Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs.
Antibodies, Monoclonal ; chemistry ; Antibody Specificity ; Binding Sites, Antibody ; Immunoconjugates ; chemistry

Objective To investigate the relationship between hyperhomocysteinaemia and unstable angina pectoris (UAP). Methods Selected 159 patients with senile hypertension combined with angina pectoris from April 2013 to April 2014, 78 cases of hyperhomocysteinaemia patients as observation group, 81 cases of simple hypertension patients as control group. All of the patients were performed coronary angiography examination, using the Gensini score method calculated the integral of the coronary lesions (CAS). Detected the level of the serum homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP), fasting blood glucose (FBG) and blood lipid levels. Results The gender, age, the levels of FBG and lipid in two groups had no significant differences ( P>0.05). The incidence of UAP,CAS and hs-CRP in observation group were 44.9%(35/78), (44.34±10.67) scores,(4.31±1.01)μg/L, in control group were14.8%(12/81), (30.24±8.76) scores, (2.13±0.95)μg/L. The incidence of UAP, CAS and hs-CRP in observation group were significantly higher than those in control group ( P<0.05). The levels of serum Hcy,TC,TG,LDL-C, hs-CRP, HDL-C in UAP patients of observation group and control group were (23.21 ± 7.35) and (8.86 ±2.43) μmol/L, (6.54 ±0.75) and (6.67 ±0.82) mmol/L, (1.84 ±0.95) and (1.62 ±0.83) mmol/L, (4.65±0.78) and (4.42±0.72)mmol/L,(5.15±1.24) and(3.21±1.15) mg/L, (1.02±0.32) and(1.01±0.35) mmol/L. The levels of serum Hcy,TC,TG,LDL-C, hs-CRP, HDL-C in SAP patients of observation group and control group were (12.54±4.37) and (6.52±1.36)μmol/L, (4.23±0.54) and (4.43±0.57) mmol/L, (1.45 ±0.76) and (1.25 ±0.68) mmol/L, (2.67 ±0.45) and (2.43 ±0.43) mmol/L, (3.02 ±1.13) and (1.52±0.98) mg/L, (1.24±0.36) and (1.26±0.34) mmol/L.There were significant differences (P<0.05). Multi-factor Logistic regression analysis showed that the senile H-type hypertension was independent risk factor of UAP (OR=4.324, 95%CI 2.463-6.874, P=0.001). Conclusions The levels of serum Hcy is closely related to the stability of the coronary artery atheromatous plaque and lesion severity of coronary artery. The senile H-type hypertension is independent risk factor of UAP.

Objective In order to explore the effects of rehabilitation training and acupuncture on the neural function deficit and motor function in patients with ischemic streke.Methods Eighty patients with ischemic stroke were randomly divided into rehabilitation and acupuncture groups.According to different recovery stages,the rehabilitation group received purposeful rehabilitation training for 28 days while the acupuncture group received scalp needling combined with body acuptmcture.The neural deficit scores(NDS)and motor fimction comprehensive assessment(FCA) were evaluated at the recruitment(M_0),the 28~(th)(M_1)and 56~(th)(M_2)days after treatment.Results No significant difierences were found in the NDS and motor FCA between the rehabilitation and the acurluncture groups at the recruitment.The significant differences appeared at the 28~(th) and the 56~(th) days comparing with baseline assessments in each group.There was no significant difference in the changes of NDS and motor FCA between the two groups at 28~(th) day,however,the NDS and motor FCA in rehabilitation group revealed better outcome than the acupuncture group at the 56~(th) day.Conclusion The study indicated that both rehabilitation training and acupuncture could improve the neural function and enhance the motor function in patients with ischemic stroke.

Objective To study the genotype distribution of insulin receptor substrate-2(IRS-2)gene 1057G/A polymorphism in Han population from Southwest China,and to explore its association with the metabolism of glucose and lipids,insulin resistance and islet?-cell function in type 2 diabetic patients and subjects with impaired glucose tolerance(IGT).Methods A total of 929 Hans[462 patients with type 2 diabetes(DM group) and 164 subjects with IGT(IGT group)and 303 normal controls(NC group)]from Chongqing and nearby regions were screened for 1057G/A polymorphism of IRS-2 gene by PCR-RFLP assay.Body mass index(BMI),plasma glucose,serum insulin and lipid profile,high-sensitive C-reactive protein(hsCRP)and non-esterified fatty acid were measured.Homeostasis model assessment of insulin resistance(HOMA-IR)and disposition index(DI)were used to estimate insulin resistance and?-cell function respectively.Results In DM group,A allele frequency was significantly lower than that in NC group(0.326 vs 0.388,X~2=6.19,P=0.01).Compared with NC group,AA genotype frequeney was lower and GG genotype frequeney was higher in DM group(0.104 vs 0.135 and 0.452 vs 0.360 respectively,X~2=6.80,P

Macrophages are involved in many important biological processes and membrane proteins are the key effector molecules for their functions. However, membrane proteins are difficult to analyze by 2-DE based method because of their intrinsic tendency to self-aggregate during the first dimension separation (IEF). To circumvent the obstacle hampering membrane protein analysis, we combined one-dimensional SDS-PAGE with capillary liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using this technique, we identified 458 GO annotated membrane proteins with extremely high confidence, including most known markers of peritoneal macrophages (e.g., CD11b, F4/80, CD14, CD18, CD86, CD44, CD16 and Toll-like receptor). Thirteen other CD antigens and 18 Ras-related small GTPase were also identified. In addition to those known macrophage membrane proteins, a significant number of novel proteins have also been identified. This research provides a valuable data set of macrophage membrane proteins, thus allowing for more comprehensive study of membrane proteins and a better understanding of the function mechanisms of macrophages in many biological processes.

