Tefeng Pharmaceutical Co., Ltd.

Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects.

An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study.

All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration (T_max) of 1.00 h, and mean values of the peak concentration (C_max) and area under the concentration-time curve (AUC_0-t) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam.

Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study.

The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).

Chickpea isoflavones have been demonstrated to play an inhibitory role in breast cancer cells. In this study, we aimed to explore the mechanism of chickpea isoflavones inhibiting the formation and development of breast carcinoma through the integration of wet and dry experiments.

Chickpea isoflavones were added to the MCF-7 cells for 48 hours, and the subsequent morphological changes of cells were observed using an inverted microscope, while apoptosis was quantified by flow cytometry. The mRNA and LncRNA expression profiles were detected by RNA-sequencing (RNA-Seq) technology. The protein-protein interaction (PPI) network was constructed from the STRINGdb database. To identify the co-expressed long non-coding RNA and messenger RNA (lncRNA-mRNA) pairs, Pearson's correlation coefficients were calculated based on the expression value between every differentially expressed lncRNA and mRNA pair. The hub gene expression was verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and survival analysis results were provided by The Human Protein Atlas website.

Microscopic observation and flow cytometry results confirmed that chickpea isoflavones with a final concentration of 32.8 µg/mL could cause apoptosis of the MCF-7 cells. Transcriptome results showed that a total of 1,094 mRNAs and 378 lncRNAs were differentially expressed in isoflavone-treated cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that inhibition of cell proliferation was mainly due to the up-regulation of genes in the apoptosis signaling pathway and the down-regulation of genes in mRNA splicing pathway. The co-expressed genes of the top 10 down-regulated lncRNAs were mainly heterogeneous nuclear ribonucleoproteins (HNRNP) family genes, which interacted with apoptosis-related genes through ubiquitin C (UBC). The abnormal expression of 11 hub genes (degree >10) of PPI networks were beneficial to improve the overall survival time of breast cancer patients.

Our results reveal a potential mechanism for chickpea isoflavones to inhibit MCF-7 breast cancer cell proliferation and provide a reference for the development of new anti-cancer drugs used in breast cancer.

Fennel, commonly used in traditional Chinese medicine, is known as Foeniculum vulgare Mill. And its clinical application has been shown to target many biological systems including gastroenterology, endocrinology, gynecology and respiratory. The main constituent of the fennel essential oil is trans‑anethole, which has been described to have anti‑inflammatory and antibacterial activities. The aim of the present study was to define the anti‑inflammatory influence in acute lung injury (ALI)‑bearing mice. For 3 days, ALI‑bearing mice were induced by lipopolysaccharide (LPS) suspension in normal saline (24 mg/kg). On the fourth day, the trans‑anethole was administrated (36.4, 72.8 or 145.6 mg/kg) as well as dexamethasone (5 mg/kg) once per day for 7 consecutive days in mice. Following the completion of drug administration mice were sacrificed. Hematoxylin and eosin staining was performed in the lung paraffin section, for comparisons between monocyte and eosinophil cells in bronchoalveolar lavage fluid. The relative gene expression of interleukin (IL)‑10 and IL‑17 was determined by reverse transcription‑quantitative polymerase chain reaction. These two cytokines and the proportion of T helper 17 (Th17) cells and T regulatory (Treg) cells were determined by flow cytometry. The main constituent of fennel, trans‑anethole, eliminated LPS‑induced histopathological changes, decreased the number of inflammatory cells and resulted in a notable reduction in IL‑17 mRNA expression. In addition, trans‑anethole increased IL‑10 mRNA expression in isolated lung tissues and resulted in a marked elevation in Treg cells and reduction in Th17 cells in spleen tissues. The results of the present study indicated that the main constituent of fennel, trans‑anethole may be an anti‑inflammation component, which influenced the regulation of Th17/Treg responses. Therefore, this medicinal herb may support a healing effect on diseases of inflammatory.