Obvious Cytotoxic Effect Research Articles

Structurally diverse meroterpenoids from Arnebia euchroma and their anti-inflammatory effects through NF-κB pathway.

Meroterpenoids in the traditional Chinese medicine Arnebia euchroma are thought to be key components in its anti-inflammatory activity. In the present study, 17 meroterpenoids including four types of structural skeletons (1-17), together with a monoterpenoid (18), were isolated from the roots of A. euchroma. HRESIMS, 1D and 2D NMR, electronic circular dichroism, and quantum computing-assisted methods were employed to determine the structures of four previously undescribed compounds (1-3, and 14). Zicaomeroterin B (2) feature with a novel benzo[b]oxepin moiety was confirmed by X-ray analysis based on the crystalline mate method. Meroterpenoids 2, 5, 6, 13, and 17 exhibited significant inhibition against the production of NO, IL-6, and TNF-α in LPS-stimulated macrophages without obvious cytotoxic effects. Furthermore, compounds 2, 5, and 6 significantly inhibited the phosphorylation activation of NF-κB p65 and its nuclear translocation in luciferase reporter test, immunoblotting, and immunofluorescence imaging, which in turn inhibited the NF-κB pathway and exerted anti-inflammatory effects. These findings suggested that meroterpenoids 2, 5, and 6 in A. euchroma are the potential lead compounds for anti-inflammatory agents based on NF-κB signaling pathway.

Zwitterionic targeting nanodrugs prepared from poly(propyleneimine) dendrimers for enhanced anti-tumor therapy

Development of targeting and high drug loading drug delivery system has been gaining great interest. Zwitterionic modification of the terminal amine groups on G2 poly(propyleneimine) (G2 PPI) dendrimers was achieved via the thiol-ene click reaction, followed by the introduction of the anti-cancer drug paclitaxel and targeting peptides c(RGDfC), then the micelles were formed through self-assembly behavior, subsequently doxorubicin was encapsulated internally, finally the targeting drug-loaded micelles PPIMPRC-DOX were synthesized. The PPIMPRC-DOX micelles were irregular spherical with good monodispersity. The average particle size from TEM image was 63.05 nm and the hydrodynamic size was 93.1 nm, both of which were relatively uniform. The critical micelle concentration was 48.52 μg/mL, the total drug loading efficiency was 32.45 %. In vitro release experiments revealed that within the mildly acidic environment of tumors, PPIMPRC-DOX micelles exhibited enhanced release efficiency and increased accumulation of DOX. The anti-nonspecific protein adsorption experiment proved that the interaction between the PPIMPRC-DOX micelles and fibrinogen was very weak, and they had good anti-nonspecific protein adsorption ability. The cytotoxicity assessments using the MTT assay on HeLa cells and A549 cells revealed obvious cytotoxic effects of PPIMPRC-DOX micelles on both cells. Hence, the utilization of zwitterionic G2 PPI dendrimers in constructing PPIMPRC-DOX micelles holds promise as a prospective nanodrug delivery system.

Potential Bioactivities of Tamarind Seed Jellose at the Cellular Level for Cosmetic Product Development

In recent years, the utilization of tamarind seeds as a potential and sustainable ingredient in green cosmetics has gained significant interest. These seeds, previously considered by-products in various food industries, are now being recognized for their interesting value and wide range of bioactive compounds. This study aimed to deeply examine the potential biological activities and underlying molecular mechanisms of tamarind seed jellose (TJ), a natural polysaccharide derived from Tamarindus indica seeds, for various cosmetic applications. Tyrosinase, a key regulator of melanin synthesis and skin color, was the main focus of this study. Through a series of in vitro experiments on skin fibroblasts and B16 melanoma cells, the cytotoxicity, antioxidant activity, and melanogenesis inhibitory potential of tamarind seed jellose were evaluated. Notably, the results revealed that TJ had no obvious cytotoxic effects on skin fibroblast cells at any tested concentrations, ranging from 0 to 10 mg/mL. Interestingly, tamarind seed jellose effectively reduced melanin synthesis by inhibiting tyrosinase expression in a dose-dependent manner. In addition, TJ exhibited a promising antioxidant activity. Collectively, these findings highlight that TJ has the potential to serve as a safe and multi-functional ingredient for green cosmetic applications, offering the potential opportunity to repurpose waste for the beauty industry.

