Identification of potential anti-hyperglycemic compounds in Cordyceps militaris ethyl acetate extract: in vitro and in silico studies.

Cordyceps militaris has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract (1-14) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against α-amylase (IC50 = 6.443 ± 0.364 mg.mL-1) and α-glucosidase (IC50 = 2.580 ± 0.194 mg.mL-1). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. 1 (ground state: -888.49715 a.u.; dipole moment 3.779 Debye; DS¯ -12.3 kcal.mol-1; polarizability 34.7 Å3; logP - 1.30), 10 (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; DS¯ -12.6 kcal.mol-1; polarizability 24.9 Å3; logP - 3.39), and 12 (ground state: -1460.07276 a.u.; dipole moment 3.976 Debye; DS¯ -12.5 kcal.mol-1; polarizability 52.4 Å3; logP - 4.39). The results encourage further experimental tests on cordycepin (1), mannitol (10), and adenosylribose (12) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications.Communicated by Ramaswamy H. Sarma.

FAS and SREBP-1c Inhibition via AMPK Activation in HepG2 Cells by Biovip, Tox-off, and Traphanoside GO1 from Glinus oppositifolius.

Glinus oppositifolius is an endemic herbaceous plant found in tropical Asian countries and is native in Vietnam. It is used in traditional folk medicine because of its flavor and antiseptic and laxative effects. In the current research, the effects of Tox-off, Biovip, and the purified compounds isolated from G. oppositifolius in the previous study were evaluated on the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) in C2C12 myoblasts. In addition, the most potent active compounds, traphanoside-GO1 (TRA-GO1) and TRA-GO5 have validated the reduction of fatty acid synthase (FAS) and sterol regulatory element binding protein (SREBP)-1c in HepG2 cells. We found that Tox-off and Biovip significantly increased the phosphorylation of AMPK and ACC in C2C12 myoblasts. Furthermore, TRA-GO1 and TRA-GO5 significantly increased the AMPK activation and phosphorylation of its downstream substrate ACC in a concentration-dependent way compared to the dimethyl sulfoxide (DMSO) control. Besides, the protein level of FAS and SREBP-1c decreased by TRA-GO1 and TRA-GO5 in a concentration-dependent manner. Taken together, our results showed that the increased AMPK and ACC phosphorylation by active components of G. oppositifolius may activate the AMPK signaling pathways, which are useful for the anti-obesity and its related metabolic disorders.

FBP1-Altered Carbohydrate Metabolism Reduces Leukemic Viability through Activating P53 and Modulating the Mitochondrial Quality Control System In Vitro.

Acute myeloid leukemia (AML)-the most frequent form of adult blood cancer-is characterized by heterogeneous mechanisms and disease progression. Developing an effective therapeutic strategy that targets metabolic homeostasis and energy production in immature leukemic cells (blasts) is essential for overcoming relapse and improving the prognosis of AML patients with different subtypes. With respect to metabolic regulation, fructose-1,6-bisphosphatase 1 (FBP1) is a gluconeogenic enzyme that is vital to carbohydrate metabolism, since gluconeogenesis is the central pathway for the production of important metabolites and energy necessary to maintain normal cellular activities. Beyond its catalytic activity, FBP1 inhibits aerobic glycolysis-known as the "Warburg effect"-in cancer cells. Importantly, while downregulation of FBP1 is associated with carcinogenesis in major human organs, restoration of FBP1 in cancer cells promotes apoptosis and prevents disease progression in solid tumors. Recently, our large-scale sequencing analyses revealed FBP1 as a novel inducible therapeutic target among 17,757 vitamin-D-responsive genes in MV4-11 or MOLM-14 blasts in vitro, both of which were derived from AML patients with FLT3 mutations. To investigate FBP1's anti-leukemic function in this study, we generated a new AML cell line through lentiviral overexpression of an FBP1 transgene in vitro (named FBP1-MV4-11). Results showed that FBP1-MV4-11 blasts are more prone to apoptosis than MV4-11 blasts. Mechanistically, FBP1-MV4-11 blasts have significantly increased gene and protein expression of P53, as confirmed by the P53 promoter assay in vitro. However, enhanced cell death and reduced proliferation of FBP1-MV4-11 blasts could be reversed by supplementation with post-glycolytic metabolites in vitro. Additionally, FBP1-MV4-11 blasts were found to have impaired mitochondrial homeostasis through reduced cytochrome c oxidase subunit 2 (COX2 or MT-CO2) and upregulated PTEN-induced kinase (PINK1) expressions. In summary, this is the first in vitro evidence that FBP1-altered carbohydrate metabolism and FBP1-activated P53 can initiate leukemic death by activating mitochondrial reprogramming in AML blasts, supporting the clinical potential of FBP1-based therapies for AML-like cancers.

