Increased Dietary Niacin Intake Improves Muscle Strength, Quality, and Glucose Homeostasis in Adults over 40 Years of Age.

BACKGROUND AND AIMS: Age-related loss of skeletal muscle mass and strength begins at 40 years of age, and limited evidence suggests that niacin supplementation increases levels of nicotinamide adenine dinucleotide in mouse muscle tissue. In addition, skeletal muscle has a key role in the body's processing of glucose. Therefore, this study aimed to investigate the relationship between dietary niacin and skeletal muscle mass, strength, and glucose homeostasis in people aged 40 years and older. METHODS: This study was an American population-based cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES). Considering that some outcomes are only measured in specific survey cycles and subsamples, we established three data sets: a grip strength dataset (2011-2014, n=3772), a body mass components dataset (2011-2018, n=3279), and a glucose homeostasis dataset (1999-2018, n=9189). Dietary niacin and covariates were measured in all survey cycles. Linear regression or logistic regression models that adjusted for several main covariates, such as physical activity and diet, was used to evaluate the relationship between dietary niacin and grip strength, total lean mass, appendicular lean mass, total fat, trunk fat, total bone mineral content, homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glycose, fasting insulin and sarcopenia risk. Subgroup analyses, a trend test, an interaction test, and a restricted cubic spline were used for further exploration. RESULTS: Higher dietary niacin intake was significantly correlated with higher grip strength (ß 0.275, 95% confidence intervals [CI] 0.192-0.357), higher total lean mass (ß 0.060, 95% CI 0.045-0.074), higher appendicular lean mass (ß 0.025, 95% CI 0.018-0.033), and higher total bone mineral content (ß 0.005, 95% CI 0.004-0.007). By contrast, higher dietary niacin intake was significantly associated with lower total fat (ß -0.061, 95% CI -0.076 to -0.046), lower trunk fat (ß -0.041, 95% CI -0.050 to -0.032) and lower sarcopenia risk (OR 0.460, 95% CI 0.233 to 0.907). In addition, dietary niacin significantly reduced HOMA-IR, fasting blood glucose (in participants without diabetes), and fasting insulin (p <0.05). CONCLUSION: Niacin is associated with improved body composition (characterized by increased muscle mass and decreased fat content) and improved glucose homeostasis in dietary doses. Dietary niacin supplementation is a feasible way to alleviate age-related muscular loss.

[One case of petroleum poisoning].

Crude oil is unrefined and purified petroleum, whose active components are alkanes, cycloalkanes, aromatic hydrocarbons, alkenes and so on. Petroleum vapor inhalation is the main route of poisoning in clinical. However, there is no case reported for acute poisoning by oral crude oil.In order to improve the understanding of this disease, we report one case with multiple organ dysfunction caused by oral poisoning of petroleum.

Effects of Flavomycin, Bacillus licheniformis and Enramycin on Performance, Nutrient Digestibility, Gut Morphology and the Intestinal Microflora of Broilers.

The effects of Flavomycin, Bacillus licheniformis and Enramycin on broiler performance, nutrient digestibility, gut morphology and the intestinal microflora were studied in a 42-d experiment. A total of 288, one-day-old, male, Arbor Acres broilers were randomly assigned to 1 of 4 dietary treatments with 12 pens per treatment and 6 birds per pen. The treatments were comprised of a control diet without supplementation, a diet supplemented with 5 ppm Flavomycin, a diet supplemented with the combination of 5 ppm Flavomycin and 1.35 × 109 CFU/kg Bacillus licheniformis, as well as a diet supplemented with 5 ppm Enramycin. The average daily gain (ADG) and feed conversion ratio (FCR) of birds fed the diet with Flavomycin combined with Bacillus licheniformis and the Enramycin diet were improved (P<0.05) compared with the control diet. The digestibility of dry matter, energy, and calcium for birds fed the combination of Flavomycin and Bacillus licheniformis and the Enramycin diet were also enhanced compared with the control diet. All additives improved the villus height and crypt depth in the duodenum, jejunum and ileum on d 21. In addition, reduced numbers of cecal E. coli (P<0.01) were found in birds fed all three supplemented diets on d 42. In conclusion, supplementation with Flavomycin and Bacillus licheniformis in combination or Enramycin would appear to be superior to supplementation with Flavomycin alone. All three supplemented diets were superior to the control.

