Effective chemotherapy is the mainstay of malaria control. However it is undergoing the serious threat by resis?tance of falciparum malaria to antimalarial drugs. In recent years with the development of molecular biology technology molec?ular markers have been widely used to monitor antimalarial drug resistance. This paper reviews the researches on the common molecular markers related to Plasmodium falciparum drug resistance.

Prodrug is an effective way to improve the oral absorption of the drugs which belong to Biopharmaceuticals Classification System (BCS) class III and IV. This review addresses the progress of the oral prodrugs in recent years, mainly including classical prodrug design and targeted prodrug design. Classical prodrug design is focused on modification of oil-water partition coefficient or decrease the metabolism of parent drugs. Targeted prodrug design is actively concerned with the physiological characteristics of the gastrointestinal tract to target tissues, enzymes and influx transporters. Intestinal influx transporter, the peptide transporter-targeted prodrug design is a growing field of the research of oral prodrugs recently. Challenges of prodrug strategy, design and investigation in vivo are also discussed.
Administration, Oral ; Animals ; Biological Transport ; Drug Delivery Systems ; Drug Design ; Humans ; Intestinal Absorption ; Prodrugs ; administration & dosage ; pharmacokinetics ; Solubility

BACKGROUND:Studies have shown that bone loss can lead to a series of diseases, such as osteoporotic fractures, thus seeking to increase bone mass has become a goal of the majority of researchers.
OBJECTIVE:To summarize the current studies of improving bone mass by using stem cel transplantation, hoping to the extensive application of stem cel transplantation in the clinical treatment of osteoporosis as early as possible.
METHODS:A computer-based search of PubMed and CNKI was performed by the first author to retrieve articles relevant to stem cel therapy for osteoporosis published from January 1997 to October 2014. The keywords were“to improve bone mass, regenerative medicine, bone marrow mesenchymal stem cel transplantation, stem cel therapy”in Chinese and English, respectively, which appeared in the title, abstract or keywords. Articles published recently or in authoritative journals were preferred, and final y 28 articles were included in result analysis.
RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cel s which are isolated and cultured easily can proliferate rapidly and have multi-lineage differentiation potential. Studies have shown that the osteogenic differentiation of bone marrow mesenchymal stem cel s can real y improve bone mass, and obtain more achievements in the treatment of orthopedic disorders. This new cel therapy can help to accelerate bone healing and reduce treatment time, offering a new therapeutic choice for orthopedic surgery, plastic surgery, oral and maxil ofacial surgery, and therefore, it has broad application prospects.

OBJECTIVETo investigate the effect of glycogen synthase kinase-3beta (GSK-3beta) on the proliferation of human ovarian cancer cells.

METHODSTwo human ovarian cancer cell lines SKOV3 and ES-2 were analysed for the expression of GSK-3beta and phosphorylated GSK-3beta (pGSK-3beta) by Western blot analysis. Cell growth curve analysis done by cell count was used to investigate the effect of GSK-3beta inhibitors on the growth of SKOV3 and ES-2 cells. Four plasmids, namely, GSK-3betaS9A, GID5-6, GID5-6LP and the control vector, were cotransfected respectively with the green fluorescent protein (GFP) into SKOV3 cells by electroporation, and then BrdU incorporation assay was adopted to analyse the role of GSK-3beta activity in the proliferation of ovarian cancer cells. After transfection, G418 was added to the medium to select those stably transfected cells, which were used to investigate the long term effect of GSK-3beta activity change on the proliferation of ovarian cancer cells by colony formation assay.

RESULTSBoth SKOV3 and ES-2 cells expressed GSK-3beta, though the expression level of pGSK-3beta was lower in SKOV3 than in ES-2 cells. GSK-3beta inhibitors attenuated the growth of SKOV3 and ES-2 cells. Transfection with GSK-3betaS9A to upregulate the GSK-3beta activity resulted in the increase of BrdU incorporation in SKOV3 cells compared with that in the control vector. On the contrary, transfection with GID5-6 to downregulate GSK-3beta activity decreased the BrdU incorporation in SKOV3 cells, compared with that in GID5-6LP, which is a control vector of GID5-6. Stable transfection with GSK-3betaS9A increased the colony number while stable transfection with GID5-6 decreased the colony number, compared with each control vector.

