scholarly journals Circadian Deregulation as Possible New Player in Pollution-Induced Tissue Damage

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 116
Author(s):  
Mascia Benedusi ◽  
Elena Frigato ◽  
Cristiano Bertolucci ◽  
Giuseppe Valacchi

Circadian rhythms are 24-h oscillations driven by a hypothalamic master oscillator that entrains peripheral clocks in almost all cells, tissues and organs. Circadian misalignment, triggered by industrialization and modern lifestyles, has been linked to several pathological conditions, with possible impairment of the quality or even the very existence of life. Living organisms are continuously exposed to air pollutants, and among them, ozone or particulate matters (PMs) are considered to be among the most toxic to human health. In particular, exposure to environmental stressors may result not only in pulmonary and cardiovascular diseases, but, as it has been demonstrated in the last two decades, the skin can also be affected by pollution. In this context, we hypothesize that chronodistruption can exacerbate cell vulnerability to exogenous damaging agents, and we suggest a possible common mechanism of action in deregulation of the homeostasis of the pulmonary, cardiovascular and cutaneous tissues and in its involvement in the development of pathological conditions.

Pteridines ◽  
2006 ◽  
Vol 17 (1) ◽  
pp. 5-10
Author(s):  
Shunichi Shimizu ◽  
Masakazu Ishii ◽  
Teruaki Wajima ◽  
Tamio Hagiwara ◽  
Takaharu Negoro

Abstract 5,6,7,8-Tetrahydrobiopterin (BH4) is an csscntial cofactor for production of nitric oxide (NO) by N O synthase (NOS). Nitric oxide (NO) is an important signaling mo!ecu!e for the regulation o f vita! functions such as vascular tone, neurotransmission and immune surveiüance. Accumu!ated evidences show that although NOS mainly re!eases N O under nonnal conditions, NOS also produces Superoxide anion and hydrogen peroxide when BH4 is decreased, suggesting the possibility that NOS is a source of reactive oxygen species (ROS) under pathological conditions. In fact, supplementation of BH4 restores N O production and availability in various diseases including hyperlipidemia, diabetes, hypertension and ischemia-reperfusion. Moreover, recent studies show that administration o f BH4 protects tissues against ischemia-reperfusion injuiy in heart, stomach and liver. Oxidative stress is a common mechanism underlying the development of vascular diseases and reperfusion injury. Regulation of BH4 levels under oxidative stress is important to understand the role of BH4 on the development of vascular diseases and reperfusion injury. We recently described that oxidative stress transiently decreased BH4 levels, and then markedly increased its levels in vascular endothelial cells. Supplementation of BH4 appears to be important therapeutic strategies in vascular diseases and reperfusion injury, and induction of BH4 synthesis may endogenous defense system against oxidative stress-mediated cardiovascular diseases.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299
Author(s):  
Vítor Ennes-Vidal ◽  
Marta Helena Branquinha ◽  
André Luis Souza dos Santos ◽  
Claudia Masini d’Avila-Levy

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?


2021 ◽  
Vol 22 (8) ◽  
pp. 3974
Author(s):  
Tuba M. Ansary ◽  
Md. Razib Hossain ◽  
Koji Kamiya ◽  
Mayumi Komine ◽  
Mamitaro Ohtsuki

Skin is the largest and most complex organ in the human body comprised of multiple layers with different types of cells. Different kinds of environmental stressors, for example, ultraviolet radiation (UVR), temperature, air pollutants, smoking, and diet, accelerate skin aging by stimulating inflammatory molecules. Skin aging caused by UVR is characterized by loss of elasticity, fine lines, wrinkles, reduced epidermal and dermal components, increased epidermal permeability, delayed wound healing, and approximately 90% of skin aging. These external factors can cause aging through reactive oxygen species (ROS)-mediated inflammation, as well as aged skin is a source of circulatory inflammatory molecules which accelerate skin aging and cause aging-related diseases. This review article focuses on the inflammatory pathways associated with UVR-mediated skin aging.


Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2636
Author(s):  
Ilona Kowalczyk-Zieba ◽  
Joanna Staszkiewicz-Chodor ◽  
Dorota Boruszewska ◽  
Krzysztof Lukaszuk ◽  
Joanna Jaworska ◽  
...  

Thyroid hormones control the functions of almost all body systems. Reproductive dysfunctions, such as abnormal sexual development, infertility, or irregularities in the reproductive cycle, might be associated with thyroid disorders. Uterine receptivity is the period when the uterus is receptive to the implantation of an embryo. During the receptivity period (implantation window), a newly formed blastocyst is incorporated into the uterine epithelium. Prostaglandins are well-known primary mediators of pathological conditions such as inflammation and cancer but are also essential for the physiology of female reproduction. The aim of this study was to evaluate the possible relationship between hypothyroidism and changes in the prostaglandin signaling pathways in the uterus and in the process of uterine receptivity in a rat model. The results show that hypothyroidism impaired uterine receptivity by decreasing the level of E2 as well as decreasing the expression of the uterine-receptivity factors homeobox A10 and osteopontin. Moreover, hypothyroidism caused changes in the expression of elements of the prostaglandin E2, F2α, and I2 signaling pathways and changed the levels of those prostaglandins in the uterine tissue. The results suggest that the mechanisms by which hypothyroidism affects female reproductive abnormalities might involve the prostaglandin signaling pathway, resulting in a subsequent reduction in uterine receptivity.


Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 21
Author(s):  
Yool Lee ◽  
Jonathan P. Wisor

The circadian clock is a fundamental biological timing mechanism that generates nearly 24 h rhythms of physiology and behaviors, including sleep/wake cycles, hormone secretion, and metabolism. Evolutionarily, the endogenous clock is thought to confer living organisms, including humans, with survival benefits by adapting internal rhythms to the day and night cycles of the local environment. Mirroring the evolutionary fitness bestowed by the circadian clock, daily mismatches between the internal body clock and environmental cycles, such as irregular work (e.g., night shift work) and life schedules (e.g., jet lag, mistimed eating), have been recognized to increase the risk of cardiac, metabolic, and neurological diseases. Moreover, increasing numbers of studies with cellular and animal models have detected the presence of functional circadian oscillators at multiple levels, ranging from individual neurons and fibroblasts to brain and peripheral organs. These oscillators are tightly coupled to timely modulate cellular and bodily responses to physiological and metabolic cues. In this review, we will discuss the roles of central and peripheral clocks in physiology and diseases, highlighting the dynamic regulatory interactions between circadian timing systems and multiple metabolic factors.


2018 ◽  
Vol 25 (8) ◽  
pp. 818-825 ◽  
Author(s):  
Simone Vidale ◽  
Carlo Campana

Air pollution has a great impact on health, representing one of the leading causes of death worldwide. Previous experimental and epidemiological studies suggested the role of pollutants as risk factors for cardiovascular diseases. For this reason, international guidelines included specific statements regarding the contribution of particulate matter exposure to increase the risk of these events. In this review, we summarise the main evidence concerning the mechanisms involved in the processes linking air pollutants to the development of cardiovascular diseases.


2004 ◽  
Vol 64 (1) ◽  
pp. 95-102 ◽  
Author(s):  
G. Moraes ◽  
V. L. P. Polez ◽  
G. K. Iwama

The non-ionized form of ammonia is very toxic to many aquatic species. It is especially important in several aspects of fish biology. A large range of organismal strategies for coping with environmental stressors is usually observed in living organisms. Among those, the responses for managing chemical stressors are well studied. The present work compares biochemical responses of two evolutionarily close species, Hoplias malabaricus and Hoplerythrinus unitaeniatus, exposed to environmental ammonia. Adult fish were submitted to 1.0 mg/L of ammonium chloride for 24 hours, and plasma ammonia and urea levels were determined. The activities of OUC enzymes OCT and ARG, and the accessory enzyme GS, were quantified in liver extract and are expressed below in mumol/min/mg of wet tissue. Increases in OUC enzymes (GS from 1.14 to 2.43, OCT from 0.81 to 1.72, and ARG from 3.15 to 4.23), plasma ammonia (from 0.95 to 1.42 mmol/L), and plasma urea (from 0.82 to 1.53 mmol/L) were observed (p < 0.05) in H. malabaricus exposed to 1 mg/L of ammonia chloride. The GS in H. unitaeniatus increased from 1.43 to 1.84, however the OCT, ARG, and plasma urea from H. unitaeniatus did not change. These data indicate that each species responds differently to the same environmental stressor.


