HNF4A as a potential target of PFOA and PFOS leading to hepatic steatosis: Integrated molecular docking, molecular dynamic and transcriptomic analyses.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are indeed among the most well known and extensively studied Per- and polyfluoroalkyl substances (PFASs), and increasing evidence confirm their effects on human health, especially liver steatosis. Nonetheless, the molecular mechanisms of their initiation of hepatic steatosis is still elusive. Therefore, potential targets of PFOA/PFOS must be explored to ameliorate its adverse consequences. This research aims to investigate the molecular mechanisms of PFOA and PFOS-induced liver steatosis, with emphasis on identifying a potential target that links these PFASs to liver steatosis. The potential target that causes PFOA and PFOS-induced liver steatosis have been explored and determined based on molecular docking, molecular dynamics (MD) simulation, and transcriptomics analysis. In silico results show that PFOA/PFOS can form a stable binding conformation with HNF4A, and PFOA/PFOS may interact with HNF4A to affect the downstream conduction mechanism. Transcriptome data from PFOA/PFOS-induced human stem cell spheres showed that HNF4A was inhibited, suggesting that PFOA/PFOS may constrain its function. PFOS mainly down-regulated genes related to cholesterol synthesis while PFOA mainly up-regulated genes related to fatty acid ß-oxidation. This study explored the toxicological mechanism of liver steatosis caused by PFOA/PFOS. These compounds might inhibit and down-regulate HNF4A, which is the molecular initiation events (MIE) that induces liver steatosis.

Microcystin-LR prenatal exposure drives preeclampsia-like changes in mice by inhibiting the expression of TGF-ß and VEGFA.

Microcystin-leucine-arginine (MC-LR) is widespread in the water and food, which has suspected to be associated with adverse pregnancy outcomes. In the present study, we aim to assess the interaction between MC-LR exposure and preeclampsia development and elucidate the molecular events involved. After exposure to MC-LR during pregnancy, the mice developed hypertension and proteinuria, the typical symptoms of preeclampsia. This was associated with decreased invasiveness of placental trophoblast and vascular dysplasia caused by MC-LR through down-regulating VEGFA and TGF-ß expression via AKT/m-TOR/HIF-1α pathway. In addition, this conclusion has been confirmed in a case-control study. Significantly, the addition of Deferoxamine (DFM), a phosphorylated serine-threonine protein kinases (p-AKT) specific agonist, can antagonize the inhibitory effect of MC-LR on the expression of related proteins, which further ameliorate the migration and invasion ability of HTR-8/Svneo cells. To sum up, our study revealed the pathologic mechanism by which MC-LR lead to preeclampsia and emphasized the importance of pregnancy management.

Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review).

Ferroptosis, a novel form of regulated cell death, is characterized by the accumulation of labile iron and lipid peroxidation, and the excessive production of reactive oxygen species (ROS). Although ferroptosis lies at the center of crucial biological activities involving O2, iron and polyunsaturated fatty acids (PUFAs), which are essential for cell proliferation and growth, the interaction between these molecules could also mediate the accumulation of toxic levels of ROS and lipid peroxides, which can then cause damage to cellular membranes and ultimately result in cell death. Recent reports have indicated that ferroptosis participates in the development and progression of inflammatory bowel disease (IBD), offering a new exploratory field which may aid in the more in­depth understanding of the pathogenesis and therapeutic targets of IBD. Of note, the mitigation of the characteristic features of ferroptosis, such as depleted glutathione (GSH) levels, inactivated glutathione peroxidase 4 (GPX4), elevated levels of lipid peroxidation and iron overload significantly relieve IBD. This has attracted the attention of researches aiming to examine therapeutic agents that inhibit ferroptosis in IBD, including radical­trapping antioxidants, enzyme inhibitors, iron chelators, protein degradation inhibitors, stem cell­derived exosomes and oral N­acetylcysteine or glutathione. The present review summarizes and discusses the current data that implicate ferroptosis in the pathogenesis of IBD and its inhibition as a novel alternate therapeutic target for IBD. The mechanisms and key mediators of ferroptosis, including GSH/GPX4, PUFAs, iron and organic peroxides are also discussed. Although the field is relatively new, the therapeutic regulation of ferroptosis has exhibited promising outcomes as a novel treatment avenue for IBD.

