Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Control of immunity and allergy by steroid hormones

Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice.     

正常小鼠胃肠运动昼夜节律及药物作用的影响

目的：观察小鼠胃肠运动昼夜节律及药物对节律的影响。方法：小鼠不同时间点灌胃给予蒸馏水及实验药物，同步测定胃排空及小肠推进运动情况。结果：小鼠胃排空及小肠推进运动存在昼夜节律；普瑞博思促进胃肠运动存在时间效应，但对节律无明显影响；阿托品抑制胃肠运动可使原有昼夜节律消失。结论：小鼠胃肠运动功能存在昼夜节律，药物对胃肠运动功能的作用存在时间效应，可使节律发生不同变化。     

利用圆形分布的统计方法分析急性脑梗死患者死亡时间昼夜节律特点

目的 回顾性分析64例急性脑梗死患者的死亡时间，探讨脑梗死患者死亡时间的昼夜节律变化的特点和规律，方法 分析64例死亡病例的临床资料，重点分析死亡时间，利用圆形分布的统计方法，计算出死亡高峰时刻和1天24小时内95％的死亡时间集中时段。结果 急性脑梗死患者的死亡高峰时刻为05：59：31，1天24小时内95％的死亡时间发生在01：04：23-10：54：39．结论 急性脑梗死患者的死亡时间有一定的昼夜节律分布的特点，清晨通常为死亡的高峰时段，与机体血栓性病理状态恶化或血压的昼夜波动有关，工作中应注意加强夜间和凌晨患者的管理和监测，必要时改变投药时间，最大限度地减少死亡率。     

Limitations of current medical treatments for depression: Disturbed circadian rhythms as a possible therapeutic target

The proportion of diagnosed depressives prescribed antidepressants has increased markedly over the last 20 years, mainly following the introduction of the selective serotonin reuptake inhibitors. However, currently available antidepressants have notable limitations, relating to their only moderate efficacy relative to placebo, relatively slow onset of action, possible withdrawal symptoms, and problems of compliance. Sleep disturbances are often used to identify newly presenting depressive patients, and may be part of a more general alteration of bodily rhythms. There are links between pharmacological treatments and circadian rhythms in depression, which might represent another, new option for the development of a therapeutic approach to depression treatment. Many antidepressants affect sleep, some are sedative, and others have been used specifically in severely insomniac depressives. Disturbances in circadian rhythms may be an integral part of depressive mechanisms, and normalising them via an innovative mechanism of antidepressant action may be a fruitful avenue in the search for improved antidepressant agents.     

汤岗子矿泉浴对大鼠血液皮质醇及甲状腺素日生物周期节律影响的实验观察

本文报告大鼠分别在6时、12时、18时、24时接受汤岗子矿泉38～39℃浸浴15分钟后,立即断头取血测定血液皮质醇及甲状腺素(T_4)。在6时、24时的矿泉浸浴组大鼠血浆皮质醇比对照组明显升高。在12时、18时矿泉浸浴组大鼠血清T_4比对照组明显升高。说明肾上腺皮质及甲状腺功能对全身矿泉浸浴热刺激的反应也遵循日周期节律。为矿泉治疗的时间生物学理论提供依据。     

Daily changes in presynaptic cholinergic activity of rat sympathetic superior cervical ganglion

The in vitro capacity of sympathetic superior cervical ganglia (SCG) to take up [³H]choline from the extracellular medium, to synthesize acetylcholine from [³H]choline, and to release [³H]acetylcholine in response to a high K⁺ concentration, were examined in rats throughout a 24-h cycle. Both the release of [³H]acetylcholine and the synthesis of [³H]acetylcholine from [³H]choline exhibited significant diurnal variations, showing maxima during the first half of the night. After these maxima, nocturnal acetylcholine release and synthesis decayed to daytime levels and remained low until the end of the night. [³H]Choline uptake by rat SCG did not vary significantly throughout a 24-h period. A 1.5-h exposure of rats to darkness at the 5th hour of light phase of the daily photoperiod did not change significantly any parameter studied. A 20-min, 5-Hz, electrical stimulation of the preganglionic trunk of SCG excised from rats at noon increased significantly subsequent K⁺-induced [³H]acetylcholine release but did not change [³H]acetylcholine synthesis. In decentralized SCG of rats subjected to a unilateral SCG decentralization and a contralateral sham-operation 7 days earlier, [³H]acetylcholine release and synthesis were highly reduced or abolished at the decentralized side, while [³H]choline uptake remained unaltered. The present results suggest that an activation of preganglionic rat SCG neurons takes place during the first half of the scotophase.     

Free plasma magnesium following glucose loading in healthy humans

The recognized existence of a circadian pattern in extracellular magnesium balance might mirror either an inherent rhythm in the homeostasis of this ion or dietary factors. Since in vitro insulin enhances cellular magnesium uptake, the circadian rhythm in extracellular magnesium metabolism might be modulated at least in part by carbohydrate intake. To assess this hypothesis, the effects of oral glucose loading on plasma total and ionized magnesium were investigted in lean healthy humans with a negative family history for essential hypertension and diabetes mellitus. Plasma total and ionized magnesium was similar before glucose loading and 30, 60, 90, 180, and 210 min thereafter. It is therefore concluded that in healthy humans the circadian pattern of extracellular magnesium is not modulated by the metabolic and hormonal mechanisms that adjust the concentration of glucose. Received: 5 February 1997 / Accepted in revised form: 14 April 1997