Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HP...Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.展开更多
There are quintillions of data on deoxyribonucleic acid(DNA)and protein in publicly accessible data banks,and that number is expanding at an exponential rate.Many scientific fields,such as bioinformatics and drug disc...There are quintillions of data on deoxyribonucleic acid(DNA)and protein in publicly accessible data banks,and that number is expanding at an exponential rate.Many scientific fields,such as bioinformatics and drug discovery,rely on such data;nevertheless,gathering and extracting data from these resources is a tough undertaking.This data should go through several processes,including mining,data processing,analysis,and classification.This study proposes software that extracts data from big data repositories automatically and with the particular ability to repeat data extraction phases as many times as needed without human intervention.This software simulates the extraction of data from web-based(point-and-click)resources or graphical user interfaces that cannot be accessed using command-line tools.The software was evaluated by creating a novel database of 34 parameters for 1360 physicochemical properties of antimicrobial peptides(AMP)sequences(46240 hits)from various MARVIN software panels,which can be later utilized to develop novel AMPs.Furthermore,for machine learning research,the program was validated by extracting 10,000 protein tertiary structures from the Protein Data Bank.As a result,data collection from the web will become faster and less expensive,with no need for manual data extraction.The software is critical as a first step to preparing large datasets for subsequent stages of analysis,such as those using machine and deep-learning applications.展开更多
Cysteine proteases continue to provide validated targets for treatment of human diseases.In neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and c...Cysteine proteases continue to provide validated targets for treatment of human diseases.In neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and cathepsins.The reactive,active-site cysteine provides specificity for many inhibitor designs over other families of proteases,such as aspartate and serine;however,a)inhibitor strategies often use covalent enzyme modification,and b)obtaining selectivity within families of cysteine proteases and their isozymes is problematic.This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders;the latter focus providing an interesting query for the contemporary assumptions that irreversible,covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.展开更多
The absorption profiles of Schisandra chinensis were evaluated using the human Caco-2 cell monolayer and rat everted gut sac models,as well as in rat plasma.By analyzing the chromatographic and MSn characteristics of ...The absorption profiles of Schisandra chinensis were evaluated using the human Caco-2 cell monolayer and rat everted gut sac models,as well as in rat plasma.By analyzing the chromatographic and MSn characteristics of individual peak acquired by HPLC-DAD-APCI-MS^(n) determination,thirteen lignans were identified as the major in vitro absorbable components of the Schisandra extract.Most of these compounds were also detected and identified in rat plasma after an oral administration of the Schisandra extract,except for angeloyl(tigloyl)gomisin H and angeloyl(tigloyl)gomisin Q,whose structures possess an ester group at the cyclooctadiene ring.In addition,four metabolites,corresponding to the hydroxylation and demethylation products of schisandrin and the hydrolysis derivative of angeloyl(tigloyl)gomisin Q,were tentatively identified.The results demonstrate that Schisandra lignans are the major absorbable components of this crude drug,and hydroxylation,demethylation and hydrolysis are important metabolic transformations of the absorbable lignans.展开更多
Cognitive impairment caused by chemotherapy,referred to as“chemobrain,”is observed in approximately 70% of cancer survivors.However,it is not completely understood how chemotherapy induces cognitive dysfunction,and ...Cognitive impairment caused by chemotherapy,referred to as“chemobrain,”is observed in approximately 70% of cancer survivors.However,it is not completely understood how chemotherapy induces cognitive dysfunction,and clinical treatment strategies for this problem are lacking.Metformin,used as a first-line treatment for type 2 diabetes mellitus,is reported to reduce the effects of chemobrain.Recently,several studies have examined the effect of metformin in rescuing chemobrain.This review discusses recent clinical/preclinical studies that addressed some mechanisms of chemobrain and evaluates the effect of metformin in rescuing chemobrain and its potential mechanisms of action.展开更多
Sixteen compounds, including two new natural products(1 and 2), were obtained from the twigs of Illicium angustisepalum. The structures were elucidated based on NMR, MS, IR data and optical rotation values. Compounds ...Sixteen compounds, including two new natural products(1 and 2), were obtained from the twigs of Illicium angustisepalum. The structures were elucidated based on NMR, MS, IR data and optical rotation values. Compounds 4,5,6 and 8 displayed moderate antibacterial activities against clinical isolates; compounds 4,5,8,9 and 15 protected neural cells against oxidative stress; and compounds 10 and 14 exhibited anti-acetylcholinesterase activity.展开更多
A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosylL-homocysteine hydrolase（SAHase） inhibitory activity. Among these compounds, 8b,8m, 8r and 8...A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosylL-homocysteine hydrolase（SAHase） inhibitory activity. Among these compounds, 8b,8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.展开更多
文摘Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.
