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This review provides a comprehensive landscape of HGF/c-MET (hepatocyte growth factor (HGF) /mesenchymal-epithelial transition factor (c-MET)) signaling pathway in cancers. First, we generalize the compelling influence of HGF/c-MET pathway on multiple cellular processes. Then, we present the genomic characterization of HGF/c-MET pathway in carcinogenesis. Furthermore, we extensively illustrate the malignant biological behaviors of HGF/c-MET pathway in cancers, in which hyperactive HGF/c-MET signaling is considered as a hallmark. In addition, we investigate the current clinical trials of HGF/c-MET-targeted therapy in cancers. We find that although HGF/c-MET-targeted therapy has led to breakthroughs in certain cancers, monotherapy of targeting HGF/c-MET has failed to demonstrate significant clinical efficacy in most cancers. With the advantage of the combinations of HGF/c-MET-targeted therapy, the exploration of more options of combinational targeted therapy in cancers may be the major challenge in the future.

The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide. There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases. Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS. The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001). Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates. Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively. Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC. Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases. One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC. This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.

With the expansion of industrialization, dye pollution has become a significant hazard to humans and aquatic ecosystems. In this study, α-Fe2O3/g-C3N4-R (where R is the relative percentage of α-Fe2O3) composites were fabricated by a one-step method. The as-prepared α-Fe2O3/g-C3N4-0.5 composites showed excellent adsorption capacities for methyl orange (MO, 69.91 mg g−1) and methylene blue (MB, 29.46 mg g−1), surpassing those of g-C3N4 and many other materials. Moreover, the ionic strength and initial pH influenced the adsorption process. Relatively, the adsorption isotherms best fitted the Freundlich model, and the pseudo-second-order kinetic model could accurately describe the kinetics for the adsorption of MO and MB by α-Fe2O3/g-C3N4-0.5. Electrostatic interaction and π–π electron donor–acceptor interaction were the major mechanisms for MO/MB adsorption. In addition, the photocatalytic experiment results showed that more than 79% of the added MO/MB was removed within 150 min. The experimental results of free-radical capture revealed that holes (h+) were the major reaction species for the photodegradation of MO, whereas MB was reduced by the synergistic effect of hydroxyl radicals (·OH) and holes (h+). This study suggests that the α-Fe2O3/g-C3N4 composites have an application potential for the removal of dyes from wastewater.

Introduction The degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how β amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice. Methods Three-month and six-month APPswe/PS1dE9 transgenic mice were used. Spatial and memory ability were measured by Morris Water Maze, Neuron and synapse number were assessed by electron microscope; Aβ, Bcl-2/Bax were determined by immunohistochemistry and western blot. Results APP/PS1 mice not only had increased Aβ accumulation, impaired memory performance, less synapse number, and much more necrosed neurons, but also had significant reduction in the Bcl-2/Bax ratio. However, GAPT and donepezil showed improved memory performance, less Aβ accumulation, increased neuron and synapse number, as well as restored balance of Bcl-2/Bax. Discussion GAPT may improve cognitive functions via both reducing Aβ deposition and restoring Bcl-2/Bax balance of neuron.

The bovine milk proteins have a wide range of functions, but the role of the attached glycans in their biological functions has not been fully understood yet. Here, the glycopatterns of whole bovine milk proteins were analyzed using lectin microarrays. Then, the proteins with Siaα2-3/6Gal-linked glycans were isolated and characterized. The roles of Siaα2-3/6Gal-linked glycans of the isolated proteins were assessed by inhibiting viral activity against influenza A viruses (IAV). In total, there were 69 sialylated proteins to be identified and annotated. The sialylated proteins have the ability to inhibit the attachment of IAV mimics to MDCK cells; however, the role of inhibition was abolished when the sialic acid moieties were destroyed. The results demonstrate that the sialic acid moieties of proteins could serve as competitive substrates to disturb the viral attachment to cell surface receptors. Our findings will help to assess the potential application of sialylated glycoproteins in bovine milk against IAV.

