Peptide P3 ameliorates foam cell formation in RAW264.7 cells and its molecular mechanisms / 中国药理学通报

Aim To examine the effect of peptide P3 on lipid accumulation in RAW264.7 cells and the underlying molecular mechanism. Methods MTT method was used to screen the concentration of peptide P3 and oxidized low density lipoprotein(ox-LDL),and RAW.264.7 cells were induced to form foam cells by ox-LDL with 80 mg·L

Immunoregulatory Effect of Jiedu Tongluo Shengjin Prescription on Sjögren's Syndrome Mice Based on Stability of Treg Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect of different doses of Jiedu Tongluo Shengjin prescription （JTSP） on serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and forkhead box P3 （FoxP3） in submandibular gland of NOD/Ltj mice with Sjögren's syndrome， and to explore the mechanism of JTSP on immune regulation in NOD/Ltj mice. MethodThirty NOD/Ltj mice （eight weeks old） were randomly divided into model group， JTSP low-dose group， JTSP medium-dose group， JTSP high-dose group and hydroxychloroquine group， and were administrated with normal saline， JTSP 9， 18， and 36 g·kg-1， and hydroxychloroquine 60 mg·kg-1 daily， respectively from the age of 12 weeks. Six ICR mice were given an equal amount of normal saline by gavage as the control group. During the experiment， daily water consumption and saliva secretion of mice at the age of 9， 12， 16 weeks were recorded. After 4 weeks of administration， submandibular gland and spleen tissues were dissected to calculate corresponding indexes. The pathological morphology of submandibular gland was observed by hematoxylin-eosin （HE） staining. Meso Scale Discovery （MSD） and immunohistochemistry were employed to detect the serum levels of IL-6， TNF-α and IL-10， and the expression and distribution of FoxP3 in submandibular gland， respectively. The protein expression of FoxP3 in mouse submandibular gland was determined by Western blot， and the mRNA expressions of FoxP3 and TNF-α were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group presented increased daily water consumption， decreased saliva secretion， lowered submandibular gland index， elevated pathological score of submandibular gland， up-regulated serum IL-6 and TNF-α and mRNA expression of TNF-α while down-regulated serum IL-10 and protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. Compared with the conditions in model group， daily water consumption in JTSP groups was reduced while saliva secretion was increased， especially in medium-dose and high-dose groups （P<0.05）， and there was an increase in the submandibular gland index of JTSP medium-dose group （P<0.05） while a decrease in the spleen index of JTSP high-dose group （P<0.05）. Additionally， JTSP groups had lower pathological score of submandibular gland than the model group （P<0.05）， especially high-dose group， as well as lower serum IL-6 and TNF-α and mRNA expression of TNF-α while higher serum IL-10 （P<0.05）. JTSP at medium and high doses up-regulated the protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. ConclusionJTSP may inhibit the secretion of inflammatory cytokines by regulating the stability of FoxP3+ regulatory T （Treg） cells， thus alleviating the systemic immune inflammation in Sjögren's syndrome.

Potencial de disparidad o Mismatch negativity y P3a en pacientes con esquizofrenia / Mismatch negativity and P3a in patients with Schizophrenia

Resumen Antecedentes: la esquizofrenia es una enfermedad crónica que genera gran discapacidad, para la cual se han reportado biomarcadores potenciales, pero sin suficiente validez clínica. El mismatch negativity (MMN) y el P3a son potenciales relacionados con eventos que han demostrado ser indicadores neurofisiológicos del procesamiento auditivo pre-atencional y potenciales biomarcadores. Objetivo: evaluar el MMN y P3a en pacientes con diagnóstico de esquizofrenia y su relación con variables sociodemográficas y clínicas. Método: estudio cuantitativo transversal de 23 sujetos con esquizofrenia (ESQ) y 22 controles sanos (SN). Las amplitudes promedio y latencias del MMN/P3a para la condición infrecuente en duración y frecuencia fueron obtenidas mediante un paradigma oddball auditivo en un EEG de 32 canales. Resultados: se encontraron diferencias para la condición frecuencia en la amplitud del MMN (p=0.046; CI 95% 0.009; 0.87) y la amplitud del P3a (p=0.042; CI 95% 0.025; 1.24) entre los grupos; la amplitud del MMN fue menor en el grupo ESQ (-0.36 DE 0.51 µV) en comparación con los participantes del grupo de SN (-0.81 DE 0.89 µV), mientras que la amplitud del P3a fue menor en el grupo SN (0.18 DE 0.97 µV) versus el grupo ESQ (0.82 DE 1.05 µV). En relación con las variables sociodemográficas y clínicas, las asociaciones con el P3a fueron moderadas y con el MMN débiles. Conclusiones: la reducción de la amplitud del MMN a la condición frecuencia exhibe mayor utilidad que el P3a como medida de alta estabilidad en pacientes con esquizofrenia, lo que reitera su posible uso como biomarcador.

