Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway.

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.

In situ quantitative measurements on MMP-9 activity in single living cells by single molecule fluorescence correlation spectroscopy.

Matrix metalloproteinase-9 (MMP-9) plays an important role in tumor progression. It is of great significance to establish a sensitive in situ assay strategy for MMP-9 activity in single living cells. Here a novel in situ single molecule spectroscopy method based on the fluorescence correlation spectroscopy (FCS) technique was proposed for measuring the MMP-9 activity at different locations within single living cells, using a fluorescent specific peptide and a reference dye as dual probes. The measurement principle is based on the decrease of the ratiometric translational diffusion time of dual probes in the detection volume due to the peptide cleavage caused by MMP-9. The peptide probe was designed to be composed of an MMP-9 cleavage and cell-penetrating peptide sequence that was labeled with a fluorophore and conjugated with a streptavidin (SAV) molecule. The ratiometric translational diffusion time was used as the measurement parameter to eliminate the effect of intracellular uncertain viscosity. The linear relationship between the ratiometric diffusion time and MMP-9 activity was established, and applied to the determination of enzymatic activity in cell lysates as well as the evaluation of the inhibitory effects of different inhibitors on MMP-9. More importantly, the method was successfully used to dynamically determine MMP-9 activity in single living cells or under the stimulation with phorbol 12-myristate 13-acetate (PMA) and inhibitors.

Hormone Regulation of CCCH Zinc Finger Proteins in Plants.

CCCH zinc finger proteins contain one to six tandem CCCH motifs composed of three cysteine and one histidine residues and have been widely found in eukaryotes. Plant CCCH proteins control a wide range of developmental and adaptive processes through DNA-protein, RNA-protein and/or protein-protein interactions. The complex networks underlying these processes regulated by plant CCCH proteins are often involved in phytohormones as signal molecules. In this review, we described the evolution of CCCH proteins from green algae to vascular plants and summarized the functions of plant CCCH proteins that are influenced by six major hormones, including abscisic acid, gibberellic acid, brassinosteroid, jasmonate, ethylene and auxin. We further compared the regulatory mechanisms of plant and animal CCCH proteins via hormone signaling. Among them, Arabidopsis AtC3H14, 15 and human hTTP, three typical CCCH proteins, are able to integrate multiple hormones to participate in various biological processes.

Bryostatin-1: a promising compound for neurological disorders.

The central nervous system (CNS) is the most complex system in human body, and there is often a lack of effective treatment strategies for the disorders related with CNS. Natural compounds with multiple pharmacological activities may offer better options because they have broad cellular targets and potentially produce synergic and integrative effects. Bryostatin-1 is one of such promising compounds, a macrolide separated from marine invertebrates. Bryostatin-1 has been shown to produce various biological activities through binding with protein kinase C (PKC). In this review, we mainly summarize the pharmacological effects of bryostatin-1 in the treatment of multiple neurological diseases in preclinical studies and clinical trials. Bryostatin-1 is shown to have great therapeutic potential for Alzheimer's disease, multiple sclerosis, fragile X syndrome, stroke, traumatic brain injury, and depression. It exhibits significant rescuing effects on the deficits of spatial learning, cognitive function, memory and other neurological functions caused by diseases, producing good neuroprotective effects. The promising neuropharmacological activities of bryostatin-1 suggest that it is a potential candidate for the treatment of related neurological disorders although there are still some issues needed to be addressed before its application in clinic.

Ginseng polysaccharide reduces autoimmune hepatitis inflammatory response by inhibiting PI3K/AKT and TLRs/NF-κB signaling pathways.

BACKGROUND: Ginseng polysaccharides (GP) have been found to exhibit significant immune regulatory effects, making them a promising candidate for treating immune-related diseases. However, their mechanism of action in immune liver injury is not yet clear. The innovation of this study lies in exploring the mechanism of action of ginseng polysaccharides (GP) in immune liver injury. While GP has been previously identified for its immune regulatory effects, this study aims to provide a clearer understanding of its therapeutic potential for immune-related liver diseases. PURPOSE: The purpose of this study is to characterize low molecular weight gingeng polysaccharides (LGP), investigate their effect on ConA-induced autoimmune hepatitis (AIH), and identify their potential molecular mechanisms. METHODS: LGP was extracted and purified using water-alcohol precipitation, DEAE-52 cellulose column, and Sephadex G200. And its structure was analyzed. It was then evaluated for anti-inflammatory and hepatoprotective effects in ConA-induced cells and mice, assessing cellular viability and inflammation with Cell Counting Kit-8 (CCK-8), Reverse Transcription-polymerase Chain Reaction (RT-PCR), and Western Blot, and hepatic injury, inflammation, and apoptosis with various biochemical and staining methods. RESULTS: LGP is a polysaccharide composed of glucose (Glu), galactose (Gal), and arabinose (Ara), with a molar ratio of 12.9:1.6:1.0. LGP has a low crystallinity amorphous powder structure and is free from impurities. LGP enhances cell viability and reduces inflammatory factors in ConA-induced RAW264.7 cells and inhibits inflammation and hepatocyte apoptosis in ConA-induced mice. LGP inhibits Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and Toll-like receptors/Nuclear factor kappa B (TLRs/NF-κB) signaling pathways in vitro and in vivo to treat AIH. CONCLUSIONS: LGP was successfully extracted and purified, exhibiting potential as a treatment for ConA-induced autoimmune hepatitis due to its ability to inhibit the PI3K/AKT and TLRs/NF-κB signaling pathways and protect liver cells from damage.

Sirtuin1-p53: A potential axis for cancer therapy.