Background: The main reason why lung cancer has maintained a high rate of morbidity and mortality is that its early diagnosis is difficult. No current lung cancer screening is recommended by any major medical organization due to the lack of sensitive and specific screening technologies. Thus, this study aimed to systematically investigate the correlation between the alterations in serum glycosylation and three main types of lung cancers (SCLC, ADC and SqCC). Materials and methods: We investigated the protein glycopatterns in sera from 333 subjects (65 healthy volunteers, 38 benign lung disease patients, 49 small cell lung cancer patients, and 181 NSCLC patients) using a lectin microarray. A serum microarray was produced to evaluate and verify the terminal carbohydrate moieties of the glycoproteins in individual serum samples from 30 cases simultaneously. Results: There were 16 lectins (e.g., RCA120, BS-I, and UEA-I), 24 lectins (e.g., HHL, PTL-I, and MAL-II), and 18 lectins (e.g., GSL-I, LEL, and ACA) that exhibited significant differences in serum protein glycopatterns in the patients with SCLC, ADC and SqCC compared with the controls (HV and BPD). There were 6 lectins (e.g., EEL, NPA, and LEL) that exhibited significantly increased NFIs in ADC and SqCC compared with SCLC. Also, there were 5 lectins (e.g., Jacalin, BS-I, and UEA-I) that exhibited significantly decreased NFIs in ADC compared with SCLC and SqCC. Conclusions: This study can facilitate the discovery of potential biomarkers for the differential diagnosis of lung cancer based on the precise alteration in serum protein glycopatterns.

Currently, the definitive diagnosis in breast cancer requires biopsy and histopathology, such the most effective markers are tissue-based. However, the advantages of saliva in collection and storage make it possible for assessing human pathology and contributing to the development of cancer-related biomarkers for clinical application. The present study validated alteration of salivary protein glycopatterns recognized by Bandeiraea simplicifolia lectin I (BS-I) in the saliva of patients with breast diseases using saliva microarrays, and the N/O-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from 259 female subjects (66 healthy volunteers (HV), 65 benign breast cyst or tumor patients (BB), 66 patients with breast cancer in stage I (BC-I) and 62 patients with breast cancer in stage II (BC-II)) were analyzed by MALDI-TOF/TOF-MS. The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with breast cancer compared with HV (p

Breast cancer remains a public-health issue on a global scale. Although mammographic screening and molecular-based classification have been applied to the clinical treatment effectively, breast cancer still has high incidence and mortality in women. Therefore, the discovery of novel biomarkers and molecular targets for early diagnosis and treatment is still essential. Glycosylation is the enzymatic addition of sugars, or oligosaccharides, to proteins and lipids. This increases the diversity of the proteome and lipidome to a level unmatched by any other post-translational modification due to the various aspects of the molecule that can be modified, including the glycosidic bond and glycan composition, structure, and length. Altered glycosylation, a predominant feature of tumor cells, plays an important role in the pathogenesis and progression of various malignancies. This review describes the variety of glycosylation processes, such as O -GlcNAcylation, sialyl-Lewis antigen, mucin type O -linked glycosylation, and b 1-6 GlcNAc-branched N -glycans with poly-LacNAc structure, involved in breast carcinogenesis, their effects in the regulation of metabolism, cell-cell adhesion of tumor cells, and preservation of tumor cell activity in the circulatory system, as well as promotion of angiogenesis of tumor tissue. Finally, the application referred to glycosylation, glycoproteins, glycan genes, enzymes, and anti-carbohydrate antibodies in the clinical management of patients with breast cancer is also discussed.

Diabetic nephropathy (DN) and nondiabetic renal disease (NDRD) are two major categories of renal diseases in diabetes mellitus patients. The clinical differentiation among them is usually not so clear and effective. In this study, sera from DN and NDRD patients were collected, and glycan profiles of serum proteins from DN and NDRD patients were investigated and compared by using lectin microarray and lectin blot. Then, altered glycoproteins were enriched by lectin coupled magnetic particle conjugate and characterized by LC-MS/MS. We found significant change in glycan patterns between DN and NDRD patients. In particular, the relative abundance of the glycopattern of Galβ1-3GalNAc which was identified by BPL (Bauhinia purpurea lectin) was significantly decreased in DN patients compared to four types of NDRD patients (p < 0.05). Moreover, BPL blotting indicated that the proteins with a molecular weight of about 53 kDa exhibited low staining signal in DN compared to all NDRD groups, which was consistent with results of lectin microarrays. After enriching by BPL and identification by LC-MS/MS, a total of 235 and 258 proteins were characterized from NDRD and DN respectively. Among these, the relative abundance of 12 isolated serum proteins exhibited significantly alteration between DN and NDRD (p < 0.05). Our findings indicated not only the relative abundance of Galβ1-3GalNAc on serum proteins but also certain glycoproteins modified with this glycopattern showed a difference between DN and NDRD patients. This suggested that the analysis of this alteration by using urine specimens may constitute an additional valuable diagnostic tool for differentiating DN and NDRD with a non-invasive method.