CONCLUSIONGSK-3beta can promote the proliferation of ovarian cancer cells. Inhibition of GSK-3 p may become a potential theraputic

Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Female ; Glycogen Synthase Kinase 3 ; antagonists & inhibitors ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Indoles ; pharmacology ; Lithium Chloride ; pharmacology ; Maleimides ; pharmacology ; Microscopy, Fluorescence ; Ovarian Neoplasms ; enzymology ; genetics ; pathology ; Phosphorylation ; drug effects ; Plasmids ; genetics ; Serine ; genetics ; metabolism ; Time Factors ; Transfection ; beta Catenin ; metabolism

Objective To investigate the relationship between the Reelin protein and schizophrenia .Methods 89 patients with schizophrenia were served as schizophrenic group and 89 healthy people as control group .Western blot was employed to detect their peripheral blood Reelin protein expression .Results The expression level of peripheral blood Reelin protein of patients in schizo-phrenic group(0 .66 ± 0 .27) was significantly lower than that in the control group(1 .01 ± 0 .23)(P<0 .05) .Reelin protein expres-sion levels of male and female patients in schizophrenic group were 0 .66 ± 0 .22 and 0 .66 ± 0 .26 ,respectively ,with no statistically significant difference(t=0 .181 ,P>0 .05) .Reelin protein expression levels of male and female subjects in the control group were 1 .01 ± 0 .25 and 1 .02 ± 0 .26 ,respectively ,with also no statistically significant difference (t=0 .201 ,P>0 .05) .Conclusion The low expression level of Reelin protein is related to schizophrenia .

Objective To preliminarily discuss the efficacy and safety of balloon protection technique in venous sinus in the embolization of lateral sinus dural arteriovenous fistula.Methods FromDecember 2012 to August 2016,7 consecutive patients with lateral sinus dural arteriovenous fistula embolized with Onyx under the protection of venous sinus balloon were enrolled retrospectively. Their clinical data,imaging data,and follow-up results were analyzed.Results In 7 patients,the fistulas of 3 cases were located in the sigmoid sinus and the fistulas of 4 cases were located in the transverse sinus. Immediately after operation, 5 patients were embolized completely and 2 were embolized mostly. All balloon protected venous sinuses maintained patency. Seven patients were followed up clinically and the follow-up time was 6-43 months. No new neurological deficits were observed. All 7 patients received whole DSA reexamination and the follow-up time was 6-11 months. It is suggested that 5 patients were completely cured,among them,the venous sinuses were patent in 4 cases,the venous sinus was occluded in 1 case;the fistula was stable and venous sinus patency in 1 case;and 1 had newly complicated venous sinus occlusion.Conclusion At the same time of embolization of the fistulas,the dural arteriovenous fistulas were embolized under the protection of venous sinus balloon. It could maintain long-term patency of venous sinus and be conductive to maintaining the stability of the embolization effect.

Objective To improve lesion detection of the radial head with adjusted elbow joint lateral position on X-ray.Methods (1)20 subjects underwent elbow joint CT three-dimensional reconstruction (average intensity projection),which was as X-ray radio-graphy image.The tilt angle of the humerus and the projection direction for fully display of the radial head in projection images and the tilt angle of the humerus against detector in X-ray radiography were measured.(2)20 subjects (patients and volunteers)with el-bow joint disease underwent routine and improved elbow joint lateral position were enrolled.And assessed the bare blocking rate of the radial head articular surface of the two positions.Results (1)The angle between the the humerus and the direction of projection were 49°-60°and 30°-41°in CT and X-ray,respectively.The average angle was (35.5±1)°.(2).The blocking rate and bare bloc-king rate of the radial head articular surface in routine elbow joint lateral position were 71.6%-100% and 0%-28.4%,respective-ly.The average rate of bare blocking was 14.2%.Fracture 13 cases and 5 cases of suspected fractures.The blocking rate and bare blocking rate of the radial head articular surface in improved elbow joint lateral position were 4.8%-25% and 75%-95.2%,re-spectively.The average rate of bare blocking was 85.1%.Fracture 1 7 cases and 1 case of suspectet fractures.Conclusion The im-proved elbow joint lateral position of X-ray can display the radial head articular surface better than the routine position.

