Fabrication of Rhenium Disulfide/Mesoporous Silica Core-Shell Nanoparticles for a pH-Responsive Drug Release and Combined Chemo-Photothermal Therapy.

A stimuli-responsive drug delivery nanocarrier with a core-shell structure combining photothermal therapy and chemotherapy for killing cancer cells was constructed in this study. The multifunctional nanocarrier ReS2@mSiO2-RhB entails an ReS2 hierarchical nanosphere coated with a fluorescent mesoporous silica shell. The three-dimensional hierarchical ReS2 nanostructure is capable of effectively absorbing near-infrared (NIR) light and converting it into heat. These ReS2 nanospheres were generated by a hydrothermal synthesis process leading to the self-assembly of few-layered ReS2 nanosheets. The mesoporous silica shell was further coated on the surface of the ReS2 nanospheres through a surfactant-templating sol-gel approach to provide accessible mesopores for drug uploading. A fluorescent dye (Rhodamine B) was covalently attached to silica precursors and incorporated during synthesis in the mesoporous silica walls toward conferring imaging capability to the nanocarrier. Doxorubicin (DOX), a known cancer drug, was used in a proof-of-concept study to assess the material's ability to function as a drug delivery carrier. While the silica pores are not capped, the drug molecule loading and release take advantage of the pH-governed electrostatic interactions between the drug and silica wall. The ReS2@mSiO2-RhB enabled a drug loading content as high as 19.83 mg/g doxorubicin. The ReS2@mSiO2-RhB-DOX nanocarrier's cumulative drug release rate at pH values that simulate physiological conditions showed significant pH responsiveness, reaching 59.8% at pH 6.8 and 98.5% and pH 5.5. The in vitro testing using HeLa cervical cancer cells proved that ReS2@mSiO2-RhB-DOX has a strong cancer eradication ability upon irradiation with an NIR laser owing to the combined drug delivery and photothermal effect. The results highlight the potential of ReS2@mSiO2-RhB nanoparticles for combined cancer therapy in the future.

Lignin-Based Nanospheres as Environmental Remediation Platforms for Anionic Dye Contaminants.

Modern manufacturing of textiles, pharmaceuticals, food, cosmetics, plastics, paper, etc. involves the utilization of anionic and cationic dyes that lead to significant water contamination. Recent research has explored the use of nanomaterials toward developing nanoadsorbents for water decontamination caused by industrial pollution. Here, we report on a novel platform for anionic dye remediation, consisting of a polyethylenimine-functionalized lignin nanosphere (PEI-LNS). The designed nanomaterial shows significant ability to adsorb an anionic dye selected as a proof-of-concept-Sulforhodamine B, from aqueous solutions. The PEI lignin nanoadsorbents (PEI-LNS) showed a better ability to adsorb Sulforhodamine B sodium salt (SBSS) when compared to the raw lignin nanosphere adsorbent (LNS), especially in acidic conditions. The nanomaterial was characterized through transmission electron microscopy, scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, elemental analysis, zeta potential, thermogravimetric analysis, Fourier transform infrared spectroscopy, and nuclear magnetic resonance. The impacts of ionic strength, contact time, pH, and adsorbent concentration have been evaluated. The ability of PEI-LNS to adsorb SBSS was found to be consistent with Langmuir isotherms and pseudo-second-order kinetic models. The PEI-LNS could be recycled three times, reaching a good (85%) adsorbing capacity even in the third cycle. The study demonstrates that PEI-LNS has a strong affinity as a novel adsorbent for anionic dyes and could be employed in environmental cleanups pertaining to such contaminations.

Infrared-Activated Bactericide: Rhenium Disulfide (ReS2)-Functionalized Mesoporous Silica Nanoparticles.

