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1.
Prog Brain Res ; 286: 67-87, 2024.
Article in English | MEDLINE | ID: mdl-38876579

ABSTRACT

Regular physical activity can potentially prevent cognitive decline. While most studies focused on the general decline of the elderly and child and adolescent population, aging is a gradual process and cognitive decline can commence in middle age. Other than the middle-aged working population, gender-specific nuances are another overlooked area regarding the relationship between physical activity and cognitive performance. Therefore, this study examines the associations and benefits of maintaining regular physical activity habits with cognitive function and body composition in middle-aged female office workers. The results show that middle-aged females exhibited age-related declines in working memory, while no significant age-related changes are observed in reaction time and executive function. However, the regular exercise group demonstrates the ability to maintain their cognitive performance across age, unlike the sedentary group, who experiences declines in reaction time and executive function with age. Our findings highlight the significant impact of age on specific cognitive functions in middle-aged females and the positive influence of regular exercise on cognitive performance. Furthermore, this study demonstrates the potential of "the Brain Gym" App for efficient cognitive function assessment. The findings underscore the importance of regular exercise for cognitive well-being in middle-aged females and provide valuable insights into the relationship between body composition and cognitive function.


Subject(s)
Body Composition , Cognition , Executive Function , Exercise , Humans , Female , Exercise/physiology , Body Composition/physiology , Cognition/physiology , Middle Aged , Executive Function/physiology , Adult , Memory, Short-Term/physiology , Reaction Time/physiology , Aging/physiology
2.
PeerJ ; 11: e15768, 2023.
Article in English | MEDLINE | ID: mdl-37637165

ABSTRACT

Objective: Recent studies indicate that acute exercise, whether aerobic exercise (AE) or resistance exercise (RE), improves cognitive function. However, the effects on cognitive function of combined exercise (CE), involving both AE and RE in an exercise session, remain unknown. The aim of this study was to investigate the effects of acute CE on cognitive function. Design: Within-subject design with counterbalancing. Methods: Fifteen healthy men with a sedentary lifestyle in the previous three months were recruited. The participants were assessed for muscular fitness after performing four upper body exercises for a 10-repetition maximum and underwent a submaximal aerobic fitness assessment for V̇O2peak and corresponding workload (watts). They were then assigned to a CE, RE, or sitting control (SC) session in counterbalanced order and were assessed with the Stroop Color and Word Test (SCWT) after each session. Results: Acute CE led to a significantly shorter response time compared to SC (p < .05) in the SCWT, wherein there were no significant differences between acute CE and RE (p = 1.00). Additionally, no significant differences in the accuracy rate were observed across the different sessions (ps > .05). Conclusion: A single session of moderate-intensity CE improved response time in the SCWT, comparable to RE. CE shows promise for enhancing cognitive function, warranting further research on its benefits and other exercise modalities.


Subject(s)
Executive Function , Resistance Training , Male , Humans , Exercise Therapy , Exercise , Cognition
3.
J Org Chem ; 87(19): 13308-13314, 2022 10 07.
Article in English | MEDLINE | ID: mdl-36130920

ABSTRACT

A straightforward method for the conversion of a low-cost carbohydrate (d-fructose) into an important carbohydrate building block (2-deoxy-l-ribose) is reported. This methodology involves a novel radical cyclization followed by a fragmentation reaction, selective enzymatic hydrolysis using a lipase, and oxidative cleavage of the vicinal diol. This method uses the cheapest starting material and employs the shortest synthetic route (7 steps) for converting a d-sugar into 2-deoxy-l-ribose.


Subject(s)
Fructose , Ribose , Cyclization , Lipase
4.
J Org Chem ; 86(21): 15033-15044, 2021 11 05.
Article in English | MEDLINE | ID: mdl-34591475

ABSTRACT

Various N-(2-bromo-allyl) benzamides were used as the starting materials to study vinyl radical cyclization reactions. The vinyl radicals underwent ipso-cyclization, fragmentation, and cyclization reactions to produce ß-aryl-γ-lactams with the carbonyl group remaining intact. To further study this cascade radical reaction, vinyl radicals were generated by the addition of a tributyltin radical to alkyne moieties, followed by radical ipso-cyclization, fragmentation, cyclization, and ß-scission reactions with the production of a series of α,ß-unsaturated-ß-aryl-γ-lactam derivatives. This new type of radical reaction was examined from the substituent effects on both the amino groups and the aryl groups. A bulky tert-butyl substituent on the amino group enhanced the formation of a Z-conformation of the benzamides and facilitated vinyl radical ipso-cyclization reactions. A synthetic method for preparing α,ß-unsaturated-ß-aryl-γ-lactams from N-propargyl benzamides was developed.


