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Activated carbon fiber (ACF) is widely used as an adsorption fiber in air purification systems. In this study, MgO and CuO nanoparticles were immobilized on ACF with enhancement of (3-aminopropyl)triethoxysilane (APTES). The obtained fibers’ coating efficiency, structural deformation, and antimicrobial activities were investigated. The MgO–CuO/APTES/ACF fiber (DA-MC) sample showed high antimicrobial activity (Escherichia coli and Staphylococcus aureus after 24-hour treatment. DA-MC also showed the highest coating efficiency, with no observed structural deformation. The presence of APTES and curing step at high temperature is believed to increase the coating efficiency and thus result in the high antimicrobial activity and also protect the ACF from deformation.

OBJECTIVE Sex differences in insulin sensitivity are present throughout the life-span, with men having a higher prevalence of insulin resistance and diabetes compared with women. Differences in lean mass, fat mass, and fat distribution-particularly ectopic fat-have all been postulated to contribute to the sexual dimorphism in diabetes risk. Emerging data suggest ectopic lipid composition and subcellular localization are most relevant; however, it is not known whether they explain sex differences in obesity-induced insulin resistance. METHODS To address this gap, this study evaluated insulin sensitivity and subcellular localization of intramuscular triacylglycerol, diacylglycerol, and sphingolipids as well as muscle acylcarnitines and serum lipidomics in people with obesity. RESULTS Insulin sensitivity was significantly lower in men (P

Pineapple (Ananas comosus) is a kind of fruit with high nutritional value. This study investigated the resistance to oxidation DPPH (2,2-Diphenyl-1picrylhydrazyl (free radical) and deionized Fe3+ of ethanol extracts from theleaves (leaves grow on stems) and crown (crown of scale leaves) of pineapples. Study of high extraction efficiency in 99,5% ethanol solvent, mixing ratio between samples with the solvent is 1 : 4, combined ultrasonic wave with a capacity of 120 Walt within 72 hours. The total polyphenol content in all treatments was high: leave sample (140,9 ± 2,86 mg GAE/g) and crown sample (204,6 ± 0,29 mg GAE/g). The results showed thatDPPH oxidation resistance and deionized Fe3+ were: crown (IC50 = 254,74 ± 1,55 mg/mL và 908,12 ± 9,35 mg/mL) higher than leaves (IC50 = 977,78 ± 30,27m mg/mL and 2156,62 ± 23,03 mg/mL). Theresearch has found that the use of waste products from pineapple peels with antioxidant capacity could be added to potential raw materials in the field of pharmaceutical production.

Titanium dioxide (TiO2) is a semiconductor photocatalyst widely applied in numerous fields due to possessing prominent photocatalytic properties. However, its practical applications in the form of nanoparticles or powders still have remained several limitations. Recently, novel photocatalytic porous composites have been discovered to be potential alternative approaches. In the present study, nanostructured magnesium-aminoclay-based TiO2 (MgAC–TiO2) was successfully deposited on an activated carbon fiber (ACF) matrix using the sol–gel approach followed by calcination at 350°C in an air atmosphere. The structure and photocatalytic activity of this as-prepared photocatalyst composite were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), the Brunauer-Emmett-Teller (BET), and UV-vis diffuse reflectance spectral analysis. The photocatalytic activity of MgAC–TiO2/ACF was investigated under batch conditions for the removal of methylene blue (MB) in solution under UV irradiation and dark conditions. The results revealed that MB is absorbed by MgAC–TiO2/ACF and that its photodecomposition occurs under UV irradiation. The addition of MgAC can prevent the sintering of TiO2 act as a dispersing agent to create a high specific surface area, and thus enhance photocatalytic efficiency. In addition, ACF in the MgAC–TiO2/ACF composite can additionally improve the photocatalytic activity by hindering electron-hole recombination, which is known as a synergetic effect, and thereby enhancing the photodegradation and removal efficiency of MB.

