Effects of circadian rhythm on the development of dental hard tissues / 中华口腔医学杂志

Circadian rhythm is regulated by circadian clock, which is formed by the body response to external cyclic stimuli through the endogenous circadian clock. Circadian rhythm disturbance is closely related to the risks of a variety of diseases, and its impact on oral health cannot be ignored. Exploring the relationship and related molecular mechanism between circadian rhythm and dental hard tissues development are helpful to deeply understand the pathogenesis of developmental defects on these tissues, which could provide a theoretical basis for prevention and treatment on disorders of dental hard tissues. In order to provide guidance for the disease prevention and treatment, based on the summarization of current research progress, this paper focuses on the involvement of biorhythm in the development of tooth hard tissues as well as the disturbance of circadian rhythm on the formation of enamel and dentin, and analyzes the related regulating mechanism of circadian rhythm and genes during the development of tooth hard tissues.

Co-regulation of circadian clock genes and microRNAs in bone metabolism / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Mammalian bone is constantly metabolized from the embryonic stage, and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation, mediated by osteoclasts and osteoblasts. It is widely recognized that circadian clock genes can regulate bone metabolism. In recent years, the regulation of bone metabolism by non-coding RNAs has become a hotspot of research. MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism, including circadian clock genes. However, research in this field has been conducted only in recent years and the mechanisms involved are not yet well established. Recent studies have focused on how to target circadian clock genes to treat some diseases, such as autoimmune diseases, but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases. Therefore, in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs, aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.

Research progress of circadian rhythm / 中国中药杂志

Circadian rhythm disorder is a common society issue caused by jet lag,shift work,sleep disruption and changes in food consumption. Light is the major factor affecting the circadian rhythm system. Disruption of the circadian rhythm system can cause damage to the body,leading to some diseases. Maintaining a normal circadian system is of great importance for good health. Ideal therapeutic effect can not only alleviate symptoms of the diseases,but also recovery the disturbed circadian rhythm to normal. The paper summarizes the modeling methods of animal circadian rhythm disorder,diseases of circadian rhythm abnormality,regulation of circadian clock genes and medicine which are related to circadian rhythm to diseases of circadian rhythm disorder.

Progression of the load of waterborne and intestinal parasitic diseases in the State of Amazonas

In the State of Amazonas, Brazil, urban expansion together with precarious basic sanitation conditions and human settlement on river banks has contributed to the persistence of waterborne and intestinal parasitic diseases. Time series of the recorded cases of cholera, typhoid fever, hepatitis A and leptospirosis are described, using data from different levels of the surveillance systems. The sources for intestinal parasitosis prevalence data (non-compulsory reporting in Brazil) were Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana (LILACS) and the annals of major scientific meetings. Relevant papers and abstracts in all languages were accessed by two independent reviewers. The references cited by each relevant paper were scrutinized to locate additional papers. Despite its initial dissemination across the entire State of Amazonas, cholera was controlled in 1998. The magnitude of typhoid fever has decreased; however, a pattern characterized by eventual outbreaks still remains. Leptospirosis is an increasing cause of concern in association with the annual floods. The overall prevalence of intestinal parasites is high regardless of the municipality and the characteristics of areas and populations. The incidence of hepatitis A has decreased over the past decade. A comparison of older and recent surveys shows that the prevalence of intestinal parasitic diseases has remained constant. The load of waterborne and intestinal parasitic diseases ranks high among the health problems present in the State of Amazonas. Interventions aiming at basic sanitation and vaccination for hepatitis A were formulated and implemented, but assessment of their effectiveness in the targeted populations is still needed.

The application of multiplex fluorimetric sensor for the analysis of flavonoids content in the medicinal herbs family Asteraceae, Lamiaceae, Rosaceae

BACKGROUND: The aim of our research work was to quantify total flavonoid contents in the leaves of 13 plant species family Asteraceae, 8 representatives of family Lamiaceae and 9 plant species belonging to familyRosaceae, using the multiplex fluorimetric sensor. Fluorescence was measured using optical fluorescence apparatus Multiplex(R) 3 (Force-A, France) for non-destructive flavonoids estimation. The content of total flavonoids was estimated by FLAV index (expressed in relative units), that is deduced from flavonoids UV absorbing properties. RESULTS: Among observed plant species, the highest amount of total flavonoids has been found in leaves ofHelianthus multiflorus (1.65 RU) and Echinops ritro (1.27 RU), Rudbeckia fulgida (1.13 RU) belonging to the family Asteraceae. Lowest flavonoid content has been observed in the leaves of marigold (Calendula officinalis) (0.14 RU) also belonging to family Asteraceae. The highest content of flavonoids among experimental plants of family Rosaceae has been estimated in the leaves of Rosa canina (1.18 RU) and among plant species of family Lamiaceae in the leaves of Coleus blumei (0.90 RU). CONCLUSIONS: This research work was done as pre-screening of flavonoids content in the leaves of plant species belonging to family Asteraceae, Lamiaceae and Rosaceae. Results indicated that statistically significant differences (P > 0.05) in flavonoids content were observed not only between families, but also among individual plant species within one family.

