Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

AbstractAttention-deficit hyperactivity disorder (ADHD) is characterized by changes to the circadian process. Many medications used to treat the condition, influence norepinephrine levels. Several studies have, in addition, reported that norepinephrine itself has an effect on circadian function. The aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after norepinephrine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with an ADHD diagnosis. Circadian preference was evaluated with German Morningness–Eveningness Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different norepinephrine concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. The exposure of 1 µM norepinephrine to confluent cultures of human dermal fibroblasts from participants with a diagnosis of ADHD, was shown to dampen Per1 rhythmicity. The expression of Bmal1, Per1 and Per3 in control subjects was also influenced by incubation with 1 µM norepinephrine. Cultures from the ADHD group revealed no statistically significant overall differences in circadian gene expression, between cultures with and without norepinephrine incubation. Per3 expression showed a significant ZT × group interaction via mixed ANOVA. Per3 expression at ZT4 was significant higher in the group of control samples incubated with 1 µM norepinephrine, compared to the control group without norepinephrine. This effect was also shown in the control samples incubated with 1 µM norepinephrine and cultures from subjects with ADHD without norepinephrine incubation. Per3 expression differed between the healthy control group and the ADHD group without norepinephrine incubation at ZT28. The results of the present study illustrate that norepinephrine impacts on circadian function. In both groups, control group and cultures taken from subjects with ADHD, the expression of the periodic genes (Per1–3) was significantly influenced by incubation with norepinephrine.

Download Full-text

Atomoxetine and circadian gene expression in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder

Journal of Neural Transmission ◽

10.1007/s00702-021-02373-5 ◽

2021 ◽

Author(s):

Frank Faltraco ◽

Denise Palm ◽

Adriana Uzoni ◽

Frederick Simon ◽

Oliver Tucha ◽

...

Keyword(s):

Gene Expression ◽

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Dermal Fibroblasts ◽

Adhd Group ◽

Healthy Controls ◽

Circadian Gene ◽

Hyperactivity Disorder ◽

Circadian Preference ◽

Study Participants

AbstractAtomoxetine (ATO) is a second line medication for attention-deficit hyperactivity disorder (ADHD). We proposed that part of the therapeutic profile of ATO may be through circadian rhythm modulation. Thus, the aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after ATO exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with a diagnosis of ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different ATO concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. No statistical significant effect of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, sleep WASO and total number of wake bouts was observed. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. ATO induced the rhythmicity of Clock in the ADHD group. This effect, however, was not observed in HDF cultures of healthy controls. Bmal1 and Per2 expression showed a significant ZT × group interaction via mixed ANOVA. Strong positive correlations for chronotype and circadian genes were observed for Bmal1, Cry1 and Per3 among the study participants. Statistical significant different Clock, Bmal1 and Per3 expressions were observed in HDFs exposed to ATO collected from ADHD participants exhibiting neutral and moderate evening preference, as well as healthy participants with morning preferences. The results of the present study illustrate that ATO impacts on circadian function, particularly on Clock, Bmal1 and Per2 gene expression.

Download Full-text

Anti Cutaneous Aging Effect of Red Djulis (Chenopodium formosanum) Extract on Gene Expression of Human Dermal Fibroblast

10.20944/preprints201909.0028.v3 ◽

2019 ◽

Author(s):

Yung-Hsiang Lin ◽

Yung-Kai Lin ◽

Shu-Ting Chan ◽

Yu-Ming Chun ◽

Yu-Ting Lin ◽

...

Keyword(s):

Gene Expression ◽

Light Exposure ◽

Dermal Fibroblast ◽

Skin Barrier ◽

Dermal Fibroblasts ◽

Control Group ◽

Gene Expressions ◽

Positive Effects ◽

Collagen Secretion ◽

Skin Collagen

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

Download Full-text

Photoprotective Effects of Ice Plant (Mesembryanthemum crystallinum) Callus Extract on Gene Expression of Human Dermal Fibroblast Against UV Exposure

Journal of Biobased Materials and Bioenergy ◽

10.1166/jbmb.2019.1877 ◽

2019 ◽

Vol 13 (4) ◽

pp. 570-575 ◽

Cited By ~ 1

Author(s):

Yung-Hsiang Lin ◽

Yung-Kai Lin ◽

Yung-Hao Lin

Keyword(s):