An attractive strategy for treating bacterial infection is the combination of antibiotic chemotherapy with photothermal therapy (PTT), which could be implemented using multifunctional nanomaterials. In this work, the intrinsic photothermal efficiency of two-dimensional (2D) rhenium disulfide (ReS2) nanosheets is enhanced by their coating on mesoporous silica nanoparticles (MSNs) to realize a highly efficient light-responsive nanoparticle endowed with controlled-release drug delivery capability, denoted as MSN-ReS2. The MSN component of the hybrid nanoparticle features augmented pore size toward facilitating increased loading of antibacterial drugs. The ReS2 synthesis is conducted in the presence of MSNs through an in situ hydrothermal reaction and leads to a uniform surface coating of the nanosphere. The MSN-ReS2 bactericide testing showed more than 99% bacterial killing efficiency in both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) upon laser irradiation. A cooperative effect that led to a 100% bactericide effect on Gram-negative bacteria (E. coli) was observed when tetracycline hydrochloride was loaded in the carrier. The results show the potential of MSN-ReS2 to be used as a wound-healing therapeutic with a synergistic bactericide role.

Neuronal-microglial liver X receptor ß activating decrease neuroinflammation and chronic stress-induced depression-related behavior in mice.

Depression is accompanied by excessive neuroinflammation. Liver X receptor ß (LXRß) has been reported as a newly emerging target that exerts systemic and organic inflammation modulation. However, the modulatory mechanism in alleviating neuroinflammation are far from being revealed. In the current study, depression-related behaviors in mice were induced by chronic unpredictable mild stress (CUMS) and corticosterone (CORT) drinking. Mice received either TO901317, PLX-5622 and intra- bilateral basolateral amygdale (BLA) injection of rAAV9-hSyn-hM3D(Gq)-eGFP to activate LXRß, eliminate microglia and pharmacogenetic activate neurons in BLA, respectively, followed by behavioral tests. Microglial pro-inflammatory and pro-phagocytic activation, as well as nuclear factor-κB (NF-κB) signaling pathway, NLRP3 inflammasome activation and interleukin-1ß (IL-1ß) release in BLA were investigated. Moreover, pro-inflammatory activation of BV2 cells-induced by CORT with or without TO901317 was detected. Neuroinflammation indicated by IL-1ß release was measured in a co-culture system of HT22-primary microglia with or without TO901317. Our results indicated that chronic stress induced depression-related behaviors, which were accompanied with microglial pro-inflammatory and pro-phagocytic activation, as well as NF-κB signaling pathway and NLRP3 inflammasome activation in BLA. Accordingly, pharmacological activation of LXRß inhibited microglial pro-inflammatory and pro-phagocytic activation, as well as NF-κB signaling pathway and NLRP3 inflammasome activation, and IL-1ß release both in vivo and in vitro. Finally, both elimination of microglia and pharmacogenetic activation of neurons in BLA protected mice from chronic stress-induced depression-related behavior. Collectively, pharmacological activation of neuronal-microglial LXRß alleviates depression-related behavior by modulating excessive neuroinflammation via inhibiting NF-κB signaling pathway and NLRP3 inflammasome activation.

Dexmedetomidine inhibits microglial activation through SNHG14/HMGB1 pathway in spinal cord ischemia-reperfusion injury mice.

OBJECTIVE: Microglial activation is an essential pathological mechanism of spinal cord ischemia-reperfusion injury (SCIRI). Previous studies showed dexmedetomidine (DEX) could alleviate SCIRI while the mechanism was not clear. This study aims to investigate the role of DEX in microglial activation and clarify the underlying mechanism. METHODS: The motion function of mice was quantified using the Basso Mouse Scale for Locomotion. The expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) was determined by qRT-PCR. The expression of high-mobility group box 1 (HMGB1) was measured by western blot. The activation of microglia was evaluated by the expression of ED-1 and the levels of TNF-α and IL-6. The interplay between SNHG14 and HMGB1 was confirmed with RNA pull-down and RIP assay. The stability of HMGB1 was measured by ubiquitination assay and cycloheximide-chase assay. RESULTS: DEX inhibited microglial activation and down-regulated SNHG14 expression in SCIRI mice and oxygen and glucose deprivation/reoxygenation (OGD/R)-treated primary microglia. Functionally, SNHG14 overexpression reversed the inhibitory effect of DEX on OGD/R-induced microglial activation. Further investigation confirmed that SNHG14 bound to HMGB1, positively regulated HMGB1 expression by enhancing its stability. In addition, the silence of HMGB1 eliminated the pro-activation impact of SNHG14 overexpression on DEX-treated microglia under the OGD/R condition. Finally, in vivo experiments showed SNHG14 overexpression abrogated the therapeutic effect of DEX on SCIRI mice by up-regulating HMGB1. CONCLUSION: DEX accelerated HMGB1 degradation via down-regulating SNHG14, thus inhibiting microglial activation in SCIRI mice.