The role of animals as a source of antimicrobial resistant nontyphoidal Salmonella causing invasive and non-invasive human disease in Vietnam.

BACKGROUND: Nontyphoidal Salmonella (NTS) are associated with both diarrhea and bacteremia. Antimicrobial resistance (AMR) is common in NTS in low-middle income countries, but the major source(s) of AMR NTS in humans are not known. Here, we aimed to assess the role of animals as a source of AMR in human NTS infections in Vietnam. We retrospectively combined and analyzed 672 NTS human and animal isolates from four studies in southern Vietnam and compared serovars, sequence types (ST), and AMR profiles. We generated a population structure of circulating organisms and aimed to attribute sources of AMR in NTS causing invasive and noninvasive disease in humans using Bayesian multinomial mixture models. RESULTS: Among 672 NTS isolates, 148 (22%) originated from human blood, 211 (31%) from human stool, and 313 (47%) from animal stool. The distribution of serovars, STs, and AMR profiles differed among sources; serovars Enteritidis, Typhimurium, and Weltevreden were the most common in human blood, human stool, and animals, respectively. We identified an association between the source of NTS and AMR profile; the majority of AMR isolates were isolated from human blood (p < 0.001). Modelling by ST-AMR profile found chickens and pigs were likely the major sources of AMR NTS in human blood and stool, respectively; but unsampled sources were found to be a major contributor. CONCLUSIONS: Antimicrobial use in food animals is hypothesized to play role in the emergence of AMR in human pathogens. Our cross-sectional population-based approach suggests a significant overlap between AMR in NTS in animals and humans, but animal NTS does explain the full extent of AMR in human NTS infections in Vietnam.

Detecting changes in facial temperature induced by a sudden auditory stimulus based on deep learning-assisted face tracking.

Thermal Imaging (Infrared-Imaging-IRI) is a promising new technique for psychophysiological research and application. Unlike traditional physiological measures (like skin conductance and heart rate), it is uniquely contact-free, substantially enhancing its ecological validity. Investigating facial regions and subsequent reliable signal extraction from IRI data is challenging due to head motion artefacts. Exploiting its potential thus depends on advances in analytical methods. Here, we developed a novel semi-automated thermal signal extraction method employing deep learning algorithms for facial landmark identification. We applied this method to physiological responses elicited by a sudden auditory stimulus, to determine if facial temperature changes induced by a stimulus of a loud sound can be detected. We compared thermal responses with psycho-physiological sensor-based tools of galvanic skin response (GSR) and electrocardiography (ECG). We found that the temperatures of selected facial regions, particularly the nose tip, significantly decreased after the auditory stimulus. Additionally, this response was quite rapid at around 4-5 seconds, starting less than 2 seconds following the GSR changes. These results demonstrate that our methodology offers a sensitive and robust tool to capture facial physiological changes with minimal manual intervention and manual pre-processing of signals. Newer methodological developments for reliable temperature extraction promise to boost IRI use as an ecologically-valid technique in social and affective neuroscience.

Cost savings through implementation of an integrated home-based record: a case study in Vietnam.