Gene Expression ◽

Dermal Fibroblast ◽

Dermal Fibroblasts ◽

Uv Exposure ◽

Control Group ◽

Ice Plant ◽

Gene Expressions ◽

Collagen Formation ◽

Positive Effects ◽

Skin Collagen

UV exposure is the principal cause of extrinsic photoaging. Antioxidant-related genes (SOD2 and CAT) and collagen-related genes (COL1A1 and TIMP1) were selected for analysis of the mRNA expression in human dermal fibroblasts (CCD-966SK) using qPCR. In this study, UVA-exposed (15 J/cm2 cells showed decrease in SOD2 , CAT (p < 0 001) and COL1A1 (p < 0 05) gene expression, indicating the decline of antioxidant ability and collagen formation. However, treatment with ice plant callus extract (2 mg/mL, 24 h) before UVA exposure significantly up-regulated SOD2 , CAT , COL1A1 and TIMP1 genes (p < 0 01) by 9.5, 2.7, 1.7 and 3.8 times, respectively, compared with those of the control group, and by 10.2, 4.3 (p < 0 001), 2.1 and 3.8 times, respectively, compared with those of the UVA (only) group. These results demonstrated that ice plant extracts affect both antioxidant- and collagen-related gene expressions, and show positive effects on endogenous antioxidant activity and skin collagen preservation.

Download Full-text

Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and activator of transcription proteins (STATs) in rheumatoid arthritis patients

Reumatismo ◽

10.4081/reumatismo.2020.1235 ◽

2020 ◽

Vol 72 (2) ◽

pp. 93-102

Author(s):

N.A.G. Gaafar ◽

M. Aslani ◽

Z. Aghazadeh ◽

S.S. Mortazavi-Jahromi ◽

A. Razavi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Conventional Therapy ◽

Gene Expression Level ◽

Expression Level ◽

Control Group ◽

Healthy Controls ◽

Signal Transducer ◽

Mannuronic Acid ◽

Significant Difference

Rheumatoid arthritis (RA), a form of inflammatory arthritis, is a chronic joint disease characterized by pain and inflammation that affects 0.5% to 1% of the population worldwide. The safety, efficacy, tolerability, and potency of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been reported by several in vitro studies, experimental models and clinical trials phase I/II and III in ankylosing spondylitis and rheumatoid arthritis (RA) patients This research is designed to study the therapeutic efficacy of oral administration of mannuronic acid in RA patients who had inadequate response to conventional drugs and to assess the effect of this drug on gene expression of the signal transducer and activator of transcription (STATs) protein (STAT1, STAT3, STAT4, and STAT6). The study has included 15 RA patients who had an insufficient response to the conventional therapy. The oral dose of mannuronic acid was 1000mg divided into two 500 mg doses per day for 3 months as an addition to conventional therapy. There were 15 healthy volunteer in the control group. Blood samples were collected from both groups, once from healthy controls and twice from RA patients before and after treatment by M2000. The peripheral blood mononuclear cells (PBMCs) were isolated to assess the gene expression level of STAT1, STAT3, STAT4, and STAT6 using the real-time PCR method. Results obtained in this study demonstrated a significant difference in the gene expression level of STAT1 between healthy controls and patients before treatment as well as a significant reduction in RA patients after treatment compared with the level before treatment. In addition, the gene expression level of STAT3 and STAT4 showed a significant reduction in RA patients after treatment compared to patients before treatment, while there was no significant difference between RA patients before treatment and the healthy control group for both molecules. On the other hand, there was no change in the gene expression level of STAT6 among all groups. The outcomes of this study confirmed that β-D-mannuronic acid (M2000) has the ability to control the levels of STAT1, STAT3 and STAT4 in RA patients, and might be beneficial in the management and therapy of RA.

Download Full-text

Anti Cutaneous Aging Effect of Red Djulis (Chenopodium formosanum) Extract on Gene Expression of Human Dermal Fibroblast

10.20944/preprints201909.0028.v2 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yung-Hsiang Lin ◽

Yung-Kai Lin ◽

Shu-Ting Chan ◽

Yu-Ming Chung ◽

Yu-Ting Lin ◽

...

Keyword(s):

Gene Expression ◽

Light Exposure ◽

Dermal Fibroblast ◽

Skin Barrier ◽

Dermal Fibroblasts ◽

Control Group ◽

Gene Expressions ◽

Positive Effects ◽

Collagen Secretion ◽

Skin Collagen

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

Download Full-text

Anti Cutaneous Aging Effect of Red Djulis (Chenopodium formosanum) Extract on Gene Expression of Human Dermal Fibroblast

10.20944/preprints201909.0028.v1 ◽

2019 ◽

Author(s):

Yung-Hsiang Lin ◽

Yung-Kai Lin ◽

Shu-Ting Chan ◽

Kai-Wen Kan ◽

Yu-Ting Lin ◽

...

