Cheonggukjang-Specific Component 1,3-Diphenyl-2-Propanone as a Novel PPARα/γ Dual Agonist: An In Vitro and In Silico Study.

BACKGROUND: Cheonggukjang is a traditional fermented soybean paste that is mostly consumed in Korea. However, the biological activities of Cheonggukjang specific compounds have not been studied. Thus, we aimed to discover a novel dual agonist for PPARα/γ from dietary sources such as Cheonggukjang specific volatile compounds and explore the potential role of PPARα/γ dual agonists using in vitro and in silico tools. METHODS: A total of 35 compounds were selected from non-fermented and fermented soybean products cultured with Bacillus subtilis, namely Cheonggukjang, for analysis by in vitro and in silico studies. RESULTS: Molecular docking results showed that 1,3-diphenyl-2-propanone (DPP) had the lowest docking score for activating PPARα (1K7L) and PPARγ (3DZY) with non-toxic effects. Moreover, DPP significantly increased the transcriptional activities of both PPARα and PPARγ and highly activated its expression in Ac2F liver cells, in vitro. Here, we demonstrated for the first time that DPP can act as a dual agonist of PPARα/γ using in vitro and in silico tools. CONCLUSIONS: The Cheonggukjang-specific compound DPP could be a novel PPARα/γ dual agonist and it is warranted to determine the therapeutic potential of PPARα/γ activation by dietary intervention and/or supplementation in the treatment of metabolic disorders without causing any adverse effects.

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

Anti-wrinkle effects of a tuna heart H2O fraction on Hs27 human fibroblasts.

With the increase in life expectancy, there is also growing interest in anti-aging treatments and technologies. The development of anti-aging functional drugs for the skin, and foods from natural sources, may offer solutions to this global matter. Aging involves structural, functional and biochemical changes that occur throughout cells and bodily tissues; the amount of hormones secreted from of all human organs, including the skin, decreases over time. Matrix metalloproteinase (MMP) genes (MMP-1 and -8) play an important role in the aging of skin fibroblasts. For example, an increased MMP expression causes accelerated aging and the degradation of skin elasticity-related genes. In the present study, we examined the anti-wrinkle effects of tuna heart extract which are mediated through the inhibition of MMPs in skin cells. Generally, tuna contains high concentrations of selenium and antioxidants, which serve to remove free radicals, and is known to delay skin and body aging. In addition, unsaturated fatty acids in tuna help to maintain the natural glossy look of skin, and increase skin elasticity, providing moisture for dry skin. A recent study confirmed the various bio-effects of boiled tuna extract and muscle. However, bioactivity studies using tuna heart are limited. Thus, in the present study, we obtained extracts and fractions of tuna heart, and examined their effects on Hs27 human fibroblast proliferation using an MTS assay. In addition, we measured procollagen type 1 levels and elastase activity, and performed ß-galactosidase staining. We then measured the expression levels of phosphatidylinositol 3-kinase/Akt and MMP-related genes by western blot analysis and RT-PCR. Our results revealed that tuna heart extract decreased MMP expression by upregulating tissue inhibitors of metalloproteinase-1 (TIMP-1) and decreasing elastase activity, thus exerting anti-aging and anti-wrinkle effects by increasing collagen synthesis and promoting skin fibroblast proliferation. Thus, our data suggest that tuna heart (TH)-H2O fractions exert anti-wrinkle effects on Hs27 cells.

Comparison of the Effects of 1 Hz and 20 Hz rTMS on Motor Recovery in Subacute Stroke Patients.

OBJECTIVE: To compare the low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) with high frequency (20 Hz) rTMS on motor functional improvement of the affected upper extremity in subacute stroke patients. METHODS: Forty patients with subacute ischemic stroke participated in this study. The first group received 10 sessions of 20 Hz rTMS at ipsilesional M1 area and the other group received 10 sessions of 1 Hz rTMS at contralesional M1 area. Motor training of the hemiparetic hand was conducted after each rTMS train. All the patients received conventional occupational therapy immediately after each rTMS session. Manual function test (MFT), Fugl-Meyer Assessment scale (FMS), Modified Barthel Index (MBI), Brunnstrom recovery stage, and grip strength were used to assess motor function before, at the end of, and one month after the last session of rTMS. RESULTS: No adverse side effects were reported during the course of the experiment using rTMS. No significant difference in motor function of the affected upper extremity was observed between the two groups before rTMS. Significant improvements in MFT, FMS, MBI, and Brunnstrom stage were observed in the both groups at the end of the last rTMS session and one month later (p<0.05). No significant difference was found between the two groups (p>0.05). CONCLUSION: There was no significant difference in motor function of the affected upper extremity between 1 Hz and 20 Hz rTMS during the subacute period of ischemic stroke. Thus, we cannot conclude which has a greater effect.

Impact of aerobic exercise training on endothelial function in acute coronary syndrome.