Enhancing antibacterial properties by regulating valence configurations of copper: a focus on Cu-carboxyl chelates.

Optimizing the antibacterial effectiveness of copper ions while reducing environmental and cellular toxicity is essential for public health. A copper chelate, named PAI-Cu, is skillfully created using a specially designed carboxyl copolymer (a combination of acrylic and itaconic acids) with copper ions. PAI-Cu demonstrates a broad-spectrum antibacterial capability both in vitro and in vivo, without causing obvious cytotoxic effects. When compared to free copper ions, PAI-Cu displays markedly enhanced antibacterial potency, being about 35 times more effective against Escherichia coli and 16 times more effective against Staphylococcus aureus. Moreover, Gaussian and ab initio molecular dynamics (AIMD) analyses reveal that Cu+ ions can remain stable in the carboxyl compound's aqueous environment. Thus, the superior antibacterial performance of PAI-Cu largely stems from its modulation of copper ions between mono- and divalent states within the Cu-carboxyl chelates, especially via the carboxyl ligand. This modulation leads to the generation of reactive oxygen species (˙OH), which is pivotal in bacterial eradication. This research offers a cost-effective strategy for amplifying the antibacterial properties of Cu ions, paving new paths for utilizing copper ions in advanced antibacterial applications.

Biosynthesis of Ag2Se nanoparticles as a broad-spectrum antimicrobial agent with excellent biocompatibility

Silver (Ag)-containing nanomaterials have emerged as promising alternatives or adjuvants to antibiotics. Ongoing research is dedicated to enhance their antimicrobial efficacy, stability, biocompatibility, and environmental sustainability. Microorganism-synthesized Ag-containing nanomaterials offer distinct advantages, especially for various surface modification, which potentially fulfill these objectives. In this study, we present the synthesis of silver-selenium (Bio-Ag2Se) nanoparticles using a yeast strain, Rhodotorula mucilaginosa PA-1. These Bio-Ag2Se nanoparticles have small size with a narrow size distribution (12.3 ± 2.9 nm) and long-term stability. They demonstrate a broad antimicrobial spectrum and high antimicrobial efficacy at very low concentrations, effectively targeting microorganisms including Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, as well as pathogenic fungus Candida albicans. Furthermore, Bio-Ag2Se nanoparticles exhibit excellent efficacy to inhibit and eliminate biofilms formed by notorious pathogen S. aureus. In contrast, Bio-Ag2Se nanoparticles at effective antibacterial concentrations demonstrate favorable biocompatibility and do not show obvious cytotoxic effects on human and plant cells. To elucidate the antibacterial mechanisms of Bio-Ag2Se nanoparticles against S. aureus and E. coli, transcriptomic analysis and phenotypic examination were employed. The results reveal significant and broad up-regulation in carbon metabolism pathways in both S. aureus and E. coli, suggesting it as one of the major antibacterial mechanisms of Bio-Ag2Se. This study presents a green synthesis strategy for Ag-containing nanoparticles with promising applications.

Phyllanthi Tannin Loaded Solid Lipid Nanoparticles for Lung Cancer Therapy: Preparation, Characterization, Pharmacodynamics and Safety Evaluation

The objective of the present study was to develop PTF-loaded solid lipid nanoparticles (PTF-SLNs) and investigate their efficacy in treating lung cancer. The PTF-SLNs were prepared by the thin film hydration method and verified by FTIR and TEM. Their physicochemical properties were characterized by particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), etc. Then, the pharmacodynamic studies of PTF-SLNs were performed on Lewis lung cancer cells and tumor-bearing mice. Finally, the safety studies were assessed by organ index, serum biochemical indicators, and histopathological changes. The PTF-SLNs were characterized by around 50 nm sphere nanoparticles, sustained ideal stability, and controlled drug release effects. The pharmacodynamic evaluation results showed that PTF-SLNs had stronger anti-tumor efficacy than PTF. An in vitro study revealed a more obvious cytotoxicity and apoptosis effect. The IC 50 values of PTF and PTF-SLNs were 67.43 μg/mL and 20.74 μg/mL, respectively. An in vivo study showed that the tumor inhibition rates of 2 g/kg PTF and 0.4 g/kg PTF-SLNs were 59.97% and 64.55%, respectively. The safety preliminary study indicated that PTF-SLNs improve the damage of PTF to normal organs to a certain extent. This study provides a nanoparticle delivery system with phenolic herbal extract to improve anti-tumor efficacy in lung cancer.