OBJECTIVES: In Vietnam, there are three major home-based records (HBRs) for maternal and child health (MCH) that have been already nationally scaled up, i.e., Maternal and Child Health Handbook (MCH Handbook), Child Vaccination Handbook, and Child Growth Monitoring Chart. The MCH Handbook covers all the essential recording items that are included in the other two. This overlapping of recording items between the HBRs is likely to result in inefficient use of both financial and human resources. This study is aimed at estimating the magnitude of cost savings that are expected to be realized through implementing exclusively the MCH Handbook by terminating the other two. STUDY DESIGN: Secondary data collection and analyses on HBR production and distribution costs and health workers' opportunity costs. METHODS: Through multiplying the unit costs by their respective quantity multipliers, recurrent costs of operations of three HBRs were estimated. Moreover, magnitude of cost savings likely to be realized was estimated, by calculating recurrent costs overlapping between the three HBRs. RESULTS: It was estimated that implementing exclusively the MCH Handbook would lead to cost savings of United States dollar 3.01 million per annum. The amount estimated is minimum cost savings because only recurrent cost elements (HBR production and distribution costs and health workers' opportunity costs) were incorporated into the estimation. Further indirect cost savings could be expected through reductions in health expenditures, as the use of the MCH Handbook would contribute to prevention of maternal and child illnesses by increasing antenatal care visits and breastfeeding practices. CONCLUSION: To avoid wasting financial and human resources, the MCH Handbook should be exclusively implemented by abolishing the other two HBRs. This study is globally an initial attempt to estimate cost savings to be realized through avoiding overlapping operations between multiple HBRs for MCH.

Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.

The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro. Amino acid supplementation rescued SCIPC from nutrient deprivation, likely by providing cellular energy. Generating SCIPC under physiological oxygen tension of 5% conferred hypoxia resistance without affecting their differentiation or function. A two-pronged strategy of physiological oxygen acclimatization during differentiation and amino acid supplementation during transplantation significantly improved SCIPC survival after transplant.

The integration of the internal and external milieu in the insula during dynamic emotional experiences.

Whilst external events trigger emotional responses, interoception (the perception of internal physiological states) is fundamental to core emotional experience. By combining high resolution functional neuroimaging with concurrent physiological recordings, we investigated the neural mechanisms of interoceptive integration during free listening to an emotionally salient audio film. We found that cardiac activity, a key interoceptive signal, was robustly synchronised across participants and centrally represented in the posterior insula. Effective connectivity analysis revealed that the anterior insula, specifically tuned to the emotionally salient moments of the audio stream, serves as an integration hub of interoceptive processing: interoceptive states represented in the posterior insula are integrated with exteroceptive representations by the anterior insula to highlight these emotionally salient moments. Our study for the first time demonstrates the insular hierarchy for interoceptive processing during natural emotional experience. These findings provide an ecologically-valid framework for elucidating the neural underpinnings of emotional deficits in neuropsychiatric disorders.

The Rise and Fall of Universal Salt Iodization in Vietnam: Lessons Learned for Designing Sustainable Food Fortification Programs With a Public Health Impact.

BACKGROUND: In 2005, more than 90% of Vietnamese households were using adequately iodized salt, and urinary iodine concentration among women of reproductive age was in the optimal range. However, household coverage declined thereafter to 45% in 2011, and urinary iodine concentration levels indicated inadequate iodine intake. OBJECTIVE: To review the strengths and weaknesses of the Vietnamese universal salt iodization program from its inception to the current day and to discuss why achievements made by 2005 were not sustained. METHODS: Qualitative review of program documents and semistructured interviews with national stakeholders. RESULTS: National legislation for mandatory salt iodization was revoked in 2005, and the political importance of the program was downgraded with consequential effects on budget, staff, and authority. CONCLUSIONS: The Vietnamese salt iodization program, as it was initially designed and implemented, was unsustainable, as salt iodization was not practiced as an industry norm but as a government-funded activity. An effective and sustainable salt iodization program needs to be reestablished for the long-term elimination of iodine deficiency, building upon lessons learned from the past and programs in neighboring countries. The new program will need to include mandatory legislation, including salt for food processing; industry responsibility for the cost of fortificant; government commitment for enforcement through routine food control systems and monitoring of iodine status through existing health/nutrition assessments; and intersectoral collaboration and management of the program. Many of the lessons would apply equally to universal salt iodization programs in other countries and indeed to food fortification programs in general.

Out-of-sync: disrupted neural activity in emotional circuitry during film viewing in melancholic depression.