Abstract Background: schizophrenia is a chronic disease that generates great disability, which currently has potential biomarkers but without sufficient clinical validity. Mismatch negativity (MMN) and P3a are event-related potentials that have been shown to be neurophysiological indicators of pre-attentional auditory processing and potential biomarkers. Objective: to evaluate MMN and P3a in patients with a diagnosis of schizophrenia and their relationship with sociodemographic and clinical variables. Method: a quantitative cross-sectional study of 23 subjects with schizophrenia and 22 healthy controls was performed. The average amplitudes and latencies of the MMN/P3a for the condition infrequent in duration and infrequent in frequency were obtained using an auditory oddball paradigm on a 32-channel EEG. Results: differences were found for the frequency condition in the amplitude of the MMN (p=0.046; 95% CI 0.009; 0.87) and the amplitude of the P3a (p=0.042; 95% CI 0.025; 1.24) between the groups; MMN amplitude was lower in schizophrenia (-0.36 SD 0.51 µV) compared to healthy controls (-0.81 SD 0.89 µV), while P3a amplitude was lower in healthy controls (0.18 SD 0.97 µV) versus the group with schizophrenia (0.82 SD 1.05 µV). In regard to sociodemographic and clinical variables, the associations with P3a were moderate, and showed weak MMN. Conclusions: MMN amplitude reduction to the frequency condition exhibits greater utility than P3a as a measure of high stability in schizophrenia, restating its potential use as a biomarker.

Evaluation of Visual Acuity of Ametropia with Visual Event-Related Potential Nogo-P3 Component / 法医学杂志

OBJECTIVES@#To analyze the Nogo-P3 component of event-related potential (ERP) in the process of visual acuity processing, to provide electrophysiological evidence for objective evaluation of visual acuity.@*METHODS@#Twenty-six subjects with no other ocular diseases except for ametropia were recruited, and all subjects had uncorrected visual acuity both eyes 1/10 (evaluated using Monoyer chart). Block letter E with different visual angles and directions were used as graphic stimuli. The Go/Nogo paradigm was used for ERP studies. The visual angle of Go stimulation angle was 1°15', Nogo stimuli were 1°15', 55', 24' and 15'. The visual acuity test was performed on each of the two naked eyes separately in all subjects, and the characteristics of the Nogo-P3 component were analyzed.@*RESULTS@#The latency of Nogo-P3 showed no difference between the stimuli of 1°15' and 55', and between Nogo stimulation angle 24' and 15'. There was significant difference between Nogo stimulation angle 1°15' and 24', and between Nogo stimulation angle 1°15' and 15' (P<0.05). There was significant difference between Nogo stimulation angle 55' and 24', and between Nogo stimulation angle 55' and 15' (P<0.05). No significant differences were observed in the Nogo-P3 amplitude among Nogo stimulation.@*CONCLUSIONS@#In the Go/Nogo paradigm, Nogo-P3 can reflect the cognitive response of subjects to Nogo stimulation, which can be used for objective evaluation of visual acuity.

Relationship between cognitive function and brain event-related potentials in patients with lacunar cerebral infarction / 中国综合临床

