Assessing heavy metal pollution in sediments from the northern margin of Chinese mangrove areas: Sources, ecological risks, and health impacts.

With the rapid economic development of coastal cities, the discharge of substantial amounts of heavy metal pollutants poses a serious hazard to mangroves; however, the potential sources of heavy metals and the resulting health risks are not fully understood. In this study, we analyzed the contents, sources, and ecological and health risks of heavy metal contamination in mangrove sediments from the northern margin of China. The accumulation of heavy metals in mangroves was primarily driven by five potential sources, namely agricultural (33.5 %), natural sources (21.3 %), industrial (19.1 %), aquaculture (14.3 %), and traffic (11.8 %). The assessment of health risks using a probabilistic approach demonstrated that noncarcinogenic risks were within acceptable limits for all populations. It was worth noting that both noncarcinogenic and carcinogenic risks were greater in children than in adults. Analysis of source-oriented health risks revealed that agricultural sources and As and Cd were priority sources and elements of pollution requiring attention.

Trophodynamics and potential health risk assessment of heavy metals in the mangrove food web in Yanpu Bay, China.

Mangroves are the cradle of coastal water biodiversity and are susceptible to heavy metal pollution. However, the trophic transfer mechanism of heavy metals in the mangrove food web and the resulting human health risks are not fully understood. Heavy metal concentration (Cr, Ni, Cu, Zn, As, Cd, Pb, V, Co) and stable isotope ratios of carbon and nitrogen (δ13C and δ15N) were evaluated in sediments and particulate organic matter, litter, and aquatic organisms (plankton, arthropods, mollusks, omnivorous fish, and carnivorous fish) from the Yanpu Bay mangroves. The results revealed that heavy metals exhibited different trophic transfer patterns. As and Hg were efficiently biomagnified, with trophic magnification factors of 1.17 and 1.42, respectively; while Cr, Ni, Cu, Cd, Pb, V, and Co were efficiently biodiluted. Zn exhibited a trophic magnification factor > 1 and was not significantly correlated with δ15N (p > 0.05), suggesting no biomagnification or biodilution. The heavy metals in the important fishery species (omnivorous fish and carnivorous fish) were below the permissible limits, except for Zn in Ophichthus apicalis. The assessment of probabilistic health risks revealed that fish consumption in adults and children posed an acceptable risk (total target hazard quotient <1).

The role of cellular senescence in metabolic diseases and the potential for senotherapeutic interventions.

Cellular senescence represents an irreversible state of cell cycle arrest induced by various stimuli strongly associated with aging and several chronic ailments. In recent years, studies have increasingly suggested that the accumulation of senescent cells is an important contributor to the decline of organ metabolism, ultimately resulting in metabolic diseases. Conversely, the elimination of senescent cells can alleviate or postpone the onset and progression of metabolic diseases. Thus, a close relationship between senescent cells and metabolic diseases is found, and targeting senescent cells has emerged as an alternative therapy for the treatment of metabolic diseases. In this review, we summarize the role of cellular senescence in metabolic diseases, explore relevant therapeutic strategies for metabolic diseases by removing senescent cells, and provide new insights into the treatment of metabolic diseases.

Prevalence and risk factors of carbapenem-resistant Enterobacterales positivity by active screening in intensive care units in the Henan Province of China: A multi-center cross-sectional study.

Objective: In intensive care units (ICUs), carbapenem-resistant Enterobacterales (CRE) pose a significant threat. We aimed to examine the distribution, epidemiological characteristics, and risk factors for CRE positivity in ICUs. Materials and methods: This cross-sectional study was conducted in 96 ICUs of 78 hospitals in Henan Province, China. The clinical and microbiological data were collected. A multivariable logistic regression model was used to analyze the risk factors for CRE positivity. Results: A total of 1,009 patients were enrolled. There was a significant difference in CRE positive rate between pharyngeal and anal swabs (15.16 vs. 19.13%, P < 0.001). A total of 297 carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 22 carbapenem-resistant Escherichia coli (CR-ECO), 6 carbapenem-resistant Enterobacter cloacae (CR-ECL), 19 CR-KPN/CR-ECO, and 2 CR-KPN/CR-ECL were detected. Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and a combination of KPC and NDM were detected in 150, 9, and 11 swab samples, respectively. Multivariable logistic regression analysis determined length of ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotics exposure as independent risk factors for CRE positivity. Age and cardiovascular diseases were independent risk factors for mixed infections of CRE. The occurrence of CRE in secondary and tertiary hospitals was 15.06 and 25.62%, respectively (P < 0.05). Patients from tertiary hospitals had different clinical features compared with those from secondary hospitals, including longer hospital stays, a higher rate of patients transferred from other hospitals, receiving renal replacement therapy, exposure to immunosuppressive drugs, use of antibiotics, and a higher rate of the previous infection. Conclusion: In ICUs in Henan Province, CRE positive rate was very high, mostly KPC-type CR-KPN. Patients with prolonged ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotic exposure are prone to CRE. Age and cardiovascular diseases are susceptibility factors for mixed infections of CRE. The CRE positive rate in tertiary hospitals was higher than that in secondary hospitals, which may be related to the source of patients, antibiotic exposure, disease severity, and previous infection.

