No abstract available.
Asian Continental Ancestry Group* ; Child* ; Frontal Bone* ; Histiocytosis, Langerhans-Cell* ; Humans ; Infant* ; Male*

Objective: Several studies have reported the therapeutic effects of phytoncides on various mental disorders. However, little is known about the therapeutic effects of phytoncides on mild cognitive impairment (MCI), a prodromal stage of dementia. In this pilot study, we aimed to clarify the effect of inhaled phytoncides on the cognitive function of patients clinically diagnosed with MCI. Methods: In total, 21 patients with MCI were randomly assigned to either a saline (no-odor) or phytoncide group and subsequently inhaled saline or phytoncide for 30 minutes indoors, respectively. To evaluate changes in cognitive function, we implemented functional near-infrared spectroscopy along with the Stroop task and compared task performance and hemodynamic responses in the dorsolateral/ventrolateral part of the prefrontal cortex (DLPFC/VLPFC) before and after inhalation. Results: While the saline group showed no significant difference in either task performance (Wilcoxon W = 18.50, p = 0.385) or hemodynamic response, a significant increase in Stroop task performance (Wilcoxon W = 1.50, p = 0.009) and hemodynamic attenuation in the left VLPFC (Wilcoxon W = 56.00, p = 0.042) were found in the phytoncide group after inhalation. Conclusion Since compensatory task-related prefrontal hyperactivation represents one of the neural indicators of cognitive dysfunction in MCI, our findings shed light on the beneficial effects of phytoncide on cognitive function in MCI.

Objective: Several studies have reported the therapeutic effects of phytoncides on various mental disorders. However, little is known about the therapeutic effects of phytoncides on mild cognitive impairment (MCI), a prodromal stage of dementia. In this pilot study, we aimed to clarify the effect of inhaled phytoncides on the cognitive function of patients clinically diagnosed with MCI. Methods: In total, 21 patients with MCI were randomly assigned to either a saline (no-odor) or phytoncide group and subsequently inhaled saline or phytoncide for 30 minutes indoors, respectively. To evaluate changes in cognitive function, we implemented functional near-infrared spectroscopy along with the Stroop task and compared task performance and hemodynamic responses in the dorsolateral/ventrolateral part of the prefrontal cortex (DLPFC/VLPFC) before and after inhalation. Results: While the saline group showed no significant difference in either task performance (Wilcoxon W = 18.50, p = 0.385) or hemodynamic response, a significant increase in Stroop task performance (Wilcoxon W = 1.50, p = 0.009) and hemodynamic attenuation in the left VLPFC (Wilcoxon W = 56.00, p = 0.042) were found in the phytoncide group after inhalation. Conclusion Since compensatory task-related prefrontal hyperactivation represents one of the neural indicators of cognitive dysfunction in MCI, our findings shed light on the beneficial effects of phytoncide on cognitive function in MCI.

Objective: Several studies have reported the therapeutic effects of phytoncides on various mental disorders. However, little is known about the therapeutic effects of phytoncides on mild cognitive impairment (MCI), a prodromal stage of dementia. In this pilot study, we aimed to clarify the effect of inhaled phytoncides on the cognitive function of patients clinically diagnosed with MCI. Methods: In total, 21 patients with MCI were randomly assigned to either a saline (no-odor) or phytoncide group and subsequently inhaled saline or phytoncide for 30 minutes indoors, respectively. To evaluate changes in cognitive function, we implemented functional near-infrared spectroscopy along with the Stroop task and compared task performance and hemodynamic responses in the dorsolateral/ventrolateral part of the prefrontal cortex (DLPFC/VLPFC) before and after inhalation. Results: While the saline group showed no significant difference in either task performance (Wilcoxon W = 18.50, p = 0.385) or hemodynamic response, a significant increase in Stroop task performance (Wilcoxon W = 1.50, p = 0.009) and hemodynamic attenuation in the left VLPFC (Wilcoxon W = 56.00, p = 0.042) were found in the phytoncide group after inhalation. Conclusion Since compensatory task-related prefrontal hyperactivation represents one of the neural indicators of cognitive dysfunction in MCI, our findings shed light on the beneficial effects of phytoncide on cognitive function in MCI.

Objective: Several studies have reported the therapeutic effects of phytoncides on various mental disorders. However, little is known about the therapeutic effects of phytoncides on mild cognitive impairment (MCI), a prodromal stage of dementia. In this pilot study, we aimed to clarify the effect of inhaled phytoncides on the cognitive function of patients clinically diagnosed with MCI. Methods: In total, 21 patients with MCI were randomly assigned to either a saline (no-odor) or phytoncide group and subsequently inhaled saline or phytoncide for 30 minutes indoors, respectively. To evaluate changes in cognitive function, we implemented functional near-infrared spectroscopy along with the Stroop task and compared task performance and hemodynamic responses in the dorsolateral/ventrolateral part of the prefrontal cortex (DLPFC/VLPFC) before and after inhalation. Results: While the saline group showed no significant difference in either task performance (Wilcoxon W = 18.50, p = 0.385) or hemodynamic response, a significant increase in Stroop task performance (Wilcoxon W = 1.50, p = 0.009) and hemodynamic attenuation in the left VLPFC (Wilcoxon W = 56.00, p = 0.042) were found in the phytoncide group after inhalation. Conclusion Since compensatory task-related prefrontal hyperactivation represents one of the neural indicators of cognitive dysfunction in MCI, our findings shed light on the beneficial effects of phytoncide on cognitive function in MCI.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

Familial amyotrophic lateral sclerosis (fALS) is caused by mutations in Cu/Zn-superoxide dismutase (SOD1), and SOD1 aggregation and calcium toxicity are involved in neuronal death. However, the effect of altered calcium homeostasis on the SOD1 aggregation is unknown. To investigate whether calcium triggers mutant SOD1 aggregation in vitro, human mutant SOD1 (G93A) was transfected into motor neuronal cell line (VSC 4.1 cells). These cells were then treated with calcium ionophore A23187 or agents that induce intracellular calcium release like cyclic ADP ribose, ryanodine or thapsigargin. A23187 was found to increase mutant SOD1 aggregation and neuronal nitric oxide synthase (nNOS) expression. Moreover, the NOS inhibitor (L-NAME) and a NO-dependent cyclic GMP cascade inhibitor (ODQ) reduced SOD1 aggregation, whereas an exogenous NO donor (GSNO) increased mutant SOD1 aggregation, which was also prevented by NOS or cGMP cascade inhibitor. Our data demonstrate that calcium-influx increases SOD1 aggregation by upregulating NO in cultured motor neuronal cells.
Amyotrophic Lateral Sclerosis/genetics/metabolism ; Animals ; Calcimycin/pharmacology ; Calcium/*metabolism ; Calpain/metabolism ; Caspase 3/metabolism ; Cell Line ; Humans ; Ionophores/pharmacology ; Motor Neurons/*metabolism ; Multiprotein Complexes ; Mutation ; Nitric Oxide/*metabolism ; Rats ; Recombinant Proteins/chemistry/genetics/metabolism ; Superoxide Dismutase/chemistry/genetics/*metabolism ; Transfection

Background/Aims: Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects. Methods: In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation. Results: All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration–time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing. Conclusions All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesisinducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.