Circadian clock of Aedes aegypti: effects of blood-feeding, insemination and RNA interference

Mosquitoes are the culprits of some of the most important vector borne diseases. A species’ potential as a vector is directly dependent on their pattern of behaviour, which is known to change according to the female’s physiological status such as whether the female is virgin/mated and unfed/blood-fed. However, the molecular mechanism triggered by and/or responsible for such modulations in behaviour is poorly understood. Clock genes are known to be responsible for the control of circadian behaviour in several species. Here we investigate the impact mating and blood-feeding have upon the expression of these genes in the mosquito Aedes aegypti . We show that blood intake, but not insemination, is responsible for the down-regulation of clock genes. Using RNA interference, we observe a slight reduction in the evening activity peak in the fourth day after dstim injection. These data suggest that, as in Drosophila , clock gene expression, circadian behaviour and environmental light regimens are interconnected in Ae. aegypti .

Genetic basis of triatomine behavior: lessons from available insect genomes

Triatomines have been important model organisms for behavioural research. Diverse reports about triatomine host search, pheromone communication in the sexual, shelter and alarm contexts, daily cycles of activity, refuge choice and behavioural plasticity have been published in the last two decades. In recent times, a variety of molecular genetics techniques has allowed researchers to investigate elaborate and complex questions about the genetic bases of the physiology of insects. This, together with the current characterisation of the genome sequence of Rhodnius prolixus allows the resurgence of this excellent insect physiology model in the omics era. In the present revision, we suggest that studying the molecular basis of behaviour and sensory ecology in triatomines will promote a deeper understanding of fundamental aspects of insect and, particularly, vector biology. This will allow uncovering unknown features of essential insect physiology questions for a hemimetabolous model organism, promoting more robust comparative studies of insect sensory function and cognition.

Circadian rhythms in insect disease vectors

Organisms from bacteria to humans have evolved under predictable daily environmental cycles owing to the Earth’s rotation. This strong selection pressure has generated endogenous circadian clocks that regulate many aspects of behaviour, physiology and metabolism, anticipating and synchronising internal time-keeping to changes in the cyclical environment. In haematophagous insect vectors the circadian clock coordinates feeding activity, which is important for the dynamics of pathogen transmission. We have recently witnessed a substantial advance in molecular studies of circadian clocks in insect vector species that has consolidated behavioural data collected over many years, which provided insights into the regulation of the clock in the wild. Next generation sequencing technologies will facilitate the study of vector genomes/transcriptomes both among and within species and illuminate some of the species-specific patterns of adaptive circadian phenotypes that are observed in the field and in the laboratory. In this review we will explore these recent findings and attempt to identify potential areas for further investigation.

Chronotype: a review of the advances, limits and applicability of the main instruments used in the literature to assess human phenotype / Cronotipo: uma revisão dos avanços, limites e aplicabilidade dos principais instrumentos utilizados na literatura para avaliar o fenótipo humano

The study of circadian typology differences has increased in the last few years. As a result, new instruments have been developed to estimate the individual circadian phase of temporal human behavior, also referred as chronotype. The current review was conducted to evaluate the differences among the questionnaires most frequently used to assess chronotype: the Morningness-Eveningness Questionnaire (MEQ), the Composite Scale of Morningness (CSM), and the Munich Chronotype Questionnaire (MCTQ). Each instrument evaluates a different aspect of chronotype. MEQ is considered to evaluate the phase preferences of individual behavior over a 24-hour day, while MCTQ measures the phase of sleep positions for both free and work days. CSM is similar to MEQ, but is more sensitive to measure shift work. The concept of chronotype has been used to refer to phase positions or phase preferences in the literature reviewed. Most of the time this is a consequence of different interpretations: it is not clear whether phase preferences are a direct manifestation of the individual’s internal clock or a result of external cues, e.g., social interaction (including the alarm clock). Also, phase preferences are not uniform throughout life. Therefore, a single assessment, not taking age into consideration, will not accurately describe the sample. We suggest that MCTQ is the best instrument for investigators dealing with desynchronization and as an instrument for sleep phase. Conversely, if the goal is to assess characteristics that change under specific situations - chronotype -, the MEQ should be used