By inquiring the medical students under the background of grouping teaching between the mainland students and the oversea Chinese students,we have got something about their attitude toward the credit system.The result will help us to improve the teaching renovation in medical education.The questionnaire including implementing of credit system,standard credit system, grouping teaching,curriculum,tutor system of the undergraduates,the administration of education,and so on.Then we analyze and get the result.

OBJECTIVESTo induce autologous bone marrow derived mesenchymal stem cell (aMSC) into chondrocyte, and to confirm the effects of 3 dimensional (3D) dynamic inducing in vitro and their long-term animal model repairing in vivo.

METHODSaMSC were separated from rabbits bone marrow aspirates, then respectively experienced 3D dynamic inducing in alginate drops in modified rotating wall bioreactor culture or in two dimensional (2D) inducing (culture flask) for 10 d. The induced cells were harvest and then mixed with fibrin sealant (FS) to repair rabbit knee femoral trochlea cartilage defects model. After 8, 12, 24, 48 weeks animals were euthanized. Gross appearance, histological appearances were examined.

RESULTSFlask culture groups showed a little chondrocyte differentiation, 3D inducing group showed obviously chondrocyte differentiation, improved collagen II and proteoglycan production. For 3D inducing ones in vivo, the cartilage defects were smoothly repaired by white translucent hard tissue with obvious hyaline-like cartilage histological appearance after 8, 12 weeks, and the defects boundary were hard to be identified with hyaline like cartilage with sustained histological appearance and score after 24, 48 weeks. For 2D ones in vivo, the cartilage defects were smoothly repaired after 8 weeks by hyaline like cartilage which showed accelerated degeneration after 24 weeks and lose cartilage performance completely after 48 weeks.

CONCLUSIONS3D dynamic inducing may assist aMSC on differentiating into chondrocyte, improve its long-term in vivo repairing effects, and enlighten its further applications in tissue engineering cartilage.

Animals ; Bone Marrow Cells ; cytology ; Cartilage, Articular ; injuries ; physiopathology ; surgery ; Cell Culture Techniques ; Cell Differentiation ; Cells, Cultured ; Chondrocytes ; cytology ; Chondrogenesis ; Disease Models, Animal ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Rabbits ; Tissue Engineering ; methods ; Transplantation, Autologous ; Wound Healing

OBJECTIVETo investigate the effects of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells on collagen gel contraction in organotypic culture.

METHODSThe hair follicle organotypic culture was prepared with different concentrations of rat tail collagen, different number of dermal papilla cells and hair follicle epithelium cells in DMEM medium, after cultured for 10 days the diameter of collagen gel was measured.

RESULTThe concentration of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells significantly influenced on collagen gel contraction in organotypic culture (P<0.01). The contraction of collagen gel was negatively related to the concentration of rat tail collagen, while the concentration of dermal papilla cells and hair follicle epithelium cells was positively related to the contraction of collagen gel.

CONCLUSIONThe key factor influencing collagen gel contraction in organotypic culture is the concentration of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells.

Animals ; Cell Division ; Cells, Cultured ; Collagen ; physiology ; Gels ; Hair Follicle ; cytology ; Rats

OBJECTIVETo investigate the effects of tanshinone IIA (TA, one of the active components of Salvia miltiorrhiza Bge), on the proliferation of cultured rat vascular smooth muscle cells (VSMC), and to clarity the probable mechanism.

METHODCell culture technique was used in vitro and treated with or without 10% FBS. The inhibitory effect of TA on proliferation of VSMC was observed by cell count, MTU metabolism measuring and BrdU incorporation assay. Flow cytometry was performed to track cell cycle progression. Western bolts were performed to evaluate ERK1/2 activity. The expression of c-fos was examined by RT-PCR.

RESULTThe results of cell number, MTU assay and BrdU incorporation showed that TA cound significantly inhibit 10% FBS induced proliferation in a dose-dependent manner. Flow cytometry (FCM) analysis indicated that the G5/G1 phase fraction ratio of TA group was higher than that of 10% FBS group, while the S-phase fraction ratio was lower than that of 10% FBS group. Western blot's results displayed that TA inhibited the phosphorylation of ERK1/2, and in accordance with this findings. TA could decrease the early elevation of c-fos expression.

CONCLUSIONThese results suggest that TA can inhibit 10% FBS induced the proliferation of VSMC. This effect may be related to its blocking VSMCs cell cycle in G0/G1 phase, inhibiting of the ERK1/2 activity, and decreasing the expression of c-fos.

Animals ; Aorta ; cytology ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Diterpenes, Abietane ; Down-Regulation ; Gene Expression ; drug effects ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Phenanthrenes ; pharmacology ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; Rats