Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR) solution or University of Wisconsin (UW) solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.

Forsythia suspensa Fructus (FS) is used to treat various inflammatory disorders in traditional Oriental medicine, including gastrointestinal diseases, but its therapeutic potential in ulcerative colitis is unclear. Thus, we investigated any potential therapeutic effects of FS against intestinal inflammation and the bioactive constituents in FS.

Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease, the occurrence of which has been increasing worldwide. Research in recent years has found that the level of lysozyme in the feces and blood of UC patients is abnormally elevated, and the bacterial product after the action of lysozyme can be used as an agonist to recognize different cell pattern receptors, thus regulating the process of intestinal inflammation. Berberine (BBR), as a clinical anti-diarrhea and anti-inflammatory drug, has been used in China for hundreds of years. In this study, results showed that BBR can significantly inhibit the expression and secretion of lysozyme in mice. Therefore, we try to investigate the mechanism behind it and elucidate the new anti-inflammatory mechanism of BBR. In vitro, lipopolysaccharide (LPS) was used to establish an inflammatory cell model, and transcriptomic was used to analyze the differentially expressed genes (DEGs) between the LPS group and the LPS + BBR treatment group. In vivo, dextran sulfate sodium salt (DSS) was used to establish a UC mice model, and histologic section and immunofluorescence trails were used to estimate the effect of BBR on UC mice and the expression of lysozyme in Paneth cells. Research results showed that BBR can inhibit the expression and secretion of lysozyme by promoting autophagy via the AMPK/MTOR/ULK1 pathway, and BBR promotes the maturation and expression of lysosomes. Accordingly, we conclude that inhibiting the expression and secretion of intestinal lysozyme is a new anti-inflammatory mechanism of BBR.

Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers may be treated with radio-iodine following transfection with the human sodium/iodide symporter (hNIS) gene. The glial fibrillary acidic protein (GFAP) promoter is an effective tumor-specific promoter for gene expression and thus may be useful in targeted gene therapy of malignant glioma. The present study used GFAP promoter-modulated expression of the hNIS gene in an experimental model of radioiodine-based treatment for malignant glioma. Cells were transfected using a recombination adeno-virus and evaluated in cells by studying the transfected transgene expression through western blot analysis, (125)I uptake and efflux, clonogenicity following (131)I treatment and radioiodine therapy using a U87 xenograft nude mouse model. Following transfection with the hNIS gene, the cells showed 95-70-fold higher (125)I uptake compared with the control cells transfected with Ad-cytomegalovirus (CMV)-enhanced green fluorescent protein (EGFP). The western blotting revealed bands of ∼70, 49 and 43 kDa, consistent with the hNIS, GFAP and β-actin proteins. The clonogenic assay indicated that, following exposure to 500 μCi of (131)I-iodide for 12 h, >90% of cells transfected with the hNIS gene were killed. Ad-GFAP-hNIS-transfected and 2 mCi (131)I-injected U87 xenograft nude mice survived the longest of the three groups. The hNIS-expressing tumor tissue accumulated (99m)TcO(4) rapidly within 30 min of it being intraperitoneally injected. The experiments demonstrated that effective (131)I therapy was achieved in the malignant glioma cell lines following the induction of tumor-specific iodide uptake activity by GFAP promoter-directed hNIS gene expression in vitro and in vivo. (131)I therapy retarded Ad-GFAP-hNIS transfected-tumor growth following injection with (131)I in U87 xenograft-bearing nude mice.

Aquatic products with high moisture and protein content are susceptible to bacterial growth and spoilage. Searching for efficient and safe natural antibacterial agents to preserve aquatic products has been concerned widely. In this study, ε-poly-lysine-epigallocatechin gallate/sodium alginate-chitosan nanoparticles (ε-PL-EGCG/SA-CS NPs) were prepared using sodium alginate and chitosan as wall materials and ε-PL-EGCG as core material. The size of nanoparticles was about 200 nm and the encapsulation efficiency was 78.2%. Transmission electron microscopy (TEM) images confirmed the prepared spherical nanoparticles. Fourier transform infrared spectroscopy (FTIR) and multifunctional polycrystalline X-ray diffraction (XRD) spectra indicated that ε-PL-EGCG was encapsulated in the nanoparticles. Thermo-gravimetric analysis (TGA) illustrated that the thermal stability of encapsulated ε-PL-EGCG was improved more than that of bare ε-PL-EGCG. In addition, in vitro release assays showed that the ε-PL-EGCG was released continuously over 36 h. Bacteria inhibition results showed that the ε-PL-EGCG/SA-CS NPs significantly inhibited specific spoilage bacteria E3 that screened out of aquatic products, Escherichia coli and Staphylococcus aureus. In conclusion, ε-PL-EGCG/SA-CS NPs are an effective antibacterial means with wide application prospects in the field of aquatic products preservation.

