Poricoic acid A (PAA) inhibits T-cell acute lymphoblastic leukemia through inducing autophagic cell death and ferroptosis.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with poor clinical outcome. Poricoic acid A (PAA) is the main chemical constituent on the surface layer of the mushroom Poria cocos, and exerts protective effects against various diseases. In the study, its effects on T-ALL progression were investigated both in vitro and in vivo. Our results showed that PAA strongly reduced the cell viability of T-ALL cell lines, and induced cell G2 cycle arrest and apoptosis in vitro. Mitochondrial dysfunction was also elevated by PAA, along with enhanced cellular reactive oxygen species (ROS) production. Importantly, PAA-suppressed cell viability and -triggered apoptosis were ROS-dependent. Additionally, autophagy was significantly induced by PAA in T-ALL cells through regulating AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and LC3 signaling pathways. PAA treatments also provoked ferroptosis in T-ALL cells with reduced glutathione (GSH) levels and elevated malonaldehyde (MDA) contents. Suppressing autophagy and ferroptosis almost abrogated the capacity of PAA to restrain T-ALL proliferation and growth. The effects of PAA to suppress T-ALL tumor growth were also confirmed in vivo with undetectable toxicity. Therefore, the present study highlighted the potential of PAA for T-ALL treatment mainly through inducing autophagic cell death and ferroptosis.

YY1-mediated up-regulation of lncRNA LINC00466 facilitates glioma progression via miR-508/CHEK1.

BACKGROUND: The abnormal expression of lncRNA LINC00466 (LINC00466) has been demonstrated in several tumor types. However, the expression pattern and functions of LINC00466 in glioma remain uninvestigated. METHODS: A reverse transcriptase-polymerase chain reaction (RT-PCR) was utilized to analyze LINC00466 in human glioma tissues and cell lines. Luciferase reporter assays were performed to explore whether YY1 could bind to the promoter region of LINC00466. Cell counting kit-8, flow cytometry, colony-formation, transwell migration and invasion assays were carried out to determine the involvement of INC00466 in glioma. Luciferase assays and pulldown assays were conducted to verify the binding sites. RESULTS: We report that LINC00466 expression is increased in glioma cells and tissues. YY1 transcription factor (YY1) can bind directly to the LINC00466 promoter region. Clinical studies revealed that the elevated expression of LINC00466 is closely correlated with an advanced World Health Organization grade (p = 0.008), Karnofsky Performance Status score (p = 0.004) and a short overall survival (p = 0.0035) of glioma patients. Functional assays revealed that LINC00466 knockdown distinctly suppresses glioma cell proliferation, migration, invasion and epithelial-mesenchymal progress, and also promotes apoptosis. Moreover, dual-luciferase reporter assays indicated that LINC00466 acts as an endogenous sponge via binding to miR-508 and decreasing its expression. Luciferase assays and RT-PCR assays demonstrated that checkpoint kinase 1 (CHEK1) is a target of miR-508, and LINC00466 modulates CHEK1 levels by competing for miR-508. LINC00466 may exhibit its anti-oncogenic roles through targeting the miR-508/CHEK1 axis. CONCLUSIONS: Our findings identified a novel glioma-related long non-coding RNA, LINC00466, which may provide a potential novel prognostic and therapeutic target for glioma.

Covalent organic framework functionalized smart membranes with under-liquid dual superlyophobicity for efficient separation of oil/water emulsions.

The smart membrane with under-liquid dual superlyophobicity, which can achieve on-demand separation of oil/water emulsions only by simple liquid pre-wetting, is of essential value for the treatment of complicated real oil/water systems. Here, we first fabricated a stable suspension of imine-linked covalent organic framework nanospheres (TPB-DMTP-COF), and subsequently fabricated COF functionalized smart membranes with under-liquid dual superlyophobicity by immersing polyacrylonitrile-based (PAN-based) membranes into TPB-DMTP-COF nanosphere suspension. Accordingly, effective switchable separation of both oil-in-water and water-in-oil emulsions by TPB-DMTP-COF/PAN membranes can be achieved by employing pre-wetting processes (both the oil contact angle under water and the water contact angle under oil are over 150°). Specifically, the separation flux and the separation efficiency are higher than 1200 L/m2‧h and 98.0 %, and 2100 L/m2‧h and 97.4 % for the surfactant-stabilized oil-in-water and water-in-oil emulsions, respectively. Furthermore, the ultralow adhesions in liquid contributed to the outstanding reusability and antifouling resistance of the prepared TPB-DMTP-COF/PAN membranes. This work provides a feasible approach for fabricating a smart membrane with under-liquid dual superlyophobicity for oily wastewater treatment.

Effects of polydatin from Huhuang Shaoshang Liniment on oxidative damage and inflammatory response in rats with cerebral ischemia-reperfusion.