Subject(s)
Benzamides , beta-Lactams , Cyclization , Molecular Structure , Morphinans
5.
J Org Chem ; 83(24): 14923-14932, 2018 12 21.
Article in English | MEDLINE | ID: mdl-30474372

ABSTRACT

The preparation of 2-deoxy-l-ribose derivatives or mirror image deoxyribonucleosides (l-deoxyribonucleosides) from d-ribose is reported. Starting from inexpensive d-ribose, an acyclic d-form carbohydrate precursor was synthesized to study a unique carbonyl translocation process. In this novel radical reaction, not only was the configuration of the sugar transformed from the d-form to the l-form, but also deoxygenation at the C(2) position of the sugar was successfully achieved. This is one of the most practical methods for converting a d-sugar to a 2-deoxy-l-sugar in a one-step reaction. To further identify the reaction product, radical reactions followed by treatment with 1,3-propanedithiol and then benzoylation were performed to afford a dithioacetal derivative. The stereochemistry and configuration of the 2-deoxy-l-ribose dithioacetal derivative were confirmed by its X-ray crystal structure. To further apply this methodology, a diethyl thioacetal derivative was formed, followed by selective benzoyl protection, and an NIS-initiated cyclization reaction to give the desired ethyl S-l-2-deoxyriboside, which can be used as a 2-deoxy-l-ribosyl synthon in the formal total synthesis of various l-deoxyribonucleosides, such as l-dT.


Subject(s)
Deoxyribonucleosides/chemistry , Deoxyribonucleosides/chemical synthesis , Ribose/chemistry , Chemistry Techniques, Synthetic , Cyclization , Stereoisomerism
6.
Exp Neurol ; 291: 62-73, 2017 05.
Article in English | MEDLINE | ID: mdl-28179153

ABSTRACT

Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared to WT mice. Inflammatory mediators within the spinal cord, calcitonin gene-related peptide (CGRP) and substance P (SP), were up-regulated in NPFFR2-Tg and chronic NPFFR2 agonist-treated mice. In DRG cultures, treatment with an NPFFR2 agonist induced the expression and release of CGRP, an action which was blocked by NPFFR2 siRNA. Furthermore, treatment with a CGRP antagonist ameliorated the pain hyperalgesia in NPFFR2-Tg mice, returning the pain threshold to a control level. However, treatment with a SP antagonist reduced the pain responses in both WT and NPFFR2-Tg mice and did not suppress pain hypersensitivity in NPFFR2-Tg mice. Together, these results demonstrate that NPFFR2 activation modulates pain transmission by up-regulating the pain mediator CGRP, leading to hyperalgesia.


Subject(s)
Calcitonin Gene-Related Peptide/metabolism , Gene Expression Regulation/genetics , Hyperalgesia/etiology , Hyperalgesia/metabolism , Myelitis/complications , Receptors, G-Protein-Coupled/metabolism , Animals , Carrageenan/toxicity , Cells, Cultured , Cerebral Cortex/diagnostic imaging , Disease Models, Animal , Forelimb/innervation , Freund's Adjuvant/toxicity , Ganglia, Spinal/cytology , Hydrazines/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myelitis/chemically induced , Neurons/drug effects , Neurons/metabolism , Neurotransmitter Agents/metabolism , Oxygen/blood , Pain Measurement , Receptors, G-Protein-Coupled/genetics , Time Factors
7.
Psychoneuroendocrinology ; 71: 73-85, 2016 09.
Article in English | MEDLINE | ID: mdl-27243477

ABSTRACT

Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.


Subject(s)
Depression/physiopathology , Receptors, Neuropeptide/metabolism , Animals , Antidepressive Agents/pharmacology , Anxiety , Anxiety Disorders/metabolism , Chronic Disease/psychology , Corticosterone/metabolism , Corticotropin-Releasing Hormone/metabolism , Depressive Disorder/physiopathology , Gene Expression , Hippocampus/metabolism , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Hypothalamus/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Animal , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/physiopathology , Prefrontal Cortex/metabolism , Receptors, Glucocorticoid/metabolism , Receptors, Neuropeptide/physiology , Stress, Physiological/drug effects , Stress, Psychological/metabolism
8.
J Org Chem ; 81(2): 469-75, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26686244