© 2020 Tam et al. Obesity and elevation of circulating free fatty acids are associated with an accumulation and proinflammatory polarization of macrophages within metabolically active tissues, such as adipose tissue, muscle, liver, and pancreas. Beyond macrophages, neutrophils also accumulate in adipose and muscle tissues during high-fat diets and contribute to a state of local inflammation and insulin resistance. However, the mechanisms by which neutrophils are recruited to these tissues are largely unknown. Here we used a cell culture system as proof of concept to show that, upon exposure to a saturated fatty acid, palmitate, macrophages release nucleotides that attract neutrophils. Moreover, we found that palmitate up-regulates pannexin-1 channels in macrophages that mediate the attraction of neutrophils, shown previously to allow transfer of nucleotides across membranes. These findings suggest that proinflammatory macrophages release nucleotides through pannexin-1, a process that may facilitate neutrophil recruitment into metabolic tissues during obesity.

The high antimicrobial ability and low toxicity of zinc-aminoclay (ZnAC) are claimed in our previous reports. In this study, we formulate a novel hand gel based on ZnAC and Opuntia humifusa (O. humifusa) extract, which is a high moisturizing agent. The antimicrobial activity, cytotoxicity, moisturizing effect, and clinical skin irritation of the hand gel are evaluated. The hand gel with 0.5 wt.% ZnAC and 1.0 v/v% O. humifusa extract can kill more than 99% Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria) after 24 h. Toxicity evaluation shows that, the hand gel does not affect the viability of mammalian HaCaT cells. Additionally, skin moisture is increased by applying the hand gel while its viscosity is at the standard level of commercial products. The hand gel has a skin irritation index of 0.0 and is classified as a non-irritating product. We successfully formulated hand gel from ZnAC, glucomannan, glycerol, and O. humifusa extract. Owing to the high antimicrobial activity and skin protection of hand gels, they are suitable to be used as hand sanitizers in restaurants, hospitals, and homes effectively.

Cerium oxide nanoparticles (CeO₂ NPs) contain a number of properties suitable for biomedical, environmental and cosmetic applications, and in fact, they are well-known as inorganic sunscreen agents. Recently, cerium aminoclay (CeAC) has been considered as a hybrid material for sunscreen application, however, the basic information on the toxicity and oxidative stress induced by CeAC and CeO₂ NPs on cell lines remains scanty. Therefore, the present study performed an MTT assay and ROS measurement to assess the cell viability and oxidative stress on HaCaT cells. The results showed that CeAC and CeO₂ NPs exhibited low toxicities (IC50 values of 88.74/86.95 μg/mL and 84.13/83.13 μg/mL for 24 and 48 h, respectively). In particular, CeAC showed less toxicity than that did CeO₂, due to its larger size, resulting in less penetration into the cell membrane, which fact reduced the level of toxicity. Notably, the coexistence of Ce3+ and Ce4+ oxidation states has been shown to promote the antioxidant activity of Ce nanomaterials, playing a major role in enhancing radical scavenging as well as reducing the intracellular ROS level on HaCaT cells. According to this estimates, CeAC and CeO₂ NPs can be considered to be promising candidates for future cosmetic applications, especially sunscreens.

CuO nanoparticles (NPs) have been used for the antimicrobial agent against different pathogenic microorganisms. In this study, CuO NPs are immobilized on the surface of activated carbon fiber (ACF) with the enhancement of (3-aminopropyl)triethoxysilane (APTES) as an organic binder. The obtained fibers are evaluated by coating efficiency, structural deformation, and antimicrobial activities. In the results, APTES can improve the immobilization of CuO on the surface of ACF. Also, the curing of silane layers at high temperature leads to the high coating efficiencies as well as structural reinforcement. The samples with drying step after APTES coating step (denoted as DA-CuO) have the highest antimicrobial activity against both Escherichia coli and Staphylococcus aureus after 24 hours treatment, respectively.