OBJECTIVE: To analyze the effect of polydatin (PD) from Huhuang Shaoshang Liniment on oxidative damage and inflammatory response in rats with cerebral ischemia-reperfusion (CI/R), and the effect of PD on NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) pathway. METHODS: The rat model of focal CI/R was established using suture-occlusion method and treated with intraperitoneal injection of PD (25 mg/kg and 50 mg/kg). High performance liquid chromatography (HPLC) was used to determine the PD content in three batches of Huhuang Shaoshang Liniment. The neurological function scores of each group were observed at 24 h, 48 h, and 72 h postoperatively. The hematoxylin and eosin (HE) staining was conducted to observe the morphological structure of brain tissue, the triphenyltetrazolium chloride (TTC) staining was used to determine the size of cerebral infarction, and the neuronal apoptotic index was calculated using image analysis system under the optical microscope. The expressions of the Nrf2/HO-1/NQO1 pathway and neuronal apoptosis-related proteins in brain tissue were measured using Western blot. RESULTS: The PD content in three batches of Huhuang Shaoshang Liniment was detected by HPLC, and the average result showed that the product contained 0.73 mg PD per 1 mL. The PD 50 mg/kg group and 25 mg/kg group showed lower neurological function scores at 24 h, 48 h, and 72 h postoperatively, lower percentage of cerebral infarction area on the ischemic side and apoptotic index, lower interleukin (IL)-1ß, IL-6, malondialdehyde (MDA), and lactate dehydrogenase (LDH) levels, and lower Bax protein expression (P < 0.05), and showed higher IL-4, IL-10, superoxide dismutase (SOD), glutathione peroxidase (GPx), Nrf2, HO-1, NQO1, and c-Myc protein expression than the CI/R group (P < 0.05). CONCLUSION: PD from Huhuang Shaoshang Liniment can alleviate neurological damage, improve neuronal morphology and structure, reduce cerebral infarction area, alleviate oxidative damage and inflammatory response, and inhibit neuronal cell apoptosis in CI/R model rats.

Effects of Huhuang Burn Liniment on wound healing and changes in IL-10 and MMP-9 levels in patients with mixed hemorrhoids.

OBJECTIVE: To explore the effects of Huhuang Burn Liniment on wound healing and levels of interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9) in patients with mixed hemorrhoids. METHODS: The clinical data of 113 patients with mixed hemorrhoids admitted to Chongqing Sanxia Central Hospital were retrospectively collected. All patients underwent Milligan-Morgan hemorrhoidectomy, and were divided into two groups according to different postoperative treatments. Group A was treated with 1/5000 potassium permanganate sitz bath after surgery, while group B was treated with Huhuang Burn Liniment. The treatment efficacy, wound healing time, level of pain, exudation, edema, granulation scores, anal function index, levels of IL-10 and MMP-9, quality of life scores, and complications were compared between the two groups. RESULTS: The effective rate of group B (94.74%) was higher than that of group A (60.71%) (P < 0.05). Group B had shorter length of anorectal hyperbaric zone, higher anal canal resting pressure, anal canal diastolic pressure, and anal canal systolic maximum pressure (P < 0.05), lower scores of trauma pain, edema, exudation, and granulation (P < 0.05), higher IL-10 levels, and lower MMP-9 levels (P < 0.05). The complication rate of group B (8.77%) was lower than that in group A (23.21%) (P < 0.05). After treatment, group B had shorter wound healing time and higher quality of life score than group A (P < 0.05). CONCLUSION: The application of Huhuang Burn Liniment in patients with mixed hemorrhoids after surgery could promote wound healing and anal function, reduce trauma pain, exudation and edema, and improve quality of life.

Long non-coding RNA LINC00858 promotes cells proliferation, migration and invasion by acting as a ceRNA of miR-22-3p in colorectal cancer.

Though long non-coding RNA LINC00858 (LINC00858) has been shown to be involved in tumours of other tissues, its involvement in colorectal cancer (CRC) is still unknown. We aimed to investigated expression and mechanism LINC00858 in human CRC. In this study, we firstly found that LINC00858 expression was significantly up-regulated in both CRC tissues and cell lines by both online data and RT-PCR assay. Then, clinical assay revealed that high LINC00858 expression was significantly associated with advanced clinical progression and poor prognosis. Multivariate analysis demonstrated that high LINC00858 expression was an independent poor prognostic factor for CRC patients. Moreover, lost-of-function assay indicated that knockdown of LINC00858 suppressed CRC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistically, bioinformatics analysis, dual-luciferase reporter assays, and western blot assays showed that LINC00858 functioned as competing endogenous RNA to repress miR-22-3p, which controlled its down-stream target YWHAZ. Then, we suggested that LINC00858 exerted its function through the miR-22-3p/YWHAZ axis. To our knowledge, this is the first report which showed the role of LINC00858 in the progression of CRC. Our findings indicated that LINC00858 played an important role in CRC, and may serve as a novel prognostic factor and therapeutic target.