In recent years, antibacterial surface modification of titanium (Ti) implants has been widely studied in preventing implant-associated infection for dental and orthopedic applications. The purpose of this study was to prepare a composite coating on a porous titanium surface for infection prevention and inducing mineralization, which was initialized by deposition of a poly-l-lysine (PLL)/sodium alginate(SA)/PLL self-assembled coating, followed by dopamine deposition, and finally in situ reduction of silver nanoparticles (AgNPs) by dopamine. The surface zeta potential, SEM, XPS, UV-vis, and water contact angle analyses demonstrate that each coating was successfully prepared after the respective steps and that the average sizes of AgNPs were 20-30 nm. The composite coating maintained Ag+ release for more than 27 days in PBS and induced mineralization when incubated in SBF. The antibacterial results showed that the composite coating inhibited/killed bacteria on the material surface and killed bacteria around them. In addition, although this coating inhibited the initial adhesion of osteoblasts, the mineralized surface greatly enhanced the cytocompatibility. Thus, we concluded that the composite coating could prevent bacterial infections and facilitate mineralization in vivo in the early postoperative period, and then, the mineralized surface could enhance the cytocompatibility.

We aim to evaluate the association of systolic and diastolic blood pressure (SBP and DBP) with estimated urinary sodium (Na) and potassium(K) excretions, and their gram-to-gram Na/K ratio across various salt-diet regions during 2005-2009 in China. A prospective cohort study was conducted to recruit 46,285 participants in China. A single fasting morning urine specimen was collected to estimate 24-hour urinary Na and K excretion using Kawasaki formula. Means of estimated Na and K were 5.7 ± 1.7 and 2.1 ± 0.5 grams/day, respectively, and mean estimated Na/K ratio was 2.8 ± 0.8. Adjusted analyses showed 1.70 mmHg SBP and 0.49 mmHg DBP increase per 1-g increment of estimated Na, while 1.10 mmHg SBP and 0.91 mmHg DBP decrease for one-gram increase of K. A significant increase in SBP (4.33 mmHg) and DBP (1.54 mmHg) per 1 unit increase in Na/K ratio was observed. More changes of SBP (4.39 mmHg) and DBP (1.67 mmHg) per one-unit increase of Na/K ratio were observed in low-salt regions, though significant changes were also found in moderate- and heavy-salt regions (P for heterogeneity < 0.01). Conclusively, decreasing sodium combined with increasing potassium is likely to have a more beneficial effect than decreasing sodium alone, even if those were living in low-salt regions.

Lung cancer harms people's health or even lives severely. Especially, the therapy of non-small cell lung cancer (NSCLC) has not been obviously improved for many years. The aim of this study is to transfer the human sodium/iodide symporter (hNIS) and the human thyroperoxidase (hTPO) genes into H460 lung cancer cell line, and to study the uptake ability of iodide after co-transfected hTPO and hNIS gene in cell lines.

We previously reported that importin 13 (IPO13), a member of the importin-β family of nuclear import proteins, regulates nuclear import of the glucocorticoid receptor in airway epithelial cells, IPO13 serves as a potential marker for corneal epithelial progenitor cells, and IPO13 is associated with corneal cell proliferation. Here we investigated the role of IPO13 in the pathogenesis of pterygium and the underlying mechanism including interaction with other cell proliferation-related factors: keratin 17 (K17), a lesional protein and a member of the type I keratins, and c-Jun, a protein of the activator protein-1 complex.

To facilitate research methodologies for investigating the role of cholinergic nerves in many diseases, establishing an in vitro cholinergic neuron model is necessary. In this study, we investigated whether human glioblastoma U87 cells could be differentiated into cholinergic neurons in vitro. Sodium butyrate was used as the differentiation agent. The differentiated cells established by inducing U87 cells with sodium butyrate were named D-U87 cells. Immunofluorescence was used to label the neuronal markers MAP2, NF-M, and ChAT and the glial marker GFAP in D-U87 cells. Flow cytometry was used to measure cell cycle distribution in D-U87 cells. PCR, protein chip, and western blot assays were used to measure the expression levels of muscarinic cholinergic receptor 1 (M1), M4, ChAT, SYP and Akt. ELISA was used to measure neurotransmitter levels. As a result, we found that sodium butyrate induced U87 cell differentiation into cells with neuronal characteristics and increased not only the expression levels of the cholinergic neuron-related proteins M1, M4, ChAT and SYP in D-U87 cells but also the acetylcholine neurotransmitters in D-U87 cells. Moreover, the Akt protein expression in D-U87 cells was increased compared with that in U87 cells. Finally, we found that M1, M4, ChAT and SYP protein expression and acetylcholine secretion levels were significantly decreased in D-U87 cells after treatment with the Akt inhibitor MK-2206. These results demonstrate that D-U87 cells exhibit cholinergic neuron characteristics and that sodium butyrate induced U87 cell differentiation into cholinergic neuron partially through Akt signaling.

Sodium (Na+) channels are the basis for action potential generation and propagation, which play a key role in the regulation of neuronal excitability. SCN3A is a gene encoding for sodium channel protein type 3 subunit alpha (or known as Nav1.3). This study aimed to explore SCN3A genetic variants in a cohort of childhood absence epilepsy (CAE) via whole exome sequencing. A novel SCN3A missense variant (c.A1816G, p.Ser606Gly) was identified in a patient with CAE. This variant had not been reported in both 1000G and ExAC databases. Bioinformatics analysis revealed that this variant was pathogenic and could transform the protein structure of Nav1.3. The reported phenotypes of SCN3A-related central nerve system disorders included multiple seizure types, polymicrogyria and different degrees of developmental delay/intellectual disability. The patient with p.Ser606Gly variant exhibited typical absence seizures. The MRI and CT scan results were normal, and EEG showed that 3-Hz spike-slow wave discharges. In conclusion, our findings not only broaden the pathogenic spectrum of SCN3A, but also extend the clinical phenotypes of SCN3A-related CAE.

To evaluate the effect of lycopene on carbon tetrachloride (CCl4)-induced hepatic fibrosis and elucidate the underlying mechanism.

Hyperlipidemia is a group of conditions with abnormally elevated levels of any or all lipids or lipoproteins in the blood. It is highly heterogeneous both genetically and clinically, which contributes to diagnostic challenges and results in many patients to be underdiagnosed and undertreated in China. Precise diagnosis and early management are critical to reduce the incidence of potential coronary artery disease and cardiovascular disease.

Owing to strong and tunable surface plasmon resonance (SPR) effect and good biocompatibility, gold nanoparticles have been suggested to be a versatile platform for a broad range of biomedical applications. In this study, a new nanoplatform of thermo-responsive polymer encapsulated gold nanorods incorporating indocyanine green (ICG) was designed to couple the photothermal properties of gold nanorods (AuNRs) and the photodynamic properties of ICG to enhance the photodynamic/photothermal combination therapy (PDT/PTT). In addition to the significantly increased payload and enhancing photostability of ICG, the polymer shell in the nanoplatform also has thermo-responsive characteristics that can control the release of drugs at tumour sites upon the laser irradiation. On the basis of these improvements, the nanoplatform strongly increased drug aggregation at the tumour site and improved the photothermal/photodynamic therapeutic efficacy. These results suggest that this nanoplatform would be a great potential system for tumour imaging and antitumour therapy.

We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.

Enormous progress has been made in cardiac regeneration using human embryonic stem cell-derived cardiomyocyte (hESC-CM) grafts in pre-clinical trials. However, the rate of cell survival has remained very low due to anoikis after transplantation into the heart as single cells. Numerous solutions have been proposed to improve cell survival, and one of these strategies is to co-transplant biocompatible materials or hydrogels with the hESC-CMs.

The hepatitis B virus (HBV) is a major etiological factor of inflammation and damage to the liver resulting in hepatocellular carcinoma. Transcription factors play important roles in the disordered gene expression and liver injury caused by HBV. However, the molecular mechanisms behind this observation have not been defined.