ABSTRACT

A practical method for the synthesis of 3-deoxy-L-ketohexoses is described. Both D- and L-ketohexoses can be transformed into rare 3-deoxy-L-ketohexoses in six steps through a group transfer process. The key step involves a radical cyclized onto a carbonyl group, followed by a fragmentation reaction, eventually resulting in the group transfer of an α-oxy carbonyl group. The process involves tin-free and environmentally benign radical conditions (TTMSS/AIBN/toluene). The acyclic form of 3-deoxy-L-fructose was prepared in only three steps from the inexpensive starting material, D-fructose. A further modification by preparing a dithioacetal derivative was accomplished, which could serve as a convenient sugar synthon for further synthetic applications. Removal of the dithioacetal protecting group results in the formation of the rare 3-deoxy-L-fructose in a total yield of 42%. This methodology could be further extended to the synthesis of other deoxy-L-ketohesoses, such as 3-deoxy-L-sorbose.

9.
J Org Chem ; 80(22): 11294-301, 2015 Nov 20.
Article in English | MEDLINE | ID: mdl-26496238

ABSTRACT

To study a recently developed radical cyclization reaction followed by a fragmentation process in more detail, a series of α-benzoyl carbonyl compounds were prepared, including precursors with aldehyde and ketone moieties. Initiated by tributyltin hydride and AIBN, radical cyclization followed by fragmentation proceeded to give the desired carbonyl translocation products in 4-benzoyl-5-pentanal, 4-benzoyl-5-pentanone, 5-benzoyl-6-hexanal, and 5-benzoyl-6-hexanone radical systems. In comparison with early reports on radical cyclization reactions of α-oxy carbonyl compounds, neither a geminal dialkyl effect nor a conformationally rigid system was required to give the desired carbonyl translocation products. This effect clearly proves that a benzoyl group serves as a protecting group in these radical processes, which not only enhances cyclization efficiency but also increases the rate of the fragmentation step, eventually producing the desired carbonyl translocation products. These observations provide an alternative point of view in the field of radical cyclization reactions. Since the fragmentation step could be enhanced by appropriately positioning an α-benzoyl group, these four radical processes could be used to convert the naturally occurring d-sugars, such as d-pentoses and d-hexoses, into rare deoxy-l-sugars. Furthermore, a cascade radical process involving radical cyclization and fragmentation followed by addition to the allyltin reagent was developed and is reported herein.

10.
J Mot Behav ; 45(1): 55-63, 2013.
Article in English | MEDLINE | ID: mdl-23405992

ABSTRACT

The authors aimed to investigate the effects of different sporting experience on nonspecific temporal preparation. They evaluated temporal preparation in tennis players (an open-skill sport) and their athletic (swimmers, a closed skill-sport) and nonathletic (sedentary students) controls using a go/no-go variable foreperiod paradigm in which one simple condition and two go/no-go conditions (central-go and mixed-go) were included, which can be used to study the temporal aspects of nonspecific preparation with decision making in inhibition with different levels of cognitive load. Tennis players responded faster than nonathletic controls while there was no significant difference relative to the athletic controls. Additionally, the main finding of the present study is that the difference in reaction time between tennis players and nonathletic controls was found selectively for short foreperiods in which temporal uncertainty is higher and less temporal preparation can occur. Moreover, correlation analysis revealed that superior temporal preparation was positively associated with enhanced go/no-go decision making in the higher difficulty condition. Our findings are consistent with tennis players showing superior temporal processing. The absence of a significant effect in athletic controls suggests that there is a specific benefit from tennis training and indicates that temporal preparation may be susceptible to modulation by fitness and appropriate training.


Subject(s)
Athletes/psychology , Cognition/physiology , Decision Making/physiology , Sedentary Behavior , Swimming/physiology , Tennis/physiology , Adult , Humans , Inhibition, Psychological , Male , Reaction Time/physiology , Time Factors
11.
PLoS One ; 8(2): e55773, 2013.
Article in English | MEDLINE | ID: mdl-23418458

ABSTRACT

BACKGROUND: Inhibitory control, or the ability to suppress planned but inappropriate prepotent actions in the current environment, plays an important role in the control of human performance. Evidence from empirical studies utilizing a sport-specific design has shown that athletes have superior inhibitory control. However, less is known about whether this superiority might (1) still be seen in a general cognitive task without a sport-related context; (2) be modulated differentially by different sporting expertise (e.g., tennis versus swimming). METHODOLOGY/PRINCIPAL FINDINGS: Here we compared inhibitory control across tennis players, swimmers and sedentary non-athletic controls using a stop-signal task without a sport-specific design. Our primary finding showed that tennis players had shorter stop-signal reaction times (SSRTs) when compared to swimmers and sedentary controls, whereas no difference was found between swimmers and sedentary controls. Importantly, this effect was further confirmed after considering potential confounding factors (e.g., BMI, training experience, estimated levels of physical activity and VO2max), indicative of better ability to inhibit unrequired responses in tennis players. CONCLUSIONS/SIGNIFICANCE: This suggests that fundamental inhibitory control in athletes can benefit from open skill training. Sport with both physical and cognitive demands may provide a potential clinical intervention for those who have difficulties in inhibitory control.


