As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs' transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.

OBJECTIVE To investigate the effects of aucubin （Auc） on the malignant biological behavior of breast cancer cells by regulating cyclin-dependent kinase 1（CDK1）/cyclin B1（CCNB1）/Polo-like kinase 1 （PLK1） signaling pathway. METHODS Human breast cancer cells MCF-7 were divided into control group， Auc low-， medium- and high-concentration groups （AUC-L， AUC-M， AUC-H groups， 20， 40 and 80 μmol/L Auc）， Auc-H+pcDNA-NC group （80 μmol/L Auc+transfected pcDNA- NC plasmid）， and Auc-H+pcDNA-CDK1 group （80 μmol/L Auc+transfected pcDNA-CDK1 plasmid）. Cell proliferation， clonal formation， invasion and migration abilities， apoptosis and cycle distribution， and the expressions of related proteins of apoptosis， epithelial-mesenchymal transformation （EMT） and CDK1/CCNB1/PLK1 signaling pathway were detected in each group. The transplanted tumor model of BALB/c nude mice was established by subcutaneous inoculation of MCF-7 cell suspension， and the mice were divided into control group and Auc group （12 mice in each group）. The tumor volume， mass and the expressions of related proteins of CDK1/CCNB1/PLK1 signaling pathway in tumor tissues were detected. RESULTS Compared with control group， the number of clonal formation， proliferation rate， cell invasion number， scar healing rate， G1/G0 phase and S phase cell proportions， and the expressions of B cell lymphoma-2 （Bcl-2）， N-cadherin， fibronectin， CDK1， CCNB1 and PLK1 were decreased significantly （P＜0.05）. The apoptotic rate， G2/M phase cell proportion and the expressions of Bcl-2 associated X protein and E-cadherin were significantly increased， in a dose-dependent manner （P＜0.05）. Compared with the Auc-H+pcDNA-NC group， there was no statistical significance in the above indexes in the Auc-H group （P＞0.05）， while the above indexes in the Auc-H+ pcDNA-CDK1 group were significantly reversed （P＜0.05）. Compared with the control group， the tumor volume and mass， and the expressions of CDK1， CCNB1 and PLK1 in tumor tissue of Auc group were significantly decreased （P＜0.05）. CONCLUSIONS Auc can inhibit the proliferation， invasion and migration of breast cancer cells， induce cell cycle arrest， and inhibit the progression of EMT， which may be related to inhibiting the activation of the CDK1/CCNB1/PLK1 signaling pathway.

BACKGROUNDFollicle stimulating hormone is necessary for normal reproduction in men. The biochemical actions of follicle stimulating hormone result from binding to the follicle stimulating hormone receptor in the plasma membrane of Sertoli cells. Here, we investigated the expression of the follicle stimulating hormone receptor in different testicular histological phenotypes of patients with idiopathic azoospermia.

METHODSFifty-seven cases of idiopathic azoospermia were classified into three groups according to the results of testicular biopsy: patients with hypospermatogenesis, patients with maturation arrest, and patients with Sertoli cell-only syndrome. Thirteen azoospermic patients identified by testicular biopsy as being capable of completing spermatogenesis acted as the control group. Immunohistochemistry and real-time quantitative reverse-transcriptase polymerase chain reaction were performed in each case, and the serum hormone level was also measured in all patients.

RESULTSThe serum follicle stimulating hormone level in patients with Sertoli cell-only syndrome was significantly higher than in patients with hypospermatogenesis, maturation arrest, and complete spermatogenesis (P < 0.01). The serum follicle stimulating hormone level in patients with maturation arrest was significantly higher than in patients with hypospermatogenesis and complete spermatogenesis (P < 0.05). There was no difference in serum follicle stimulating hormone levels in patients with hypospermatogenesis and complete spermatogenesis. The follicle stimulating hormone receptor expression level of testicular samples with Sertoli cell-only syndrome was significantly higher than in those with hypospermatogenesis, maturation arrest, and complete spermatogenesis (P < 0.05), but no significant difference was observed among hypospermatogenesis, maturation arrest, and complete spermatogenesis testicular samples.

CONCLUSIONSDifferent serum follicle stimulating hormone levels and follicle stimulating hormone receptor expression were found in the different testicular histology phenotypes in azoospermic patients. Differential follicle stimulating hormone receptor expression in testicular tissue of patients with idiopathic azoospermia may be associated with the degree of spermatogenesis.

Adult ; Azoospermia ; blood ; metabolism ; Follicle Stimulating Hormone ; blood ; Humans ; Male ; Oligospermia ; blood ; metabolism ; Receptors, FSH ; genetics ; metabolism ; Spermatogenesis ; physiology ; Testis ; metabolism