Background Colorectal carcinoma (CRC) is the third most common cancer in the world and also the third leading cause of cancer-related mortality in Taiwan. CRC tumorigenesis is a multistep process, starting from mutations causing loss of function of tumor suppressor genes, canonically demonstrated in adenomatous polyposis coli pathogenesis. Although many genes or chromosomal alterations have been shown to be involved in this process, there are still unrecognized molecular events within CRC tumorigenesis. Elucidating these mechanisms may help improve the management and treatment. Methods In this study, we aimed to identify copy number alteration of the smallest chromosomal regions that is significantly associated with sporadic CRC tumorigenesis using high-resolution array-based Comparative Genomic Hybridization (aCGH) and quantitative Polymerase chain reaction (qPCR). In addition, microsatellite instability assay and sequencing-based mutation assay were performed to illustrate the initiation event of CRC tumorigenesis. Results A total of 571 CRC patients were recruited and 377 paired CRC tissues from sporadic CRC cases were used to define the smallest regions with chromosome copy number changes. In addition, 198 colorectal polyps from 160 patients were also used to study the role of 20q13.33 gain in CRC tumorigenesis. We found that gain in 20q13.33 is the main chromosomal abnormalities in this patient population and counts 50.9 and 62.8% in CRC and colon polyps, respectively. Furthermore, APC and KRAS gene mutations were profiled simultaneously and co-analyzed with microsatellite instability and 20q13.33 gain in CRC patients. Our study showed that the frequency of 20q13.33 copy number gain was highest among all reported CRC mutations. Conclusion As APC or KRAS mutations are currently identified as the most important targets for CRC therapy, this study proposes that 20q13.33 copy number gain and the associated chromosomal genes function as promising biomarkers for both early stage detection and targeted therapy of sporadic CRCs in the future.

Background. The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is a very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) in the blood and urine is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. This study was aimed to evaluate the diagnostic efficacy of plasma NGAL in the diagnosis of CRS1. Methods. There were 139 patients with AHF or ADHF in the department of Cardiovascular Resuscitation and Interventional Cardiology at Ho Chi Minh City 115 People Hospital from September 2018 to March 2019. This was a prospective cohort study. Results. There were 48 cases (rate 34.5%) with CRS1, mean age was 66.12 ± 15.77 and men accounted for 50.4%. There were no significant differences of vital signs at admission, diagnosis, and EF-based heart failure between CRS1 and non-CRS1 groups. The urea, creatinine on first day (creatinine D1) and third day (creatinine D3), NT-proBNP, and NGAL levels were higher in the CRS1 group than the non-CRS1 group, p < 0.05 . The optimal cutoff plasma NGAL for diagnosing CRS1 was >353.23 ng/ml, area under curve (AUC) 0.732 (95% CI 0.65–0.80, p < 0.001 ), sensitivity 74.47%, specificity 68.48%, positive predictive value 54.7%, and negative predictive value 84%. Multivariable logistic regression analysis eGFRCKDEPID1 remained the strongest independent predictor of CRS1. Building the optimal regression model (without eGFRCKDEPID1) by the BMA (Bayesian model average) method with two variables NGAL and Creatinine D1, we had the equation: odds ratio = ey while y = −2.39 + 0.0037 × NGAL + 0.17 × Creatinine D1. The nomogram (without eGFRCKDEPID1) was designed to predict the likelihood of CRS1 with AUC 0.79. Conclusions. The combination of plasma NGAL and creatinine D1 on the first day at admission had a high accuracy of predictive model for CRS1.

Introduction: It is generally accepted that laminoplasty is a safe and reliable surgical treatment for cervical spine myelopathy (CSM) due to spinal canal stenosis. There are multiple techniques of laminoplasty for spinal cord decompression and most of them require expensive instruments to stabilize the laminae. From 2005 to 2015, we applied the modified Z-plasty (Sakou's technique) for CSM patients in an attempt to reduce the cost of treatment. Materials and methods: This is a retrospective study. CSM patients treated by modified Z-plasty technique were selected. We applied the Sakou’s technique, according to which the laminae will be opened in different directions alternatively. We use the JOA score and recovery rate of Hirabayashi to assess the neurological recovery and the Neck Disability Index (NDI) for the cervical functional outcome. Results: There were 42 patients with the mean follow-up duration of 10 years (5-15 years), male: female ratio of 3:1 and mean age of 61. The mean operating time and blood loss per lamina were 40 minutes and 45ml, respectively. The canal expanding index was 4.2mm (3-5 mm). The mean pre- and postoperative JOA score were 11.1 and 14.7, respectively (p