Improvement of viscous substance production during Cheonggukjang fermentation added with glycine.

When Bacillus subtilis NB-NUC1 associated with Cheonggukjang fermentation was aerobically grown in a synthetic medium containing 1 to 2% glycine (w/v), cell growth was inhibited in a dose-dependent manner. Subsequently, different concentrations of glycine (0, 1, and 2%) were used in Cheonggukjang fermentation for 96 h at 40 °C. Supplementation of 1% glycine increased extracellular γ-glutamyl transpeptidase (γ-GTPase), responsible for the production of viscous substance. Based on correlation studies, we conclude that the production of viscous substance is correlated with viscous extension (r = 0.867), extracellular proteins contents (r = 0.821), and γ-GTPase activity (r = 0.807). The molecular weight of the viscous substance obtained during Cheonggukjang fermentation by B. subtilis NB-NUC1 was also affected by glycine supplementation. Our results demonstrate that glycine supplementation before solid-state fermentation may increase the mass production of mucilage in food industry.

Propofol alleviates oxidative stress via upregulating lncRNA-TUG1/Brg1 pathway in hypoxia/reoxygenation hepatic cells.

Reducing oxidative stress is an effective method to prevent hepatic ischaemia/reperfusion injury (HIRI). This study focuses on the role of propofol on the oxidative stress of hepatic cells and the involved lncRNA-TUG1/Brahma-related gene 1 (Brg1) pathway in HIRI mice. The mouse HIRI model was established and was intraperitoneally injected with propofol postconditioning. Hepatic injury indexes were used to evaluate HIRI. The oxidative stress was indicated by increasing 8-isoprostane concentration. Mouse hepatic cell line AML12 was treated with hypoxia and subsequent reoxygenation (H/R). The targeted regulation of lncRNA-TUG1 on Brg1 was proved by RNA pull-down, RIP (RNA-binding protein immunoprecipitation) and the expression level of Brg1 responds to silencing or overexpression of lncRNA-TUG1. Propofol alleviates HIRI and induces the upregulation of lncRNA-TUG1 in the mouse HIRI model. Propofol increases cell viability and lncRNA-TUG1 expression level in H/R-treated hepatic cells. In H/R plus propofol-treated hepatic cells, lncRNA-TUG1 silencing reduces cell viability and increased oxidative stress. LncRNA-TUG1 interacts with Brg1 protein and keeps its level via inhibiting its degradation. Brg1 overexpression reverses lncRNA-TUG1 induced the reduction of cell viability and the increase in oxidative stress. LncRNA-TUG1 silencing abrogates the protective role of propofol against HIRI in the mouse HIRI model. LncRNA-TUG1 has a targeted regulation of Brg1, and thereby affects the oxidative stress induced by HIRI. This pathway mediates the protective effect of propofol against HIRI of hepatic cell.

Secondary Fermented Extract of Chaga-Cheonggukjang Attenuates the Effects of Obesity and Suppresses Inflammatory Response in the Liver and Spleen of High-Fat Diet-Induced Obese Mice.

Cheonggukjang and chaga mushrooms have numerous health benefits, and have been used in alternative medicine. Therefore, a powder mixture of 98: Cheonggukjang and 2: Chaga extracts was fermented with Lactobacillus acidophilus KCTC3925 (FCC) and its anti-obesity effects in high-fat diet (HFD)-induced obese mice were determined. Five-week-old male ICR mice were fed a normal diet or HFD in the presence or absence of 3% and 5% FCC by weight (n = 10 per group). After 12 weeks, the mice were sacrificed, and the serum and tissue samples were collected for analysis. Body weight and epididymal fat pad weight were significantly lowered in the 3% and 5% FCC groups compared with those in the HFD control group (p < 0.01). FCC supplementation suppressed serum triglyceride and increased serum HDL-C levels (p < 0.01). Serum GOT, GPT, and leptin levels, hepatic COX-2 mRNA expression, and splenic COX-2 and IL-4 mRNA expression were significantly higher in the HFD groups than in the control group (p > 0.05); however, except for splenic IL-4 levels, the increases were significantly attenuated by FCC supplementation. Expression of ICAM-1, an aortic inflammatory marker, was significantly increased in the HFD group; this effect was suppressed in the 3% FCC group (p < 0.01) but not in the 5% FCC group. FCC suppressed the body weight and epididymal fat pad weight gain, as well as inflammatory responses in the liver and spleen of HFD-fed mice. Thus, FCC supplementation will be beneficial for the treatment of obesity-related effects.

