Sodium Alginate Hydrogel-Mediated Cancer Immunotherapy for Postoperative In Situ Recurrence and Metastasis.

With the development of technology, adjuvant immunotherapy has become a promising strategy for prevention of postoperative tumor regression and metastasis by stimulating the host immune response. However, the therapeutic effects are still unsatisfactory due to the lack of synergy between different methods. In this study, an efficient synergistic immunotherapy system based on injectable sodium alginate hydrogels was designed to inhibit in situ recurrence and metastasis at the same time. On the one hand, an injectable sodium alginate (SA) hydrogel microsystem loaded with toll-like receptor (TLR) agonists (CpG ODNs) was synthesized for inhibiting in situ recurrence, and then carcinoembryonic antigen (CEA) probe was also added to detect CEA based on fluorescence resonance energy transfer (FRET) technology to monitor the occurrence and development of tumor recurrence. On the other hand, an anti-programmed cell death 1 ligand 1 antibody (anti-PD-L1)-modified SA nanogel loaded with indocyanine green (ICG@SA-anti-PD-L1 nanogel) was prepared for diagnosing and inhibiting lung metastasis by assisting orthotopic tumor therapy. In vitro and in vivo results demonstrated that this SA micro/nanosystem could monitor and inhibit postoperative recurrence and metastasis. We hope that this micro/nano-synergistic system will become an effective strategy for postoperative adjuvant immunotherapy.

Anticancer effect of histone deacetylase inhibitor scriptaid as a single agent for hepatocellular carcinoma.

Recurrence is one of the major causes of poor prognosis for patients with hepatocellular carcinoma (HCC), and drug resistance is closely associated with disease recurrence. Histone deacetylase (HDAC) inhibitor scriptaid functions as an anticancer agent in many different types of tumors, but its possible roles in HCC progression have not been explored to date. Herein, we show that HDAC inhibitor scriptaid decreases HCC cell proliferation and induces cell cycle G2/M-phase arrest in a dose-dependent manner. Furthermore, scriptaid triggered HCC cell death via transcriptional activation of p21 and subsequent elevated global H3Ac levels. Importantly, we found that scriptaid showed robust antitumor activity against HCC. Thus, our findings indicate that HDAC inhibitor scriptaid could be an important potential candidate for treatment of HCC patients.

Anti-Proliferative Activity of HPOB against Multiple Myeloma Cells via p21 Transcriptional Activation.

Histone acetylation or deacetylation is closely associated with the progression of multiple myeloma (MM). Currently, many histone deacetylase (HDAC) inhibitors have been approved for being used in clinical trials, but theirtherapeutic effectsarestill not ideal. As a novel HDAC inhibitor, hydroxamicacid-based small-moleculeN-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB)'s possible roles in MM have not been studied. In this present study, the effect of HPOB as a potential anti-tumor agent in preventingproliferation and inducing apoptosis of MM cells had been investigated in detail. Our results showed that HPOB decreased the survival of MM cells in dose- and time-dependent manner. In addition, HPOB caused the accumulation of MM cells in G1 phase compared with the dimethylsulfoxide (DMSO) control group. Interestingly, we found that HPOB could overcome bortezomib (BTZ) resistance inMM cells and combining HPOB with BTZ could further sensitize MM cells. Certainly, our data illuminated that HPOB-mediated cell death occurs via transcriptional activation of p21, which was associated with an elevated level of global histone 3 acetylation (H3Ac) modification. Therefore, HPOB could be a potential candidate for MM treatment and the combination of HPOB and bortezomibcould bea possible therapeutic strategy for relapsed and refractory MM.

Numerical simulation of hemodynamics in membranous obstruction of the suprahepatic inferior vena cava based on a subject-specific Budd-Chiari syndrome model.

