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Qingjie Fuzheng granule (QFG) is a traditional Chinese medicinal formula used extensively as an alternative medicine for cancer treatment, including colorectal cancer (CRC). But its pathological mechanism in CRC is unclear. To study antitumor treatment effects and mechanisms of QFG, we established a CRC HCT-116 xenograft mouse model and assessed QFG on EMT and autophagy progression in vivo. The mice were randomly divided into 2 groups (n = 10 each group) and treated with intragastric administration of 1 g/kg of QFG or saline 6 days a week for 28 days (4 weeks). Body weight was measured every other day with electronic balance. At the end of the treatment, the tumor weight was measured. Immunohistochemical (IHC) and western blot (WB) assay were used to detect the expression level of E-cadherin, N-cadherin, vimentin, and TWIST1 to evaluate the effect of QFG on tumor cell EMT progression. IHC and WB assay were also used to detect the expression level of beclin-1, LC3-II, and p62 to evaluate the effect of QFG on tumor cell autophagy progression. Furthermore, the expression level of relative proteins in mTOR pathway was detected by WB assay to investigate the mechanism of QFG effect on CRC. We discovered that QFG inhibited the rise of tumor weight while it had no effect on mice body weight, which proved that QFG could inhibit CRC growth progression without significant side effects in vivo. In addition, QFG treatment inhibited EMT and induced autophagy progression in CRC tumor cells, including that QFG upregulated the expression of E-cadherin, beclin-1, and LC3-II, but downregulated the expression of N-cadherin, vimentin, TWIST1, and p62. And, QFG decreased the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR, but increased the ratio of p-AMPK/AMPK. All findings from this research proved that QFG can induce autophagy and inhibit EMT progression in CRC via regulating the mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

The development of imaging technique to visualize and quantify the structural alteration of the spinal cord injury (SCI) may lead to better understanding and treatments of the injuries. In this work, multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) was tentatively applied to quantitatively visualize the cellular microstructures of SCI to demonstrate the feasibility and superiority of MPM in SCI imaging. High-contrast MPM images of normal and injured spinal cord tissue were obtained for comparison. Moreover, the changes of injured spinal cord were characterized by the quantitative analysis of the MPM images. These results showed that MPM combined with quantitative method has the ability to identify the characteristics of spinal cord injury including the changes in the contents of nerve fibers and extracellular matrix. With the advancement of MPM, we believe that this technique has great potential to provide the histological diagnosis for the monitoring and evaluation of SCI. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to decode the underlying mechanism of Herba Sarcandrae that indicated antipurpuric effect and to unveil one of its primary components, flavonoids, which play an important role. An immune mediated bone marrow failure (BMF) model in mouse was established by infusion thymus suspension cells after radiation in vivo. Platelets isolated in vitro were prepared from normal mice and BMF mice, respectively. The expressions of PS, P-selectin, PAC-1, Bax, Bad, Bid, and caspase-9 were examined by flow cytometry, and alteration of morphology of platelets under different conditions was observed. Our results indicated that the number of platelets was increased by addition of total flavonoids, and some of apoptotic markers such as Bax, Bad, Bid, and Caspase-9 were downregulated. In addition, the phosphatidylserine (PS) exposure on platelets was inhibited by total flavonoids, and the expressions of PAC-1 and P-selectin were decreased. In conclusion, it is suggested that the total flavonoids of Herba Sarcandrae may inhibit the excessive platelet apoptosis through mitochondrial pathway. In addition, activation of platelets may be also involved in mediating apoptosis of platelets. [ABSTRACT FROM AUTHOR]

Aidi injection (AD) is a traditional medical preparation that has a Chinese origin. It is extensively used particularly in combination with doxorubicin (DOX) for the management of hepatocellular carcinoma (HCC). However, the combination's synergistic mechanism has not yet been clarified. To investigate the anti-tumor impact of AD in combination with DOX and their synergistic mechanism in HCC. An H22 mouse xenograft model was utilized to study the impact of AD, DOX, and their combination on HCC in vivo. Their effects on cell vitality, apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) production, caspase-3, and cleaved caspase-3 protein expression were also investigated in H22 cells in vitro. Subsequently, human umbilical vein endothelial cells (HUVECs) were utilized to investigate the impacts of AD, DOX, and their combination on cell viability, migration, invasion, tube formation, and vascular endothelial growth factor (VEGF) protein expression. The study established that the tumor inhibition rate of AD combined with DOX reached 79.51%, which was significantly higher than that of AD (25.14%) or DOX (49.48%) alone. Additionally, the Q-value characterizing the synergy between AD and DOX was 1.72, demonstrating a strong synergistic effect. Furthermore, compared to AD or DOX administration alone, the combined administration group significantly decreased the alpha-fetoprotein (AFP) level in the serum, increased the tumor necrosis area, increased the Bax/Bcl-2, Cyt-c, caspase-9, Fas, Fasl, caspase-8, and caspase-3 protein expression, and significantly increased the CD31 and Ki67 protein expression in tumor tissue. Compared to AD or DOX alone, AD combined with DOX treatment had a synergistic effect on H22 cells (combination index values < 0.9), which inhibited cell viability, reduced mitochondrial membrane potential (MMP), induced apoptosis, promoted MMP loss, and increased ROS generation, cleaved caspase-3/caspase-3 levels, and caspase-3 activity. Moreover, combined administration showed a more pronounced inhibition of cell viability, migration, invasion, tube formation, and VEGF protein expression in HUVECs. AD enhances the anti-tumor effect of DOX by promoting apoptosis and inhibiting angiogenesis and cell proliferation. The findings of this study lay experimental foundations for the clinical combination of AD and DOX. [Display omitted] [ABSTRACT FROM AUTHOR]