Quantitative analysis of acetylsalicylic acid in human blood using volumetric absorptive microsampling

Volumetric absorptive microsampling (VAMS) is a novel sampling technique that allows for the collection of an accurate volume of blood by dipping a microsampler tip. The purpose of this study is to compare the requirement of a stabilizing reagent for the conventional venous blood sampling method versus VAMS in the analytical measurement of the concentration of acetylsalicylic acid. A high-performance liquid chromatography with mass spectrometry (LC-MS/MS) method was developed and validated for the accurate determination of acetylsalicylic acid in human blood. The blood samples spiked with acetylsalicylic acid with and without stabilizing reagent were absorbed into VAMS tips. In the whole blood sample, the same concentration was shown regardless of the addition of the stabilizing reagent, but the concentration decreased when the stabilizing reagent was not added to the VAMS sample. To apply the VAMS technology as a new blood sampling method, stabilizing reagents should be added before the analysis of acetylsalicylic acid concentration.

Increased risk of thyroid cancer in female residents nearby nuclear power plants in Korea: was it due to detection bias?

BACKGROUND: The Korea Radiation Effect & Epidemiology Cohort METHODS: Using the KREEC-R raw data, we calculated age standardized rates (ASRs) of female thyroid cancer and re-analyzed the results of survey on the use of medical services. We also marked the administrative districts of residents who received the Radiation Health Research Institute (RHRI) health examinations and those in which thyroid cancer case occurred as per the Chonnam National University Research Institute of Medical Sciences (RIMS) final report on maps where the locations of NPPs and 5 km-radii around them were also indicated. And we compared the incidence rates of Radiation-induced cancer measured between the first period when RHRI health examinations were not yet implemented, and the second period when the RHRI health examinations were implemented. RESULTS: The ASR for the far-distance group, which comprised residents living in areas outside the 30 km radius of the NPPs, increased rapidly after 2000; however, that of the exposed group, which comprised residents living within a 5 km radius of the NPPs, started to increase rapidly even before 1995. The frequencies of the use of medical services were significantly higher in the intermediate proximate group, which comprised residents living within a 5–30 km radius of the NPPs, than in the exposed group in women. In case of female thyroid cancer, the second period ASR was higher than the first period ASR, but in case of female liver cancer and female stomach cancer no significant difference were observed between the periods. On map, many administrative districts of residents who received RHRI health examinations and most administrative districts in which thyroid cancer case occurred on RIMS final report were outside 5 km-radii around NPPs. CONCLUSIONS: We could not find any evidence supporting the assertion that detection bias influenced the increased risks of female thyroid cancer observed in the exposed group of the KREEC-R study, as opposed to the control group.

Epigenetic modification of α-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer

Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified α-Nacetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly downregulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.

Clinical Features of Spontaneous Bacterial Peritonitis: A 10-year Experience from a Single Center.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is one of critical complications in liver cirrhosis patients with ascites. We aimed to review clinical course of SBP patients in a 10-year period from single center. METHODS: This study enrolled SBP patients between 2005 and 2015. Their medical records were reviewed. The laboratory findings of serum and ascites were examined, and characteristics of isolated microorganisms in ascites were analyzed. RESULTS: Total 51 patients were enrolled. Male patients were predominant (64.7%), and mean age was 59.20 years. The most common etiology of cirrhosis was alcohol (41.2%), followed by hepatitis B (39.2%). Microorganism was isolated from the ascites in 31 patients (60.78%). The proportions of Gram negative and Gram positive were 80.64% and 19.36%. The proportions of Escherichia coli, Klebsiella, and Streptococcus species were 29.41%, 19.61% and 11.76%. Among Escherichia colis, 4 cases were ESBL positive (7.84%). The most commonly used first-line antibiotic was cefotaxime (80.40%). Prophylactic antibiotics treatment was performed only in 8 patients, and SBP was recurred in 7 patients (13.72%). When comparing the SBP recurrence group and the non-recurrence group, there were no significant differences in laboratory findings of serum and ascitic fluid. CONCLUSIONS: SBP is still a critical complication in cirrhosis patients with ascites, and the clinical features of SBP have not been altered much compared with those in 1990's. The effective treatment of SBP is still very important for a better prognosis of cirrhosis patients.