Ceramides contribute to obesity-linked insulin resistance and inflammation in vivo, but whether this is a cell-autonomous phenomenon is debated, particularly in muscle, which dictates whole-body glucose uptake. We comprehensively analyzed lipid species produced in response to fatty acids and examined the consequence to insulin resistance and pro-inflammatory pathways. L6 myotubes were incubated with BSA-adsorbed palmitate or palmitoleate in the presence of myriocin, fenretinide, or fumonisin B1. Lipid species were determined by lipidomic analysis. Insulin sensitivity was scored by Akt phosphorylation and glucose transporter 4 (GLUT4) translocation, while pro-inflammatory indices were estimated by IκBα degradation and cytokine expression. Palmitate, but not palmitoleate, had mild effects on Akt phosphorylation but significantly inhibited insulin-stimulated GLUT4 translocation and increased expression of pro-inflammatory cytokines Il6 and Ccl2. Ceramides, hexosylceramides, and sphingosine-1-phosphate significantly heightened by palmitate correlated negatively with insulin sensitivity and positively with pro-inflammatory indices. Inhibition of sphingolipid pathways led to marked changes in cellular lipids, but did not prevent palmitate-induced impairment of insulin-stimulated GLUT4 translocation, suggesting that palmitate-induced accumulation of deleterious lipids and insulin resistance are correlated but independent events in myotubes. We propose that muscle cell-endogenous ceramide production does not evoke insulin resistance and that deleterious effects of ceramides in vivo may arise through ancillary cell communication.

Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of diacylglycerol (DAG) into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms, and DAG preferences. DGKe has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKe in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKe-KO and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGKe KO mice, which was paradoxically associated with increased glucose tolerance. Although skeletal muscle insulin sensitivity was unaltered, whole-body respiratory exchange ratio was reduced, and abundance of mitochondrial markers was increased, indicating a greater reliance on fat oxidation and intracellular lipid metabolism in DGKe KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGKe KO mice may undergo rapid turnover because of increased mitochondrial function and lipid oxidation, rather than storage, which in turn may preserve insulin sensitivity. In conclusion, DGKe plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-018-35426-z, published online 05 February 2019 In Figure 1, in the Historic/Modern Samples map, Cambodia, Celebes, Hainan, Laos, Papua New Guinea, Seman, South Moluccas and Vietnam are labelled incorrectly.

Lysophosphatidylcholine acyltransferase 3 (Lpcat3) is involved in phosphatidylcholine remodeling in the small intestine and liver. We investigated lipid metabolism in inducible intestine-specific and liver-specific Lpcat3 gene knock-out mice. We produced Lpcat3-Flox/villin-Cre-ERT2 mice, which were treated with tamoxifen (at days 1, 3, 5, and 7), to delete Lpcat3 specifically in the small intestine. At day 9 after the treatment, we found that Lpcat3 deficiency in enterocytes significantly reduced polyunsaturated phosphatidylcholines in the enterocyte plasma membrane and reduced Niemann-Pick C1-like 1 (NPC1L1), CD36, ATP-binding cassette transporter 1 (ABCA1), and ABCG8 levels on the membrane, thus significantly reducing lipid absorption, cholesterol secretion through apoB-dependent and apoB-independent pathways, and plasma triglyceride, cholesterol, and phospholipid levels, as well as body weight. Moreover, Lpcat3 deficiency does not cause significant lipid accumulation in the small intestine. We also utilized adenovirus-associated virus-Cre to deplete Lpcat3 in the liver. We found that liver deficiency only reduces plasma triglyceride levels but not other lipid levels. Furthermore, there is no significant lipid accumulation in the liver. Importantly, small intestine Lpcat3 deficiency has a much bigger effect on plasma lipid levels than that of liver deficiency. Thus, inhibition of small intestine Lpcat3 might constitute a novel approach for treating hyperlipidemia.