Human skin is a known target site of inorganic arsenic with effects ranging from hyperkeratosis to dermal malignancies. Tert-butylhydroquinone (tBHQ), approved food-grade phenolic antioxidant, is demonstrated to induce remarkable antioxidant activity in a variety of cells and tissues. The present study aimed at the protective effects of tBHQ on arsenic-induced cytotoxicity and apoptosis in human keratinocytes. Our results demonstrated that tBHQ antagonized arsenic-induced decrease of cell viability, generation of reactive oxygen species (ROS) and lipid peroxidation, as well as reduction of antioxidative enzymes superoxide dismutase (SOD) and catalase (CAT) activities. We also found that tBHQ relieved the G2/M phase arrest by arsenic exposure, which was associated with altering the expression of cell cycle regulators cyclin D1 and CDK4. tBHQ treatment further reduced the numbers of arsenic-induced mitochondrial-mediated apoptotic cells, which occurred concomitantly with the effective recovery of mitochondrial membrane potential (ΔΨm) depolarization, the release of cytochrome c releasing from the mitochondrial as well as the survival signal related factor caspase 3 activation. Our experiments then confirmed that tBHQ activated nuclear factor E2-related factor 2 (NRF2) pathway by increasing NRF2 protein in both nucleus and cytoplasm and upregulating NRF2 downstream targets

Microglial activation and the resulting neuroinflammation are associated with a variety of brain diseases, such as Alzheimer's disease and Parkinson's disease. Thus, the control of microglial activation is an important factor in the development of drugs that can treat or prevent inflammation-related neurodegenerative disorders. Atractylodis Rhizoma Alba (ARA) has been reported to exhibit antioxidant, gastroprotective, and anti-inflammatory effects. However, the effects of ARA ethanolic extract (ARAE) on microglia-mediated neuroinflammation have not been fully elucidated. In this work, we explored the anti-neuroinflammatory properties and underlying molecular mechanisms of ARAE in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Our results showed that ARAE significantly attenuates the production of nitric oxide (NO) and inflammatory cytokines induced by LPS. ARAE treatment also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 without causing cytotoxicity. ARAE markedly attenuated the transcriptional activities of nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPK) phosphorylation, and induced heme oxygenase (HO)-1 expression. High-performance liquid chromatography (HPLC) analysis showed that ARAE contains three main components-atractylenolide I, atractylenolide III, and atractylodin-all compounds that significantly inhibit the production of inflammatory factors. These findings indicate that ARAE may be a potential therapeutic agent for the treatment of inflammation-related neurodegenerative diseases.

Recently, nano-sized ultrasound contrast agents encapsulating drugs for cancer diagnosis and therapy have attracted much attention. However, the ultrasound signal of these agents is too weak to obtain an ideal ultrasound imaging effect. Furthermore, conventional ultrasound contrast agents with strong echo signal are not suitable for drug delivery against cancer because of their large size. To circumvent this problem, phase-transition ultrasound contrast agents are believed to be an excellent choice. Methods: Liposomes co-encapsulating doxorubicin (DOX), hollow gold nanospheres (HAuNS), and perfluorocarbon (PFC) were synthesized by film dispersion method. The morphology, particle size, and stability of these liposomes (DHPL) were investigated. The photothermal effect, drug release, particle size change, cytotoxicity, and ultrasound imaging were studied by using the near infrared (NIR) light. Furthermore, tumor accumulation of DHPL was observed by in vivo fluorescence imaging and the antitumor effect was verified in a 4T1 tumor model. Results: The nanosystem displayed a homogeneous size distribution (~200 nm) and an efficient light-to-heat conversion effect under 808 nm NIR laser irradiation. The nanometer size enabled considerable accumulation of DHPL in the tumor sites. The localized hyperthermia resulting from the photothermal effect of HAuNS could trigger the size transformation of DHPL followed by significant DOX release. Due to the gasification of PFC, a remarkably enhanced ultrasound signal was detected. DHPL also exhibited a prominent photothermally reinforced chemotherapeutic effect under the control of NIR light both in vitro and in vivo. Importantly, no systemic toxicity was observed by DHPL treatment. Conclusion: In this study, we fabricated multi-functional perfluorocarbon liposomes for ultrasound imaging-guided photothermal chemotherapy which have the potential to serve as a prospective cancer treatment approach.