Clinical value of circadian clock related biomarkers for the diagnosis of chronic pancreatitis with pancreatic exocrine insufficiency / 中华胰腺病杂志

Objective:To examine the expression of core clock genes in the peripheral blood mononuclear cells (PBMCs) and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis (CP) patients with pancreatic exocrine insufficiency (PEI), and explore their potential diagnostic value in clinical practice.Methods:The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected. Peripheral blood samples from 30 healthy individuals were used for control. The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP. The mRNA expression of the core clock genes, including Clock, Bmal1, Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR, and the expression of circadian disturbance-related proteins like TrkB, CD 36 and Rbp in serum was measured with ELISA. The receiver operating characteristic curve(ROC) and the area under curve (AUC) was used to test the efficiency for diagnozing PEI. Results:The mRNA expression of Per1 in CP patients was significantly decreased (0.76 vs 1, P<0.05), and the AUC for diagnozing PEI was 0.744 (95% CI 0.628-0.860), with a cut-off value of 0.72; and the sensitivity and specificity was 84.8% and 57.1%, respectively. The protein abundance of serum CD 36 was significantly increased in CP patients (33.85±19.74ng/ml vs 24.71±11.53 ng/ml, P<0.05); the AUC for diagnozing PEI was 0.834 (95% CI 0.735-0.932), with a cut-off value of 29.75 pg/ml; and the sensitivity and specificity was 74.3% and 84.8%, respectively. The expression of CD 36 was increased with the increase of CP clinical stage, and there were statistically significant differences between either two stages (all P value <0.05). The mRNA expression of Per1 in patients with CP in Stage Ⅰ was significantly higher than that in patients with CP in Stage Ⅱ or Ⅲ, and the differences were statistically significant ( P<0.05), but no statistical difference was found between Stage Ⅱ and Stage Ⅲ. Conclusions:The decreased expression of Per1 mRNA in PBMCs and increased level of CD 36 in serum are significantly related to the occurrence of PEI in CP, suggesting that they may have potential value for diagnozing PEI and guiding the clinical practice.

Acute retinal pigment epitheliitis: a case presentation and literature review / Epitelite pigmentar retiniana aguda: apresentação de caso e revisão da literatura

ABSTRACT Acute retinal pigment epitheliitis (ARPE) is an idiopathic, self-limiting inflammatory retinal disorder that particularly affects healthy young individuals. The characteristic fundoscopic appearance of the acute retinal pigment epitheliitis includes a fine pigment stippling surrounded by a yellow-white hypopigmented halos in the macula. Although the exact pathogenesis of the disease remains unknown, some reports have suggested a relationship between a viral infection and acute retinal pigment epitheliitis. Acute retinal pigment epitheliitis is a rare disorder, and only single case reports or case series are found in the literature. The clinical and demographic characteristics of patients with this disease are not fully understood because of its rarity. In this study, we searched the literature to collect clinical and demographic features of the reported cases. We detail the characteristics of acute retinal pigment epitheliitis were pointed and discuss the pathogenesis of the disease.(AU)

RESUMO A epitelite pigmentar retiniana aguda (EPRA) é uma doença inflamatória idiopática e autolimitada da retina, que afeta especialmente indivíduos jovens e saudáveis. À fundoscopia, a aparência característica dessa entidade é de um pontilhado fino do pigmento, cercado de halos hiperpigmentados branco-amarelados na mácula. A patogênese exata da doença ainda é desconhecida, mas alguns relatos apontam uma relação entre epitelite pigmentar retiniana aguda e infecções virais. A epitelite pigmentar retiniana aguda é uma condição rara e na literatura há apenas relatos de casos individuais ou séries de casos. As características clínicas e demográficas da doença não são totalmente compreendidas, devido à sua raridade. Para este relato, foi feita uma busca na literatura para coletar os dados clínicos e demográficos dos casos relatados. Finalmente, são apontadas as características da epitelite pigmentar retiniana aguda e discute-se a patogênese da doença.(AU)

Mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure / 国际脑血管病杂志

Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.