A modified CVD method for the synthesis of monolayer MoS2and photoelectric improvement by HfO2passivation.

Molybdenum disulfide (MoS2) is an emerging class of new materials with a wide range of potential practical applications. However, the uncontrollability of monolayer MoS2synthesized by traditional chemical vapor deposition method and the low responsivity of MoS2photodetectors limit its further development in the field of photoelectric detection. To achieve controlled growth of monolayer MoS2and construct MoS2photodetectors with a high responsivity, we propose a novel single crystal growth strategy of high-quality MoS2by controlling the Mo to S vapor ratio near the substrate, and deposit a layer of hafnium oxide (HfO2) on the surface of MoS2to enhance the performance of the pristine metal-semiconductor-metal structure photodetector. At a reverse bias of 8 V, the HfO2passivated MoS2photodetector features an extremely high responsivity of1201AW-1,a response time of around 0.5 s, and a detectivity of7.7×1011Jones.Meanwhile, we deeply investigate the effect of the HfO2layer on the performance of the fabricated MoS2photodetector and propose a physical mechanism to interpret the obtained experiment results. These results might facilitate a better understanding on the performance modulation of the MoS2photodetectors and accelerate the development of MoS2-based optoelectronic devices.

Prediction of the Endocrine disruption profile of fluorinated biphenyls and analogues: An in silico study.

Fluorinated biphenyls and their analogues (FBAs) are considered new persistent organic pollutants, but their endocrine-disrupting effects are still unknown. To fill this gap, the binding probability of 44 FBAs to different nuclear hormone receptors (NHRs) was predicted using Endocrine Disruptome. And molecular similarity and network toxicology analysis were used to strengthen the docking screening. The docking results showed that FBAs could have high binding potential for various NHRs, such as estrogen receptors ß antagonism (ERß an), liver X receptors α (LXRα), estrogen receptors α (ERα), and liver X receptors ß (LXRß). The similarity analysis found that the degree of overlap of the NHR repertoire was related to the Tanimoto coefficient of FBAs. Network toxicology verified a part of docking screening results and identified endocrine-disrupting pathways worthy of attention. This study found out potential endocrine-disrupting FBAs and their vulnerable, and developed a workflow that would leverage in silico approaches including molecular docking, similarity, and network toxicology for risk prioritization of potential endocrine-disrupting compounds.

Exosomes derived from human umbilical cord mesenchymal stem cells regulate lymphangiogenesis via the miR-302d-3p/VEGFR3/AKT axis to ameliorate inflammatory bowel disease.

BACKGROUND: Exosomes released from human umbilical cord mesenchymal stem cell (hucMSC-Ex) have been revealed to hold great potential for the development of new treatment approaches for various diseases, including inflammatory bowel disease (IBD). Lymphatic vessels are vital for IBD development and progression to colorectal cancer (CRC), as an occluded conduit for lymphatic fluid to return to the blood. OBJECTIVE: The mechanism involved remains largely unexplored. Here, we investigate the therapeutic effect of hucMSC-Ex in a mouse model of IBD during the modulation of lymphangiogenesis. METHODS: We established a dextran sulfate sodium (DSS)-induced IBD model in BALB/c mice and observed the influence of hucMSC-Ex on tissue repair, intestinal lymphatic function, changes in lymphangiogenesis, and infiltration of macrophages. We also evaluated the functional changes of human lymphatic endothelial cells (hLECs) in vitro to determine the mechanism by which hucMSC-Ex regulate lymphangiogenesis. Finally, we identified key molecules in hucMSC-Ex by sequencing, database comparison, and cell validation. RESULTS: Results showed that hucMSC-Ex alleviates IBD in mice by improving intestinal lymphatic drainage, inhibiting lymphangiogenesis, and infiltration of macrophages. Mechanistically, the miRNA sequencing results showed that miR-302d-3p was highly expressed in hucMSC-Ex and played an important role in inhibiting lymphangiogenesis by targeting Fms-related receptor tyrosine kinase 4 (FLT4). At the same time, the phosphorylation of AKT was inhibited and vascular endothelial growth factor receptor 3 (VEGFR3) was reduced. CONCLUSION: Collectively, our study suggests that hucMSC-Ex can regulate lymphangiogenesis via the miR-302d-3p/VEGFR3/AKT axis to ameliorate IBD. Our findings identify VEGFR3 as a potential therapeutic target in IBD, where tightly regulated lymphangiogenesis is crucial in its pathogenesis and progression.