E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial.

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% ± 26.1% (p < 0.001) in the regular-dose group and -21.1% ± 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development.

AIMS: Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1. Therefore, the aim of this study was to determine the ability of E4orf1 to improve glycemic control independent of insulin despite high fat diet. MATERIALS & METHODS: 8-9wk old male C57BL/6J mice fed a high-fat diet (60% kcal) were injected with a retrovirus plasmid expressing E4orf1, or a null vector (Control). Glycemic control was determined by glucose and insulin tolerance test. Islet cell size, amount of insulin and glucagon were determined in formalin-fixed pancreas. Rat insulinoma cell line (832/13) was infected with E4orf1 or control to determine changes in glucose stimulated insulin secretion. Protein from flash frozen adipose tissue depots, liver and muscle was used to determine molecular signaling by western blotting. RESULTS: In multiple experiments, retrovirus-mediated E4orf1 expression in C57BL/6J mice significantly and reproducibly improved glucose excursion following a glucose load despite a high fat diet (60% energy). Importantly, E4orf1 improved glucose clearance without increasing insulin sensitivity, production or secretion, underscoring its insulin-independent effect. E4orf1 modulated molecular signaling in mice tissue, which included greater protein abundance of adiponectin, p-AKT and Glucose transporter Glu4. CONCLUSIONS: This study provides the proof of concept for translational development of E4orf1 as a potential anti-diabetic agent. High fat intake and impaired insulin signaling are often associated with obesity, diabetes and insulin resistance. Hence, the ability of E4orf1 to improve glycemic control despite high fat diet and independent of insulin, is particularly attractive.

Human adenovirus Ad36 and its E4orf1 gene enhance cellular glucose uptake even in the presence of inflammatory cytokines.

BACKGROUND: Aging and obesity are associated with elevated pro-inflammatory cytokines such as monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)α, which are linked to insulin resistance. Anti-inflammatory agents have marginal effect in improving insulin resistance. Hence, agents are needed to improve glycemic control despite the inflammation. Ad36, a human adenovirus, increases TNFα and MCP1 mRNA in adipose tissue, yet improves glycemic control in mice. Ad36 via its E4orf1 gene, up-regulates AKT/glucose transporter (Glut)-4 signaling to enhance cellular glucose uptake. OBJECTIVE: Directly test a role of Ad36, or E4orf1 in enhancing cellular glucose uptake in presence of inflammatory cytokines. METHODS: Experiment 1: 3T3-L1 preadipocytes were treated with 0, 10 or 100 ng/mL lipopolysaccharides (LPS), and infected with 0 or 5 plaque forming units (PFU) of Ad36/cell. 3T3-L1 cells that stably and inducibly express E4orf1 or a null vector (pTRE-E4orf1 or pTRE-null cells), were similarly treated with LPS and then with doxycycline, to induce E4orf1. Experiment 2: 3T3L1 preadipocytes were treated with 25 nM MCP1 or 20 nM TNFα for 16 h, followed by infection with 0 or 5 PFU of Ad36/cell. Experiment 3: pTRE-E4orf1 or -null cells were similarly treated with MCP1 or TNFα followed by doxycycline to induce E4orf1. Cellular glucose uptake and cellular signaling were determined 72 h post-Ad36 infection or E4orf1-induction, in continued presence of MCP1 or TNFα. RESULTS: In 3T3-L1 preadipocytes, Ad36, but not E4orf1, increased MCP1 and TNFα mRNA, in presence of LPS stimulation. Ad36 or E4orf1 up-regulated AKT-phosphorylation and Glut4 and increased glucose uptake (P < 0.05) in the presence of MCP1 or TNFα. CONCLUSIONS: Unlike Ad36, E4orf1 does not appear to stimulate inflammatory response. Ad36 and E4orf1 both enhance cellular glucose uptake even in presence of inflammation. Further research is needed to harness this novel and beneficial property of E4orf1 to improve hyperglycemia despite chronic inflammation that is commonly present in aging and obesity.

