Amino-Acid-Encoded Supramolecular Nanostructures for Persistent Bioluminescence Imaging of Tumor.

Bioluminescence imaging (BLI) is a powerful technique for noninvasive monitoring of biological processes and cell transplantation. Nonetheless, the application of D-luciferin, which is widely employed as a bioluminescent probe, is restricted in long-term in vivo tracking due to its short half-life. This study presents a novel approach using amino acid-encoded building blocks to accumulate and preserve luciferin within tumor cells, through a supramolecular self-assembly strategy. The building block platform called Cys(SEt)-X-CBT (CXCBT, with X representing any amino acid) utilizes a covalent-noncovalent hybrid self-assembly mechanism to generate diverse luciferin-containing nanostructures in tumor cells after glutathione reduction. These nanostructures exhibit efficient tumor-targeted delivery as well as sequence-dependent well-designed morphologies and prolonged bioluminescence performance. Among the selected amino acids (X = Glu, Lys, Leu, Phe), Cys(SEt)-Lys-CBT (CKCBT) exhibits the superior long-lasting bioluminescence signal (up to 72 h) and good biocompatibility. This study demonstrates the potential of amino-acid-encoded supramolecular self-assembly as a convenient and effective method for developing BLI probes for long-term biological tracking and disease imaging.

Characterization of thyroid metastasis from clear cell renal cell carcinoma on ultrasonography: a report of three cases and literature review.

Introduction: Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy. Case presentation: The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC. Discussion/Conclusion: For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.

An enhanced chemiluminescence hybrids of luminol by sulfonated polyaniline decorated copper-based metal organic frame composite applicable to the measurement of hydrogen peroxide in a wide pH range.

Here, sulfonated polyaniline (SPAN) was decorated on the surface of copper-based metal organic frame (HKUST-1) and the composite was functionalized by luminol to construct a chemiluminescence (CL) hybrids (SPAN/HKUST-1@Luminol). The as-prepared SPAN/HKUST-1@Luminol demonstrated a great dispersion and stability performance in aqueous solution. Moreover, the resultant SPAN/HKUST-1@Luminol hybrids exhibited extremely strong CL properties, and the CL quantum yield was 136 times higher than that of luminol. In particular, it exhibited outstanding CL activity not only under alkaline conditions, but also under neutral conditions. The sensitive response of the hybrid to hydrogen peroxide was used to construct CL methods for the detection of hydrogen peroxide at a wide range of pH, with the detection limit of 60 nM at a neutral condition and 25 pM at alkaline condition. Due to strong and stable signal of the SPAN/HKUST-1@Luminol, the CL method provides a viable tool for determination of H2O2 in biological systems and enabled the monitoring of stimulated production of H2O2 released by living cells.

Hypoglycemic Effect of Nobiletin via Regulation of Islet ß-Cell Mitophagy and Gut Microbiota Homeostasis in Streptozocin-Challenged Mice.

Nobiletin is a natural nutrient (or polymethoxyflavonoid) in orange peels exerting a preventive effect against metabolic diseases. However, there are very few reports on the hypoglycemic effect of nobiletin. In the present study, the hypoglycemic effect of nobiletin was investigated using NIT-1 cells and streptozocin (STZ)-challenged mouse models. Our results indicated that nobiletin could significantly suppress the high blood glucose in STZ-challenged mice. In addition, nobiletin could effectively activate the mitophagy and inhibit the inflammatory pathways in NIT-1 cells. The mitochondria membrane potential dysbiosis induced by glucotoxicity in NIT-1 cells was restored after treatment by nobiletin. Further investigation revealed that the hypoglycemic effect of nobiletin was mainly through regulation of gut microbiota dysbiosis, activation of mitophagy flux, inhibition of inflammasome expression, and restoration of islet morphological destruction in the pancreas of STZ-challenged mice. Our study revealed that nobiletin could be used as a functional food or drug candidate for the treatment of diabetes.

Discovery of novel 2-aryl-4-bis-amide imidazoles (ABAI) as anti-inflammatory agents for the treatment of inflammatory bowel diseases (IBD).

