MicroRNA-132 (miR‑132) has been reported to play a tumor suppressive role in different human malignancies. However, its role and underling mechanism in hepatocellular carcinoma (HCC) remains poorly defined due to lack of target gene information. In the present study, we demonstrated that the mean level of miR‑132 in hepatocellular carcinoma (HCC) tissues was significantly lower than that in matched tumor-adjacent tissues, and its expression negatively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Similarly, the expression of miR‑132 was obviously reduced in HCC cell lines as compared with a normal hepatic cell line. Ectopic expression of miR‑132 inhibited cell proliferation, colony formation, migration and invasion, and induced apoptosis in HepG2 cells. In vivo studies showed that miR‑132 inhibited tumor growth of HCC and decreased tumor volume and weight. In addition, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR‑132 by a luciferase reporter assay. Western blot and qRT-PCR analysis indicated that PIK3R3 was significantly downregulated by miR‑132 in HCC cells. miR‑132 expression inversely correlated with PIK3R3 mRNA expression in clinical HCC tissues. Investigations into possible mechanisms revealed that miR‑132 inactivated the AKT/mTOR signaling pathway, which may contribute to inhibition of proliferation, migration, and invasion of HCC. These findings suggested that miR‑132 may serve as a potential target in the treatment of human HCC.

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Prolactin receptor (PRLR) and growth hormone receptor (GHR) are closely related to the occurrence and development of breast cancer, and breast cancer cell endogenously express GHR, PRLR and GHR-PRLR heterodimer. In this case, the combined use of PRLR or GHR inhibitors may produce better anti-breast cancer potential than PRLR or GHR inhibitors alone. In this case, it is necessary to develop the dual-function GHR/PRLR antagonists with anti-breast cancer potential. For this, we used hybridoma technology to generate an anti-idiotypic antibody (termed H53). We then used various techniques, including competitive ELISA, competitive receptor binding analysis, and indirect immunofluorescence assay to identify H53, and the results show that H53 behaves as a typical internal image anti-idiotypic antibody (Ab2β). Further experiments indicate that H53 is a dual-function inhibitor, which not only inhibited PRLR-mediated intracellular signaling, but also blocked GHR-mediated intracellular signaling in a dose-dependent manner. Furthermore, H53 could inhibit PRL/GH-driven cancer cell proliferation in vivo and in vitro. This study indicates that H53 exhibits potential biological activity against breast tumors, which implies that internal image anti-idiotypic antibodies may be a useful strategy for the development of PRLR/GHR dual-function antagonists for breast cancer therapy.

The present study was designed to assess the bioequivalence of two agomelatine formulations (25-mg tablets) in healthy Chinese male subjects. This single-dose, open-label, randomized, four-way replicate study with a 1-week washout period was conducted in 60 healthy Chinese male volunteers under fasting conditions. Blood samples were collected over a 12-h period after a single dose of the 25-mg agomelatine test (T) formulation or a reference (R) formulation, and the drug concentrations were assayed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated using a noncompartmental model. Bioequivalence between the formulations was assessed. Tolerability and safety were monitored by physical examination, electrocardiogram (

A stable doxorubicin (DOX)-loaded stereocomplex micelle drug delivery system was developed via the stereocomplex interaction between enantiomeric 4-armed poly(ethylene glycol)–poly(D-lactide) and poly(ethylene glycol)–poly(L-lactide) to realize control drug release and improve tumor cell uptake for efficient cervical carcinoma therapy. All these DOX-loaded micelles including poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) exhibited appropriate sizes of ∼100 nm for the enhanced permeability and retention (EPR) effect. In addition, compared to PDM/DOX and PLM/DOX, SCM/DOX exhibited the slowest DOX releaser, highest tumor cell uptake and the most efficient tumor cell suppression in vitro. Moreover, the excellent tumor inhibiting rates of the DOX-loaded micelles, especially SCM/DOX, were verified in the U14 cervical carcinoma mouse model. Increased tumorous apoptosis and necrosis areas were observed in the DOX-loaded micelles treatment groups, especially the SCM/DOX group. In addition, all these DOX-loaded micelles obviously alleviated the systemic toxicity of DOX. As a result, SCM can be a promising drug delivery system for the future therapy of cervical carcinoma.

A selective and sensitive liquid chromatography tandem mass spectrometry method was developed for the simultaneous determination of salviaflaside and rosmarinic acid in rat plasma. Sample preparation was carried out through liquid-liquid extraction with ethyl acetate using curculigoside as internal standard (IS). The analytes were determined by selected reaction monitoring operated in the positive ESI mode. Chromatographic separation was performed on an Agilent Eclipse Plus C column (100 × 4.6 mm, 1.8 μm) with a mobile phase consisting of methanol-water-formic acid (50:50:0.1, v/v/v) at a flow rate of 0.3 mL/min. The run time was 1.9 min per sample and the injection volume was 5 μL. The method had an LLOQ of 1.6 ng/mL for salviaflaside and 0.94 ng/mL for rosmarinic acid in plasma. The linear calibration curves were fitted over the range of 1.6-320 ng/mL for salviaflaside and 0.94-188 ng/mL for rosmarinic acid in plasma with correlation coefficients (r ) >0.99. Intra- and inter-day precisions (relative standard deviation) were < 13.5%, and accuracies (relative error) were between -8.6% and 14.5% for all quality control samples. The method was validated and applied to the pharmacokinetics of salviaflaside and rosmarinic acid in plasma after oral administration of Prunella vulgaris extract to rats.

Most diseases might be associated with acute or chronic inflammation, and the role of vitamin D in diseases has been extensively explored in recent years. Thus, we examined the associations of one of the best markers for inflammation-C-reactive protein (CRP) with 25-hydroxyvitamin D [25(OH)D] in 24 specific diseases. We performed cross-sectional analyses among 9,809 subjects aged ≥18 years who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) in 2007~2010. The generalized additive model (GAM) was used to explore the associations of CRP with 25(OH)D in different diseases, adjusted for the age, gender, examination period and race. Distributions of CRP were significantly different (P < 0.05) in gender, examination period and race, and distributions of 25(OH)D were different (P < 0.05) in the examination period and race. Generally, CRP was negatively associated with 25(OH)D for majority diseases. 25(OH)D was negatively associated with CRP generally, and the associations were disease-specific and disease category-specific. In respiratory, gastrointestinal and mental diseases, the associations tended to be approximately linear. While in metabolic diseases, the associations were nonlinear, and the slope of the nonlinear curve decreased with 25(OH)D, especially when 25(OH)D < 30 μg/L.

The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significantly higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of an antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy.