BACKGROUND:Epithelial cel s are commonly used as the seed cel in tissue engineering;however, there is stil a lack of an effective in vivo noninvasive trace technology. OBJECTIVE:To investigate the feasibility of labeling canine oral epithelial cel s with ultrasmal superparamagnetie iron oxide (USPIO) and magnetic resonance imaging (MRI) in vitro. METHODS:Oral epithelial cel s from beagles were primary cultured, and then labeled by 0.75 mg/L poly-L-lysine combined with USPIO (0, 5, 10, 25, 50 and 100 mg/L), respectively. To determine the optimal dosage, the intracel ular iron expression was identified by Prussian blue staining, and the cel viability in different groups was detected by cel counting kit-8. Final y, 2×105 labeled cel s were suspended with 1 mL PBS buffer, and were screened using 3.0 T MR on T2*WI sequences in vitro. RESULTS AND CONCLUSION:USPIO prepared with 0.75 mg/L poly-L-lysine could successful y label dog oral epithelial cel s. Prussian blue staining showed intracel ular blue spots, and the intracel ular blue spots became more with the concentration increasing and saturated at the concentration of 25 mg/L. Cel counting kit-8 indicated that the cel viability did not change when the concentration<25 mg/L. Among the T2*WI sequences, the MRI signal intensity decreased with the concentration increasing. In conclusion, canine oral epithelial cel s can be effectively labeled with USPIO making no impact on cel viability when the concentration<25 mg/L, and MRI can be used to track these labeled cel s in vitro.

Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.

OBJECTIVETo compare two equations for calculating glomerular filtration rate (GFR) in the evaluation of the prevalence of chronic kidney disease (CKD) and the risk factors of CKD in urban healthy population.

METHODSA total of 40377 subjects (24164 males and 16213 females) participated in this study. Body height, weight and blood pressure were measured, and morning urine and venous blood samples were collected for routine urine and blood tests with measurements of blood glucose, total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and uric acid.

RESULTS AND CONCLUSIONUsing Japanese CKD Epidemiology Collaboration (J-EPI) equation and Chinese modified Modification of Diet in Renal Disease (C-MDRD) equation, the prevalence of CKD calculated was 3.9% and 6.3% in this population, respectively. The independent risk factors of CKD included an age over 60 years, high uric acid, and high blood glucose.

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Physical Examination ; Prevalence ; Renal Insufficiency, Chronic ; epidemiology ; physiopathology ; Risk Factors ; Sex Distribution ; Young Adult

Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.
Animals ; Ganglia, Spinal ; drug effects ; Male ; Nervous System Diseases ; chemically induced ; drug therapy ; Pregabalin ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; drug effects ; Taxoids ; adverse effects ; gamma-Aminobutyric Acid ; analogs & derivatives ; pharmacology

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.