A series of 2-Aryl-4-Bis-amide Imidazoles (ABAI-1 to 30) were designed as anti-inflammatory agents. These compounds were synthesized and evaluated for the in vitro anti-inflammatory activities (inhibition of NO production and release of inflammatory cytokines). Several compounds effectively inhibited NO production in lipopolysaccharide (LPS) induced RAW264.7 cells. Among them, ABAI-30 exhibited the highest NO-inhibitory effect (inhibition rate of 87% at 20 µM). The anti-inflammatory mechanism of ABAI-30 was examined and found to be inhibiting the TLR4-pp65 and NLRP3-caspase-1 signaling pathway, thus leading to the downregulation of IL6, IL-1ß and TNFα at both transcriptional and translational levels. Importantly, ABAI-30 demonstrated high in vivo anti-inflammatory efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model without causing obvious toxicity. Collectively, our study provides a potent anti-inflammatory agent, which deserves further investigation as a novel therapeutic candidate for treating inflammatory bowel diseases.

Discovery of novel 3-hydroxyandrosta-5,7-Diene-17-Carboxylic acid derivatives as anti-inflammatory bowel diseases (IBD) agents.

A series of steroidal compounds based on 3-hydroxyandrosta-5,7-diene-17-carboxylic acid core structure were designed, synthesized and bio-evaluated for their anti-inflammatory potency. Among them, compound 5c, 6f, and 6q effectively inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. They inhibited the expression of inducible NO synthase (iNOS) and prostaglandin synthase-2 (COX-2) at mRNA level. Compound 6q displayed inhibitory effects on both iNOS and COX-2 expression in a concentration-dependent manner. Furthermore, 6q was found to effectively decrease the mRNA and protein levels of interleukin 6 (IL-6). Mechanically, 6q could potently downregulate NF-κB signaling via suppression of the Akt/PI3K pathway. Moreover, 6q demonstrated high in vivo anti-inflammatory activities in a mouse colitis model induced by dextran sulfate sodium (DSS). Taken together, these data indicate that 6q represents a novel and promising anti-inflammatory bowel diseases (IBD) agent worthy of further investigation.

Bacteroides vulgatus diminishes colonic microbiota dysbiosis ameliorating lumbar bone loss in ovariectomized mice.

There is a need to discover additional kinds of intestinal microbiota to supplement the probiotic-treatment of postmenopausal osteoporosis. Increasing evidence has indicated that Bacteroides vulgatus has potential as a probiotic for ameliorating postmenopausal bone loss. In this study, ovariectomized female C57/BL6 mice were treated with B. vulgatus ATCC 8482 gavage to investigate the differences in colonic microbiota composition, inflammation signal pathways, inflammatory cytokines, bone turnover markers, and lumbar vertebrae microstructure compared with the control group. Our results show that B. vulgatus ATCC 8482 diminished microbiota dysbiosis and subsequently down-regulated the colonic lipopolysaccharide/TLR-4/p-NF-κB pathway leading to decreased serum TNF-α. This reduced TNF-α/RANKL expression and induced ALP and Runx-2 expression in the 5th lumbar vertebra, leading to amelioration of bone loss and microstructure destruction in the lumbar vertebra of ovariectomized mice. Taken together, these results indicate that B. vulgatus could be a probiotic for treatment of postmenopausal lumbar osteoporosis.

Flammulina velutipes polysaccharide improves C57BL/6 mice gut health through regulation of intestine microbial metabolic activity.

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.

Increased Preoperative Glucose Variability Is Associated with Adverse Perioperative Outcomes Following Orthopedic Surgery in Patients with Type 2 Diabetes Mellitus.

The association between glucose variability (GV) and adverse perioperative outcomes in type 2 diabetes mellitus (T2DM) patients undergoing orthopedic surgery was investigated. A retrospective cohort study was performed by analyzing data on T2DM patients receiving continuous blood glucose (BG) monitoring and continuous subcutaneous insulin infusion treatment due to poorly controlled preoperative BG prior to orthopedic surgery. GV was assessed with coefficient of variation (CV). Postoperative and perioperative CV, hypoglycemia cases, and other perioperative outcomes (diabetes preparation time [DPT], length of stay [LOS], and perioperative and infective complication cases) were analyzed. Results showed that a total of 168 patients were grouped into preoperative CV tertiles: 1st (n=56): 0-0.2921, 2nd (n=58): 0.2922-0.3779, and 3rd (n=54): 0.3780-0.5750. Fasting blood glucose (FBG), perioperative CV, rate of hypoglycemia cases (OR: 5.53, 95%CI: 2.43-12.59) (all P<0.001) and DPT (P=0.024) were higher in the 3rd than in the 1st tertile. After adjustments of covariates, regression analysis indicated that the 3rd tertile was associated with increased perioperative CV (adjusted coefficient=0.515, P<0.001), DPT (adjusted coefficient =0.169, P=0.073), rate of hypoglycemia cases (OR: 6.72, 95%CI: 2.69-16.82, P<0.001) and perioperative complication cases (OR: 2.50, 95%CI: 0.90-7.01, P=0.080). In conclusion, preoperative GV is associated with increased perioperative GV and adverse perioperative outcomes including longer DPT and higher rates of hypoglycemia and perioperative complications.