Subject(s)
Inhibition, Psychological , Psychomotor Performance/physiology , Swimming/physiology , Tennis/physiology , Adolescent , Humans , Male , Neuropsychological Tests , Reaction Time/physiology , Young Adult
12.
J Org Chem ; 78(3): 996-1013, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23289405

ABSTRACT

An advanced intermediate related to the structures of CP-225,917 and CP-263,114 was constructed by a sequence based on the use of Grob-like fragmentation, intramolecular conjugate displacement, and [2,3]-Wittig rearrangement. A variant of the [2,3]-Wittig rearrangement was developed.


Subject(s)
Heterocyclic Compounds, 4 or More Rings/chemistry , Maleic Anhydrides/chemical synthesis , Magnetic Resonance Spectroscopy , Maleic Anhydrides/chemistry , Stereoisomerism
13.
Bioorg Med Chem ; 18(9): 3147-58, 2010 May 01.
Article in English | MEDLINE | ID: mdl-20382537

ABSTRACT

L-type Ca(2+) channels in mammalian brain neurons have either a Ca(V)1.2 or Ca(V)1.3 pore-forming subunit. Recently, it was shown that Ca(V)1.3 Ca(2+) channels underlie autonomous pacemaking in adult dopaminergic neurons in the substantia nigra pars compacta, and this reliance renders them sensitive to toxins used to create animal models of Parkinson's disease. Antagonism of these channels with the dihydropyridine antihypertensive drug isradipine diminishes the reliance on Ca(2+) and the sensitivity of these neurons to toxins, pointing to a potential neuroprotective strategy. However, for neuroprotection without an antihypertensive side effect, selective Ca(V)1.3 channel antagonists are required. In an attempt to identify potent and selective antagonists of Ca(V)1.3 channels, 124 dihydropyridines (4-substituted-1,4-dihydropyridine-3,5-dicarboxylic diesters) were synthesized. The antagonism of heterologously expressed Ca(V)1.2 and Ca(V)1.3 channels was then tested using electrophysiological approaches and the FLIPR Calcium 4 assay. Despite the large diversity in substitution on the dihydropyridine scaffold, the most Ca(V)1.3 selectivity was only about twofold. These results support a highly similar dihydropyridine binding site at both Ca(V)1.2 and Ca(V)1.3 channels and suggests that other classes of compounds need to be identified for Ca(V)1.3 selectivity.


Subject(s)
Calcium Channel Blockers/chemical synthesis , Calcium Channels, L-Type/drug effects , Calcium Channels/drug effects , Dicarboxylic Acids/chemical synthesis , Dihydropyridines/chemical synthesis , Animals , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/pharmacology , Cell Line , Dicarboxylic Acids/chemistry , Dicarboxylic Acids/pharmacology , Dihydropyridines/chemistry , Dihydropyridines/pharmacology , Humans , Inhibitory Concentration 50 , Molecular Structure , Nifedipine/chemistry , Nifedipine/pharmacology
14.
J Org Chem ; 67(11): 3773-82, 2002 May 31.
Article in English | MEDLINE | ID: mdl-12027693

ABSTRACT

Two general methods are explored for the stereoselective synthesis of exo-glycals. One method utilizes a nucleophilic addition of fully protected sugar lactones of gluco-, galacto-, and manno-types, followed by the subsequent dehydration, to give the desired exo-glycals with (Z)-configuration. The other method proceeds with selenylation of C-glycosides in a stereoselective manner. The subsequent selenoxide elimination also provides (Z)-exo-glycals. The prepared exo-glycal conjugated esters of either gluco- or manno-type react with allyl alcohol to give exclusively alpha-anomers.


Subject(s)
Carbohydrates/chemical synthesis , Carbohydrate Conformation , Galactose/chemistry , Lactones/chemistry , Mannose/chemistry , Stereoisomerism
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