Combination of Adsorption and Cellulose Derivative Membrane Coating for Efficient Immobilization of Laccase.

Immobilization of enzyme based on combination of adsorption and cellulose derivative membrane coating was established in this work for the first time. Laccase, a commonly used enzyme in varied fields, was chosen as the model enzyme to demonstrate this method. After investigating operational conditions, the optimal process was obtained as follows: diatomite or HPD-417 as the adsorption carrier, 0.5% (w/v) methylcellulose (40,000~50,000) acetone solution as the coating solution, 0.75% (w/v) polyethylene glycol or maltose as the protective agent, and drying at 4 °C for 9 h. Under the optimal conditions, the residual activities of diatomite and HPD-417 immobilized laccase reached 99.33% and 94.15%, respectively. The study on properties showed that the immobilized laccases held high pH tolerance and thermal stability. The immobilized laccases were further applied to the indigo decolorization and 2, 4-dichlorophenol degradation. They showed high catalytic efficiency and could be reused for several batches. On the whole, the immobilization method developed in this work can effectively avoid the inactivation of laccase during immobilization and improve the stability of immobilized laccase. The laccase immobilized by this method shows obvious potential for environmental governance.

MicroRNA-10b expression in breast cancer and its clinical association.

MicroRNAs (miRNAs) are short non-coding RNA molecules that play a significant role in many types of cancers including breast cancer. In the current study, we evaluated the expression levels of microR-10b (miR-10b) in 115 breast cancer patients from Sichuan Cancer Center. Real time reverse transcription-PCR was used to assess miR-10b expression. Clinical data including disease stage, survival status, age, ER/PR/HER2 status, molecular subtypes, tumor size, lymph node status and Ki-67 expression levels were correlated with miR-10b expression levels. Our data showed that the miR-10b expression is correlated with disease stage, living status and tumor sizes. We also found that miR-10b expression levels are higher in the lymph node positive group and the Ki-67 higher scoring group (score > 20). No statistically significant differences were observed based on age or molecular sub-type grouping. In conclusion, miR-10b may be a biomarker for breast cancer and is a potential treatment target.

Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance.

The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes it a potential target for the treatment of type 2 diabetes and obesity. In the present study, we have designed two parental peptides and 55 modified peptides based on the structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed increased inhibitory activity in a fluorescence polarization-based assay. In the in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51 were protected against high-fat diet-induced obesity and insulin resistant. These inhibitors may potentially lead to new therapeutic alternatives for obesity and type 2 diabetes.

Development of a fluorescence polarization based high-throughput assay to identify Casitas B-lineage lymphoma RING domain regulators.

The E3 ubiquitin protein ligase Casitas B-lineage Lymphoma (Cbl) proteins and their binding partners play an important role in regulating signal transduction pathways. It is important to utilize regulators to study the protein-protein interactions (PPIs) between these proteins. However, finding specific small-molecule regulators of PPIs remains a significant challenge due to the fact that the interfaces involved in PPIs are not well suited for effective small molecule binding. We report the development of a competitive, homogeneous, high-throughput fluorescence polarization (FP) assay to identify small molecule regulators of Cbl (RING) domain. The FP assay was used to measure binding affinities and inhibition constants of UbCH7 peptides and small molecule regulators of Cbl (RING) domains, respectively. In order to rule out promiscuous, aggregation-based inhibition, two assay conditions were developed and compared side by side. Under optimized conditions, we screened a 10,000 natural compound library in detergent-free and detergent-present (0.01% Triton X-100) systems. The results indicate that the detergent-present system is more suitable for high-throughput screens. Three potential compounds, methylprotodioscin, leonuride and catalpol, have been identified that bind to Cbl (RING) domain and interfere with the Cbl (RING)-UbCH7 protein-protein interaction.

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive oxygen species.