Polysaccharide from flammuliana velutipes improves colitis via regulation of colonic microbial dysbiosis and inflammatory responses.

The aim of this study is to investigate whether Flammuliana Velutipes Polysaccharide (FVP) could aid in the prevention of colitis. Effect of FVP on colitis was evaluated using dextran sulfate sodium (DSS)-induced colitis in rats. Influence of FVP on the expression of inflammation related biomarkers and signal pathway element of TLR4\NF-κB were assessed. The composition and taxonomy of colonic microbiota were analyzed by 16S rDNA high throughput sequencing, and the concentrations of caecal short fatty chain acids were assessed by chromatography-mass spectrometry. Our results showed that FVP treatment could regulate the colonic microbial dysbiosis and promote the levels of caecal short fatty chain acids, leading to down-regulation of TLR4\NF-κB signal pathway, which finally ameliorate the colitis. Thus, the present study is the first attempt to elucidate the effect of FVP on colitis and support the potential application of FVP as a functional food ingredient or preventive drugs for colitis.

A Composite Hydrogel Based on Pectin/Cellulose via Chemical Cross-Linking for Hemorrhage.

Hydrogel-based material have been demonstrated promising potential for hemostasis. Herein, we prepared a composite hydrogel (CH-P 40%) by combining pectin and cellulose in ionic liquid. The superficial morphology of the CH-P 40% was explored by SEM; the internal chemical bonds, crystal form and thermal stability were determined via FTIR, XRD and thermogravimetric analysis, respectively. The biocompatibilities of the CH-P 40% hydrogel was evaluated by MTT, flow cytometry, and histological observation with H&E staining. Furthermore, the hemostatic effect was evaluated via the blood clotting index and mouse liver hemostatic model. The results showed that the CH-P 40% hydrogel exhibited a dense network structure and retained its chemical bonds, including the OH, CH, C=O, -CH2, CO, C1-H, and ß-glycosidic bonds. Simultaneously, the hydrogel retained the Cellulose I and II crystal structure and favorable thermal stability. Moreover, the proliferation rates of CH-P 40%-treated cells increased (P > 0.05), and there were no pathological lesions in the mouse organs, which suggests favorable biocompatibility. The results showed less bleeding in the hydrogel-treated liver wound within 3 min. Overall, the pectin-cellulose hydrogel is stable and possesses favorable biocompatibility and hemostatic ability, further highlighting that the composite hydrogel has the potential to be rapid hemostatic biomedical material.

[Clinical significance of hypersensitive C-reactive protein, fribrinogen and D-dimmer in connective tissue disease-related interstitial lung disease].

OBJECTIVE: To investigate the clinical significance of plasma levels of hypersensitive C-reactive protein (hs-CRP), fibriogen and D-dimmer (D-DI) in patients with connective tissue disease (CTD)-related interstitial lung disease (CTD-ILD). METHODS: Sixty-nine patients with interstitial lung disease admitted in Zhujiang Hospital between January, 2010 and April, 2016, including 29 with CTD-ILD and 40 with non-CTD-ILD were analyzed for plasma levels of hs-CRP, fibriogen and D-DI, with 25 healthy subjects as the control group. RESULTS: The plasma level of hs-CRP, fibriogen and D-DI in patients with CTD-ILD and non-CTD-ILD were all significantly higher than those in the control group. The patients with CTD-ILD had a significantly higher hs-CRP level than those with non-CTD-ILD, but the levels of fibriogen and D-DI were comparable between the two groups. Correlation analysis indicated that Hs-CRP level was positively correlated with the levels of D-DI (r=0.539, P<0.01) and fibrinogen (r=0.534, P<0.01). CONCLUSION: Hs-CRP, fibriogen and D-DI levels show an important value in clinical diagnosis of CTD, and an obvious elevation of hs-CRP is correlated with the CTD.