Blood pressure rhythm and circadian clock protein expression after cerebral ischemia-reperfusion in spontaneously hypertensive rats / 国际脑血管病杂志

Objective:To investigate the changes of blood pressure and serum circadian clock protein levels after cerebral ischemia-reperfusion in spontaneously hypertensive rat (SHR) and their correlation.Methods:The middle cerebral artery occlusion method was used to prepare the SHR cerebral ischemia-reperfusion model at zero point of Zeitgeber Time (ZT), and the systolic blood pressure within 24 h was continuously monitored after the model was made. The tail vein blood of rats was taken every 3 h, and the changes in serum circadian clock proteins (CLOCK, BMAL1, PER1 and CRY1) levels were detected by enzyme-linked immunosorbent assay. Pearson correlation analysis was used to determine the relationship between blood pressure circadian rhythm pattern and circadian clock protein level fluctuation after cerebral ischemia-reperfusion.Results:In the sham operation group, there were various blood pressure patterns, including dipper (53%), non-dipper (27%), super dipper (13%), and reverse dipper (7%), and the main pattern was dipper. In contrast, the degree of blood pressure disorder in the model group was aggravated, and the non-dipper was the main type, with the proportion as high as 40%. The proportion of super dipper and reverse dipper increased to 27% and 13% respectively; proportion of dipper blood pressure decreased to 20%. The serum level of CLOCK in the model group was relatively stable, while the circadian rhythm of BMAL1, PER1 and CRY1 was significantly changed compared with the sham operation group. Pearson analysis showed that PER1 was negatively correlated with the dipper ( r=-0.565, P=0.002) and super dipper ( r=-0.531, P=0.001) blood pressure patterns, and positively correlated with the non-dipper blood pressure pattern ( r=0.620, P<0.001). Conclusion:The circadian rhythm pattern of blood pressure in SHR after cerebral ischemia-reperfusion was obviously disordered, which was closely associated with the regulation of Per1 gene.

Differential gene expression analysis of human cumulus cells / 대한생식의학회지

OBJECTIVE: This study was performed to explore the possibility that each oocyte and its surrounding cumulus cells might have different genetic expression patterns that could affect human reproduction. METHODS: Differential gene expression analysis was performed for 10 clusters of cumulus cells obtained from 10 cumulus-oocyte complexes from 10 patients. Same procedures related to oocyte maturation, microinjection, and microarray analyses were performed for each group of cumulus cells. Two differential gene expression analyses were performed: one for the outcome of clinical pregnancy and one for the outcome of live birth. RESULTS: Significant genes resulting from these analyses were selected and the top 20 affected pathways in each group were analyzed. Circadian entrainment is determined to be the most affected pathway for clinical pregnancy, and proteoglycans in cancer pathway is the most affected pathway for live birth. Circadian entrainment is also amongst the 12 pathways that are found to be in top 20 affected pathways for both outcomes, and has both lowest p-value and highest number of times found count. CONCLUSION: Although further confirmatory studies are necessary, findings of this study suggest that these pathways, especially circadian entrainment in cumulus cells, may be essential for embryo development and pregnancy.

Relationship between intestinal dysbacteriosis and circadian clock disturbance / 中国病理生理杂志

The human gut harbours a certain quantity and variety of microbes called intestinal flora, which is in a state of balance under normal circumstances, and dysbacteriosis occurs when the balance of the intestinal flora is dis-turbed by the host and the changes of the external environment.Circadian clock is the biological regulation system to adapt to natural circadian rhythm, including central clock and peripheral clock.Circadian clock disturbance, particularly rotating shift-workers with irregular light-night schedules, is associated with an increased risk of immune-related diseases.The de-velopment of these diseases is closely related to intestinal dysbacteriosis.Therefore, the correlation between intestinal dys-bacteriosis and circadian clock disturbance has attracted much attention.This review aims to explore the pathophysiological basis of the development in some immune-related diseases based on the latest scientific findings about the relationship be-tween intestinal microbial flora and circadian clock.

Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

BACKGROUND: In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. METHODS: To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. RESULTS: BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. CONCLUSION: These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity.

Circadian Rhythms in Urinary Functions: Possible Roles of Circadian Clocks? / 대한배뇨장애요실금학회지

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.

Regulation of the Circadian Gene CLOCK Expression by KCl Depolarization in B35 Rat Neuroblastoma Cells / 신경정신의학

OBJECTIVES: To investigate the effects of KCl on regulation of circadian gene CLOCK expression, we observed whether induction of CLOCK is influenced by KCl depolarization in B35 rat neuroblastoma cells. METHODS: B35 rat neuroblastoma cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% FBS and 1% penicillin-streptomycin in a 37 degrees C humidified incubator with 5% CO2. Inhibitors including cycloheximide and actinomycin D were pretreated 1 hour before treatment with 50mM KCl. Immunoblotting with anti-CLOCK antibody was done. RESULTS: CLCOK is induced by 50 mM KCl in B35 Rat Neuroblastoma cells, and a maximal induction in CLOCK level reached peak at 8 to 20 hours. The pretreatment of cycloheximide and actinomycin D prevented the induction of CLOCK by 50 mM KCl. CONCLUSION: We suggest that KCl depolarization may play critical roles in several aspects of the circadian gene CLOCK expression.