Silver nanoparticles (AgNPs) are among the most widely used engineered nanomaterials and may eventually accumulate in sediments. Limited information is currently available regarding the toxicity, bioaccumulation and distribution of sediment-associated AgNPs in aquatic organisms. In the present study, a freshwater snail Bellamya aeruginosa was exposed via sediment to commercial Ag particles of four nominal sizes: 20 nm (AgNPs-20), 40 nm (AgNPs-40), 80 nm (AgNPs-80), and 10 μm (bulk Ag), and to silver nitrate at sub-lethal concentrations (1, 10 and 100 μg Ag/g sediment). Ag burden and biomarkers of oxidative stress were assessed in different tissues of B. aeruginosa: hepatopancreas, gonad, foot and digestive tracts. All five Ag types were available for uptake by B. aeruginosa when spiked into sediment, and Ag accumulation in different tissues presented the following pattern: hepatopancreas gonad ≈ digestive tracts foot. Snails accumulated higher levels of Ag from aqueous Ag than from particulate Ag. In contrast, AgNPs-40 and AgNPs-80 treatments occasionally induced higher oxidative stress than aqueous Ag, indicating the significant role of nanoparticle itself in exerting toxicity. Size-dependent toxicity of AgNPs in sediment was also found, with AgNPs-20 showing lower toxicity than other Ag particles. Overall, this study demonstrated that the toxicity of sediment-associated AgNPs to B. aeruginosa varies with size and differs from aqueous Ag.

Hepatocellular carcinoma (HCC) is most common malignant cancer worldwide; however, the mortality rate of HCC remains high due to the invasion and metastasis of HCC. Thus, exploring novel treatments to prevent the invasion of HCC is needed for improving clinical outcome of this fatal disease. In this study, we identified lectin from Bandeiraea simplicifolia seeds (BS‐I) binds to metastasis‐associated HCC cell surface glycans by a lectin microarray and inhibits HCC cell migration and invasion through downregulating the matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9) and urokinase‐type plasminogen activator (uPA) production. These effects of BS‐I were mediated by inhibiting the activation of AKT/GSK‐3β/β‐catenin pathway and depended on specificity of lectin BS‐I binding to GalNAc. GSK3β inhibitors rescued BS‐I‐mediated inhibition of migration and invasion of HCC cell. Further, we identified that lectin BS‐I interacts with sGrp78, affects membrane localization of sGrp78 and attenuates the binding of sGrp78 and p85 to inhibit the activation of AKT/GSK‐3β/β‐catenin pathway. Overexpression of Grp78 or P85 rescues BS‐I‐mediated inhibition of migration and invasion of HCC cell. These findings demonstrated for the first time that BS‐I can act as a novel potential drug to prevent the invasion of HCC.

Gastric cancer (GC) is still an extremely severe health issue with high mortality due to the lacking of effective biomarkers. In this study, we aimed to investigate the alterations of salivary protein glycosylation related to GC and assess the possibility of salivary glycopatterns as potential biomarkers for the diagnosis of GC. Firstly, 94 patients with GC (n = 64) and atrophic gastritis (AG) (n = 30), as well as 30 age- and sex-matched healthy volunteers (HV) were enrolled in the test group to probe the difference of salivary glycopatterns using lectin microarrays, the results were validated by saliva microarrays and lectin blotting analysis. Then, the diagnostic model of GC (Model GC) and AG (Model AG) were constructed based on 15 candidate lectins which exhibited significant alterations of salivary glycopattern by logistic stepwise regression. Finally, two diagnostic models were assessed in the validation group including HV (n = 30) and patients with GC (n = 23) and AG (n = 24) and achieved high diagnostic power (Model GC (AUC: 0.89, sensitivity: 0.96 and specificity: 0.80), Model AG (AUC: 0.83, sensitivity: 0.92 and specificity: 0.72)). This study provides pivotal information to distinguish HV, AG and GC based on precise alterations in salivary glycopatterns, which have great potential to be biomarkers for diagnosis of GC.