O estudo das diferenças de tipologia circadiana tem aumentado nos últimos anos. Como resultado, novos instrumentos têm sido desenvolvidos para estimar as preferências interindividuais de fase circadiana, denominada de cronotipo, responsável pela organização temporal do processo de regulação do organismo. O objetivo desta revisão foi avaliar as diferenças dos principais questionários utilizados para avaliar cronotipos: o Questionário de Matutinidade e Vespertinidade (Morningness-Eveningness Questionnaire, MEQ), o Composite Scale of Morningness (CSM) e o Questionário de Cronotipo de Munique (Munich Chronotype Questionnaire, MCTQ). Cada instrumento avalia um aspecto diferente dos cronotipos. Considera-se que o MEQ avalia as preferências de fase do comportamento individual ao longo de um dia de 24 horas, ao passo que o MCTQ mede a posição da fase de sono tanto em dias livres como em dias de trabalho. O CSM é semelhante ao MEQ, mas é mais sensível para ser utilizado em indivíduos que realizam trabalho em turnos. O conceito de cronotipo tem sido utilizado para se referir a posições de fase ou preferências de fase na literatura revisada. Na maioria das vezes, isso é consequência de diferentes interpretações: não está claro se as preferências de fase são uma manifestação direta do relógio interno do indivíduo ou um resultado de sinais externos, como por exemplo, interação social (incluindo o uso de despertador). Além disso, as preferências de fase não são uniformes ao longo da vida. Sendo assim, uma única avaliação, sem levar em consideração a idade do indivíduo nos escores utilizados nessas escalas, não descreverá a amostra com precisão. Sugerimos, através desta revisão, que o MCTQ deve ser considerado como instrumento para investigações que lidam com dessincronização e como instrumento de medida de fase de sono. Por outro lado, se o objetivo é avaliar características que mudam em determinadas situações - cronotipo -, o MEQ deve ser utilizado

Do Caucasian and Asian clocks tick differently?

The Period 3 and Clock genes are important components of the mammalian molecular circadian system. Studies have shown association between polymorphisms in these clock genes and circadian phenotypes in different populations. Nevertheless, differences in the pattern of allele frequency and genotyping distribution are systematically observed in studies with different ethnic groups. To investigate and compare the pattern of distribution in a sample of Asian and Caucasian populations living in Brazil, we evaluated two well-studied polymorphisms in the clock genes: a variable number of tandem repeats (VNTR) in PER3 and a single nucleotide polymorphism (SNP) in CLOCK. The aim of this investigation was to search for clues about human evolutionary processes related to circadian rhythms. We selected 109 Asian and 135 Caucasian descendants. The frequencies of the shorter allele (4 repeats) in the PER3 gene and the T allele in the CLOCK gene among Asians (0.86 and 0.84, respectively) were significantly higher than among Caucasians (0.69 and 0.71, respectively). Our results directly confirmed the different distribution of these polymorphisms between the Asian and Caucasian ethnic groups. Given the genetic differences found between groups, two points became evident: first, ethnic variations may have implications for the interpretation of results in circadian rhythm association studies, and second, the question may be raised about which evolutionary conditions shaped these genetic clock variations.

Moléculas que marcam o tempo: implicações para os fenótipos circadianos / Timekeeping molecules: implications for circadian phenotypes

OBJETIVO: Revisar resumidamente a literatura dos últimos 36 anos de pesquisa em cronobiologia molecular a fim de informar aos profissionais de saúde os avanços obtidos nesta área e os potenciais para aplicação na clínica médica. MÉTODO: Buscas na literatura foram realizadas utilizando as bases de dados PubMed e Scopus usando como palavras-chave "clock genes, circadian rhythms, diurnal preference, delayed sleep phase syndrome, advanced sleep phase syndrome, photoperiod and mood disorder". DISCUSSÃO: Atualmente, o mecanismo molecular da regulação da ritmicidade circadiana é compreendido em grande detalhe. Muitos estudos publicados mostram associações de polimorfismos nos genes relógio com transtornos do ritmo circadiano e com transtornos do humor. CONCLUSÕES: De maneira geral, o progresso obtido na área de cronobiologia molecular traz um melhor entendimento da regulação do sistema de temporização biológico. O desenvolvimento de estudos nesta área tem o potencial de ser aplicável ao tratamento dos transtornos dos ritmos circadianos e certos transtornos do humor, além de prevenir riscos à saúde causados por viagens intercontinentais (Jet Lag) e por trabalhos noturnos e por turnos.