Keyword(s):

Gene Expression ◽

Light Exposure ◽

Dermal Fibroblast ◽

Skin Barrier ◽

Dermal Fibroblasts ◽

Control Group ◽

Gene Expressions ◽

Positive Effects ◽

Collagen Secretion ◽

Skin Collagen

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

Download Full-text

Remdesivir shifts circadian rhythmicity to eveningness; similar to the most prevalent chronotype in ADHD

Journal of Neural Transmission ◽

10.1007/s00702-021-02375-3 ◽

2021 ◽

Cited By ~ 1

Author(s):

Frank Faltraco ◽

Denise Palm ◽

Andrew Coogan ◽

Adriana Uzoni ◽

Isabell Duwe ◽

...

Keyword(s):

Gene Expression ◽

Sleep Quality ◽

Ex Vivo ◽

Dermal Fibroblast ◽

Human Dermal Fibroblast ◽

Circadian Clocks ◽

Circadian Gene ◽

Qrt Pcr ◽

Significant Difference ◽

And Shifts

AbstractCircadian clocks control immunity and virus replication, as well as pharmacokinetics and efficacy therapeutics. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after remdesivir exposure. In the current study, we analysed circadian gene expression in a cohort of participants without a neuropsychiatric diagnosis. After ex vivo exposure to remdesivir to human dermal fibroblast (HDF) cultures and dexamethasone synchronization, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analysed via qRT-PCR. In this study, D-MEQ scores indicated that participants without a neuropsychiatric diagnosis had no evening preference. Remdesivir leads to a slight phase-shift in Clock, Per1 and Per2. Significant different expressions of Bmal1 and Per3 were detected after remdesivir exposure: Bmal1 at ZT8 (t(22) = 3.26, p = 0.004), ZT24 (t(22) = − 2.66, p = 0.015), ZT28 (t(20) = − 2.14, p = 0.045) and Per3 at ZT8 (t(22) = − 4.27, p < 0.001) and ZT12 (t(22) = − 2.61, p = 0.016). A significant difference between chronotype and circadian gene expression for Bmal1, Cry1 and Per3 was observed. The present study shows that remdesivir has an impact on circadian function. It is well known that the circadian rhythm effects sleep and, moreover, sleep quality. The results suggest that remdesivir medication may alter sleep quality in participants without a neuropsychiatric diagnosis and shifts chronotype to eveningness; similar as prevalent in ADHD.

Download Full-text

Mainstream and Remedial School Attention Deficit Hyperactivity Disorder Boys: More Alike than Different

South African Journal of Psychology ◽

10.1177/008124630503500105 ◽

2005 ◽

Vol 35 (1) ◽

pp. 73-88

Author(s):

J. B. Savitz ◽

P. Jansen

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Control Group ◽

Adhd Group ◽

Hyperactivity Disorder ◽

Significant Difference ◽

Executive Deficits ◽

Mainstream School ◽

The Difference ◽

Neuropsychological Tasks

The literature on the neuropsychology of Attention Deficit Hyperactivity Disorder (ADHD) is plagued by inconsistent findings, which are usually attributed to a variety of extraneous variables. One of the most inadequately explored of these variables is the difference between ADHD children attending remedial and mainstream schools. This study aimed to investigate whether the performance of remedial and mainstream school ADHD boys differs on relevant neuropsychological tasks. The sample consisted of three groups of 8- to 12-year-old boys. Two of these groups consisted of children with ADHD: one from remedial schools and one from mainstream schools. The third group was made up of participants without ADHD, who attended mainstream schools. The performance of the remedial school learners on the Stroop, Lurian and cancellation tasks was investigated and compared to a mainstream school ADHD sample. The performance of the ADHD group as a whole was compared with that of a control group. No significant difference in performance was found between the two ADHD groups, except for the length of time taken to read words in the control condition of the Stroop. The control group out-performed the ADHD samples on the Stroop, Lurian and cancellation tasks. The findings suggest that mainstream and remedial ADHD boys do not differ in the severity of their executive deficits, but that boys with ADHD attending remedial schools may be more likely to have another learning disorder than their counterparts at mainstream schools.

Download Full-text

MO477SERUM C-REACTIVE PROTEIN AND PROCALCITONIN LEVELS IN HEMODIALYSIS AND INTRADIALYTIC ALTERATIONS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab090.0039 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Makrouhi Sonikian ◽

Aggeliki Barbatsi ◽

Eugenia Karakou ◽

Theodoros Chiras ◽

Jacob Skarakis ◽

...

Keyword(s):

Healthy Subjects ◽

Control Group ◽

Healthy Controls ◽

C Reactive Protein ◽

Polysulfone Membrane ◽

Reactive Protein ◽

Markers Of Inflammation ◽

Dialysate Flow Rate ◽

Significant Difference ◽

Serum Crp

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p<0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p<0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p<0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.

Download Full-text