A 38-year-old African American male presented with progressive pain, swelling, numbness, and warmth of the left upper extremity ten days before admission. A chest computerized tomography scan showed a large 8.3 cm × 6.1 cm x 9.9 cm anterior mediastinal mass with compression of the left brachiocephalic vein and superior vena cava. A venous doppler showed multiple occlusive venous thrombi in bilateral upper extremities, including the bilateral internal jugular and subclavian veins, as well as the left subclavian, axillary, cephalic, brachial and median cubital veins. Further laboratory workup came positive for acetylcholine receptor binding antibody suggesting myasthenia gravis, but the patient was asymptomatic for myasthenia gravis. A percutaneous core CT guided biopsy pathology resulted in a predominant T-cell population CD5 positive with few B cells; the immunophenotypic features suggested Type B2 thymoma. To the best of our knowledge, this case is the only reported thymoma presenting with bilateral deep vein thrombosis of the upper extremities. The deep vein thrombosis therapy was enoxaparin 1mg/kg subcutaneously every 12 hours and dexamethasone 4mg intravenously every 4 hours as an anti-inflammatory drug for thymoma related compression of the mediastinum. The patient was referred to a tertiary oncological medical center for a total thymectomy, chemotherapy, and adjuvant radiotherapy.

Viral hepatitis infection is a major global issue and a leading cause of liver disease and associated deaths. Over time, patients infected with hepatitis B (HBV) or C virus (HCV) develop cirrhosis and, eventually, hepatocellular carcinoma (HCC). For this reason, they need to be constantly monitored. Current Asian guidelines recommend the determination of serum alpha-fetoprotein (AFP) together with liver ultrasounds every six months to detect HCC nodules. However, both methods have several limitations, and other biomarkers have been studied for monitoring cirrhosis, including SCCA-IgM, an immune-complex formed by Squamous Cell Carcinoma Antigen and IgM. To date, SCCA-IgM has been validated as a novel biomarker for liver diseases only in European populations. The aim of our study was to analyze SCCA-IgM as a biomarker to monitor cirrhosis evolution in an Asian cohort of patients and to compare its performance to that of AFP. We analyzed the concentration of AFP and SCCA-IgM in serum samples obtained from a group of Asian adult patients with cirrhosis or HCC and a control group of patients admitted for gastrointestinal disorders. In untreated patients and similarly to AFP, SCCA-IgM levels were significantly higher in patients with cirrhosis compared to those with HCC. In addition, SCCA-IgM, but not AFP serological levels, were significantly lower in HCC patients who were treated with surgical resection compared to those who received a different therapy.

Ceramides and sphingolipids are a family of lipid molecules that circulate in serum and accumulate in skeletal muscle, promoting insulin resistance. Plasma ceramide and dihydroceramide are related to insulin resistance, yet less is known regarding other ceramide and sphingolipid species. Despite its association with insulin sensitivity, chronic endurance exercise training does not change plasma ceramide and sphingolipid content, with little known regarding a single bout of exercise. We measured basal relationships and the effect of acute exercise (1.5 h at 50% V̇o2 max) and recovery on serum ceramide and sphingolipid content in sedentary obese individuals, endurance-trained athletes, and individuals with type 2 diabetes (T2D). Basal serum C18:0, C20:0, and C24:1 ceramide and C18:0 and total dihydroceramide were significantly higher in T2D and, along with C16:0 ceramide and C18:0 sphingomyelin, correlated positively with insulin resistance. Acute exercise significantly increased serum ceramide, glucosylceramide, and GM3 gangliosides, which largely decreased to basal values in recovery. Sphingosine 1-phosphate and sphingomyelin did not change during exercise but decreased below basal values in recovery. Serum C16:0 and C18:0 ceramide and C18:0 sphingomyelin, but not the total concentrations of either of them, were positively correlated with markers of muscle NF-κB activation, suggesting that specific species activate intracellular inflammation. Interestingly, a subset of sphingomyelin species, notably C14:0, C22:3, and C24:4 species, was positively associated with insulin secretion and glucose tolerance. Together, these data show that unique ceramide and sphingolipid species associate with either protective or deleterious features for diabetes and could provide novel therapeutic targets for the future.