Objective:To investigate the relationship between cognitive function and brain event-related potential in patients with lacunar cerebral infarction.Methods:A total of 464 patients with lacunar cerebral infarction admitted to the Department of Neurology, Kailuan General Hospital from 2014 to 2019 were prospectively selected as observation subjects (case group). According to mini-mental state examination (MMSE) score, the patients in the case group were divided into 352 cases of lacunar cerebral infarction with normal cognition and 112 cases of mild cognitive impairment. At the same time, 100 healthy volunteers were selected as the control group. All subjects were assessed by simple intelligent mental state, Zung self-rating anxiety scale, Zung self-rating depression scale and brain event-related potential P3a and P3b. The measurement data of normal distribution adopts one-way ANOVA, the measurement data of non normal distribution adopts Kruskal Wallis H test, and the counting data adopts χ2. Multivariate statistical analysis was performed by unconditional Logistics (stepwise method). Results:The proportions of smokers in control group, lacunar cerebral infarction cognitive normal group and lacunar cerebral infarction mild cognitive impairment group were 20.00% (20/100), 38.07% (134/352) and 46.42% (52/112), respectively. The proportions of drinkers were 18.00% (18/100), 33.24% (117/352), 33.93% (38/112), respectively. The proportions of hypertension were 38.00% (38/100), 58.24% (205/352), 59.82% (67/112), respectively. The proportions of hyperhomocysteinemia were 19.00% (19/100), 34.00% (120/352) and 68.75% (77/112), respectively, and the differences among the three groups were statistically significant ( χ2 values were 15.66, 7.91, 11.86 and 54.57, respectively; P<0.001, 0.019, 0.003, <0.001). The peak latency CZ leads of visual P3b wave group N2 were (271.48±40.65), (285.67±44.08) and (290.57±68.41) ms, respectively. PZ leads were (276.70±50.92), (287.86±43.28) and (312.16±62.75) ms. P3b peak latency FZ leads were (392.67±42.50), (405.82±52.43) and (410.34±64.27) ms. CZ leads were (395.04±42.44), (412.51±55.86) and (433.28±66.32) ms. PZ leads were (398.24±40.93), (411.17±49.48) and (435.78±67.69) ms. N2 amplitude CZ leads were (-3.99±2.81), (-3.60±3.00) and (-2.70±2.37) μV, PZ leads were (-3.18±2.69), (-2.91±2.62) and (-1.87±2.89) μV, respectively. Leads P3b amplitude of FZ were 5.27 (3.27, 7.40), 4.21 (2.31, 6.49) and 3.12 (1.61, 5.08) μV. CZ leads were 4.81 (2.78, 6.71), 4.15 (2.76, 6.16) and 3.51 (1.75, 5.15) μV. PZ leads were 5.17 (3.03, 6.97), 4.40 (2.89, 6.12) and 3.43 (1.52, 5.34) μV. There were statistically significant differences among the 3 groups ( F=3.29, 14.49, 3.95, 11.73, 14.06, 5.66 and 3.57, H=18.23, 10.33,18.25; P=0.027, <0.001, 0.025, <0.001, <0.001, 0.004, 0.042, <0.001, 0.006, <0.001). The peak latency FZ leads of visual P3a wave group N2 were 265.00 (256.00, 286.00), 277.00(260.00,300.00), 282.00(270.00,304.00) ms, respectively. CZ leads weres 274.00(255.00,305.00), 285.00(262.00,329.00), 293.50(270.00,346.00) ms. P3a peak latency FZ leads were (413.83±49.58), (429.83±55.38) and (449.04±54.79) ms, CZ leads were (441.53±61.78), (457.12±69.29) and (460.23±72.24) ms. PZ leads were (430.14±54.53), (462.31±69.2) and (470.02±74.92) ms. N2 amplitude FZ leads were (-6.34±3.13), (-5.72±2.96) and (-4.92±2.05) μV, respectively. Leads P3a amplitude of FZ were 4.00 (2.28, 5.55), 3.15 (2.14, 4.91) and 2.80 (2.19, 4.19) μV. CZ lead were 3.37 (1.98, 4.66), 2.73 (1.70, 3.97) and 2.41 (1.64, 3.45) μV. There were statistically significant differences among the three groups ( H=13.92, 8.65, 9.17, 10.02, F=8.18, 6.33, 10.73, 4.62, P =0.001,0.013,0.010,0.007, <0.001,0.002, <0.001,0.010). Logistic regression analysis showed that alcohol consumption, P3b peak latency and wave amplitude PZ lead, N1 wave amplitude of visual P3a group FZ lead were the influencing factors of MMSE ( OR=0.04, 1.01, 0.76, 1.51, 95% Cl were 0.00-0.30, 1.00-1.03, 0.59-0.97, 1.08-2.10, P=0.002,0.007,0.029,0.016). Conclusion:The peak latency and amplitude of endogenous psychological cognitive potentials N2, P3b and P3a of event-related potentials P3b and P3a in patients with lacunar cerebral infarction were prolonged and decreased. At the same time, with the occurrence of clinical cognitive impairment, the peak latency and amplitude of these cognitive potentials were further prolonged and decreased more significantly. Alcohol consumption, P3b peak latency and PZ lead of visual P3b wave group, and FZ lead of N1 wave of visual P3a wave group were the influencing factors of simple intelligent mental state.

Visual attention impairment in patients with cerebral small vessel disease: an event-related potential P3 study / 中华行为医学与脑科学杂志

Objective:To investigate the value of event-related potential (ERP) P3 in the assessment of visual attention impairment in patients with cerebral small vessel disease (CSVD).Methods:Twenty-five patients with CSVD diagnosed in the Shandong Provincial Hospital Affiliated to Shandong First Medical University from July 2019 to December 2020 were selected as the CSVD group, while 25 healthy subjects who underwent physical examination in the same period were selected as the control group.The neuropsychological evaluation of CSVD group and control group was carried out by Montreal cognitive assessment (MoCA), 7-items generalized anxiety disorder (GAD-7) and patient health questionnaire-9 (PHQ-9). Magnetic resonance imaging brain white matter high signal of CSVD group and control group was carried out by Fazekas score.The amplitude and latency of ERP component P3 were measured by visual tristimulation Oddball experimental paradigm.SPSS 23.0 software was used for statistical analysis.The differences of amplitude and latency between the two groups were compared by repeated measurement analysis of variance.Pearson or Spearman correlation analysis were used to explore the correlation between P3 amplitude, latency and related scale scores.Results:(1)In the amplitude of P3, the interaction effect between group and stimulation was significant( F(2, 96)=3.922, P=0.023). The main effect between groups was significant( F(1, 46)=15.976, P<0.01). The main effect of stimulation was significant( F(2, 96)=86.212, P<0.01). Further simple effect analysis showed that compared with the control group((9.82±5.14)μV, (11.12±4.72)μV) the P3 amplitude induced by target stimulation ((6.59±4.22)μV, F(1, 48)=7.363, P=0.009) and novel stimulation ((7.08±3.91)μV, F(1, 48)=13.907, P=0.001) in CSVD group decreased significantly.(2)In the latency of P3, the main effect between groups was significant( F(1, 48)=4.870, P=0.032). The main effect of stimulation was significant( F(2, 96)=86.212, P<0.01). The interaction effect between group and stimulation was significant( F(2, 96)=4.561, P=0.013). The main effect of stimulation was significant( F(2, 96)=16.299, P<0.01). Further simple effect analysis showed that the P3 latency induced by novel stimulation in CSVD group was longer than that in control group( F(1, 48)=17.124, P<0.01). (3)P3 amplitude induced by target stimulation was positively correlated with MoCA score ( r=0.255, P=0.027). The P3 amplitude ( r=-0.502, P<0.01) and P3 latency ( r=-0.265, P=0.022) induced by novel stimulation were negatively correlated with Fazekas score. Conclusion:The speed and ability of patients with CSVD to process visual spatial information are impaired, especially for rare stimulation.ERP examination may be a rapid, objective and sensitive method for the diagnosis of visual attention impairment in patients with CSVD.