While a rich body of research in controlled experiments has established changes in the neural circuitry of emotion in major depressive disorders, little is known as to how such alterations might translate into complex, naturalistic settings--namely involving dynamic multimodal stimuli with rich contexts, such as those provided by films. Neuroimaging paradigms employing dynamic natural stimuli alleviate the anxiety often associated with complex tasks and eschew the need for laboratory-style abstractions, hence providing an ecologically valid means of elucidating neural underpinnings of neuropsychiatric disorders. To probe the neurobiological signature of refined depression subtypes, we acquired functional neuroimaging data in patients with the melancholic subtype of major depressive disorder during free viewing of emotionally salient films. We found a marked disengagement of ventromedial prefrontal cortex during natural viewing of a film with negative emotional valence in patients with melancholia. This effect significantly correlated with depression severity. Such changes occurred on the background of diminished consistency of neural activity in visual and auditory sensory networks, as well as higher-order networks involved in emotion and attention, including bilateral intraparietal sulcus and right anterior insula. These findings may reflect a failure to re-allocate resources and diminished reactivity to external emotional stimuli in melancholia.

Evaluation of the protective effect of Pterocarpus marsupium on acetic acid-induced ulcerative colitis in rats.

The aim of the study was to evaluate the effect of Pterocarpus marsupium (PM) on acetic acid (AA)-induced ulcerative colitis (UC) in rats. The rats were divided into five groups, each having six rats. PM extract 100 mg and 200 mg/kg was given orally to groups four and five, respectively, and standard drug sulfasalazine (100 mg/kg, p.o) to group three. Group two served as UC control animals, and group one control animals received vehicle for 7 days. UC was induced by administering AA (3 % v/v of 2 ml) to all the animals except group one. After 72 h, the animals were killed and the colon was dissected out for microscopic, clinical evaluation, histopathological study and biochemical estimation. PM (100 and 200 mg/kg)-treated group had significantly reduced colon inflammation and mucosal damage. The treatment also normalized the altered antioxidant enzyme levels (LPO, SOD and GSH). Histopathological studies support the effect. The protective effect of PM may be due to antiinflammatory and antioxidant properties.

Development of antimicrobial biomaterials produced from chitin-nanofiber sheet/silver nanoparticle composites.

BACKGROUND: Chitin nanofibers sheets (CNFSs) with nanoscale fiber-like surface structures are nontoxic and biodegradable biomaterials with large surface-to-mass ratio. CNFSs are widely applied as biomedical materials such as a functional wound dressing. This study aimed to develop antimicrobial biomaterials made up of CNFS-immobilized silver nanoparticles (CNFS/Ag NPs). MATERIALS AND METHODS: CNFSs were immersed in suspensions of Ag NPs (5.17 ± 1.9 nm in diameter; mean ± SD) for 30 min at room temperature to produce CNFS/Ag NPs. CNFS/Ag NPs were characterized by transmission electron microscopy (TEM) and then tested for antimicrobial activities against Escherichia (E.) coli, Pseudomonas (P.) aeruginosa, and H1N1 influenza A virus, three pathogens that represent the most widespread infectious bacteria and viruses. Ultrathin sectioning of bacterial cells also was carried out to observe the bactericidal mechanism of Ag NPs. RESULTS: The TEM images indicated that the Ag NPs are dispersed and tightly adsorbed onto CNFSs. Although CNFSs alone have only weak antimicrobial activity, CNFS/Ag NPs showed much stronger antimicrobial properties against E. coli, P. aeruginosa, and influenza A virus, with the amount of immobilized Ag NPs onto CNFSs. CONCLUSIONS: Our results suggest that CNFS/Ag NPs interacting with those microbes exhibit stronger antimicrobial activities, and that it is possible to apply CNFS/Ag NPs as anti-virus sheets as well as anti-infectious wound dressings.

Surgical outcomes of hyperthermic intraperitoneal chemotherapy: analysis of the american college of surgeons national surgical quality improvement program.