Objective:To detect the value of utilizing bpMRI in prostate biopsy in the detection of prostate cancer with PSA≤20ng/ml.Methods:The clinical data of 394 patients who underwent prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from November 2017 to October 2019 were retrospectively analyzed. Of all the patients, 177 underwent modified systematic biopsy, named TRUS group, 217 patients accepted pre-biopsy bpMRI examination, undergoing modified systematic biopsy if Prostate Imaging Reporting and Data System (PI-RADS) score < 3 or MRI-TRUS cognitive fusion targeted prostate + systematic biopsy if PI-RADS score ≥ 3, named MRI group. The median age of TRUS group was 66 (61, 74) years old, prostate specific antigen (PSA) was 9.52 (7.26, 12.30) ng / ml, and prostate volume (PV) was 36.84 (28.95, 57.72)ml. The median age of MRI group was 66 (59, 72) years old, PSA was 8.84 (6.65, 12.16) ng/ml, and PV was 39.45 (29.25, 58.69)ml. There was no difference in above parameters between the two groups. The χ 2 test was used to compare the detection rate of prostate cancer and clinically significant prostate cancer (CsPCa) between the two groups. Results:There was no significant difference in the detection rates of prostate cancer between TRUS group and MRI group [51.41% (91/177) vs. 48.39% (105/ 217), P = 0.550], but the detection rates of CsPCa were significantly different [26.55% (47/177) vs. 36.41% (79/217), P = 0.037]. In patients with PSA ≤ 10 ng / ml, there was no significant difference in the detection rates of prostate cancer between the two groups [43.62% (41/94) vs. 43.08% (56/130), P = 0.936], but there was a significant difference in the detection rates of CsPCa [17.02% (16/94) vs. 28.46% (37/130), P = 0.047]. There was no significant difference in the detection rates of prostate cancer [60.24% (50/83) and 56.17% (48/87), P= 0.504] and the detection rates of CsPCa [37.35% (31/83) vs. 48.28% (42/87), P = 0.150] between the two groups. The total detection rates of the last two needles in TRUS group and MRI group were 23.16% (41/177) and 36.63% (86/217), respectively, with significant difference ( P=0.001); the detection rates of CsPCa in the last two needles were 11.86% (26/177) and 29.03% (63/ 217), respectively, with significant difference ( P < 0.001). In MRI group, the detection rates of prostate cancer in patients with PI-RADS score <3, 3, 4, 5 were 21.21% (7/33), 25.84% (23/89), 73.24% (52/71), 95.83% (23/24), respectively; the detection rates of CsPCa were 12.12% (4/33), 17.98% (16/89), 54.93% (39/71), 83.33% (23/24), respectively. Conclusions:In patients with PSA ≤ 20 ng / ml, prostate biopsy based on bpMRI may improve the detection of CsPCa, especially in patients with PSA ≤ 10 ng/ml.

OBJECTIVEChildren with nephrotic syndrome are always associated with retardation of growth. Growth hormone (GH) administration to these children can stimulate their growth, but it plays an important role in glomerulosclerosis. Thus these children would take a risk to use it to improve their growth. This study was designed to investigate the effect of GH on the kidney of rats with adriamycin-induced nephropathy (AN) and its mechanism, and to observe the renoprotective effect of angiotensin II (AngII) receptor antagonist, irbesartan, in GH-treated AN rats.

METHODSRats were divided into the following groups: normal control rats, AN rats, GH-treated AN rats and GH plus irbesartan-treated AN rats. There were 8 developing male SD rats (120-130 g) in each group. Urinary protein was measured at weeks 3, 6 and 9. Blood pressure, serum creatinine, BUN, albumin, cholesterol, triglyceride, as well as ACE activity and AngII concentration of the kidney were detected at the end of the study. Renal pathological changes were evaluated also. Immunohistochemistry was used to examine the protein expressions of TGF beta(1), collagen IV and fibronectin in glomeruli.