Rod-like hybrid nanomaterial with tumor targeting and pH-responsive for cancer chemo/photothermal synergistic therapy.

The development of chemo/photothermal nanotherapeutic systems with excellent photothermal performance, stable drug loading, tumor targeting and strong membrane penetration still remains a challenge. To address this problem, herein a rod-like nanocomposite system (AuNR@FA-PR/PEG) forming from folic acid (FA) terminated carboxylated cyclodextrin (CD) pseudopolyrotaxane (FA-PR) and polyethylene glycol (PEG) modifying gold nanorods (AuNR) was reported. Cisplatin (CDDP) was loaded in AuNR@FA-PR/PEG via coordination bonds to prepare a rod-like pH-responsive nanosystem (AuNR@FA-PR/PEG/CDDP) with chemotherapy/photothermal therapy. The rod-like morphology of AuNR@FA-PR/PEG was characterized by transmission electron microscope. In vitro drug release experiments showed the pH-responsive of AuNR@FA-PR/PEG/CDDP. In vivo real-time imaging assays proved AuNR@FA-PR/PEG/CDDP could rapidly enrich in the tumor area and stay for a long time because of folate targeting and their rod-like morphology. In vivo photothermal imaging assays showed AuNR@FA-PR/PEG/CDDP excellent photothermal performance, the average temperature of tumor region could reach 63.5 °C after 10 min irradiation. In vitro and in vivo experiments also demonstrated that the combined therapy of chemotherapy and photothermal therapy had an outstandingly synergistic effect and improved the therapeutic efficacy comparing with chemotherapy and photothermal therapy alone. Therefore, the prepared rod-like AuNR@FA-PR/PEG/CDDP will provide a new strategy for the effective treatment of cancer.

Emerging role of protein modification in inflammatory bowel disease.

The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-|κB (NF-|κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1ß (IL-||1ß), tumor necrosis factor-α (TNF|-|α), and interferon-|γ (IFN-|γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.

Prediction of the endocrine-disrupting ability of 49 per- and polyfluoroalkyl substances: In silico and epidemiological evidence.

The toxic effects of per- and polyfluoroalkyl substances (PFASs) on humans are mediated by nuclear hormone receptors (NHRs). However, data on the interaction of PFASs and NHRs is limited. Endocrine Disruptome, an inverse docking tool, was used in this study to simulate the docking of 49 common PFASs with 14 different types of human NHRs. According to the findings, 25 PFASs have a high or moderately high probability of binding to more than five NHRs, with androgen receptor (AR) and mineralocorticoid receptor (MR) being the most likely target NHRs. Molecular docking analyses revealed that the binding modes of PFASs with the two NHRs were similar to those of their corresponding co-crystallized ligands. PFASs, in particular, may disrupt the endocrine system by binding to MR. This finding is consistent with epidemiological research that has linked PFASs to MR-related diseases. Our findings may contribute to a better understanding of the health risks posed by PFASs.

The Effects of Mesenchymal Stem Cell on Colorectal Cancer.