OBJECTIVE: To confirm the improvement in arterial endothelial function by aerobic exercise training, flow-mediated dilation (FMD) was tested by ultrasonography. METHODS: Patients who received percutaneous coronary intervention due to acute coronary syndrome were included. The patients who participated in cardiac rehabilitation (CR) program were categorized as the CR group, and others who did not participate as the control. Both groups underwent initial graded exercise test (GXT) and FMD testing. Subsequently, the CR group performed aerobic exercise training sessions. Patients in control only received advice regarding the exercise methods. After six weeks, both groups received follow-up GXT and FMD testing. RESULTS: There were 16 patients in each group. There were no significant differences in the general characteristics between the groups. The VO2peak was 28.6±4.7 mL/kg/min in the CR group and 31.5±7.4 mL/kg/min in the control at first GXT, and was 31.1±5.1 ml/kg/min in the CR group and 31.4±6.0 ml/kg/min in the control at the follow-up GXT in six weeks. There was a statistically significant improvement in VO2peak only for CR group patients. FMD value was 7.59%±1.26% in the CR group, 7.36%±1.48% in the control at first and 9.46%±1.82% in the CR group, and 8.31%±2.04% in the control after six weeks. There was a statistically significant improvement in FMD value in the CR group. CONCLUSION: According to the results of GXT and FMD testing, six-week exercise-based CR program improved VO2peak and endothelial functions significantly. Thus, exercise-based CR program is necessary in patients with coronary artery disease.

Cardiac rehabilitation after acute myocardial infarction resuscitated from cardiac arrest.

OBJECTIVE: To examine the safety and effectiveness of cardiac rehabilitation on patients resuscitated from cardiac arrest due to acute myocardial infarction. METHODS: The study included 23 subjects, including 8 with history of cardiac arrest and 15 without history of cardiac arrest. Both groups underwent initial graded exercise test (GXT) and subsequent cardiac rehabilitation for 6 weeks. After 6 weeks, both groups received follow-up GXT. RESULTS: Statistically significant (p<0.05) increase of VO2peak and maximal MVO2 but significant (p<0.05) decrease of submaximal MVO2 and resting heart rate were observed in both groups after 6 weeks of cardiac rehabilitation. An increasing trend of maximal heart rates was observed in both groups. However, the increase was not statistically significant (p>0.05). There was no statistically significant change of resting heart rate, maximal heart rate, maximal MVO2, or submaximal MVO2 in both groups after cardiac rehabilitation. Fatal cardiac complications, such as abnormal ECG, cardiac arrest, death or myocardial infarction, were not observed. All subjects finished the cardiac rehabilitation program. CONCLUSION: Improvement was observed in the exercise capacity of patients after aerobic exercise throughout the cardiac rehabilitation program. Therefore, cardiac rehabilitation can be safely administered for high-risk patients with history of cardiac arrest. Similar improvement in exercise capacity can be expected in patients without cardiac arrest experience.

Isoreticular metal-organic polyhedral networks based on 5-connecting paddlewheel motifs.

A metal-organic polyhedral network with a unique 5-connected topology is expanded into a series using different metal ions or dicarboxylate ligands. The prototype material (ZmID), [Zn(4)(mip)(4)(dabco)(OH(2))(2)] (mip = 5-methylisophthalate, dabco = diazabicyclo[2.2.2]octane), is based on 5-connecting paddlewheel motifs and possesses large cage-like pores (8-20 A diameter). The metal ion is replaced by Co(2+) and/or the dicarboxylate by isophthalate (ip) or 2,7-naphthalenedicarboxylate (2,7-ndc) to give isoreticular frameworks [Zn(4)(ip)(4)(dabco)(OH(2))(2)] (ZID), [Co(4)(ip)(4)(dabco)(OH(2))(2)] (CID), and [Zn(4)(2,7-ndc)(4)(dabco)(OH(2))(2)] (ZND). X-ray powder diffraction and gas sorption studies reveal that ZID and CID have sustainable pore structures and show higher N(2) uptakes than ZmID. ZND is found unstable with respect to the removal of guest solvents. ZmID, ZID, and CID are all similar in terms of the H(2) sorption capacities (1.4-1.5 wt % at 77 K and 1 bar) and isosteric heat of H(2) adsorption (6-7 kJ/mol at low coverage).

Targeted synthesis of a prototype MOF based on Zn4(O)(O2C)6 units and a nonlinear dicarboxylate ligand.

A surprisingly small number of topologies are known in metal-organic frameworks (MOFs) that possess Zn(4)(O)(O(2)C)(6) building units. One of such MOFs having a simple, nonlinear dicarboxylate ligand, 5-methylisophthalate (mip), is targeted and successfully synthesized. The framework, [Zn(4)(O)(mip)(3)], is based on a nonuniform, uninodal six-connected net and is featured by complicated meshlike pores with narrow passages. Gas sorption studies reveal the potentials as a prototype from which new MOFs having interesting properties can be derived.

Efficient hydrogen sorption in 8-connected MOFs based on trinuclear pinwheel motifs.

Two new metal-organic frameworks based on trinuclear pinwheel motifs are prepared using dicarboxylate and diamine ligands. The structure of [Co3(bdc)3(dabco)] (1) (bdc = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane) is described as pillared layers, whereas [Co3(ndc)3(dabco)] (2) (ndc = 2,6-naphthalenedicarboxylate) forms a variation of primitive cubic net with 3D connected pores. The two 8-connected MOFs are thermally stable at 160 and 250 degrees C for 1 and 2 respectively in the air and possess corrugated channels owing to the high connectivities of the secondary building unit. As a result, they show highly efficient hydrogen sorption capabilities. Especially, a high hydrogen uptake (2.45 wt % at 77 K and 1 bar) is observed for 2 that has the unique combination of high surface area and small portals.

Two novel furan derivatives from Phellinus linteus with anti-complement activity.

Two novel stereoisomers of furan derivatives, phellinusfurans A (1) and B (2), were isolated from the fruiting body of Phellinus linteus. Their structures were elucidated by spectroscopic analysis. Compounds 1 and 2 exhibited significant anti-complement activity with IC50 values of 33.6 and 33.7 microM, respectively, in inhibiting the hemolytic activity of human serum against erythrocytes.