Exploration of IRES Elements within the ORF of the Coxsackievirus B3 Genome / 生物医学与环境科学（英文）

Objective@#This study aimed to identify internal ribosome entry sites (IRESs) in the open reading frame (ORF) of the Coxsackievirus B3 (CVB3) genome.@*Methods@#The sequences of P1, P2, or P3 of the CVB3 genome or the truncated sequences from each antithymocyte globulin (ATG) to the end of the P1, P2, or P3 gene were inserted into the pEGFP-N1 vector. After transfection, possible IRES-dependent green fluorescent protein (GFP)-fused proteins were detected by anti-GFP western blotting. The sequences of possible IRESs were inserted into specific Fluc/Rluc bicistronic vectors, in which the potential IRESs were determined according to the Fluc/Rluc activity ratio. Expression of Fluc and Rluc mRNA of the bicistronic vector was detected by RT-qPCR.@*Results@#After transfection of full length or truncated sequences of the P1, P2, or P3 plasmids, six GFP-fused protein bands in P1, six bands in P2 and nine bands in P3 were detected through western blotting. Two IRESs in VP2 (1461-1646 nt) and VP1 (2784-2983 nt) of P1; one IRES in 2C (4119-4564 nt) of P2; and two IRESs in 3C (5634-5834 nt) and 3D (6870-7087 nt) of P3 were identified according to Fluc/Rluc activity ratio. The cryptic promoter was also excluded by RT-qPCR.@*Conclusion@#Five IRESs are present in the CVB3 coding region.

Effect of short-chain thioesterase deficiency on P(3HB-co-LA) biosynthesis in Escherichia coli / 生物工程学报

Polyhydroxyalkanoates (PHAs) have obtained much attention in biomaterial fields due to their similar physicochemical properties to those of the petroleum-derived plastics. Poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] is one member of the PHAs family, and has better toughness and transparency compared to existing polylactic acid (PLA) and poly[(R)-3-hydroxybutyrate] [P(3HB)]. First, we confirmed the one-step biosynthesis of P(LA-co-3HB) with the lactate fraction of 23.8 mol% by introducing P(3HB-co-LA) production module into Escherichia coli MG1655. Then, the lactate fraction was increased to 37.2 mol% in the dld deficient strain WXJ01-03. The genes encoding the thioesterases, ydiI and yciA, were further knocked out, and the lactate fraction in the P(3HB-co-LA) was improved to 42.3 mol% and 41.1 mol% respectively. Strain WXJ03-03 with dld, ydiI and yciA deficient was used for the production of the LA-enriched polymer, and the lactate fraction was improved to 46.1 mol%. Notably, the lactate fraction in P(3HB-co-LA) from xylose was remarkably higher than from glucose, indicating xylose as a potent carbon source for P(3HB-co-LA) production. Therefore, the deficiency of thioesterase may be considered as an effective strategy to improve the lactate fraction in P(3HB-co-LA) in xylose fermentation.

Effect of Acupuncture-rehabilitation Therapy on Neural Function and Expression of Forkhead Box P3 and Retinoic Acid-related Orphan Receptor γt in Mice with Cerebral Ischemia / 中国康复理论与实践

Objective To explore the effect of acupuncture-rehabilitation therapy on the expression of transcription factor forkheadbox P3 (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) protein in cerebral ischemic mice. Methods Forty-five female C57BL/6 mice were randomly assigned to sham operation group, model group, acupuncture group, rehabilitation group, and acupuncture-rehabilitation group, with nine mice in each group. Subsequently, each group was divided into three days, seven days and 14 days subgroups. The permanent middle cerebral artery occlusion models were established by the suture method, except the sham operation group. The sham operation group and the model group received no treatment. The acupuncture group received scalp cluster acupuncture, the rehabilitation group received treadmill training, and the acupuncture-rehabilitation group received scalp cluster acupuncture combined with treadmill training. Three days, seven days and 14 days after modeling, the modified Neurological Severity Score (mNSS) was obtained, and the expression of Foxp3 and RORγt in brain tissue of ischemic side was analyzed by Western blotting. Results The mNSS in the sham operation group was 0, and was higher in the model group than in the sham operation group at each postoperative time point. Three days after operation, the mNSS decreased in the rehabilitation group and the acupuncture-rehabilitation group, compared to the model group (P < 0.05). Fourteen days after operation, the mNSS decreased in the acupuncture-rehabilitation group, compared to the model group and acupuncture group (P < 0.05). The expression of Foxp3 protein was significantly lower in the acupuncture-rehabilitation group than in other groups at all time points after surgery( P < 0.05). Three days after operation, the expression of RORγt was higher in the acupuncture-rehabilitation group than in other groups (P < 0.05). Seven days after operation, the expression of RORγt was higher in the acupuncture-rehabilitation group than in the acupuncture group and sham operation group (P < 0.05). Conclusion Acupuncture-rehabilitation therapy may improve the tissue injury of cerebral ischemia mice, and promote the recovery of neural function, possibly by regulating Foxp3 and RORγT expression to reduce the level of inflammation, and then exert neuroprotective effects.