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract with nonobvious early symptoms and late symptoms of anemia, weight loss, and other systemic symptoms. Its morbidity and fatality rate are next only to gastric cancer, esophageal cancer, and primary liver cancer among digestive malignancies. In addition to the conventional surgical intervention, other therapies such as radiotherapy and chemotherapy and new treatment methods such as biologics and microbiological products have been introduced. As a promising cell therapy, mesenchymal stem cell (MSC) has attracted extensive research attention. MSCs are early undifferentiated pluripotent stem cells, which have the common features of stem cells, including self-replication, self-division, self-renewal, and multidirectional differentiation. MSCs come from a wide range of sources and can be extracted from a variety of tissues such as the bone marrow, umbilical cord, and fat. Current studies have shown that MSCs have a variety of biological functions such as immune regulation, tissue damage repair, and therapeutic effects on tumors such as CRC. This review outlines the overview of MSCs and CRC and summarizes the role of MSC application in CRC.

hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis.

BACKGROUND: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. METHODS: In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. RESULTS: hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1ß, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. CONCLUSION: hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

Regulatory Effect of Mesenchymal Stem Cells on T Cell Phenotypes in Autoimmune Diseases.

Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulatory abilities, making them potential treatment options for many diseases. Therefore, the therapeutic potential of MSCs in various diseases including autoimmune conditions has been explored. In addition to an imbalance of T cell subsets in most patients with autoimmune diseases, they also exhibit complex disease manifestations, overlapping symptoms among diseases, and difficult treatment. MSCs can regulate T cell subsets to restore their immune homeostasis toward disease resolution in autoimmune conditions. This review summarizes the role of MSCs in relieving autoimmune diseases via the regulation of T cell phenotypes.

Specific modification and self-transport of porphyrins and their multi-mechanism cooperative antitumor studies.

In order to reduce the toxicity and side effects of anti-tumor drugs and improve their therapeutic effect against cancer, photodynamic and chemical combination therapy has been exploited. However, the complicated preparation and metabolic toxicity of photosensitizer-loaded materials remain major obstacles for bioapplications. In this study, we designed and prepared a specific photosensitizer self-transporting drug-delivery system. First, 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphine (TAPP) was modified using specific molecules of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) with a certain antitumor effect, to prepare a specific fluorescent amphiphilic system (TAPP-TPGS). Then, the drug-loaded fluorescence nanomicelle (TAPP-TPGS/PTX) was formed via self-assembly using the amphiphilic system and the anticancer drug paclitaxel (PTX). The carrier material could be used as a drug tracer and cancer therapy reagent to synergistically trace the chemotherapy drug and treat cancers. The biocompatibility and the enhanced antitumor effect of TAPP-TPGS/PTX were confirmed by in vitro and in vivo experiments. To detect the synergistic anticancer effect enhanced by TPGS, TAPP-mPEG synthesized with a similar method as TAPP-TPGS was used for a comparative analysis. The results showed that the excellent synergistic anticancer effect of the TAPP-TPGS/PTX was enhanced due to the introduction of TPGS. Thus, the specific porphyrin self-transporting nanomicelle is a very promising carrier material for applications in biomedicine.

HucMSC-exosomes carrying miR-326 inhibit neddylation to relieve inflammatory bowel disease in mice.

BACKGROUND: Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammation that is a risk factor for many gastrointestinal cancers. Exosomes are gradually gaining attention as an emerging treatment method for IBD due to their important biological characteristics. NF-κB is an important pro-inflammatory transcription factor kept inactive by IκB protein in the cytoplasm by masking the nuclear localization signal of NF-κB. The deterioration of IκB is mainly ubiquitination, and this depends on neddylation. METHODS: In this study, we established a dextran sulfate sodium (DSS)-induced IBD model in BABL/C mice to evaluate the effect of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exosomes, hucMSC-Ex) on the repair of IBD. At the same time, human colorectal mucosa cells (FHC) were stimulated by LPS (lipopolysaccharide) in vitro to activate the inflammatory environment to study the mechanism of hucMSC-Ex regulating neddylation. The microRNA (miRNA) obtained by sequencing and transfection with hucMSC-Ex was used to verify the role of miR-326/neddylation/IκB/NF-κB signaling pathway in IBD repair. RESULTS: HucMSC-Ex inhibited the process of neddylation in relieving DSS-induced IBD in mice. The binding of NEDD8 (neural precursor cell-expressed, developmentally downregulated gene 8) to cullin 1 and the activation of NF-κB signaling pathway were suppressed along with reduced expression levels of neddylation-related enzyme molecules. The same phenomenon was observed in FHC cells. The miRNA comparison results showed that miR-326 was highly expressed in hucMSC-Ex and played an important role in inhibiting the neddylation process. The therapeutic effect of hucMSC-Ex with high expression of miR-326 on IBD mice was significantly stronger than that of ordinary hucMSC-Ex. CONCLUSIONS: HucMSC-Ex relieves DSS-induced IBD in a mouse model by inhibiting neddylation through miR-326.