BACKGROUND: This study was performed to determine the hemodynamic changes of Budd-Chiari syndrome when the inferior vena vein membrane is developing. METHODS: A patient-specific Budd-Chiari syndrome vascular model was reconstructed based on magnetic resonance images using Mimics software and different degrees (16%, 37%, and 54%) of idealized membrane were built based on the Budd-Chiari syndrome vascular model using Geomagic software. Three membrane obstruction Budd-Chiari syndrome vascular models were established successfully and fluent software was used to simulate hemodynamic parameters, including blood velocity and wall shear stress. FINDINGS: The simulation results showed that there is low velocity and a low wall shear stress region at the junction of the inferior vena cava and the branches of the hepatic veins, and swirl may occur in this area. As the membrane develops, the size of the low velocity and low wall shear stress regions enlarged and the wall shear stress was increased at the membrane region. There was a significant difference in the mean values of wall shear stress between the different obstruction membrane models (P<0.05). INTERPRETATION: Hemodynamic parameters play an important role in vascular disease and there may be a correlation between inferior vena cava wall shear force changes and the slow development process of the inferior vena cava membrane.

Serum Iodine Is Increased in Subjects Having Budd-Chiari Syndrome.

This study was performed to investigate the status of serum iodine concentration among the Budd-Chiari syndrome (BCS) patients and its effect on thyroid hormone. The study group serum specimens were collected from 233 BCS patients and 60 healthy people. Serum iodine was analyzed with the Sandell-Kolthoff method, and the ELISA method was used to detect thyroid function: TSH, T3, T4, FT3, and FT4. The serum iodine level of patients with BCS was 316.7 ± 256.8 µg/L, greatly higher than 76.3 ± 25.7 µg/L of serum iodine for control group (p < 0.001), but with no significant difference among different types of BCS. There were no statistically significant differences in thyroid hormone levels (TSH, T3, T4, FT3, and FT4) between people with BCS and control group, although the TSH level of BCS group is slightly higher than that of normal control group. This study demonstrates that iodine may be related to the pathogenesis of BCS and needs to be paid more attention.

A "light-up" and "spectrum-shift" response of aptamer-functionalized silver nanoclusters for intracellular mRNA imaging.

We have designed a novel multifunctional DNA scaffold for the synthesis of fluorescent silver nanoclusters (Ag NCs) using a one-pot approach. The obtained DNA/Ag NCs presented a "light-up" and "spectrum-shift" response to target DNA in vitro and could further image the tumor-related mRNA in living cells.

The study of a remote-controlled gastrointestinal drug delivery and sampling system.

A micromachined capsule based on microelectromechanical systems (MEMS) technology is introduced in this paper. It is an effective tool for diagnosing and treating gastrointestinal diseases. The microcapsule can carry out real-time drug release and the gastrointestinal fluid sampling in the gastrointestinal tract. According to the structural and metabolic characters of the gastrointestinal tract, the configuration of the microcapsule was designed as a cylinder. This nondigestible oral device can smoothly pass through the gastrointestinal tract for drug delivery and liquid sampling. The working mechanism of the capsule was the mechanic movement mode of a piston, which was regulated through a MEMS calorific element. The action of drug delivery and gastrointestinal fluid sampling in the gastrointestinal tract was performed wirelessly. The remote control device can be connected with a computer through a serial port (RS-232), and it can be used in telemedicine applications. Some experimental research has been carried out to validate the design. The experimental results indicated that the microcapsule can achieve drug delivery and liquid sample reliably.

Multi-scale methodology: a key to deciphering systems biology.

Presently, it is widely accepted complex systems couldn't be comprehended by studying parts in isolation without examining integrative and emergent properties, and system-level understanding thus has become the focus in biological science. However, it should also be noted that common systematic analysis was restricted to large-scale analysis at a certain level, while the facts that the nature of complex systems is their multi-scale structures was usually neglected or ignored. Therefore, this paper described a multi-scale methodology to investigate the nature of biological complexity and prospected this methodology could lead to a promising revolution in current system-level understanding and the integration of molecular biology databases.