Oxidized low density lipoprotein (ox-LDL) and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) have been implicated in the development of atherosclerosis. This study was designed to investigate the expression regulation of LOX-1 by ox-LDL and the potential underlying mechanisms in cultured rat vascular smooth muscle cells (VSMCs). VSMCs were treated with ox-LDL, and the expressions of LOX-1 mRNA and proteins were determined by RT-PCR and western blotting, respectively. The intracellular reactive oxygen species (ROS) production was monitored by flow cytometry with fluorescence probe, DCFH(2) -DA. The effect of several inhibitors including aspirin, NDGA, allopurinol, apocynin, and rotenone on ox-LDL-induced ROS formation and LOX-1 expression was also investigated. The roles of NF-κB p65 and JNK were explored. Ox-LDL significantly induced LOX-1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. Aspirin, NDGA, and preconditioned apocynin suppressed ox-LDL-induced intracellular ROS production and LOX-1 expression, while allopurinol and rotenone failed to do so. Vitamin C and N-acetyl-l-cysteine demonstrated similar effect. Furthermore, both NF-κB p65 expression and phosphorylated JNK (p-JNK) to JNK expression ratio were elevated after ox-LDL treatment. In addition, the NF-κB inhibitor PDTC and JNK inhibitor SP600125 pretreatment partly abolished ox-LDL-induced LOX-1 expression. These findings suggested that ROS mediated ox-LDL-induced LOX-1 expression in VSMCs through NF-κB and JNK signaling pathways.

Synthesis and characterization of graft copolymer of chitosan and polyethylene glycol.

MPEG was modified with 1,1'-carbonyldiimidazole, then the activated MPEG reacted with primary amino groups of chitosan. Synthesize the graft copolymer of chitosan and polyethylene glycol in two steps. The structure of the copolymer was characterized by FT-IR and 1H-NMR. It agrees with the PEG content of classical stealth nanoparticles materials. The X-ray diffraction and DSC analysis proved that the crystallinity of the copolymer increased. It is a promising material for the stealth nanoparticles. It is a potential new carrier for the drug delivery systems of long-circulation and solid carcinoma.

Experimental investigation of the immunoregulatory and anti-inflammatory effects of the traditional Chinese medicine "Li-Yan Zhi-Ke Granule" for relieving chronic pharyngitis in rats.

Chronic pharyngitis, a chronic inflammation of the pharyngeal mucous membrane and submucous lymphoid tissues, is often caused by unsatisfactory treatment of acute pharyngitis or repeated occurrences of upper respiratory tract infection and is related to a high-dust environment. Traditional herbal pharmacotherapy is well known for combining plant species to create complex phytochemical mixtures in the attempt to ameliorate pathophysiological processes. The aim of current study is to investigate the effect of immunoregulation and anti-inflammation with the traditional Chinese medicine (TCM) "Li-Yan Zhi-Ke Granule" in rats. Determination of serum hemolysin and the carbon particle clearance test were performed. The results demonstrate that administration of the TCM "Li-Yan Zhi-Ke Granule" may improve the effect of phagocytosis by mononuclear macrophages and immune function in rats, and may also increase the immunoregulatory and anti-inflammatory responses of rats with chronic pharyngitis. This traditional drug could relieve the symptoms of sore throat and cough in rats with chronic pharyngitis.

The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects.

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941-1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013-1.242; for dominant model: OR = 1.128, 95% CI = 1.01-1.26; for recessive model: OR = 1.151, 95% CI = 0.950-1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000-1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134-2.256; for dominant model: OR = 1.269, 95% CI = 1.134-2.256; for recessive model: OR = 1.664, 95% CI = 1.070-2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Differential proteomics identification of HSP90 as potential serum biomarker in hepatocellular carcinoma by two-dimensional electrophoresis and mass spectrometry.

The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC) carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patients was confirmed using ELISA analysis. The observations suggest that HSP90 might be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of HCC. This work demonstrates that a comprehensive strategy of proteomic identification combined with further validation should be adopted in the field of cancer biomarker discovery.

Effect of adiponectin on apoptosis: proapoptosis or antiapoptosis?

Adiponectin is a protein hormone mainly secreted by adipose tissue that regulates energy homeostasis and glucose and lipid metabolism. Compared with other adipose-derived hormones, adiponectin is very abundant in plasma and is proposed to be a convenient biomarker for many diseases. A large number of in vitro and in vivo studies support the beneficial effects of adiponectin on metabolic syndrome, diabetes, and atherosclerosis. However, the protective actions were challenged occasionally by the controversies in its role in inflammation and in the specific functions of its different conformations. Recently, quite a few reports suggested that the antiapoptotic activity of adiponectin might contribute to its therapeutic potential during ischemia/reperfusion injury in vivo, whereas some studies demonstrated that adiponectin induced apoptosis both in vitro and in vivo. Herein, this review attempts to summarize the present consensus and divergence and to provide possible alternative and/or complementary explanations for this apparent paradox.