Objective— Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined. Approach and Results— We crossed PLTP-Flox-ΔNeo and adipocyte protein 2 (aP2)-Cre recombinase (Cre) transgenic mice to create PLTP-Flox-ΔNeo/aP2-Cre mice that have a 90 and a 60% reduction in PLTP mRNA in adipose tissue and macrophages, respectively. PLTP ablation resulted in a significant reduction in plasma PLTP activity (22%), high-density lipoprotein-cholesterol (21%), high-density lipoprotein-phospholipid (20%), and apolipoprotein A-I (33%) levels, but had no effect on nonhigh-density lipoprotein levels in comparison with those of PLTP-Flox-ΔNeo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-ΔNeo/aP2-Cre mice and PLTP-Flox-ΔNeo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type→PLTP-Flox-ΔNeo/aP2-Cre and wild-type→PLTP-Flox-ΔNeo mice. Thus, we constructed a mouse model (wild-type→PLTP-Flox-ΔNeo/aP2-Cre) with PLTP deficiency in adipocytes but not in macrophages. These knockout mice also showed significant decreases in plasma PLTP activity (19%) and cholesterol (18%), phospholipid (17%), and apolipoprotein A-I (26%) levels. To further investigate the mechanisms behind the reduction in plasma apolipoprotein A-I and high-density lipoprotein lipids, we measured apolipoprotein A-I–mediated cholesterol efflux in adipose tissue explants and found that endogenous and exogenous PLTP significantly increased cholesterol efflux from the explants. Conclusions— Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.

Background: The intake of a Western diet enriched in animal fat has been shown to be a major risk factor for Type 2 diabetes and obesity. Previous rodent studies have indicated that these conditions may be triggered by the accumulation of the sphingolipid ceramide in insulin-sensitive tissues. However, data are lacking in this regard from both humans and non-human primates. Objective: Here we have investigated the relationship between plasma ceramides and metabolic syndrome in Rhesus macaques fed a high-fat and high-fructose (HFFD) ‘western' diet. Methods: We investigated this relationship in cohorts of monkeys fed a HFFD for a period of 8 months to 5 years. Animals were classified as control, pre-diabetic or diabetic based on fasting plasma parameters and insulin sensitivity. Results: HFFD treatment produced significant increases in body weight and body fat and also resulted in a decline in insulin sensitivity. In parallel to the reduction in insulin sensitivity, significant increases in both plasma ceramide and dihydroceramide levels were observed, which further increased as animals progressed to the diabetic state. Plasma levels of the rare sphingolipid C18:0 deoxysphinganine, a marker of increased metabolic flux through serine palmitoyl transferase (SPT), were also elevated in both pre- and diabetic animals. Furthermore, plasma serine levels were significantly elevated in diabetic monkeys, which may indicate a shift in SPT substrate selectivity from serine to alanine or glycine. In contrast, branch chain amino acids were unchanged in pre-diabetic non-human primates, and only plasma valine levels were elevated in diabetic animals. Conclusion: Together, these data indicate that HFFD induces de novo synthesis of ceramides in non-human primates, and that increased production of plasma ceramides is significantly correlated with the decline in insulin sensitivity.

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D ( P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH ( P < 0.05), tended to be elevated in OB vs. ATH ( P = 0.07), and was inversely related to insulin sensitivity among the entire cohort ( r = −0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio.

Ceramides are a class of sphingolipids implicated in cellular signaling and may be involved in systolic heart failure. The relationship between ceramide levels and heart failure phenotypes has not been carefully investigated. We analyzed circulating sphingolipid levels in 1,131 patients undergoing