Effect of Acupuncture-rehabilitation Therapy on Neural Function and Expression of Forkhead Box P3 and Retinoic Acid-related Orphan Receptor γt in Mice with Cerebral Ischemia / 中国康复理论与实践

Objective To explore the effect of acupuncture-rehabilitation therapy on the expression of transcription factor forkheadbox P3 (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) protein in cerebral ischemic mice. Methods Forty-five female C57BL/6 mice were randomly assigned to sham operation group, model group, acupuncture group, rehabilitation group, and acupuncture-rehabilitation group, with nine mice in each group. Subsequently, each group was divided into three days, seven days and 14 days subgroups. The permanent middle cerebral artery occlusion models were established by the suture method, except the sham operation group. The sham operation group and the model group received no treatment. The acupuncture group received scalp cluster acupuncture, the rehabilitation group received treadmill training, and the acupuncture-rehabilitation group received scalp cluster acupuncture combined with treadmill training. Three days, seven days and 14 days after modeling, the modified Neurological Severity Score (mNSS) was obtained, and the expression of Foxp3 and RORγt in brain tissue of ischemic side was analyzed by Western blotting. Results The mNSS in the sham operation group was 0, and was higher in the model group than in the sham operation group at each postoperative time point. Three days after operation, the mNSS decreased in the rehabilitation group and the acupuncture-rehabilitation group, compared to the model group (P < 0.05). Fourteen days after operation, the mNSS decreased in the acupuncture-rehabilitation group, compared to the model group and acupuncture group (P < 0.05). The expression of Foxp3 protein was significantly lower in the acupuncture-rehabilitation group than in other groups at all time points after surgery( P < 0.05). Three days after operation, the expression of RORγt was higher in the acupuncture-rehabilitation group than in other groups (P < 0.05). Seven days after operation, the expression of RORγt was higher in the acupuncture-rehabilitation group than in the acupuncture group and sham operation group (P < 0.05). Conclusion Acupuncture-rehabilitation therapy may improve the tissue injury of cerebral ischemia mice, and promote the recovery of neural function, possibly by regulating Foxp3 and RORγT expression to reduce the level of inflammation, and then exert neuroprotective effects.

Effect of Warming and Heat-clearing Method on Expressions of FoxP3 and ROR-γt in Colon Tissue of Rats with Intestinal Endotoxemia Caused by Acute-on-chronic Liver Failure / 中国实验方剂学杂志

Objective::To study the effect of warming and heat-clearing method (Wenyang Jiedu Huayu decoction) on the expressions of Forkhead box P3 (FoxP3), Retinoic acid-related orphan receptor gamma t (ROR-γt) in colon tissue of mice with acute-on-chronic liver failure (ACLF), in order to explore the possible regulatory mechanism on intestinal endotoxemia (IETM) in liver failure mice. Method::The 130 SD rats were randomly divided into normal group (10 rats) and model group (120 rats). The ACLF mice model was established through the subcutaneous injection with bovine serum albumin and the intraperitoneal injection with D-galactosamine(D-Gal) and lipopolysaccharide (LPS). The model mice were randomly divided into model group, heat-clearing group (Yinchenhao decoction, 6.68 g·kg-1), warming group (Yinchen Zhufu decoction, 7.09 g·kg-1) and warming and heat-clearing group (Wenyang Jiedu Huayu decoction, 19.53 g·kg-1). The normal group and the model group were given distilled water by gastric lavage, while the other groups were given equal volume of corresponding Chinese herbal medicines for a week. The value of each index at 1, 12 and 24 h was measured. The ratio of Treg/Th17 cell in peripheral blood were detected and calculated by flow cytometry. Real-time fluorescence quantitative PCR (Real-time PCR) was used to detect the expressions of FoxP3 and ROR-γt in colon tissues of mice at different time points. In situ hybridization and immunohistochemistry were used to observe the expressions of FoxP3 and ROR-γt genes and proteins. Result::Compared with normal group, the ratio of Treg/Th17 in the model group decreased significantly at each time point (P<0.01). Compared with the model group, the Treg/Th17 ratio increased only in the warming and heat-clearing method group (P<0.05). Compared with normal group, the expression of ROR-γt in the model group was significantly higher (P<0.01), and the expression of ROR-γt in the model group was higher than FoxP3.Compared with the model group, the expressions of FoxP3 and ROR-γt mRNA in the heat-clearing group and the warming group decreased at each time point (P<0.05), and the expressions of FoxP3 and ROR-γt in the warming and heat-clearing method group decreased significantly (P<0.01). The expressions of FoxP3 and ROR-γt mRNA in warming and heat-clearing group decreased compared with those in the warming group and heat-clearing group (P<0.05). Conclusion::The mechanism of the warming and heat-clearing method on IETM in liver failure may be related to the regulation of FoxP3 and ROR-γt expressions.