IMPORTANCE: Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery have been shown to benefit selected patients with peritoneal carcinomatosis. However, these procedures are associated with high morbidity and mortality. Available data investigating the outcomes of HIPEC are mostly limited to single-center studies. To date, there have been few large-scale studies investigating the postoperative outcomes of HIPEC. OBJECTIVE: To determine the associated 30-day morbidity and mortality of cytoreductive surgery-HIPEC in the treatment of metastatic and primary peritoneal cancer in American College of Surgeons National Surgical Quality Improvement Program centers. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of HIPEC cases performed for primary and metastatic peritoneal cancer diagnoses was conducted. The cytoreductive surgical procedures were sampled, and disease processes were identified. Patient demographics, intraoperative occurrences, and postoperative complications were reviewed from the American College of Surgeons National Surgical Quality Improvement Program from 2005-2011. MAIN OUTCOMES AND MEASURES: Thirty-day mortality and morbidity. RESULTS: Of the cancers identified among the 694 sampled cases, 14% of patients had appendiceal cancer, 11% had primary peritoneal cancer, and 8% had colorectal cancer. The American Society of Anesthesiologists classification was 3 for 70% of patients. The average operative time was 7.6 hours, with 15% of patients requiring intraoperative transfusions. Postoperative bleeding (17%), septic shock (16%), pulmonary complications (15%), and organ-space infections (9%) were the most prevalent postoperative complications. The average length of stay was 13 days, with a 30-day readmission rate of 11%. The rate of reoperation was 10%, with an overall mortality rate of 2%. CONCLUSIONS AND RELEVANCE: American College of Surgeons National Surgical Quality Improvement Program hospitals performing HIPEC have acceptable rates of morbidity and mortality.

Prevalence and correlates of zinc deficiency in pregnant Vietnamese women in Ho Chi Minh City.

BACKGROUND: Although Vietnam is a region with a plant-based diet that has a high zinc deficiency, epidemiological data showing how this affects pregnant women are limited. This study explores the prevalence of zinc deficiency and possible correlates in pregnant Vietnamese women in Ho Chi Minh City. METHODS: This was a cross-sectional study conducted at a general hospital in Ho Chi Minh City, Vietnam. All pregnant women who came to their first antenatal care visit from November 2011 to June 2012 were recruited. Those taking a vitamin and/or mineral supplement were excluded. Serum zinc concentrations, determined by a standard colorimetric method, of 10.7 µmol/L-17.5 µmol/L (70.0 g/dL-114 g/dL) were classified as normal and under 10.7 µmol/L (70.0 g/dL) as zinc deficient. RESULTS: In total, 254 pregnant women were invited and 107 (42%) participated. The mean age of participants was 29 years, and mean gestational age was 10 weeks. Median zinc concentration in serum was 13.6 µmol/L, and the prevalence of zinc deficiency was 29% (95% CI=21%-39%). The daily intake of a milk product supplement was the only significant correlate of zinc deficiency of the items investigated (adjusted OR=0.40, 95% CI=0.16-0.99, p=0.049). DISCUSSION: This is the first study reporting that more than 25% of pregnant Vietnamese women in Ho Chi Minh City are zinc deficient. Further academic and clinical input is needed to confirm the scale of this neglected issue and to investigate the potential of milk product supplementation in this population.

Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation.

Individuals with Down syndrome over age 40 years are at risk for developing dementia of the Alzheimer type and have evidence for chronic oxidative stress. There is a paucity of treatment trials for dementia in Down syndrome in comparison to Alzheimer disease in the general (non-Down syndrome) population. This 2-year randomized, double-blind, placebo-controlled trial assessed whether daily oral antioxidant supplementation (900 IU of alpha-tocopherol, 200 mg of ascorbic acid and 600 mg of alpha-lipoic acid) was effective, safe and tolerable for 53 individuals with Down syndrome and dementia. The outcome measures comprised a battery of neuropsychological assessments administered at baseline and every 6 months. Compared to the placebo group, those individuals receiving the antioxidant supplement showed neither an improvement in cognitive functioning nor a stabilization of cognitive decline. Mean plasma levels of alpha-tocopherol increased ~2-fold in the treatment group and were consistently higher than the placebo group over the treatment period. Pill counts indicated good compliance with the regimen. No serious adverse events attributed to the treatment were noted. We conclude that antioxidant supplementation is safe, though ineffective as a treatment for dementia in individuals with Down syndrome and Alzheimer type dementia. Our findings are similar to studies of antioxidant supplementation in Alzheimer disease in the general population. The feasibility of carrying out a clinical trial for dementia in Down syndrome is demonstrated.