Evaluation of toxicity and biocompatibility of a novel Mg-Nd-Gd-Sr alloy in the osteoblastic cell.

We investigated the toxicity and biocompatibility of a novel Mg-3Nd-1Gd-0.3Sr-0.2Zn-0.4Zr (abbreviated to Mg-Nd-Gd-Sr) alloy in the osteoblastic cell line MC3T3-E1 as osteoblasts play an important role in bone repair and remodeling. We used cytotoxicity tests and apoptosis to investigate the effects of the Mg-Nd-Gd-Sr alloy on osteoblastic cells. Cell bioactivity, cell adhesion, cell proliferation, mineralization, ALP activity, and expression of BMP-2 and OPG by osteoblastic cells were also used to investigate the biocompatibility of Mg-Nd-Gd-Sr alloy. The results showed that the Mg-Nd-Gd-Sr alloy had no obvious cytotoxicity, and did not induce apoptosis to MC3T3-E1 cells. Compared with the control group, the number of adherent cells within 12h was increased significantly in each experimental group (P < 0.05); the OD value of MC3T3-E1 cells was increased significantly in each experimental group on days 1 and 3 of culture (P < 0.05); the number of mineralized nodules formed in each experimental group was significantly increased (P < 0.05), and ALP activity was significantly increased in each experimental group (P < 0.05). RT-PCR results showed that the mRNA expression of BMP-2 and OPG was significantly higher in each experimental group compared with the control group (P < 0.05). Western blotting showed that the Mg-Nd-Gd-Sr alloy extract significantly increased the protein expression of BMP-2 and OPG compared with the control group (P < 0.05). Our data indicated that the novel Mg-Nd-Gd-Sr-Zn-Zr alloy had no obvious cytotoxic effects, and did not cause apoptosis to MC3T3-E1 cells; meanwhile it promoted cell adhesion, cell proliferation, mineralization, and ALP activity of osteoblasts. During this process, there was an increase in the expressions of BMP-2 and OPG mRNAs and proteins.

Lipid metabolic disturbance induced by triphenyl phosphate and hydroxy metabolite in HepG2 cells

Triphenyl phosphate (TPHP) has been widely used as flame retardants and been detected with increasing frequency in environment. TPHP can transform into mono-hydroxylated phosphate (OH-TPHP) and diester diphenyl phosphate (DPHP) through biotransformation. So far, information on the cytotoxicity and molecular regulatory mechanisms of TPHP metabolites are still limit. This study investigated the adverse effects of TPHP, OH-TPHP, and DPHP in HepG2 cells in terms of cell proliferation, lactate dehydrogenase release, reactive oxygen species generation, and mitochondrial membrane potential. The transcriptomic changes were measured using RNA sequencing, and bioinformatics characteristics including biological functions, signal pathways and protein-protein interaction were analyzed to explore the potential molecular mechanisms. Results displayed that the order of cytotoxicity was OH-TPHP> TPHP> DPHP. The prioritized biological functions changes induced by TPHP and OH-TPHP were correlated with lipid metabolism. Significant lipid accumulation was observed as confirmed by increased total cholesterol and triglycerides contents, and enhanced oil red O staining. Enrichment of PPARα/γ and down-stream genes suggested the participation of PPARs signal pathway in lipid metabolism disorder. In addition, TPHP and OH-TPHP induced endoplasmic reticulum stress (ERS), which was further confirmed by the ERS inhibitor experiment. In general, TPHP and OH-TPHP had obvious cytotoxic effects in HepG2 cells. PPARs signal pathway and endoplasmic reticulum stress may be involved in the lipid metabolism disorder induced by TPHP and OH-TPHP.