Ceramides and other sphingolipids comprise a family of lipid molecules that accumulate in skeletal muscle and promote insulin resistance. Chronic endurance exercise training decreases muscle ceramides and other sphingolipids, but less is known about the effects of a single bout of exercise. We measured basal relationships and the effect of acute exercise (1.5 h at 50% $$ \overset{.}{V}{\mathrm{O}}_{2 \max } $$ ) and recovery on muscle sphingolipid content in obese volunteers, endurance trained athletes and individuals with type 2 diabetes. Muscle C18:0 ceramide (p = 0.029), dihydroceramide (p = 0.06) and glucosylceramide (p = 0.03) species were inversely related to insulin sensitivity without differences in total ceramide, dihydroceramide, and glucosylceramide concentration. Muscle C18:0 dihydroceramide correlated with markers of muscle inflammation (p = 0.04). Transcription of genes encoding sphingolipid synthesis enzymes was higher in athletes, suggesting an increased capacity for sphingolipid synthesis. The total concentration of muscle ceramides and sphingolipids increased during exercise and then decreased after recovery, during which time ceramide levels reduced to significantly below basal levels. These data suggest ceramide and other sphingolipids containing stearate (18:0) are uniquely related to insulin resistance in skeletal muscle. Recovery from an exercise bout decreased muscle ceramide concentration; this may represent a mechanism promoting the insulin-sensitising effects of acute exercise.

Superoxide radicals have been implicated in the pathogenesis of ischemia/reperfusion, aging, and inflammatory diseases. In the present work, we have shown that the Fe(3+) complexes of flavonoids (polyphenols) were much more effective than the uncomplexed flavonoids in protecting isolated rat hepatocytes against hypoxia-reoxygenation injury. The 2:1 flavonoid-metal complexes of Cu(2+), Fe(2+), or Fe(3+) were more effective than the parent compounds in scavenging superoxide radicals generated by xanthine oxidase/hypoxanthine (an enzymatic superoxide-generating system). The 2:1 [flavonoid:Fe(3+)] complexes but not the [deferoxamine:Fe(3+)] complex readily scavenged superoxide radicals. These results suggest that the initial step in superoxide radical scavenging (SRS) activity involves a redox-active flavonoid:Fe(3+) complex. Flavonoid:Fe(3+) complexes should, therefore, be tested as a therapy for the treatment of ischemia/reperfusion injury.

The GPR119 receptor plays an important role in the secretion of incretin hormones in response to nutrient consumption. We have studied the ability of an array of naturally occurring endocannabinoid-like lipids to activate GPR119 and have identified several lipid receptor agonists. The most potent receptor agonists identified were three N-acylethanolamines: oleoylethanolamine (OEA), palmitoleoylethanolamine, and linoleylethanolamine (LEA), all of which displayed similar potency in activating GPR119. Another lipid, 2-oleoylglycerol (2-OG), also activated GPR119 receptor but with significantly lower potency. Endogenous levels of endocannabinoid-like lipids were measured in intestine in fasted and refed mice. Of the lipid GPR119 agonists studied, the intestinal levels of only OEA, LEA, and 2-OG increased significantly upon refeeding. Intestinal levels of OEA and LEA in the fasted mice were low. In the fed state, OEA levels only moderately increased, whereas LEA levels rose drastically. 2-OG was the most abundant of the three GPR119 agonists in intestine, and its levels were radically elevated in fed mice. Our data suggest that, in lean mice, 2-OG and LEA may serve as physiologically relevant endogenous GPR119 agonists that mediate receptor activation upon nutrient uptake.

Cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that disseminates to the CNS causing fatal meningitis in immunocompromised patients. Dendritic cells (DCs) phagocytose C. neoformans following inhalation. Following uptake, cryptococci translocate to the DC lysosomal compartment and are killed by oxidative and non-oxidative mechanisms. DC lysosomal extracts kill cryptococci in vitro; however, the means of antifungal activity remain unknown. Our studies determined non-oxidative antifungal activity by DC lysosomal extract. We examined DC lysosomal killing of cryptococcal strains, anti-fungal activity of purified lysosomal enzymes, and mechanisms of killing against C. neoformans. Results confirmed DC lysosome fungicidal activity against all cryptococcal serotypes. Purified lysosomal enzymes, specifically cathepsin B, inhibited cryptococcal growth. Interestingly, cathepsin B combined with its enzymatic inhibitors led to enhanced cryptococcal killing. Electron microscopy revealed structural changes and ruptured cryptococcal cell walls following treatment. Finally, additional studies demonstrated that osmotic lysis was responsible for cryptococcal death.

The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the "a" determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of "a" determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly underappreciated.