OBJECTIVE: The aim of this study was to review the molecular chronobiology studies in the last 36 years in order Eto point out the advances in this area to health professionals. METHOD: We searched in the PubMed and Scopus data banks for articles related with human molecular chronobiology. The keywords used were "clock genes, circadian rhythms, diurnal preference, delayed sleep phase syndrome, advanced sleep phase syndrome, photoperiod and mood disorder". DISCUSSION: The knowledge about molecular mechanism of circadian rhythms increased a lot in the last years and now we are able to better understand the details of molecular processes involved in circadian and sleep regulation. Studies show that polymorphisms in clock genes are associated with sleep and mood disorders. These studies will be helpful to further elucidate the regulation of molecular mechanisms of circadian rhythms. CONCLUSIONS: The development of these studies in molecular chronobiology can be helpful to treat circadian and mood disorders and to prevent health risks caused by intercontinental flights (Jet Lag), nocturnal or shift work schedule.

Phenotypic effects of genetic variability in human clock genes on circadian and sleep parameters.

Circadian rhythms and sleep are two separate but intimately related processes. Circadian rhythms are generated through the precisely controlled, cyclic expression of a number of genes designated clock genes. Genetic variability in these genes has been associated with a number of phenotypic differences in circadian as well as sleep parameters, both in mouse models and in humans. Diurnal preferences as determined by the selfreported Horne-Ostberg (HO) questionnaire, has been associated with polymorphisms in the human genes CLOCK, PER1, PER2 and PER3. Circadian rhythm-related sleep disorders have also been associated with mutations and polymorphisms in clock genes, with the advanced type cosegrating in an autosomal dominant inheritance pattern with mutations in the genes PER2 and CSNK1D, and the delayed type associating without discernible Mendelian inheritance with polymorphisms in CLOCK and PER3. Several mouse models of clock gene null alleles have been demonstrated to have affected sleep homeostasis. Recent findings have shown that the variable number tandem polymorphism in PER3, previously linked to diurnal preference, has profound effects on sleep homeostasis and cognitive performance following sleep loss, confirming the close association between the processes of circadian rhythms and sleep at the genetic level.

Egg-laying rhythm in Drosophila melanogaster.

Extensive research has been carried out to understand how circadian clocks regulate various physiological processes in organisms. The discovery of clock genes and the molecular clockwork has helped researchers to understand the possible role of these genes in regulating various metabolic processes. In Drosophila melanogaster, many studies have shown that the basic architecture of circadian clocks is multi-oscillatory. In nature, different neuronal subgroups in the brain of D. melanogaster have been demonstrated to control different circadian behavioural rhythms or different aspects of the same circadian rhythm. Among the circadian phenomena that have been studied so far in Drosophila, the egg-laying rhythm is unique, and relatively less explored. Unlike most other circadian rhythms, the egg-laying rhythm is rhythmic under constant light conditions, and the endogenous or free-running period of the rhythm is greater than those of most other rhythms. Although the clock genes and neurons required for the persistence of adult emergence and activity/rest rhythms have been studied extensively, those underlying the circadian egg-laying rhythm still remain largely unknown. In this review, we discuss our current understanding of the circadian egg-laying rhythm in D. melanogaster, and the possible molecular and physiological mechanisms that control the rhythmic output of the egg-laying process.

Oscillating perceptions: the ups and downs of the CLOCK protein in the mouse circadian system.

A functional mouse CLOCK protein has long been thought to be essential for mammalian circadian clockwork function, based mainly on studies of mice bearing a dominant negative, antimorphic mutation in the Clock gene. However, new discoveries using recently developed Clock-null mutant mice have shaken up this view. In this review, I discuss how this recent work impacts and alters the previous view of the role of CLOCK in the mouse circadian clockwork.

The role of microRNAs (miRNA) in circadian rhythmicity.

MicroRNA (miRNA) is a recently discovered new class of small RNA molecules that have a significant role in regulating gene and protein expression. These small RNAs (approximately 22 nt) bind to 3' untranslated regions (3'UTRs) and induce degradation or repression of translation of their mRNA targets. Hundreds of miRNAs have been identified in various organisms and have been shown to play a significant role in development and normal cell functioning. Recently, a few studies have suggested that miRNAs may be an important regulators of circadian rhythmicity, providing a new dimension (posttranscriptional) of our understanding of biological clocks. Here, we describe the mechanisms of miRNA regulation, and recent studies attempting to identify clock miRNAs and their function in the circadian system.