Surfactant-assisted combustion synthesis of agglomerated-free, size- and shape-controlled magnetic iron oxide nanoparticles for biomedical applications

An advanced version of the solution combustion synthesis (SCS) method was developed to prepare iron oxide (IO) nanoparticles, through controlling the agglomeration, size and shape of nanoparticles by assisting a cationic surfactant, “cetyltrimethylammonium bromide (CTAB)” and ethanol. Various IO nanoparticles were prepared in the presence of different CTAB:ethanol molar compositions of 0:0, 0.27:0, 0.55:0, 0.27:17.1, 0.55:17.1 and 0.82:17.1. The morphological evolution from agglomerated-shape particles to the well-dispersed as well as the size- and shape-controlled particles depended directly on the CTAB:ethanol molar composition. A shift from ferromagnetic behavior to superparamagnetic was observed by the application of CTAB along with ethanol, where the lowest blocking temperature (Tb, 60 K), highest saturation magnetization (Ms, 83.5 emu g−1), zero coercivity and remanance magnetization were revealed for the particles prepared by CTAB:ethanol molar compositions of 0.55:17.1. These particles showed an acceptable specific absorption rate (SAR) value (320 W g−1) as well as no obvious hemolytic and cytotoxic effects. This work provides new insights into advancing the SCS method and thus controlling the morphology, size and shape of metal oxide nanoparticles.

Design and synthesis optimization of novel diimide indoles derivatives for ameliorating acute lung injury through modulation of NF-κB signaling pathway

Acute lung injury (ALI) is a common respiratory disease caused by local or systemic inflammatory reaction. Based on the natural 7-chain diaryl anti-inflammatory framework, a series of diimide indoles derivatives were designed by combining curcumin and indole in this study. The synthesis of diimide compounds was extended using dichloromethane (DCM) as solvent and 1,1′-carbonyldiimidazole (CDI) and sodium hydride (NaH) as double activators, and a total of 40 diimide-indole derivatives were obtained. The results of in vitro anti-inflammatory activity showed that most compounds could inhibit the production of interleukin-6 (IL-6) better than curcumin and indomethacin. Among the compounds, the IC50 of compound 11f on IL-6 reached 1.05 μM with no obvious cytotoxic side effects. Mechanistically, compound 11f could block the expression of NF-κB P65 phosphorylation, and nuclear translocation of P65. The acute toxicity tests in-vivo also showed no obvious toxicity in mice after the intragastric administration of 1000 mg/kg. In addition, the compound 11f could significantly inhibit the LPS-induced inflammatory response in mice and reduce the number of neutrophils and wet/dry lung weight ratio, thereby alleviating ALI. These results indicated that the novel diimide indoles were promising anti-inflammatory agents for the treatment of ALI.

Selective cytotoxicity of copper-coated magnesium composite on human hepatoma carcinoma cells : a preliminary investigation

A copper-coated magnesium (Cu@Mg) composite has been prepared by electroless plating, with the aim of generating a novel antitumor agent. The cytotoxic effects in vitro of this composite on normal hepatocyte cells (L02) and hepatoma cells (97H) were evaluated by CCK-8 assay. Extract and direct contact tests were conducted with blank groups as the control. Moreover, cell adhesion test was performed with 316L medical stainless steel as the cell carrier. It was found that Cu@Mg composite showed obvious cytotoxic effects on 97H cells but acceptable cytocompatibility whit L02 cells. As illustrated by CCK-8 assay, the cytotoxicity of Cu@Mg on 97H and L02 cells were grade I and III, respectively, and more apoptosis occurred to 97H cells than to L02 cells. During direct contact test, much more pathological reactions such as rounding, shrinking, atrophic edges and clustering were found in 97H cells than those in L02 cells. Similar evidence was shown in the adhesion tests. According to the single-factor cytotoxicity evaluation of pH, Cu2+ and Mg2+, the selective cytotoxicity of Cu@Mg on 97H cells is attributed to the fast release of Cu2+ and OH−, resulting from the degradation of Cu@Mg in the culture medium, but the Mg2+ released in the same process shows no toxicity on the both cells. Therefore, it is promising to develop novel antitumor materials on liver cancers with good biocompatibility based on Cu@Mg composite.

Lentinan-functionalized selenium nanoparticles induce apoptosis and cell cycle arrest in human colon carcinoma HCT-116 cells.

