:To explore the efifcacy and safety for radiofrequency catheter ablation (RFCA) of left bundle branch guided by left bundle potential (LBP), X-ray image with EnSiteNavX System in canine model.
Methods:The RFCA of left bundle branch was conducted in 13 dogs. A mapping catheter was positioned in right atrium to record right-sided His-bundle (R-His) potential, and an ablation catheter via right femoral artery was retrograded to left ventriclefor LBP mapping and ablation. Meanwhile, EnSiteNavX System was used to identify R-His, L-His and LBP at the same time. The potential characteristics in dogs with successful ablation were observed, the PR interval, QRS shape and time limit, AH interval, HV interval, the A/V electro-gram ratio in ablationcatheter at before and after ablation were recorded. The procedural time and X-ray exposure time between LBP with X-ray image method and LBP, X-ray image with EnSiteNavX System method were compared.
Results: There were 9/13 dogs received successful left bundle branch ablation, 3 dogs failed and 1 suffered from complete A-V block. At the successful ablation target site, the LBP-V was (17.8 ± 2.6) ms with the range of (13-21) ms, and the A/V electro-gram ratio<1/10. The procedural time and X-ray expose time were signiifcantly decreased in LBP, X-ray image with EnSiteNavX System method than those in LBP with X-ray image method P=0.007 and P<0.001.
Conclusion:Under the LBP, X-ray image with EnSiteNavX System guidance method, left bundle branch could be safely and effectively ablated to establish left bundle branch block (LBBB) model in experimental canine.

AIMTo study the diffusion behaviors of drugs in thermosensitive in situ gels, and provide valuable information for designing such delivery systems.

METHODSA free diffusion model was used to evaluate the effects of concentration, the property of drugs, as well as the gel compositions on the diffusivity of drugs.

RESULTSDrug transport through the aqueous channels of the gel followed Fickian mechanism, and no significant influence on the diffusivity was observed when the drug concentration was lowered from 5% to 0.25%. The diffusion coefficients of propranolol, timolol maleate, and salbutamol sulfate were 0.91, 1.32, and 3.30 x 10(-6) cm2 x s(-1), respectively. The flux of hydrophilic drug was 3.6 fold faster than that of the lipophilic one implied the latter partitioned into the hydrophobic micellar core, and consequently the diffusion was retarded. The diffusivity was decreased with increased poloxamer and sodium hyaluronate concentration, due to the distorted aqueous channels and higher microviscosity.

CONCLUSIONThe result suggested that sustained release could be achieved for the thermosensitive in situ gel by incorporating lipophilic drug or increasing polymer concentration.

Albuterol ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Diffusion ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Gels ; Poloxamer ; chemistry ; Propranolol ; administration & dosage ; chemistry ; Surface-Active Agents ; chemistry ; Timolol ; administration & dosage ; chemistry

To clarify the active components in Guizhi Fuling capsule in treatment of intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma, main components were gradually knocked out from the capsules, the effects of knockout capsules on uterine contraction, TNF-α secretion, murine splenocytes (SPL) and hysteromyoma cells proliferation were evaluated, respectively. The inhibition of capsules on uterine contraction was weakened by gradient knockout of paeoniflorin, paeonol, and amygdalin. The suppression of capsulte on TNF-α secretion was reduced by gradient knockout of gallic acid, cinnamaldehyde, pentagalloylglucose, and pachyman. The promotion of SPL cells proliferation was reversed by gradient knockout of gallic acid, paeoniflorin, cinnamaldehyde, quercetin, and pachyman. The depression of capsules on hysteromyoma cells proliferation was attenuated by gradient knockout of paeoniflorin, paeonol, pentagalloylglucose, and albiflorin. In conclusion, the compounds mentioned-above could be the key active basis of Guizhi Fuling capsule in treatment of intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma.
Animals ; Capsules ; administration & dosage ; chemistry ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Dysmenorrhea ; drug therapy ; metabolism ; physiopathology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Molecular Imprinting ; methods ; Tumor Necrosis Factor-alpha ; metabolism