RESULTSGlomerular sclerosis score of GH-treated AN rats (49.4 +/- 9.8) was significantly higher than that of AN rats (12.8 +/- 5.5, P < 0.01), and this score of GH-treated AN rats plus irbesartan (26.2 +/- 7.5) was significantly lower than the score of GH-treated AN rats (P < 0.01). The changes of urinary protein, hyperlipidemia and hypoalbuminemia in rats of each group consisted with the degree of glomerular injury in rats of each group. There was azotemia in GH-treated AN rats, but rats in the other groups did not have azotemia. ACE activity of kidney was significantly (P < 0.01) increased in GH-treated AN rats [(28.1 +/- 4.1) U/mg pro] and GH-treated AN rats plus irbesartan [(27.6 +/- 3.4) U/mg pro] compared with that in AN rats [(14.6 +/- 4.4) U/mg pro]. AngII concentrations in the kidney of GH-treated AN rats [(17.8 +/- 3.3) pg/mg pro] and GH-treated AN rats plus irbesartan [(27.3 +/- 5.1) pg/mg pro] were significantly higher than that in AN rats [(8.3 +/- 1.9) pg/mg pro] (P < 0.01). The protein expressions of TGF-beta(1), collagen IV and fibronectin in GH-treated AN rats were the most distinct in all groups. These expressions were significantly (P < 0.05) reduced in GH-treated AN rats plus irbesartan.

CONCLUSIONGH is able to exacerbate adriamycin-induced nephropathy in rats, which was partly through activating renal tissue RAS and initiating the function of the AngII-TGF beta(1)-ECM axis. Angiotensin II receptor antagonist, irbesartan, has some renal protective effects on AN rats treated with GH.

Angiotensin II ; analysis ; Angiotensin Receptor Antagonists ; Animals ; Antibiotics, Antineoplastic ; toxicity ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Blood Urea Nitrogen ; Collagen Type IV ; analysis ; Creatinine ; blood ; Disease Models, Animal ; Doxorubicin ; toxicity ; Fibronectins ; analysis ; Growth Hormone ; pharmacology ; Immunohistochemistry ; Kidney Diseases ; chemically induced ; drug therapy ; Kidney Glomerulus ; chemistry ; drug effects ; pathology ; Male ; Peptidyl-Dipeptidase A ; analysis ; Proteinuria ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; metabolism ; Tetrazoles ; pharmacology ; therapeutic use ; Transforming Growth Factor beta ; analysis ; Triglycerides ; blood

AIMTo establish the fundamentals for the design of scutellarin prodrug and formulation with feasible physicochemical and biopharmaceutical properties by esterifying scutellarin, an active component with poor absorption extracted from Erigeron breviscapus of Chinese medicine.

METHODSWith the method of salifying followed by esterifying, ethyl and benzyl ester of scutellarin were synthesized. Glycolamide ester of scutellarin was also synthesized with an improved method. Their structures were confirmed by MS and 1H NMR. The solubility and partition coefficient of the prodrugs were determined and their degradations were investigated in various buffers and in human plasma. The emulsion and cyclodextrin complex of glycolamide ester were prepared and the protection of the ester from degradation was compared in the intestinal tract contents. Furthermore, the degradation of glycolamide ester in the homogenates of various intestinal segments was studied. Results Three prodrugs were synthesized successfully and their structures were confirmed. Glycolamide ester of scutellarin showed better stability in the aqueous solution (t(1/2) approximately =16 d, pH 4.2) and the shortest half-life in the human serum (t(1/2) approximately =7 min). Compared with scutellarin, the solubility of glycolamide ester was increased about ten times in pH 4.0 buffer, and about thirty five times in water. Partition coefficient of the glycolamide ester increased significantly from -2.56 to 1.48. However, the ester degradation in the homogenates of intestinal mucus would be an obstacle for its absorption. The degradation rates were in the order duodenum > ileum > or = jejunum > colon. The emulsion showed a better protection of glycolamide ester from the degradation than cyclodextrin complex.

CONCLUSIONGlycolamide ester of scutellarin shows better physicochemical properties than ethyl and benzyl eater of scutellarin, but its stability in intestinal tract needs to be improved. The emulsion or / and colon-targeted delivery may be selected as one of strategies to decrease the presystemic degradation.

Animals ; Apigenin ; chemistry ; isolation & purification ; pharmacokinetics ; Emulsions ; Erigeron ; chemistry ; Esters ; Flavones ; chemical synthesis ; chemistry ; pharmacokinetics ; Glucuronates ; chemistry ; isolation & purification ; pharmacokinetics ; Glucuronides ; chemical synthesis ; chemistry ; pharmacokinetics ; Humans ; Intestinal Mucosa ; metabolism ; Intestines ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Prodrugs ; chemical synthesis ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley