The Potential Role of Virus Infection in the Progression of Thyroid Cancer.

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

Drug delivery system based on metal-organic framework improved 5-Fluorouracil against spring viremia of carp virus.

Spring viremia of carp virus (SVCV), as a high pathogenicity pathogen, has seriously restricts the healthy and sustainable development of cyprinid farming industry. In this study, we selected 5-Fluorouracil (5-Fu) as the drug model based on zeolitic imidazolate framework-8 (ZIF-8) to construct a drug delivery system (5-Fu@ZIF-8), and the anti-SVCV activity was detected in vitro and in vivo. The results showed 5-Fu@ZIF-8 was uniform cubic particle with truncated angle and smooth surface, and the particle size was 90 nm. The anti-SVCV activity in vitro results showed that the highest inhibition rate of 5-Fu was 77.93% at 40 mg/L and the inhibitory concentration at half-maximal activity (IC50) was 20.86 mg/L. For 5-Fu@ZIF-8, the highest inhibition rate was 91.36% at 16 mg/L, and the IC50 value was 5.85 mg/L. In addition, the cell viability was increased by 18.1% after 5-Fu treatment. Similarly, after 5-Fu@ZIF-8 treatment, the cell viability increased by 27.3%. Correspondingly, in vivo experimental results showed the viral loads reduced by 18.1% on the days 7 and the survival rate increased to 19.4% at 80 mg/L after 5-Fu treatment. For 5-Fu@ZIF-8, the viral loads reduced by 41.2% and the survival rate increased to 54.8%. Mechanistically, 5-Fu inhibits viral replication by regulating p53 expression and promoting early apoptosis in infected cells. All results indicated that 5-Fu@ZIF-8 improved the anti-SVCV activity; it may be a potential strategy to construct a drug-loaded system with ZIF-8 as a carrier for the prevention and treatment of aquatic diseases.

Resveratrol-induced SIRT1 activation inhibits glycolysis-fueled angiogenesis under rheumatoid arthritis conditions independent of HIF-1α.

OBJECTIVE: This study investigated the impacts of SIRT1 activation on rheumatoid arthritis (RA)-related angiogenesis. METHODS: HUVECs were cultured by different human serum. Intracellular metabolites were quantified by UPLC-MS. Next, HUVECs and rat vascular epithelial cells under different inflammatory conditions were treated by a SIRT1 agonist resveratrol (RSV). Cytokines and biochemical indicators were detected by corresponding kits. Protein and mRNA expression levels were assessed by immunoblotting and PCR methods, respectively. Angiogenesis capabilities were evaluated by migration, wound-healing and tube-formation experiments. To down-regulate certain signals, gene-specific siRNA were applied. RESULTS: Metabolomics study revealed the accelerated glycolysis in RA serum-treated HUVECs. It led to ATP accumulation, but did not affect GTP levels. RSV inhibited pro-angiogenesis cytokines production and glycolysis in both the cells, and impaired the angiogenesis potentials. These effects were mimicked by an energy metabolism interrupter bikini in lipopolysaccharide (LPS)-primed HUVECs, largely independent of HIF-1α. Both RSV and bikinin can inhibit the activation of the GTP-dependent pathway Rho/ROCK and reduce VEGF production. Abrogation of RhoA signaling reinforced HIF-1α silencing-brought changes in LPS-stimulated HUVECs, and overshadowed the anti-angiogenesis potentials of RSV. CONCLUSION: Glycolysis provides additional energy to sustain Rho/ROCK activation in RA subjects, which promotes VEGF-driven angiogenesis and can be inhibited by SIRT1 activation.

Illness uncertainty, self-perceived burden and quality of life in patients with chronic myeloid leukaemia: A cross-sectional study.

AIMS AND OBJECTIVES: To investigate the relationship between illness uncertainty, self-perceived burden and quality of life and explore the mediating role of self-perceived burden between illness uncertainty and quality of life in patients with chronic myeloid leukaemia. BACKGROUND: Patients with chronic myeloid leukaemia need long-term, potentially lifelong therapy to control the disease, which affects their quality of life. There is a need for exploring potentially changeable factors to develop interventions. Little is known about the effects of illness uncertainty and self-perceived burden on quality of life in this population. DESIGN: A cross-sectional study. METHODS: A convenience sample of 248 patients with chronic myeloid leukaemia was recruited from four university hospitals from February to August 2020. Participants were assessed with the Mishel Uncertainty in Illness Scale, Self-Perceived Burden Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The STROBE checklist was used to report the results. RESULTS: Illness uncertainty and self-perceived burden were negatively associated with quality of life in patients with chronic myeloid leukaemia. Self-perceived burden partially mediated the relationship between illness uncertainty and quality of life. The indirect effect was -0.101, accounting for 22.9% of the total effect. CONCLUSION: The findings revealed the relationship between illness uncertainty, self-perceived burden and quality of life in patients with chronic myeloid leukaemia. Self-perceived burden exerted a mediating role between illness uncertainty and quality of life in this population. RELEVANCE TO CLINICAL PRACTICE: This study alerts healthcare providers to pay attention to patients' illness uncertainty and self-perceived burden, which can contribute to develop effective interventions to improve the quality of life among patients with chronic myeloid leukaemia in the clinical practice.

Qing-Luo-Yin Alleviated Monocytes/Macrophages-Mediated Inflammation in Rats with Adjuvant-Induced Arthritis by Disrupting Their Interaction with (Pre)-Adipocytes Through PPAR-γ Signaling.

BACKGROUND: The Chinese herbal formula Qing-Luo-Yin (QLY) has been successfully used in rheumatoid arthritis treatment for decades. It exhibits notable immune and metabolism regulatory properties. Thereby, we investigated its effects on the interplay between (pre)-adipocytes and monocytes/macrophages under adjuvant-induced arthritis (AIA) circumstances. METHODS: Fat reservoir and histological characteristics of white fat tissues (WAT) in AIA rats receiving QLY treatment were examined upon sacrifice. Metabolic parameters, clinical indicators, and oxidative stress levels were determined using corresponding kits, while mRNA/protein expression was investigated by PCR and immunoblotting methods. M1 macrophage distribution in WAT was assessed by flow cytometry. The effects of QLY on (pre)-adipocytes were further validated by experiments in vitro. RESULTS: Compared with normal healthy controls, body weight and circulating triglyceride were declined in AIA rats, but serological levels of free fatty acids and low-density lipoprotein cholesterol were increased. mRNA IL-1ß and iNOS expression in white blood cells and rheumatoid factor, C-reactive protein, anti-cyclic citrullinated peptide antibody, MCP-1 and IL-1ß production in serum/WAT were up-regulated. Obvious CD86+CD11b+ macrophages were enriched in WAT. Meanwhile, expression of PPAR-γ and SIRT1 and secretion of adiponectin and leptin in these AIA rats were impaired. QLY restored all these pathological changes. Of note, it significantly stimulated PPAR-γ expression in the treated AIA rats. Accordingly, QLY-containing serum promoted SCD-1, PPAR-γ, and SIRT1 expression in pre-adipocytes cultured in vitro. AIA rats-derived peripheral blood mononuclear cells suppressed PPAR-γ and SCD-1 expression in co-cultured pre-adipocytes, but serum from AIA rats receiving QLY treatment did not exhibit this potential. The changes on PPAR-γ expression eventually resulted in varied adipocyte differentiation statuses. PPAR-γ selective inhibitor T0070907 abrogated QLY-induced MCP-1 production decline in LPS-primed pre-adipocytes and reduced adiponectin secretion. CONCLUSION: QLY was potent in promoting PPAR-γ expression and consequently disrupted inflammatory feedback in WAT by altering monocytes/macrophages polarization and adipocytes differentiation.

Nicotinamide mononucleotide-elicited NAMPT signaling activation aggravated adjuvant-induced arthritis in rats by affecting peripheral immune cells differentiation.

Supplement of nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD+) has gained prominence due to the significant anti-aging potentials of nicotinamide phosphoribosyltransferas (NAMPT)/NAD+ signaling. Because over-expression of NAMPT is deeply implicated in inflammatory arthritis, we investigated the effects of NMN supplement on rats with adjuvant-induced arthritis (AIA). Tested rats were given oral treatment of NMN at 200 mg/kg/day for 25 days. Arthritis score and body weight were periodically recorded. Clinical outcomes were evaluated based on arthritic manifestations, ELISA analysis and histological examination. T cells subsets were analyzed by flow cytometry. Expressions of protein and mRNA were assessed by immunoblotting and PCR methods, respectively. Levels of CD172a, CD43, and NAMPT in peripheral blood mononuclear cells (PBMCs) were investigated by immunofluorescence approach. Obtained results were further validated by experiments in vitro. Generally, NMN exacerbated AIA severity in rats. It deteriorated MMP3-controlled tissues damages, and altered immune profile by increasing Th17/Treg cells ratio. The up-regulation of NAMPT in PBMCs from NMN-treated rats was confirmed by both immunofluorescence and PCR experiments, which was synchronized with significant increase in iNOS, MCP-1, IL-1ß expression. NMN-primed AIA PBMCs were potent in up-regulating MCP-1, IL-1ß, MMP3 and p-JNK expression in synovioblast. NMN stimulus barely affected Th17 cells count in in vitro cultured splenocytes, but it greatly potentiated the capability of AIA monocytes in inducing IL-17α secretion and Th17 cells differentiation in the co-cultured splenocytes. It suggested that long-term NMN supplement could exacerbate inflammatory arthritis by reshaping the immune milieu through the up-regulation of NAMPT.

Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling.

BACKGROUND: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown. MATERIALS AND METHODS: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses. RESULTS: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1ß and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect. CONCLUSION: This study revealed the joint protective  advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.

α-Mangostin Alleviated HIF-1α-Mediated Angiogenesis in Rats With Adjuvant-Induced Arthritis by Suppressing Aerobic Glycolysis.

A previously validated anti-rheumatic compound α-mangostin (MAN) shows significant metabolism regulatory effects. The current study aimed to clarify whether this property contributed to its inhibition on synovial angiogenesis. Male wistar rats with adjuvant-induced arthritis (AIA) were orally treated by MAN for 32 days. Afterwards, biochemical parameters and cytokines in plasma were determined by corresponding kits, and glycometabolism-related metabolites were further accurately quantified by LC-MS method. Anti-angiogenic effects of MAN were preliminarily assessed by joints based-immunohistochemical examination and matrigel plug assay. Obtained results were then validated by experiments in vitro. AIA-caused increase in circulating transforming growth factor beta, interleukin 6, hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in blood and local HIF-1α/VEGF expression in joints was abrogated by MAN treatment, and pannus formation within matrigel plugs implanted in AIA rats was inhibited too. Scratch and transwell assays revealed the inhibitory effects of MAN on human umbilical vein endothelial cells (HUVECs) migration. Furthermore, MAN inhibited tubule formation capability of HUVECs and growth potential of rat arterial ring-derived endothelial cells in vitro. Meanwhile, MAN eased oxidative stress, and altered glucose metabolism in vivo. Glycolysis-related metabolites including glucose 6-phosphate, fructose 6-phosphate, 3-phosphoglyceric acid and phosphoenolpyruvic acid in AIA rats were decreased by MAN, while the impaired pyruvate-synthesizing capability of lactate dehydrogenase (LDH) was recovered. Consistently, MAN restored lipopolysaccharide-elicited changes on levels of glucose and LDH in HUVECs culture system, and exerted similar effects with LDH inhibitor stiripentol on glycometabolism and VEGF production as well as tubule formation capability of HUVECs. These evidences show that MAN treatment inhibited aerobic glycolysis in AIA rats, which consequently eased inflammation-related hypoxia, and hampered pathological neovascularization.

The occurrence and spatial-temporal distribution of tetrabromobisphenol A in the coastal intertidal zone of Qingdao in China, with a focus on toxicity assessment by biological monitoring.

Tetrabromobisphenol A (TBBPA) is a widely used flame retardant that has increasingly been found as contaminant in aquatic environments. The main goal of this study was to evaluate the pollution level of TBBPA at six locations around Qingdao and assess its biotoxicity through a two-generation toxicity study looking at a copepod species. In the chemical monitoring, the concentration of TBBPA in seawater samples ranged from nd to 1.8 µg/L. Next, the biological indicator monitoring used 1.8 µg/L as the middle exposure concentration to perform quantitative evaluations of the influence of TBBPA on the demographic traits of Pseudodiaptomus inopinus. The results showed that copepods became more sensitive to TBBPA exposure even in environmental concentration (1.8 µg/L) as the generations developed. The detrimental effects of TBBPA further increased naupliar mortality and impaired copepodite development to adulthood. This study demonstrated that the water pollution condition of TBBPA was measured at all 6 sampling locations of Qingdao. Therefore, the present results call for a decreased discharge of TBBPA into the marine environment to avoid impairing copepod reproduction and development.