Selenium nanoparticles (SeNPs) have gained extensive attention for their excellent biological activity and low toxicity. However, SeNPs are extremely liable to aggregate into non-bioactive or gray elemental selenium, which limits their application in the biomedicine field. This study aimed to prepare stable SeNPs by using lentinan (LNT) as a template and evaluate its anti-colon cancer activity. The average particle diameter of obtained lentinan-selenium nanoparticles (LNT-SeNPs) was approximately 59 nm and presented zero-valent, amorphous, and spherical structures. The monodisperse SeNPs were stabilized by LNT through hydrogen bonding interactions. LNT-SeNPs solution remained highly stable at 4°C for at least 8 weeks. The stability of LNT-SeNPs solution sharply decreased under high temperature and strong acidic conditions. LNT-SeNPs showed no obvious cytotoxic effect on normal cells (IEC-6) but significantly inhibited the proliferation of five colon cancer cells (HCT-116, HT-29, Caco-2, SW620, and CT26). Among them, LNT-SeNPs exhibited the highest sensitivity toward HCT-116 cells with an IC50 value of 7.65 μM. Also, LNT-SeNPs displayed better cancer cell selectivity than sodium selenite and selenomethionine. Moreover, LNT-SeNPs promoted apoptosis of HCT-116 cells through activating mitochondria-mediated apoptotic pathway. Meanwhile, LNT-SeNPs induced cell cycle arrest at G0/G1 phase in HCT-116 cells via modulation of cell cycle regulatory proteins. The results of this study indicated that LNT-SeNPs possessed strong potential application in the treatment of colorectal cancer (CRC).

Screening and Identification of a Novel Anti-Siglec-15 Human Antibody 3F1 and Relevant Antitumor Activity.

Sialic acid-binding Ig-like lectin-15 is an important immunosuppressive molecule considered to be a key target in next-generation tumor immunotherapy. In this study, we screened 22 high-affinity antibodies that specifically recognize human Siglec-15 by using a large human phage antibody library, and five representative sequences were selected for further study. The results showed the binding activity of five antibodies to Siglec-15 (EC50 ranged from 0.02368 μg/mL to 0.07949 μg/mL), and in two Siglec-15-overexpressed cell lines, three antibodies had the strongest binding activity, so the two clones were discarded for further study. Subsequently, the affinity of three antibodies were measured by bio-layer interferometry technology (5-9 × 10E-09M). As the reported ligands of Siglec-15, the binding activity of Siglec-15 and sialyl-Tn, cluster of differentiation 44, myelin-associated glycoprotein, and leucine-rich repeat-containing protein 4C can be blocked by three of the antibodies. Among these, 3F1 had a competitive advantage. Then, the antibody 3F1 showed an obvious antibody-dependent cell-mediated cytotoxicity effect (EC50 was 0.85 μg/mL). Further, antibody 3F1 can reverse the inhibitory effect of Siglec-15 on lymphocyte proliferation (especially CD4+T and CD8+T) and cytokine release Interferon-γ. Given the above results, 3F1 was selected as a candidate for the in vivo pharmacodynamics study. In the tumor model of Balb/c Nude mice, 3F1 (10 mg/kg) showed certain antitumor effects [tumor growth inhibition (TGI) was 31.5%], while the combination of 3F1 (5 mg/kg) and Erbitux (5 mg/kg) showed significant antitumor effects (TGI was 48.7%) compared with the PBS group. In conclusion, novel human antibody 3F1 has antitumor activity and is expected to be an innovative candidate drug targeting Siglec-15 for tumor immunotherapy. SIGNIFICANCE STATEMENT: Siglec-15 is considered as an important target in the next generation of tumor immunotherapy. 3F1 is expected to be the most promising potential candidate for targeting Siglec-15 for cancer treatment and could provide a reference for the development of antitumor drugs.

Phytochemical Characterization of Taxus baccata L. Aril with Emphasis on Evaluation of the Antiproliferative and Pro-Apoptotic Activity of Rhodoxanthin.

Taxus baccata L., an evergreen tree, was known until recently due to its high concentration of toxic compounds. The purpose of the present study was to focus on the only non-poisonous part, the red arils, which have recently been described as an important source of various bioactive constituents. To establish total phenolic, flavonoid, and carotenoid content, antioxidant capacity, and cytotoxic properties, two types of extracts were obtained. The chemical profile of the ethanolic extract was evaluated using chromatographic (HPLC-DAD-ESI+) and spectral (UV-Vis) methods, and the antioxidant activity of the ethanolic extract was assessed using DPPH and FRAP assays, yielding moderate results. In the second type of extract (methanol: ethyl acetate: petroleum ether (1:1:1, v/v/v)) we identified three carotenoids using open column chromatography and RP–PAD–HPLC, with rhodoxanthin being the most abundant. Considering the above and mainly because of the lack of information in the literature about this pigment and its biological effects, we decided to further investigate the cytotoxic activity of rhodoxanthin, the main carotenoid presented in aril, and its protective effect against H2O2-induced oxidative stress using two cell lines: human HaCaT keratinocytes and B16F10 murine malignant melanoma. The MTT and Annexin-V Apoptosis assays showed a substantial cytotoxic potential expressed in a dose-dependent manner towards the melanoma cell line, however, no obvious cytotoxic effects on human keratinocytes were noticed.