基金This work was funded by the Graduate Scientific Research School at Yarmouk University under Grant Number:82/2020。
文摘There are quintillions of data on deoxyribonucleic acid(DNA)and protein in publicly accessible data banks,and that number is expanding at an exponential rate.Many scientific fields,such as bioinformatics and drug discovery,rely on such data;nevertheless,gathering and extracting data from these resources is a tough undertaking.This data should go through several processes,including mining,data processing,analysis,and classification.This study proposes software that extracts data from big data repositories automatically and with the particular ability to repeat data extraction phases as many times as needed without human intervention.This software simulates the extraction of data from web-based(point-and-click)resources or graphical user interfaces that cannot be accessed using command-line tools.The software was evaluated by creating a novel database of 34 parameters for 1360 physicochemical properties of antimicrobial peptides(AMP)sequences(46240 hits)from various MARVIN software panels,which can be later utilized to develop novel AMPs.Furthermore,for machine learning research,the program was validated by extracting 10,000 protein tertiary structures from the Protein Data Bank.As a result,data collection from the web will become faster and less expensive,with no need for manual data extraction.The software is critical as a first step to preparing large datasets for subsequent stages of analysis,such as those using machine and deep-learning applications.
文摘Cysteine proteases continue to provide validated targets for treatment of human diseases.In neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and cathepsins.The reactive,active-site cysteine provides specificity for many inhibitor designs over other families of proteases,such as aspartate and serine;however,a)inhibitor strategies often use covalent enzyme modification,and b)obtaining selectivity within families of cysteine proteases and their isozymes is problematic.This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders;the latter focus providing an interesting query for the contemporary assumptions that irreversible,covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.
基金supported by an International Center for Complementary and Alternative Medicine(ICRC)Grant(1-U19-AT003266PI:Brian Berman,University of Maryland)of the National Center for Complementary and Alternative Medicine(NCCAM),USA.
文摘The absorption profiles of Schisandra chinensis were evaluated using the human Caco-2 cell monolayer and rat everted gut sac models,as well as in rat plasma.By analyzing the chromatographic and MSn characteristics of individual peak acquired by HPLC-DAD-APCI-MS^(n) determination,thirteen lignans were identified as the major in vitro absorbable components of the Schisandra extract.Most of these compounds were also detected and identified in rat plasma after an oral administration of the Schisandra extract,except for angeloyl(tigloyl)gomisin H and angeloyl(tigloyl)gomisin Q,whose structures possess an ester group at the cyclooctadiene ring.In addition,four metabolites,corresponding to the hydroxylation and demethylation products of schisandrin and the hydrolysis derivative of angeloyl(tigloyl)gomisin Q,were tentatively identified.The results demonstrate that Schisandra lignans are the major absorbable components of this crude drug,and hydroxylation,demethylation and hydrolysis are important metabolic transformations of the absorbable lignans.
基金This work was supported by the Deanship of Scientific Research,Qassim University。
文摘Cognitive impairment caused by chemotherapy,referred to as“chemobrain,”is observed in approximately 70% of cancer survivors.However,it is not completely understood how chemotherapy induces cognitive dysfunction,and clinical treatment strategies for this problem are lacking.Metformin,used as a first-line treatment for type 2 diabetes mellitus,is reported to reduce the effects of chemobrain.Recently,several studies have examined the effect of metformin in rescuing chemobrain.This review discusses recent clinical/preclinical studies that addressed some mechanisms of chemobrain and evaluates the effect of metformin in rescuing chemobrain and its potential mechanisms of action.
文摘Sixteen compounds, including two new natural products(1 and 2), were obtained from the twigs of Illicium angustisepalum. The structures were elucidated based on NMR, MS, IR data and optical rotation values. Compounds 4,5,6 and 8 displayed moderate antibacterial activities against clinical isolates; compounds 4,5,8,9 and 15 protected neural cells against oxidative stress; and compounds 10 and 14 exhibited anti-acetylcholinesterase activity.
基金supported by National Natural Science Foundation of China (No. 81560653)Guangxi Natural Science Foundation of China (No. 2015GXNSFBA139124)
文摘A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosylL-homocysteine hydrolase（SAHase） inhibitory activity. Among these compounds, 8b,8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.