Preparation and characterization of folate-poly(ethylene glycol)-grafted-trimethylchitosan for intracellular transport of protein through folate receptor-mediated endocytosis.

To develop a receptor-mediated intracellular delivery system that can transport therapeutic proteins to specific tumor cells, folate-poly(ethylene glycol)-grafted-trimethylchitosan (folate-PEG-g-TMC) was synthesized. Nano-scaled spherical polyelectrolyte complexes between the folate-PEG-g-TMC and fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) were prepared under suitable weight ratio of copolymer to FITC-BSA by ionic interaction between the positively charged copolymers and the negatively charged FITC-BSA. Intracellular uptake of FITC-BSA was specifically enhanced in SKOV3 cells (folate receptor over-expressing cell line) through folate receptor-mediated endocytosis compared with A549 cells (folate receptor deficient cell line). Folate-PEG-g-TMC shows promise for intracellular transport of negatively charged therapeutic proteins into folate receptor over-expressing tumor cells.

A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs.

Natural products represent a rich reservoir of potential small chemical molecules exhibiting antiproliferation and anticancer properties. An example is berberine, a protoberberine alkaloid widely distributed in medical plants used in traditional Chinese prescriptions. Recent advances have shown that berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. Berberine shows inhibitory effects on the proliferation and reproduction of certain tumorigenic microorganisms and viruses, such as Heliobacter pylori and hepatitis B virus. Transcriptional regulation of some oncogene and carcinogenesis-related gene expression and interaction with both DNA and RNA are also well documented. Besides, berberine is a broad spectrum enzyme inhibitor, which affects N-acetyltransferase, cyclooxygenase-2, and topoisomerase activities and gene/protein expression. These actions, together with the regulation of reactive oxygen species production, mitochondrial transmembrane potential, and nuclear factor-kappaB activation might underlie its antiproliferative and proapoptotic effects. More importantly, the suppression of tumor growth and metastasis, the beneficial application in combined medication, and the improvement of multidrug resistance both in vivo and in vitro clearly show its potential as an alternative medicine for tumor chemotherapy.

Adiponectin, an unlocking adipocytokine.

A large number of studies revealed that adiponectin, a protein secreted specifically by adipose tissue, exhibits antiinflammatory, antiatherogenic, and antidiabetic properties. This 247-amino acid protein contains four differentiable domains and exists in five different configurations, which binds three kinds of receptors. The plasma adiponectin concentration is at amazing microgram level and the gender difference is very clear. Obese subjects showed decreased plasma level of adiponectin while exercise seems to restore it. Many researchers demonstrated that it could be a reliable biomarker for multiple diseases. However, there is controversy about its role in inflammation since its plasma concentration decreases in some inflammatory diseases and increases under some other inflammatory conditions. The signal transduction pathway is still not very clear yet. Could adiponectin be a promising drug target?

[Preparation of mitoxantrone liposomes and study on its in vivo distribution in rats after transdermal delivery].

OBJECTIVE: To investigate in vivo distribution of the mitoxantrone(MIT) liposomes in SD rats after transdermal delivery. METHODS: The mitoxantrone liposomes were prepared by thin-film method. Particle size, particle distribution and delta-potential of colloid solution were obtained on laser scatterometer; the encapsulation efficiency was measured by membrane diffusion technique. The time courses of mitoxantrone concentration in vivo after the transdermal delivery of mitoxantrone liposomes were measured by HPLC assays and compared with the injection of mitoxantrone solution. RESULTS: The mean diameter of the MIT liposomes was 50.98 nm, with the entrapping efficiency of 100%. The liposomes had perfect shape. A significantly higher amount of mitoxantrone was delivered in cutis after transdermal delivery of mitoxantrone liposomes, compared with the injection of mitoxantrone solution; meanwhile, a significantly lower amount of mitoxantrone was delivered in plasma and other tissues after transdermal delivery of mitoxantrone liposomes, compared with the injection of mitoxantrone solution. CONCLUSION: Transdermal delivery of mitoxantrone liposomes could be a potential therapy for cutaneous malignant melanoma.

[Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

OBJECTIVE: To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. METHOD: BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. RESULT: D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. CONCLUSION: The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.