The biological activities of 5,15-diaryl-10,20-dihalogeno porphyrins for photodynamic therapy.

Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy. The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I1-6, II1-4) were tested. The cytotoxicity of I1-6 and II1-4 were measured by MTT assay. The pathway of cell death was studied by flow cytometry. In vivo photodynamic efficacy of I3 and II2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined. 5,15-Diaryl-10,20-dihalogeno porphyrins I1-6 and II1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λmax = 660nm) displayed a red shift around 30nm compared to the unhalogenated porphyrins PS1 (λmax = 630nm). The singlet oxygen generation rates of I1-6 and II1-4 were significantly higher than PS1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II4 exhibited appropriate absorption in the phototherapeutic window, higher 1O2 generation rate (k = 0.0061s-1), the strongest phototoxicity (IC50 = 0.4μM), lower dark toxicity, high generation of intracellular ROS in Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II4 mediated PDT. All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug.

Maslinic Acid Inhibits Myocardial Ischemia-Reperfusion Injury-Induced Apoptosis and Necroptosis via Promoting Autophagic Flux.

Apoptosis, necroptosis, and autophagy are the major programmed cell death in myocardial ischemia-reperfusion injury (MIRI). Maslinic acid (MA) has been found to regulate pathophysiological processes that mediate programmed cell death in MIRI, such as inflammation and oxidative stress. However, its effects on MIRI remain unclear. This study intends to explore the role of MA in MIRI. In vitro, MA had no obvious cytotoxic effects on H9C2 cells, and significantly improved the impaired cell viability caused by hypoxia reoxygenation (HR). In vivo, MA significantly alleviated ischemia reperfusion (IR)-induced left ventricular myocardial tissue injury, downregulated creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) levels in serum as well as reducing infarct size. Moreover, MA inhibited HR-induced mitochondrial apoptosis and necroptosis in vitro and in vivo. Of interest, MA interacts with lysosome-associated membrane protein 2 (LAMP2). MA protected LAMP2 from IR and promoting autophagic flux to inhibit apoptosis and necroptosis, whereas these effects were reversed by co-treatment with lysosomal inhibitor BarfA1. In conclusion, MA can inhibit MIRI-induced apoptosis and necroptosis by promoting autophagic flux. These results support that MA is a potential agent to ameliorate MIRI.

Effect of Malvidin on Induction of Apoptosis and Inhibition of Cell Proliferation on Myeloid and Lymphoid Leukemia

Malvidin is one of 6 most common anthocyanidins found in fruits and vegtables. studies suggest that anthocyanidins are bioactive chemicals have potential for treatment of cancer. Malvidin have been demonstrated to induce apoptosis and inhibition of cell proliferation in a number of cancer cell lines. However, to date, few studies have tested the potential of malvidin in the treatment of leukemia. In the present study, we investigated the antiproliferative and proapoptotic properties of malvidin in two human leukemia cell lines lymphoid cell line: SUP-B15 (acute lymphoblastic leukemia) and myeloid cell line: KG-1a (acute myelogenous leukemia) in addition to non-tumour control cells (CD133+ HSC). We found that treatment of cells with malvidin at concentration 0, 25, 50 and 100 µM for 24 h resulted in significant inhibition of cell proliferation in both leukemia cell lines with obvious less cytotoxic effect on non-tumour control cells. In addition, malvidin induce apoptosis in a dose and dependent manner in both leukemia cells and confirmed that by activation of caspas-3 following 24 h treatment. Cell arrest at S phase has been indicated in both cell lines using DNA analysis by flow cytometry. These finding indicated that malvidin could inhibit leukemic cell proliferation and induce their apoptosis and might be used as one kind of functional food component or a novel nutraceutical beneficial for blood health.

In Vitro Immunomodulation of the Polysaccharides from Yam (Dioscorea opposita Thunb.) in Response to a Selenylation of Lower Extent.