The Association of Glutaminase (glut) P3 Different Alleles of Trichomonas vaginalis with Infertility in a sample of Iraqi women

Trichomonas vaginalis (T. vaginalis), the etiologic agent of human trichomoniasis, is a flagellated protozoan parasite, has been associated sith advese pregnancy outcomes, HIV transmission, and infertilityh. A total of one hundred and fifty-seven (157) women at childbearing age (14-49 years), were included in the presnt study, eighty six (86) symptomatic fertile while the other seventy-one (71) were infertile with or without sumptoms attending the Gynecology outpatient Department in Al-Emamayn Al-Kadhimayn Medical City, the High Institute of Infertility Diagnosis and Assisted Reproductive Technoligies at Al-Nahrain University in Baghdad, the maternity Teaching hospital, and Dr. Khawer center for infertility and IVF in Erbil province in Iraq. Two vaginal swab specimens were obtained from each of them:; one swab was immediately examined by wet mount microscopy, the other swab for molecular study (DNA extraction and p3 nested PCR). One hundred (100) samples positive in one or more test were identified: 20 (12.7%) infecions were detected by wet mount microscopy, while nested PCR was positive in 100 (63.7%) samples. These positive samples were seguenced and phylogenetic tree were done and, there was no association between the variations in glut (p3) gene of T. vaginalis isolated from infected women (fertile and infertile)

Adaptações do cérebro durante uma tarefa de longa duração: Um estudo de Potencial Relacionado a Evento / Brain adaptations during a long-time task: An Event-Related Potential (ERP) study

Resumo O objetivo deste estudo é investigar o efeito da demanda cognitiva prolongada na modulação do Potencial Relacionado a Evento (ERP) em um paradigma de controle inibitório. Os dados foram coletados em 19 voluntários destros, com a média de idade de 21,21 (±1,77) anos, que realizaram o paradigma do Go/NoGo durante 50 minutos, com gravação sincronizada do eletroencefalograma para obtenção dos ERPs. O efeito do tempo de realização da tarefa provocou alterações significativas nas variáveis subjetivas, de desempenho cognitivo e nas amplitudes máximas dos componentes N2 e P3. Nossos resultados sugerem que quando nosso cérebro está submetido a demandas cognitivas extensas, ocorrem adaptações para a manutenção do desempenho comportamental através da estratégia de realocação de recursos energéticos.

Abstract The aim of this study is to investigate the effect of prolonged cognitive demand in Event Related Potential (ERP) modulation in inhibitory control paradigm. Data were collected in 19 right-handed volunteers with mean age of 21.21 (±1,77) years who performed the Go/NoGo paradigm for 50 minutes, with synchronized electroencephalogram recording to obtain the ERPs. The time on task effect induced significant changes in subjective variable, cognitive performance and maximum amplitudes of the N2 and P3 component. Our results suggest that when our brain is subjected to extensive cognitive demands, there are adaptations to maintain the behavioral performance through strategy reallocation of energy resources.

Pro-Inflammatory Role of S1P₃ in Macrophages

Sphingosine kinase 1 and its product, sphingosine 1-phosphate (S1P), as well as their receptors, have been implicated in inflammatory responses. The functions of receptors S1P₁ and S1P₂ on cell motility have been investigated. However, the function of S1P₃ has been poorly investigated. In this study, the roles of S1P₃ on inflammatory response were investigated in primary perito-neal macrophages. S1P₃ receptor was induced along with sphingosine kinase 1 by stimulation of lipopolysaccharide (LPS). LPS treatment induced inflammatory genes, such iNOS, COX-2, IL-1β, IL-6 and TNF-α. TY52156, an antagonist of S1P₃ suppressed the induction of inflammatory genes in a concentration dependent manner. Suppression of iNOS and COX-2 induction was further confirmed by western blotting and NO measurement. Suppression of IL-1β induction was also confirmed by western blotting and ELISA. Caspase 1, which is responsible for IL-1β production, was similarly induced by LPS and suppressed by TY52156. Therefore, we have shown S1P₃ induction in the inflammatory conditions and its pro-inflammatory roles. Targeting S1P₃ might be a strategy for regulating inflammatory diseases.

Effects of RuanJianXiaoYing Granule on expressions of Treg and Th17 cytokines in Hashimoto thyroiditis model rats with liver depression and spleen deficiency / 吉林大学学报(医学版)