Discovery of a Novel HDAC2 Inhibitor by a Scaffold-Merging Hybrid Query.

Histone deacetylases (HDACs) are part of a vast family of enzymes with crucial roles in numerous biological processes, largely through their repressive influence on transcription, with serious implications in a variety of human diseases. Among different isoforms, human HDAC2 in particular draws attention as a promising target for the treatment of cancer and memory deficits associated with neurodegenerative diseases. Now the challenge is to obtain a compound that is structurally novel and truly selective to HDAC2 because most current HDAC2 inhibitors do not show isoforms selectivity and suffer from metabolic instability. In order to identify novel, and isoform-selective inhibitors for human HDAC2, we designed a shape-based hybrid query from multiple scaffolds of known chemical classes and validated it to be a more effective approach to discover diverse scaffolds than single-molecule query. The hybrid query-based screening rendered a hit compound with the N-benzylaniline scaffold which showed moderate inhibitory activity against HDAC2, and its chemical structure is diverse compared to known HDAC2 inhibitors. Notably, this compound shows the selectivity against the HDAC6, a Class II enzyme, thus has the potential to further develop into the class- and isoform-selective inhibitors. Our present study supplies an useful approach to identifying novel HDAC2 inhibitors, and can be extended to the inquires of other important biomedical targets as well.

Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation.

Geranylgeranylation is critical to the function of several proteins including Rho, Rap1, Rac, Cdc42, and G-protein gamma subunits. Geranylgeranyltransferase type I (GGTase-I) inhibitors (GGTIs) have therapeutic potential to treat inflammation, multiple sclerosis, atherosclerosis, and many other diseases. Following our standard workflow, we have developed and rigorously validated quantitative structure-activity relationship (QSAR) models for 48 GGTIs using variable selection k nearest neighbor (kNN), automated lazy learning (ALL), and partial least squares (PLS) methods. The QSAR models were employed for virtual screening of 9.5 million commercially available chemicals, yielding 47 diverse computational hits. Seven of these compounds with novel scaffolds and high predicted GGTase-I inhibitory activities were tested in vitro, and all were found to be bona fide and selective micromolar inhibitors. Notably, these novel hits could not be identified using traditional similarity search. These data demonstrate that rigorously developed QSAR models can serve as reliable virtual screening tools, leading to the discovery of structurally novel bioactive compounds.

Combinatorial QSAR modeling of specificity and subtype selectivity of ligands binding to serotonin receptors 5HT1E and 5HT1F.

The Quantitative Structure-Activity Relationship (QSAR) approach has been applied to model binding affinity and receptor subtype selectivity of human 5HT1E and 5HT1F receptor-ligands. The experimental data were obtained from the PDSP Ki Database. Several descriptor types and data-mining approaches have been used in the context of combinatorial QSAR modeling. Data mining approaches included k Nearest Neighbor, Automated Lazy Learning (ALL), and PLS; descriptor types included MolConnZ, MOE, DRAGON, Frequent Subgraphs (FSG), and Molecular Hologram Fingerprints (MHFs). Highly predictive QSAR models were generated for all three data sets (i.e., for ligands of both receptor subtypes and for subtype selectivity), and different individual techniques were proved best in each case. For real value activity data available for 5HT1E and 5HT1F ligand binding, models were characterized by leave-one-out cross-validated R(2) (q(2)) for the training sets and predictive R(2) values for the test sets. The best models for 5HT1E ligands were obtained with the kNN approach combined with MolConnZ descriptors (q(2)=0.69, R(2)=0.92); for 5HT1F ligands ALL QSAR method using MolConnZ descriptors gave the best results (R(2)=0.92). Rigorously validated classification models were also developed for the 5HT1E/5HT1F subtype selectivity data set with high correct classification accuracy for both training (CCRtrain=0.88) and test (CCRtest=1.00) sets using kNN with MolConnZ descriptors. The external predictive power of QSAR models was further validated by virtual screening of The Scripps Research Institute (TSRI) screening library to recover 5HT1E agonists and antagonists (not present in the original PDSP data set) with high enrichment factors. The successful development of externally predictive and interpretative QSAR models affords further design and discovery of novel subtype specific GPCR agents.

[Effects of Andrographis paniculata component on nitric oxide, endothelin and lipid peroxidation in experimental atherosclerotic rabbits].