Porphyrin-terminated nanoscale fluorescent polyrotaxane as a biodegradable drug carrier for anticancer research.

Drug delivery carriers hold tremendous promise for improving cancer treatment, and polyrotaxane (PR) has shown excellent drug-carrying properties. However, there have been some reports that, when used as a drug carrier, water-soluble PR is not easily labeled with organic fluorescent dyes. Herein, we synthesized a drug-loaded fluorescent porphyrin-terminated PR (PR-COOH) which can be used as a tracer material in drug and gene delivery. The structure, morphology and zeta potential of PR-COOH were characterized by nuclear magnetic resonance, high-resolution transmission electron microscopy and zeta potentiometry. In this research, cisplatin (CDDP) is used as a model drug. The zeta potential, drug encapsulation efficiency and drug release of CDDP-loaded PR (PR-COOH-Pt) were studied. Confocal laser scanning microscopy showed that PR-COOH could be internalized by HeLa and CT26 cells. The antitumor efficacy of PR-COOH-Pt was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model. The results showed that PR-COOH-Pt could significantly inhibit tumor growth; thus PR-COOH-Pt has a promising role in cancer therapy.

Human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease by inhibiting ERK phosphorylation in neutrophils.

Inflammatory bowel disease (IBD) can be caused by a variety of factors, including hereditary and environmental influences, that lead to dysfunction of the intestinal immune system. Mesenchymal stem cells (MSCs) exhibit important regulatory roles in relieving inflammation and repairing damaged tissues. Although neutrophils are important participants in the development of inflammatory reactions, they are also essential for maintaining intestinal balance during the process of mitigation of IBD by MSCs. Here, we constructed a dextran sulfate sodium (DSS)-induced mouse IBD model and evaluated the effects of treatment with human umbilical cord MSCs. Mouse body weight, faecal traits, colon/spleen gross morphology, tissue histology and immunohistochemical staining, and inflammatory factors were analysed. Magnetic beads were used to sort infiltrating neutrophils from intestinal tissues, and their phenotypes were identified. The neutrophil inflammatory environment was also simulated in vitro, and signalling pathways involved in MSC regulation of neutrophil phenotype were analysed. Human umbilical cord MSCs effectively alleviated DSS-induced weight loss, colon shortening, and intestinal mucosal injury, and reduced clinical disease activity index. The number of neutrophils that infiltrated the intestines of mice treated with human umbilical cord MSCs were decreased and polarised toward the N2 phenotype; at the same time, ERK phosphorylation was inhibited. In vitro experiments showed that addition of the ERK phosphorylation inhibitor, PD98059, down-regulated the expression of N1 neutrophils, while up-regulating that of N2 neutrophils. The colon tissues from patients with IBD were infiltrated with neutrophils. Further, relative to healthy controls, the markers of N1 neutrophils (ICAM-1, FAS, and CCL3) were highly expressed in colon tissues from patients with IBD, whereas the markers of N2 neutrophils (VEGF, CCL2, and CXCR4) were almost undetectable. In conclusion, during alleviation of IBD, human umbilical cord MSCs polarise neutrophils toward the "N2" phenotype by inhibiting activation of ERK signalling.

Preparation, Surface Modification, and Characteristic of α-Fe2O3 Nanoparticles.