Objective: To observe the effects of RuanJianXiaoYing Granule on the expressions of specific transcription factors and cytokines of Treg and Th17 in the Hashimoto thyroiditis (HT) rats with liver depression and spleen deficiency, and to investigate the therapeutic effect of RuanJianXiaoYing Granule on HT and its immunological mechanism. Methods: A total of 48 SD rats were randomly divided into normal group (12 rats) and modeling group (36 rats). The HT model was established by subcutaneous injection of excessive iodine drinking water and thyroglobulin, and then combined with chronic restraint stress, excessive fatigue and dietary disorders to prepare the rat models with liver depression and spleen deficiency. After modeling, the rats were randomly divided into model group (n=12), Tripterygium wilfordii group (n=12), and RuanJianXiaoYing group (n=12), and the rats were treated for 8 weeks. In addition to the dead rats and unqualified specimens during the experiment, the test results of 10 rats in each group were retained. The general situation of the rats in various groups was observed; the abdominal aortic blood and thyroid gland tissue of the rats in various groups were collected after the last administration; the levels of thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) in serum and the levels of IL-17, IL-23 and IL-10 were detected by ELISA method; the pathomorphology of thyroid gland tissue of the rats in various groups were detected by HE staining; the expression levels of Foxp3 and RORyt proteins in thyroid gland tissue of the rats in various groups were detected by Western blotting method. Results: Compared with normal group, the levels of serum TGAb and TPOAb of the rats in model group, Tripterygium wilfordii group and RuanJianXiaoYing - group were increased (P0. 05); the level of serum IL-10 was increased (P<0. 05), and the levels of serum IL-17 and IL-23 were decreased (P<0. 05). The follicular cavity of thyroid gland in normal group had regular morphology, complete structure and no lymphocyte infiltration. In model group, the follicular cavity of thyroid gland was enlarged, the follicular structure was destroyed, and a large number of lymphocyte infiltration was observed in and around the follicular cavity. In Tripterygium wilfordii group, the follicular cavity of thyroid gland was enlarged, part of the follicular structure was destroyed, and there was a small amount of lymphocyte infiltration in and around the follicular cavity, which was less than that in model group. The morphological changes of thyroid gland in RuanJianXiaoYing group were similar to those in Tripterygium wilfordii group Conclusion: RuanJianXiaoYing Granule has the therapeutic effect in the HT rats with liver depression and spleen deficiency by regulating the expressions of the specific transcription factors Foxp3 and RORγt protein and related cytokines of Treg and Th17.

Relationship between hydrogen sulfide and P2X3 receptors in dorsal root ganglion of rats with neuropathic pain / 中华麻醉学杂志

Objective To evaluate the relationship between hydrogen sulfide (H2S) and P2X3 receptors in dorsal root ganglions (DRGs) of rats with neuropathic pain (NP).Methods Thirty-six healthy male Sprague-Dawley rats,aged 4-6 weeks,weighing 180-200 g,in which IT catheters were successfully implanted,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),group NP and endogenous H2S synthase (cystathionine beta-syntheses [CBS]) inhibitor animooxyacetic acid (AOAA) group (group A).NP was induced by chronic constriction injury (CCI) to the sciatic nerve at 3 days after IT catheters were successfully implanted.AOAA (10 μg/kg) 10 μl and normal saline 10 μl were intrathecally injected once a day for 14 consecutive days starting from 1 day after CCI in group A,and normal saline 20 μl was intrathecally injected instead in S and NP groups.At 1 day before CCI and 1,3,7,10 and 14 days after CCI,the thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 30 min after intrathecal injection.The animals were sacrificed at 7 and 14 days after CCI,and ipsilateral DRGs of the lumbar segment (L4-6) were removed for detection of the expression of CBS and P2X3 receptors by Western blot.Results Compared with group S,the TWL was significantly shortened,MWT was decreased,and the expression of CBS and P2X3 receptors in DRGs was up-regulated at each time point after CCI in group NP (P＜0.05).Compared with group NP,the TWL was significantly prolonged,the MWT was increased,and the expression of CBS and P2X3 receptors in DRG s was down-regulated at each time point after CCI in group A (P＜0.05).Conclusion H2S in DRG s can up-regulate the expression of P2X3 receptors,which may be involved in the pathophysiological mechanism of NP in rats.

Study on attention cognitive function and event-related potential in the children with the first-episode tic disorder / 中华行为医学与脑科学杂志

Objective To explore the changes of attention cognitive function by studying Oddball task behavior and event-related potentials(ERPs) in children with first-episode tic disorder(TD). Methods Oddball task was tested in 30 children with TD and 30 normal children,and their behavioral data and P3a/P3b components of ERPs were analyzed. Results Children with TD had a lower hitting number (49(48, 50)) than control group (50(49,50),P<0. 05). The main effect of group ( F=6. 047,P=0. 015) and the interaction effect between group and condition (F=4. 619,P=0. 034) on the amplitude of P3a were signifi-cant(P<0. 05). The amplitude of P3a component ((5. 91±4. 51)μV ) in TD group were smaller than that in the control group((9. 57±5. 80)μV)(P<0. 05). However,there was no significant interaction effect be-tween group and condition on P3a latency,P3b amplitude and latency (P>0. 05). Conclusion Attentional orienting is impaired in children with TD.

P3 Cognitive Potential in Cochlear Implant Users

Abstract Introduction The P3 cognitive evoked potential is recorded when a subject correctly identifies, evaluates and processes two different auditory stimuli. Objective to evaluate the latency and amplitude of the P3 evoked potential in 26 cochlear implant users with post-lingual deafness with good or poor speech recognition scores as compared with normal hearing subjects matched for age and educational level. Methods In this prospective cohort study, auditory cortical responses were recorded from 26 post-lingual deaf adult cochlear implant users (19 with good and 7 with poor speech recognition scores) and 26 control subjects. Results There was a significant difference in the P3 latency between cochlear implant users with poor speech recognition scores (G-) and their control group (CG) (p= 0.04), and between G- and cochlear implant users with good speech discrimination (G+) (p= 0.01). We found no significant difference in the P3 latency between the CG and G+. In this study, all G- patients had deafness due to meningitis, which suggests that higher auditory function was impaired too. Conclusion Post-lingual deaf adult cochlear implant users in the G- group had prolonged P3 latencies as compared with the CG and the cochlear implant users in the G+ group. The amplitudes were similar between patients and controls. All G- subjects were deaf due to meningitis. These findings suggest that meningitis may have deleterious effects not only on the peripheral auditory system but on the central auditory processing as well.