The immunomodulation of chemically selenylated polysaccharides has been attracting more attention recently, but the corresponding performance of the yam polysaccharides (YPS) with lower selenylation extent remains, thus far, unsolved. In this study, the YPS was selenylated with Na2SeO3 under acidic conditions generated by HNO3 to reach two lower selenylation extents, yielding two selenylated YPSs, namely SeYPS-1 and SeYPS-2 with selenium contents of 715 and 1545 mg/kg, respectively. The results indicated that YPS, SeYPS-1, and SeYPS-2 all had in vitro immuno-modulation when using RAW 264.7 macrophages and murine splenocytes as cell models. In detail, the three polysaccharide samples at dose levels of 5–160 μg/mL showed insignificant cytotoxicity to the macrophages and splenocytes with cell exposure times of 12–24 h, because of the measured values of cell viability larger than 100%. However, Na2SeO3 at dose levels of 1.3–3.25 μg/mL mostly caused obvious cytotoxic effects on the cells, resulting in reduced cell viability values or cell death, efficiently. The results demonstrated that, compared with YPS, both SeYPS-1 and SeYPS-2 at a lower dose level (5 μg/mL) were more active at promoting phagocytosis activity, increasing the CD4+/CD8+ ratio of the T-lymphocyte sub-population in the murine splenocyte, improving cytokine secretion, including interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in the macrophages, or increasing interferon-γ secretion, but suppressing IL-4 production in the splenocytes. Consistently, SeYPS-2 has more potential than SeYPS-1 at exerting these assessed bioactivities in the cells. Thus, we conclude that a chemical modification of YPS using trace element Se at a lower selenylation extent could bring about higher immunomodulatory activity towards macrophages and splenocytes, while selenylation extent of YPS is a critical factor used to govern the assessed activity changes of YPS.

Template-free construction of hollow mesoporous Fe3O4 nanospheres as controlled drug delivery with enhanced drug loading capacity

Monodisperse hollow mesoporous Fe3O4 nanospheres have been successfully synthesized via a template-free one-pot solvothermal method under the existence of iron chloride hexahydrate, polyvinylpyrrolidone and urea. A proposed gas-bubble-assisted Ostwald ripening mechanism was allowed to explain the possible fabrication of hollow nanostructures. The formed Fe3O4 nanospheres possessed a narrow particle size distribution with a average hydrodynamic diameter of 392 nm, superparamagnetic characteristics with high saturation magnetization of 74.9 emu/g, as well as the typical mesoporous structures with specific surface area of 27.3 m2/g. Furthermore, it was found that the bare hollow mesoporous Fe3O4 nanospheres showed an insignificant cytotoxicity, but exhibited obvious cytotoxic effects towards HeLa cells after being loaded with the anti-cancer drug of DOX, which could be recommended as a promising and effective drug delivery system with high drug loading capacity and pH-responsive feature. The determined maximum drug loading capacity of DOX on this kind of hollow mesoporous Fe3O4 nanospheres was as high as 0.36 ± 0.04 g/g, which can store and deliver effectively the anticancer drugs to induce death of cancer cells.

Revealing the mechanism of zinc oxide nanoparticles facilitating hydrogen production in alkaline anaerobic fermentation of waste activated sludge

Zinc oxide nanoparticles (ZnO NPs) has been documented to accumulate in waste activated sludge (WAS). Nevertheless, its potential effect on hydrogen accumulation during anaerobic fermentation has never been reported. Such impact exists in anaerobic sludge treatment systems but is unrecognized before. Therefore, this work aims to explore the effect of ZnO NPs on hydrogen accumulation during WAS fermentation while avoiding hydrogen consumption by maintaining pH around 10. Deep insights into the mechanisms of the enhanced hydrogen production after dosing ZnO NPs can then be provided. The 21.1 to 74.0 mL-H2/g-VS hydrogen yields were obtained after dosing 0–150 mg/g-TS ZnO NPs into the system, which is 2.5 times higher than the control. The zinc ions released from ZnO NPs did not pose obvious cytotoxic effect on organisms based on the mechanism exploration of this study. The reactive oxygen species (ROS) induced by ZnO NPs facilitated sludge disintegration and improved the biodegradability of released organics, but restrained the bio-processes of hydrolysis and acetogenesis simultaneously. This was further verified by the microbial community analysis, as the abundance of key microbes related to hydrolysis and acetogenesis was reduced evidently in the presence of 150 mg/g-TS ZnO NPs. This study would provide a green and economic strategy for the sustainable engineering application of WAS containing ZnO NPs.