Evaluation of mercury exposure level, clinical diagnosis and treatment for mercury intoxication

Mercury occurs in various chemical forms, and it is different to health effects according to chemical forms. In consideration of the point, the evaluation of the mercury exposure to human distinguished from occupational and environmental exposure. With strict to manage occupational exposure in factory, it is declined mercury intoxication cases by metallic and inorganic mercury inhalation to occupational exposure. It is increasing to importance in environmental exposure and public health. The focus on the health impact of exposure to mercury is more on chronic, low or moderate grade exposure—albeit a topic of great controversy—, not high concentration exposure by methylmercury, which caused Minamata disease. Recently, the issue of mercury toxicity according to the mercury exposure level, health effects as well as the determination of what mercury levels affect health are in the spotlight and under active discussion. Evaluating the health effects and Biomarker of mercury exposure and establishing diagnosis and treatment standards are very difficult. It can implement that evaluating mercury exposure level for diagnosis by a provocation test uses chelating agent and conducting to appropriate therapy according to the result. but, indications for the therapy of chelating agents with mercury exposure have not yet been fully established. The therapy to symptomatic patients with mercury poisoning is chelating agents, combination therapy with chelating agents, plasma exchange, hemodialysis, plasmapheresis. But the further evaluations are necessary for the effects and side effects with each therapy.

Unbiased proteomic profiling strategy for discovery of bacterial effector proteins reveals that Salmonella protein PheA is a host cell cycle regulator.

Salmonella utilizes a type III secretion system to inject bacterial effector proteins into the host cell cytosol. Once in the cytosol, these effectors hijack various biochemical pathways to regulate virulence. Despite the importance of effector proteins, especially for understanding host-pathogen interactions, a potentially large number of effectors are yet to be identified. Here, we demonstrate that unbiased chemical proteomic profiling using off-the-shelf fluorescent probes leads to the discovery of a host cell cycle regulator encoded in the Salmonella genome. Our profiling combined with bioinformatic analysis implicates 29 Salmonella as potential effectors. We follow up on the top candidate, chorismate mutase-P/prehenate dehydratase, PheA, and present evidence that PheA is an effector that mimics E2F7 transcription factor of the host cell and promotes G1/S cell cycle arrest. This validates our strategy and opens opportunities for effector identification in the future.

Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: A prenatal diagnosis report

Distal limb deformities are congenital malformations with phenotypic variability and high genetic heterogeneity. Split hand/foot malformation, also known as ectrodactyly, is a congenital limb malformation characterized by a defect of the central rays of the hands and/or feet. Split hand/foot malformation with long-bone deficiency (SHFLD) is a rare condition related to a 17p13.3 duplication. Recently, genomic duplications encompassing BHLHA9 have been associated with SHFLD. We report a case of SHFLD presenting with campomelia of the right femur, bilateral agenesis of fibulae, bilateral club feet, and oligosyndactyly of the hands and feet, that was associated with a 17p13.3 duplication, as determined prenatally using array comparative genomic hybridization.

Evaluation and management of lead exposure

Lead, which is widely used in industry, is a common element found in low concentrations in the Earth's crust. Implementations to reduce environmental lead concentrations have resulted in a considerable reduction of lead levels in the environment (air) and a sustained reduction in the blood lead levels of the average citizen. However, people are still being exposed to lead through a variety of routes in everyday commodities. Lead causes health problems such as toxicity of the liver, kidneys, hematopoietic system, and nervous system. Having a carcinogenic risk as well, the IARC classifies inorganic lead compounds as probably carcinogenic to humans (Group 2A). Occupational lead poisonings have decreased due to the efforts to reduce the lead concentrations in the working environment. In contrast, health hazards associated with long-term environmental exposure to low concentrations of lead have been reported steadily. In particular, chronic exposure to low concentrations of lead has been reported to induce cognitive behavioral disturbances in children. It is almost impossible to remove lead completely from the human body, and it is not easy to treat health hazards due to lead exposure. Therefore, reduction and prevention of lead exposure are very important. We reviewed the toxicity and health hazards, monitoring and evaluation, and management of lead exposure.