OBJECTIVE: To observe the effects of Andrographis Paniculata component (API0134) on nitric oxide (NO), endothelin (ET), cyclic guanosine monophosphate (cGMP), lipid peroxide (LPO) and superoxide dismutase (SOD) in experimental atherosclerotic rabbit. METHODS: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and API0134 treated group. Blood samples were collected before 4 weeks and 8 weeks after relevent treatment. RESULTS: Before 4 and after 8 weeks API0134 administration, compared with model group, the NO, cGMP and activity of SOD increased (P < 0.01), while LPO and ET decreased (P < 0.01). CONCLUSIONS: API0134 possesses the effects of antioxidation, preserving endothelial function, and maintaining the balance of NO/ET.

Modulation of B-cell immunoglobulin synthesis by retinoic acid.

Retinoic acid (RA) and its parent compound retinol (ROH, vitamin A) have been recognized as important immunopotentiating agents since the early 1900s. We have focused our studies on the effects of retinoids on B-cell immune function in the newborn infant. The response of cord blood mononuclear cells (CBMC) to formalinized Cowan I strain Staphylococcus aureus (SAC), a T-cell-dependent factor for inducing the differentiation of B cells into immunoglobulin (Ig)-secreting cells, was used as a model system for studying whether RA could alter the immunoglobulin synthesis of newborn B lymphocytes. The addition of RA to SAC-stimulated CBMC cultures produced a 2- to 47-fold increase in IgM synthesis. An ELISA-spot assay showed that the RA-induced enhancement in Ig synthesis was due to the recruitment of more B cells to differentiate into Ig-secreting cells. Whereas RA enhanced IgM production of CBMC stimulated with SAC, RA augmented only IgG production of SAC-stimulated adult peripheral blood mononuclear cells (PBMC). To determine if the differences in dose-response characteristics between CBMC and adult PBMC resided within the target cell, i.e., the B cell, T-cell-enriched and T-cell-depleted (B-cell) fractions from CBMC and adult PBMC were cocultured in various combinations. The isotype, i.e., IgM vs IgG, and the dose-response curve characteristics were intrinsic to the responding B-cell source, i.e., newborn vs adult. Highly purified T cells from CBMC, when preincubated for 36 hr with RA, enhanced IgM synthesis of cord blood B cells. Supernatants from purified T cells generated a factor which could enhance B-cell synthesis. Although interleukin (IL)-2, IL-4, and IL-6 could not be detected by ELISA in the T-cell-derived supernatants, RA probably generates a cytokine/interleukin from T cells which modulates B-cell Ig secretion. RA can also act directly on B cells as evidenced by the augmentation in Ig synthesis of Epstein-Barr virus (EBV)-transformed B-cell lines. These data suggest that RA can have a direct effect on B cells. Since increased proliferation (numbers) of lymphoblastoid B cells was not responsible for the increased amounts of Ig in the supernatant fluids, we examined whether cytokines secreted by EBV-transformed B cells could be acting as an autocrine factor in increasing Ig synthesis. EBV-transformed B-cell clones incubated with RA for 6 days produced a 20- to 45-fold increase in IL-6. An understanding of the mechanisms by which RA enhances B-cell immune function may lead to the use of RA or its derivatives in patients with immune deficiencies and in preterm infants with immature immune systems.

Effects of nifedipine on diastolic function in hypertensive patients--an echocardiographic study.

This study was undertaken to observe the changes in heart function and evaluate the effects of nifedipine on diastolic function in 70 patients with uncomplicated hypertension by M-mode and Doppler echocardiography. The results showed that diastolic abnormalities in hypertensive patients may precede systolic dysfunction and that nifedipine can improve diastolic function. It is easy and quick to estimate the diastolic function by measuring the EF slope, EA and EPSS, especially the E wave velocities. This method proved to be applicable to clinical practice.

Assessment of topical therapy of the burn wound with silver sulphadiazine after its use for 15 years in a burn unit.

A comparative study of patients receiving or not receiving topical applications of 1 per cent silver sulphadiazine cream as treatment for burn wounds has shown that the drug is still effective in significantly reducing the amount of bacterial contamination of burn wounds, even after 15 years of use in our Burn Unit. Consequently the overall mortality due to burn wound sepsis has been decreased in this Burn Unit.