AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway.

BACKGROUND: Despite the advancement in chemotherapeutic drugs for colon cancer treatment, it is still a life-threatening disease worldwide due to drug resistance. Therefore, an urgently needed to develop novel drugs for colon cancer therapies. AGA is a combination of traditional Chinese medicine Antler's extract (A), Ganoderma lucidum (G), and Antrodia camphorata (A); it contains a lot of biomolecules like polysaccharides, fatty acids, and triterpenoids that are known to exerting anti-oxidative, anti-inflammatory, anti-microbial and anti-tumor activities in oral cancer. In this study, we investigate AGA anti-proliferative, anti-metastatic and apoptotic activity to explore its anti-cancer activity against colon cancer cells and its underlying mechanism. METHOD: Here, in-vitro studies were performed to determine the antiproliferative activity of AGA through MTT and colony formation assays. Wound healing and transwell migration assay were used to evaluate the metastasis. Flow cytometry and protein expression were used to investigate the involved molecular mechanism by evaluating the cell cycle and apoptosis. The in-vivo anti-cancerous activity of AGA was assessed by xenograft mice model of colon cancer cells. RESULTS: We found that AGA significantly inhibited the proliferative capacity and metastasis of colon cancer cells in-vitro. In addition, AGA induced cell cycle arrest in the sub-G1 phase through upregulating p21 and downregulating CDK2, CDK6 in SW620, and CDK4 in SW480 and HT29, respectively. Annexin-v assay indicated that colon cancer cells had entered early and late apoptosis after treatment with AGA. Furthermore, a mechanistic protein expressions study revealed that AGA in p53-dependent and independent regulated the apoptosis of colon cancer by downregulating the p53 protein expression in SW620 and SW480 cells but upregulating in a dose-dependent manner in HT29 cells and increasing the expression of Bax and caspase-9 to inhibit the colon cancer cells. In vivo study, we found that AGA significantly reduced the xenograft tumor growth in NOD/SCID mice with no adverse effect on the kidney and liver. CONCLUSION: Collectively, AGA has the potential to inhibit colon cancer through inhibiting proliferation, migration, and cell cycle kinase by upregulating p21 protein expression and promoting the apoptotic protein in a p53-dependent and independent manner.

Performance of hydrogen evolution reaction of R3C ferroelectric ZnSnO3 nanowires.

The synthesis of LiNbO3-type R3C ZnSnO3 is still a challenging task under an extremely high-pressure condition. In this work, we have not only successfully synthesized R3C ZnSnO3 nanowires (NWs) through a hydrothermal process, but ZnSnO3 NWs with a high concentration of oxygen vacancies (referred to as [Formula: see text] NWs), exhibiting a highly efficient hydrogen evolution reaction compared to unannealed ZnSnO3 and ZnO NWs. The x-ray diffraction pattern and Raman spectra both confirm that the as-synthesized ZnSnO3 NWs mainly belong to the R3C space group with a second phase of ZnSn(OH)6. The conversion efficiency of the solar-to-hydrogen [Formula: see text] NWs and the unannealed ZnSnO3 NWs is 4.8% and 1.5%, respectively. The enhancement factor of the [Formula: see text] NWs is up to 320%. The photocurrent of the ZnSnO3 NWs and the [Formula: see text] NW photoelectrodes is even 5.39 and 16.23 times higher than that of the ZnO NWs, demonstrating that the high concentration of oxygen vacancies is regarded as a useful approach to enhance the photoelectrochemical response. To the best of our knowledge, this is the first report to reveal the performance of hydrogen evolution reaction by LiNbO3-type R3C ZnSnO3 NWs, which could offer a promising way of energy harvesting when using ferroelectric materials.

Interpenetration Networked Polyimide-Epoxy Copolymer under Kinetic and Thermodynamic Control for Anticorrosion Coating.

Epoxy (EP) was copolymerized with polyamic acid (PAA, precursor of polyimide (PI)) with termanil monomers of (1) 4,4'-Oxydianiline (ODA) and (2) pyromellitic dianhydride (PMDA) individually to form (PI-O-EP) and (PI-P-EP) copolymers. The FTIR spectrum of PI-O-EP copolymerization intermediates shows that some amide-EP linkages were formed at low temperature and were broken at higher temperature; in additoin, the released amide was available for subsequent imidization to form PI. The curing and imidization of the amide groups on PAA were determined by reaction temperature (kinetic vs. thermodynamic control). In PI-P-EP, the released amide group was very short-lived (fast imidization) and was not observed on FTIR spectra. Formation and breakage of the amide-EP linkages is the key step for EP homopolymerization and formation of the interpenetration network. PI contributed in improving thermal durability and mechanical strength without compromising EP's adhesion strength. Microphase separations were minimal at PI content less than 10 wt%. The copolymerization reaction in this study followed the "kinetic vs. thermodynamic control" principle. The copolymer has high potential for application in the field of higher-temperature anticorrosion.

Time- and Kellgren⁻Lawrence Grade-Dependent Changes in Intra-Articularly Transplanted Stromal Vascular Fraction in Osteoarthritic Patients.

Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee cartilage. OA patients were classified on the basis of age, gender, body mass index (BMI), and x-ray-derived Kellgren-Lawrence (KL) grade. They were treated with SVF and followed-up for 24 months. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index were used to determine treatment efficacy. Cartilage healing was assessed using the MRI-based Outerbridge score (OS) and evaluation of bone marrow edema (BME) lesions, while a placebo group was used as a control. Time- and KL-dependent changes were also monitored. We observed a decreasing trend in VAS score and WOMAC index in the SVF-treated group up to 24 months, as compared with the placebo group. Besides, a significant increase and decrease in Lysholm and OS, respectively, were observed in the treatment group. Compared with the values before treatment, the greatly reduced WOMAC scores of KL3 than KL2 groups at 24 months, indicate more improvement in the KL3 group. Highly decreased BME in the treated group was also noted. In conclusion, the SVF therapy is effective in the recovery of OA patients of KL3 grade in 24 months.

Cerebro- and renoprotective activities through platelet-derived biomaterials against cerebrorenal syndrome in rat model.

Though the cross-induction of either acute kidney (AKI) injury to ischemic stroke (IS) or IS to AKI might not be encountered in the early stages of cerebrorenal syndrome (CRS), both pathologies coexist in late stages. Therefore, we firstly established a late stage CRS rat model by simultaneous induction of both diseases, and further, cerebro and reno-protective activities of human platelet-rich plasma (hPRP), a blood-derived tissue engineering biomaterial, were tested in this pathology. hPRP was administrated via left common carotid artery and abdominal aorta 2 h post-sham procedure in Sprague-Dawley rats. Circulatory inflammatory markers (TNF-α/MPO/IL-6/Ly6G/CD11b/c), histopathologic cerebro and renal changes and oxidative stress were determined. Inflammation, infarct size, brain-associated inflammatory/DNA and mitochondrial damage and oxidative-stress with reduced neurons and neurological function were manifested in CRS group compared to other groups. CRS group also demonstrated declined renal function, accelerated renal collagen deposition, fibrosis and compromised glomerular podocyte components (podocin/ZO-1/fibronectin/synaptopodin). However, hPRP simultaneously suppressed all the inflammatory, cerebral and renal pathologic characteristics. hPRP also inhibited the expression of brain-associated inflammatory/DNA/mitochondrial damage and oxidative-stress biomarkers. These findings imply that hPRP may effectively exert cerebro- and renoprotective activities in late stage CRS through anti-oxidative, anti-inflammatory, anti-DNA and anti-mitochochondrial damaging activities.

Single-Step Preparation of Silver-Doped Magnetic Hybrid Nanoparticles for the Catalytic Reduction of Nitroarenes.

This study adopts a simple but facile process for preparing silver-doped magnetic nanoparticles by the spontaneous oxidation-reduction/coprecipitation method. The preparation can be achieved in one pot with a single step, and the prepared silver-doped magnetic nanoparticles were utilized as nanocatalysts for the reduction of o-nitroaniline. Utilizing the magnetic characteristics of the prepared nanoparticles, the catalytic reactions can be carried out under quasi-homogeneous condition and the nanocatalysts can be easily collected after the conversion is achieved. It can be revealed from the results that the morphologies and the composition of the prepared silver-doped magnetic nanoparticles can be adjusted by changing the conditions during the production, which affects the efficacy of the catalysis. In addition, the catalysis efficiency is also controlled by the pH, temperature, and the amounts of nanocatalysts used during the catalytic reaction. Finally, the silver-doped magnetic nanocatalysts prepared in this study own the advantages of easy preparation, room-temperature catalysis, high conversion ability, and recyclability, which make them more applicable in real utilities.

Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression.

Major depressive disorder (MDD), one of the most common mental disorders, is a significant risk factor for suicide and causes a low quality of life for many people. However, the causes and underlying mechanism of depression remain elusive. In the current work, we investigated epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. Mice were exposed to inescapable stress and divided into learned helplessness (LH) and resilient (LH-R) groups depending on the number they failed to escape. We found that the LH group had longer immobility duration in the forced swimming test (FST) and tail suspension tests (TST), which is consistent with a depression-related phenotype. Western blotting analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the LH group had lower BDNF expression than that of the LH-R group. The LH group consistently had lower BDNF mRNA levels, as detected by qPCR assay. In addition, we found BDNF exon IV was down-regulated in the LH group. Intraperitoneal injection of imipramine or histone deacetylase inhibitors (HDACi) to the LH mice for 14 consecutive days ameliorated depression-like behaviors and reversed the decrease in BDNF. The expression of HDAC5 was up-regulated in the LH mice, and a ChIP assay revealed that the level of HDAC5 binding to the promoter region of BDNF exon IV was higher than that seen in other groups. Knockdown of HDAC5 reduced depression-like behaviors in the LH mice. Taken together, these results suggest that epigenetic regulation of BDNF by HDAC5 plays an important role in the learned helplessness model of depression.