Author(s):  
Yu Tian ◽  
Ling Wu ◽  
Le Yuan ◽  
Shaozhen Ding ◽  
Fu Chen ◽  
...  

Abstract Summary The biosynthetic ability of living organisms has important applications in producing bulk chemicals, biofuels and natural products. Based on the most comprehensive biosynthesis knowledgebase, a computational system, BCSExplorer, is proposed to discover the unexplored chemical space using nature’s biosynthetic potential. BCSExplorer first integrates the most comprehensive biosynthetic reaction database with 280 000 biochemical reactions and 60 000 chemicals biosynthesized globally over the past 130 years. Second, in this study, a biosynthesis tree is computed for a starting chemical molecule based on a comprehensive biotransformation rule library covering almost all biosynthetic possibilities, in which redundant rules are removed using a new algorithm. Moreover, biosynthesis feasibility, drug-likeness and toxicity analysis of a new generation of compounds will be pursued in further studies to meet various needs. BCSExplorer represents a novel method to explore biosynthetically available chemical space. Availability and implementation BCSExplorer is available at: http://www.rxnfinder.org/bcsexplorer/. Supplementary information Supplementary data are available at Bioinformatics online.


2019 ◽  
Vol 14 (6) ◽  
pp. 804-815 ◽  
Author(s):  
A. E. Imaeva ◽  
Yu. A. Balanova ◽  
A. V. Kontsevaya ◽  
A. V. Kapustina ◽  
D. V. Duplyakov ◽  
...  

Aim. To evaluate the availability and affordability of medicines used to treat of cardiovascular diseases (CVD) in several regions of the Russian Federation with different climatic, geographic, economic and demographic characteristics. Material and methods. The study was conducted in 6 regional capitals, chosen to differ in geographically, economically, and demographically. In each city, 5 pharmacies providing free medicines to certain categories of citizens (beneficiaries) and 5 private pharmacies serving anyone were selected at random. Medicine availability was assessed in all pharmacies, along with price only in the private pharmacies. Data were obtained for both original drug and appropriate generics. A list of 25 of the most frequently prescribed medicines for cardiovascular diseases was compiled. Results. Some general findings emerged. With the existence of a generic drug, the original drug was not available in the pharmacy supplying beneficiaries. Diuretics, as well as some ACE inhibitors, are not available in a number of pharmacies for beneficiaries. Enalapril in most licensed pharmacies is represented by generics, lisinopril in a number of cities is represented by both the original drug and generics. The presence of sartans was much lower than ACE inhibitors. Bisoprolol was most common beta-blocker. Calcium antagonists: if amlodipine was present in all licensed pharmacies, at list as generic, then nifedipine was not available in many licensed pharmacies. Among antiplatelet agents, aspirin was available in most pharmacies, and clopidogrel was mostly represented by generics. As for statins, only simvastatin could be found in almost all pharmacies. When analyzing the cost of drugs in licensed pharmacies, it was found that drugs containing furosemide are the cheapest among generics – about 17 rubles. The most expensive treatment with generics of rosuvastatin – about 4,374 rubles a month. The most expensive original medicine was also rosuvastatin – about 4,500 rubles for 30 tablets, the cheapest – the original drug of furosemide – about 35 rubles. On average, the cost of CVD treatment with major classes of drugs, including ACE inhibitor, beta-blocker, antiplatelet drug and statin, is 1,921.9 rubles per month. Conclusion. The basic cardiovascular medicines were characterized by a relatively high availability in 6 regions of the Russian Federation included in the analysis both by the criterion of the availability of drugs and by the criterion of the minimum price.


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