Diabetic nephropathy is a major cause of chronic kidney disease and end-stage kidney disease. However, so little is known about alterations of the glycopatterns in urine with the development of diabetic nephropathy. Presently, we interrogated glycopatterns in urine specimens using a lectin microarray. The results showed that expression levels of Siaα2-6Gal/GalNAc recognized by SNA exhibited significantly increased tendency with the development of diabetic nephropathy; moreover, SNA blotting indicated glycoproteins (90 kDa, 70 kDa, and 40 kDa) in urine may contribute to this alteration. Furthermore, the glycopatterns of(GlcNAc)2–4recognized by STL exhibited difference between diabetic and nondiabetic nephropathy. The results of urinary protein microarray fabricated by another 48 urine specimens also indicated(GlcNAc)2–4is a potential indictor to differentiate the patients with diabetic nephropathy from nondiabetic nephropathy. Furtherly, STL blotting showed that the 50 kDa glycoproteins were correlated with this alteration. In conclusion, our data provide pivotal information to monitor the development of diabetic nephropathy and distinguish between diabetic nephropathy and nondiabetic renal disease based on precise alterations of glycopatterns in urinary proteins, but further studies are needed in this regard.

Background:Mid-life obesity can increase the risk for developing dementia later in life, particularly Alzheimer’s disease (AD), and experimental diet-induced obesity increases AD-like pathology and/or behavioural deficits in transgenic mouse models of AD. However, most of these experimental studies assess the effect of high fat diet (HFD) in male mice only, and effects in female mice are less clear. Moreover, our previous work has shown that HFD also affects memory in healthy controls and that this effect is gender dependent.Resveratrol (RSV) has recently showed to improve health and life span of mice on a HFD and to improve learning and memory in both aged and AD mice, effects that are thought to be due to its anti-oxidant and/or anti-inflammatory properties. However until now no studies have been done taking into account both AD and co-morbidities (obesity). Therefore, the aim of this study was to test the effect of RSV in female 3xTgADmice fed with a HFD.Methods:Groups of female 3xTgAD and control (Non-Tg) mice w ere maintained on a control (12% fat) or a HFD (60% fat) for 12 months with or without RSV supplementation in the drinking water (5 mg/Kg/day). Body weight (BW) was monitored weekly. Behaviour was assessed at 12 months of treatment using the open-field and Y-maze spontaneous alternation tests. Epididymal fat, brown adipose tissue (BAT) and liver weight were measured after culling.Results: RSV did not affect BW in female 3xTgADmice fed a HFD but a decrease in weight gain was observed in Non-Tg HFD animals. HFD increased epididymal fat and BAT weight in both Non-Tg and 3xTgAD mice, and RSV reversed this effect only in Non-Tg mice. HFD also elevated liver weight in Non-Tg mice, which was reversed by RSV. RSV had no effect on behaviour or memory in both groups. Conclusions: These results suggest that RSV is able to reverse metabolic changes induced by the HFD in female Non-Tg mice but not in 3xTgAD animals, with no effect on behaviour in either. In conclusion, the effect of a HFD on memory is not affected by RSV and therefore is unlikely to be due to changes in oxidative stress and/or inflammation.

Background. Syndromes are defined by traditional Chinese medicine as consisting of different pattern elements. Few scales have been designed for differentiating pattern elements of dementia and have shown major flaws. Thus, a new pattern element scale (PES) was developed. This study aimed to evaluate the utility of the PES in dementia patients.Methods. A total of 171 dementia patients were enrolled, and their pattern elements were ascertained, first by clinicians using the PES, then compared with results by two experts to be used as a standard criterion independently. Reliability of the subscales of the PES was assessed by receiver operator characteristic curves. Correlations between the subscales of the PES and cognition were calculated by canonical correlation analysis.Results. The PES consisted of 11 pattern element subscales. The area under the curves of all subscales was 0.7 or above. Phlegm muddiness, blood stasis, and yang hyperactivity subscales showed optimal sensitivity and specificity in discriminating pattern elements. Other subscales showed relatively lower sensitivity but higher specificity. Memory and language were significantly correlated toqideficiency and the blood stasis pattern element.Conclusion. The PES can accurately and easily discriminate pattern elements and is a helpful tool for traditional medical subtyping of dementia.