The α-Fe2O3 nanoparticles were prepared via the co-precipitation process, and they were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and selected area electron diffraction (SAED). The effect of the water bath temperature on the average grain size of the α-Fe2O3 nanoparticles was investigated. The minimum grain size of the α-Fe2O3 nanoparticles was 19.6 nm when the water bath temperature was 40 °C. Furthermore, the α-Fe2O3 nanoparticles were successfully modified with silica (SiO2) and chitosan (CTS) using the idea of nanoarchitectonics. the experimental results showed that, the average diameter of the as-prepared α-Fe2O3/SiO2 nanocomposites was around 65 nm; while, the average hydrodynamic diameter of the α-Fe2O3/CTS nanocomposites increased gradually with the increase of chitosan in solution. When the mass ratio of chitosan and the α-Fe2O3 nanoparticles reached 40:1, the diameter distribution range of the α-Fe2O3/CTS nanocomposites was very wide of 100- 900 nm, so the mass ratio of chitosan and the α-Fe2O3 nanoparticles was selected from 10:1 to 20:1 to be applied.

Specific Modification with TPGS and Drug Loading of Cyclodextrin Polyrotaxanes and the Enhanced Antitumor Activity Study in Vitro and in Vivo.

A kind of specific cyclodextrin polyrotaxanes (PRs) drug delivery system was developed for an effective drug delivery and enhancing antitumor effect. In this work, we prepared the PR by using α-CD derivatives and dicarboxyl-PEG (Mn = 4200) self-assembling and end-capping with ß-CD derivatives. Then, we chose d-a-Tocopheryl polyethylene glycol 1000 succinate (TPGS) with an antitumor effect to modify the PR. The modified PRs have a certain anticancer effect and can assist the anticancer drug to treat cancer. The 10-hydroxycamptothecin (HCPT) was combined to the specific PRs by covalent bonds to prepare drug-loaded specificity PRs (PR-TPGS-HCPT). The enhanced antitumor activities of PR-TPGS-HCPT were studied by in vitro and in vivo experiments, and the experiment results proved that the TPGS could effectively assist the drug to treat cancer and prolong the lifetime of the tumor-bearing mice. Therefore, this research provides a promising drug-loaded material for the cancer treatment and the specific water-soluble PRs will have potential applications in the biomedical field.

MSC: immunoregulatory effects, roles on neutrophils and evolving clinical potentials.

Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic stem cells capable of differentiating into varieties of mature cell types such as osteoblasts, chondrocytes, adipocytes, and myoblasts. MSCs can be isolated from different kinds of tissues and cultivated in vitro for amplification and passage easily. These cells have drawn researcher's attention lately due to their ability of tissue repair, properties of hematopoiesis support and function of immunoregulation through the secretion of a variety of cytokines and growth factors that have both paracrine and autocrine activities. MSCs can regulate the proliferation of T cells, the antibodies secretion of B cells, maturation of DC, polarization of macrophages and also have many effects on neutrophils such as the suppression of NO secretion, inhibition of apoptosis, reduction of their infiltration, decreasing of N-Formy l-L-Methionine-L-leucy l-L-phenylalanine, induction of respiratory bursts and promotion of survivals. In some conditions, MSCs exert their function of treatment through immunoregulation. We reviewed the multifaceted roles of MSCs in communicating with immune cells mainly neutrophils in both in vivo and in vitro experiments. MSCs may provide promising trends for cell therapy in future.

Prognostic value of miRNA-181a/b in colorectal cancer: a meta-analysis.

AIMS: miR-181a and miR-181b have been investigated as prognostic biomarkers of colorectal cancer (CRC). However, there is controversy about the role of miR-181a and miR-181b in predicting CRC prognosis. Therefore, we performed this meta-analysis to evaluate prognostic values of miR-181a and miR-181b in CRC patients. MATERIALS & METHODS: Studies were systemically searched from publications and analyzed, and 999 CRC cases in nine studies were examined in this meta-analysis. RESULTS: Hazard ratio for overall survival of high miR-181a and miR-181b expression in CRC was 1.65. More prominent predictive effects were observed in black people, miR-181b group and small-sample-size group. CONCLUSION: High levels of miR-181a and miR-181b predict poor overall survival in CRC patients. miR-181a and miR-181b are promising biomarkers for CRC prognosis.