Sirtuin1 (SIRT1) is a conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that plays key roles in a range of cellular events, including the maintenance of genome stability, gene regulation, cell proliferation, and apoptosis. P53 is one of the most studied tumor suppressors and the first identified non-histone target of SIRT1. SIRT1 deacetylates p53 in a NAD+-dependent manner and inhibits its transcriptional activity, thus exerting action on a series of pathways related to tissue homeostasis and various pathological states. The SIRT1-p53 axis is thought to play a central role in tumorigenesis. Although SIRT1 was initially identified as a tumor promoter, evidence now indicates that SIRT1 may also act as a tumor suppressor. This seemingly contradictory evidence indicates that the functionality of SIRT1 may be dictated by different cell types and intracellular localization patterns. In this review, we summarize recent evidence relating to the interactions between SIRT1 and p53 and discuss the relative roles of these two molecules with regards to cancer-associated cellular events. We also provide an overview of current knowledge of SIRT1-p53 signaling in tumorigenesis. Given the vital role of the SIRT1-p53 pathway, targeting this axis may provide promising strategies for the treatment of cancer.

Study on hypoglycemic effects of irradiated ginseng adventitious roots.

We aimed to explore the effects of the 60Co-γ irradiated ginseng adventitious root (GAR) with different radiation doses on the hypoglycemic effects of its extract (GARSE) through in vivo and in vitro experiments. The total saponin of GARSE was increased by 4.50% after 5 kGy irradiation, and the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability was enhanced by 5.10%. At 50 µg/mL, GARSE irradiated by 5 kGy displayed superior protective effects on human glomerular mesangial cells (HMCs) with high glucose damage. After feeding type 1 diabetes mellitus (T1DM) mice with GARSE irradiated by 5 kGy at 500 mg/kg·BW for 4 weeks, the glucose values was decreased by 16.0% compared with the unirradiated. The Keap1/Nrf2/HO-1 pathway was activated and the oxidative stress was attenuated, which further alleviated T1DM.

The regulatory effect of total flavonoids of Sedum aizoon L. on oxidative stress in type 1 diabetic mice.

In this study, the optimal extraction conditions for the total flavonoids of Sedum aizoon L. (STF) were optimized by response surface methodology. Evaluation of the antioxidant in vitro of STF, and modulatory effects of glucolipid metabolism, and oxidative stress in mice with type 1 diabetes mellitus (T1DM). STF showed good antioxidant capacity in vitro. STF could improve glucolipid metabolism, organ coefficients, and antioxidant stress enzymes in T1DM mice effectively, reduce the damage to liver tissue, and regulate redox imbalance in the organism by modulating the Nrf2/Keap1/ARE signaling pathway. The results of this study could provide a theoretical reference for the application of Sedum aizoon L. in the development of auxiliary hypoglycemic functional foods and improvement of diabetes.

Designed synthesis of nickel-cobalt-based electrode materials for high-performance solid-state hybrid supercapacitors.

Supercapacitors with high security, excellent energy and power densities, and superior long-term cycling performance are becoming increasingly essential for flexible devices. Herein, this study has reported a novel method to synthesize CoNi2S4, which delivered a high specific capacitance of 1836.6 F g-1 at 1 A g-1, with a slight fluctuation in the testing temperature rising up to 50 °C (1855.2 F g-1) or decreasing to 0 °C (1587.6 F g-1). In addition, the corresponding solid-state CoNi2S4//AC HSC could achieve a high energy density of 35.8 W h kg-1 at a power density of 800.0 W kg-1, with nearly no change when tested at 0 °C and 50 °C, and possessed excellent long-term electrochemical cycling stability of 132.3% after 50 000 cycles; the solid-state hybrid supercapacitor using biomass-derived carbon (BC) as the negative electrode (CoNi2S4//BC HSC) could also deliver a high energy density of 38.9 W h kg-1 at a power density of 850.0 W kg-1 and the specific capacitance retention was 101.2% after cycling for 50 000 times. This work has provided a promising method to prepare high-performance electrode materials for solid-state hybrid supercapacitors with superior cycling stability and energy density.

Octreotide-Conjugated Core-Cross-Linked Micelles with pH/Redox Responsivity Loaded with Etoposide for Neuroendocrine Neoplasms Therapy and Bioimaging with Photoquenching Resistance.

The study of multifunctional polymer micelles combined with chemotherapy due to reduced systemic toxicity and enhanced efficacy has attracted intensive attention. Herein, a multifunctional core-cross-linked hybrid micelle system based on mPEG- b-PGu(BA-TPE) and OCT-PEG- b-PGu(DA-TPE) with pH- and redox-triggered drug release and aggregation-induced emission (AIE) active imaging has been developed for active targeting of neuroendocrine neoplasms (NENs), especially neuroendocrine carcinomas (NECs) with poor prognosis. These micelles showed excellent biocompatibility and stability. After the formation of borate ester bonds, core-cross-linked micelles (CCLMs) showed enhanced emission properties. In addition, etoposide (ETO), one of the most important anticancer drugs of NECs, was loaded into the hydrophobic core of micelles by self-assembly with an average diameter of 274.6 nm and spherical morphology. Octreotide (OCT) conjugated onto the micelles enhanced cellular uptake by receptor-mediated endocytosis. ETO-loaded micelles demonstrated the dual-responsive triggered intracellular drug release and great tumor suppression ability in vitro. Compared with free ETO, ETO-loaded CCLMs exhibited a considerable antitumor effect and significantly reduced side effects. Considering the active tumor targeting, dual-responsive drug release and the AIE effect, the polymer micelle system will be a potential candidate for diagnosis and oncotherapy of NENs.