Rapamycin affect the apoptosis of splenic CD4+CD25+ regulatory T cells of mouse severe aplastic anemia model / 中华血液学杂志

Objective: To explore the effects and possible mechanism of rapamycin (RAPA) on apoptosis of CD4+CD25+ Tregs from the mouse severe aplastic anemia (SAA) model. Methods: The BALB/c female SAA model mice were induced by interferon-gamma in combination with busulphan. The SAA model mice were intraperitoneal injection with RAPA at daily dose of 0.5 mg/kg for 5 days (the RAPA-treated group, n=15) in the SAA group (n=15) and the un-treated group (n=15) were control. Bone marrow hematopoiesis changes were observed by the patho-morphological examination of femurs. The mononuclear cells of the peripheral blood and spleen were subjected to assess the intracellular Foxp3 expression in CD4+CD25+ Tregs by flow cytometry (FCM). In addition, after being pured by immunomagnetic beads, the splenic CD4+CD25+ Tregs was subjected to assess apoptosis by FCM and the Akt and Stat3 phosphorylation by using of western blot. Results: The patho-morphological examination of femurs showed normal marrow cell proliferation in un-treated group and hypocellularity in both SAA group and RAPA-treat group, with an increase in the number of fat cells. The bone marrow hematopoietic tissue ratio in RAPA-treat group was higher than SAA group [(9.75±1.83)% vs (7.00±2.00)%, Δx=2.15% (95%CI 0.15%-5.35%), P=0.037]. In the SAA group, FCM analysis showed down-expression of Foxp3 in CD4+CD25+ Tregs compared with the un-treated group. However, after treatment with RAPA, the expression of Foxp3 in CD4+CD25+ Tregs was increased (P<0.017). Compared with the un-treated group, increased CD4+CD25+ Tregs apoptosis [(19.84±1.39)% vs (29.85±2.72)%] with increased Akt phosphorylation accompanied by increased Stat3 phosphorylation was found in SAA group (P<0.05, respectively). On the contrary, RAPA-treated group exhibited CD4+ CD25+ Tregs with a reduction in apoptosis rate [(22.39±3.71)%], Akt phosphorylation and Stat3 phosphorylation compared with the SAA group (P<0.05, respectively). Conclusion: These results indicate that RAPA may increase the expression of Foxp3 by down-regulation the levels of Akt and Stat3 phosphorylation and reduce apoptosis in splenic CD4+CD25+ Tregs from the mice model of SAA.

Rapamycin affect the apoptosis of splenic CD4+CD25+ regulatory T cells of mouse severe aplastic anemia model / 中华血液学杂志

Objective@#To explore the effects and possible mechanism of rapamycin (RAPA) on apoptosis of CD4+CD25+ Tregs from the mouse severe aplastic anemia (SAA) model.@*Methods@#The BALB/c female SAA model mice were induced by interferon-gamma in combination with busulphan. The SAA model mice were intraperitoneal injection with RAPA at daily dose of 0.5 mg/kg for 5 days (the RAPA-treated group, n=15) in the SAA group (n=15) and the un-treated group (n=15) were control. Bone marrow hematopoiesis changes were observed by the patho-morphological examination of femurs. The mononuclear cells of the peripheral blood and spleen were subjected to assess the intracellular Foxp3 expression in CD4+CD25+ Tregs by flow cytometry (FCM). In addition, after being pured by immunomagnetic beads, the splenic CD4+CD25+ Tregs was subjected to assess apoptosis by FCM and the Akt and Stat3 phosphorylation by using of western blot.@*Results@#The patho-morphological examination of femurs showed normal marrow cell proliferation in un-treated group and hypocellularity in both SAA group and RAPA-treat group, with an increase in the number of fat cells. The bone marrow hematopoietic tissue ratio in RAPA-treat group was higher than SAA group [(9.75±1.83)% vs (7.00±2.00)%, Δx=2.15% (95%CI 0.15%-5.35%), P=0.037]. In the SAA group, FCM analysis showed down-expression of Foxp3 in CD4+CD25+ Tregs compared with the un-treated group. However, after treatment with RAPA, the expression of Foxp3 in CD4+CD25+ Tregs was increased (P<0.017). Compared with the un-treated group, increased CD4+CD25+ Tregs apoptosis [(19.84±1.39)% vs (29.85±2.72)%] with increased Akt phosphorylation accompanied by increased Stat3 phosphorylation was found in SAA group (P<0.05, respectively). On the contrary, RAPA-treated group exhibited CD4+ CD25+ Tregs with a reduction in apoptosis rate [(22.39±3.71)%], Akt phosphorylation and Stat3 phosphorylation compared with the SAA group (P<0.05, respectively).@*Conclusion@#These results indicate that RAPA may increase the expression of Foxp3 by down-regulation the levels of Akt and Stat3 phosphorylation and reduce apoptosis in splenic CD4+CD25+ Tregs from the mice model of SAA.