[Occurrence of PFOA and PFOS in the aquatic environments and their ecological toxicities in the aquatic environments].

Based on current researches, described the sources, toxicities, analytical methods and occurrence of PFOA and PFOS in wastewater treatment plants, lakes, rivers, coastal areas and tap waters in different countries in the world. According to the limited concentrations of PFOA + PFOS in effluents of wastewater treatment plants (WTPs) put forward by Germany, the concentrations of PFOA + PFOS in WTP effluents in Singapore, Germany, Korea and England were assessed. The results showed that the concentrations of PFOA + PFOS in WTP effluents in Singapore were higher than the liminted concentration of 300 microg/L. Researches done by China, Japan, USA, and other countries showed that the concentrations of POFA and PFOS in rivers and coastal areas reached to ng/L, and the concentrations in Tennessee River, USA were the highest, reached to 100 ng/L. The risk assessments of PFOA and PFOS in tap water in some cities in China were assessed according to the risk quotients(RQ). The assessment results showed that tap waters from 19 cities in China were all below the risk level.

[Study on ecoregion techniques of lake nutrients in Yunnan-Guizhou plateau Lake regions].

The primary objective of this research is to present an ecoregion model based on the principle components analysis (PCA), the cluster analysis (CA), the discriminant analysis (DA) and the spatial autocorrelation analysis (SAA), which were applied to establish the ecorigion of lake nutrients in Yunnan-Guizhou Plateau Lakes. First, the principle components analysis method was used not only to reduce the dimensionality of the feature space, but also to deal with new indexes. The accumulation contribution ratio of the four new indexes achieved 93.69%, which had the full representation. These complementary indexes which reflect the conditions of lakes were helpful to establish the index system of ecorigion of lake nutrients in Yunnan-Guizhou Plateau Lakes. Second, initial classification of lake drainage area was accomplished by new indicator values and cluster analysis which contained five classes, and then the categories of non-lake drainage area could be identified by the discriminant analysis. Finally, the cluster result was carried on the global statistics, Moran's I was 0.32 which was higher than 0, and the examination value Z was 68.28 which was higher than marginal value (remarkable level 1% correspond 2.58), it was indicated that the cluster result and the space position had the remarkable relativity, afterward spatial distribution pattern of the region was achieved by the quantificational analysis about over score of principle components and application of local spatial autocorrelation method. Then the ecorigion of lake nutrients was accomplished by the association and difference between different districts of the scattered regions' s spatial character. These results indicated that the ecoregion model initiated in the paper was appropriate and feasible to receive objective results and avoid artificial factors. Also it has provided a new method to explore the index system and techniques about the ecoregion of lake nutrients. Scientifically, the model was in favor of the foundation of lake nutrient criteria and eutrophication control standards in China.

Effect of chilling on porcine germinal vesicle stage oocytes at the subcellular level.

The potential subcellular consequence of chilling on porcine germinal vesicle (GV) stage oocytes was examined. Prior to in vitro maturation (IVM), Cumulus-oocyte complexes (COCs) freshly collected from antral follicles (3-6mm in diameter) were evenly divided into four groups and immediately incubated in PVA-TL-HEPES medium at the temperature of 39 degrees C (control group), 23 degrees C (room temperature), 15 degrees C and 10 degrees C for 10min, respectively. Following 42h of IVM at 39 degrees C, the survival rates were examined. There was no significant difference between the survival rate of 23 degrees C chilled group and control group (77.92 and 91.89%), but the survival rate of 15 and 10 degrees C chilled group were significantly decreased (46.34 and 4.81%, P<0.01). A further experiment on 15 degrees C group showed that most oocytes died from 2 to 4h of IVM. In order to investigate the effects of chilling on oocytes at the subcellular level, the control and 15 degrees C chilled group COCs fixed at different time points of the IVM cultures (2, 2.5, 3, 3.5 and 4h of IVM) were prepared for transmission electron microscope (TEM) observation. As the result, compared with the control group, there were two significant changes in the ultrastructural morphology of 15 degrees C treatment group: (1) dramatic reduction of heterogeneous lipid, (2) disorganized mitochondria-endoplasmic reticulum-lipid vesicles (M-E-L) combination. These results indicate that 15 degrees C is a critical chilling temperature for porcine GV stage oocyte and the alteration of cellular chemical composition and the destruction of M-E-L combination maybe responsible for chilling injury of porcine oocyte at this stage.