The aim of our study was to determine morpho-functional state (area of nucleus, brown adipocytes and also area and number of lipid droplets in each cells, general optical density of tissue) of brown adipose tissue in rats with high-calorie (high fat) dietinduced obesity after melatonin administration in different time of the day (morning and evening). Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg either 1 h after lights-on (ZT01) or 1 h before lights-off (ZT11) rats with high-calorie diet (HCD). Besides morphometric parameters as well were measured related visceral fat weight and related brown adipose tissue mass. Rats with HCD had huge changes in brown adipocytes morphology, which summarized in become resembles of classical white adipocytes: grown lipid droplets and cells area, but goes down lipid droplets number and optical density of brown adipose tissue. In general brown adipose tissue with above mentioned characteristic from HCD rats lose their ability to conduct strongly thermoproduction function. After melatonin used in rats with HCD arise leveling of pathological changes, which associated with consumption of HCD. Namely, in groups HCD ZT01 and HCD ZT11 we obtain decreased cells and lipid droplets area, increased lipid droplets number and optical density of brown adipose tissue, in relation to group HCD. Therese received changes has evidence about functionally active brown adipose tissue state, which can also dissipate of exceed energy (lipids – triacylglycerols) amount into whole organism during heat production for avoid to its storage in white adipose tissue and in outside adipose tissue. In addition, evening administration of melatonin (group HCD ZT11) demonstrate more activated state of brown adipose tissueand also related visceral weight gain less, than morning(group HCD ZT01). In conclusions, melatonin influence on morpho-functional state brown adipose tissue in rats with HCD, moreover evening administration can use for obesity therapy via its strong action on activate brown adipocytes .

https://biovestnik.com/index.php/biology/article/download/372/277

The effects of melatonin administration in different times of day on the brown adipose tissue in rats with high-calorie diet-induced obesity

Currently, opportunities for the melatonin use in the obesity treatment are being studied because of his action on the: normalization of adipocyte secretion, the reduction of the pro-inflammatory state in adipose tissue, the stimulation of the beige adipocytes appearance, modulation of the eating behavior via influence on hypothalamic signals, and thermoregulation through affecting on brown adipocyte function, however, the mode, pathways and dose levels of the administration require detailed research. The aim of our study was to determine the influence of melatonin different time and mode treatment on body weight changes of diet-induced (high-calorie diet, HCD) obesity in rats. Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg either 1 h after lights-on (ZT01) or 1 h before lights-off (ZT11) or continuously with drinking water (HCD water). Parameters, including weight gain, weight gain rate, body mass index, Lee index, related visceral fat weight, relative daily food and water consumption, were measured. Melatonin use significantly reduce weight gain rate in HCD ZT11 and HCD water group in 2 and 2,5 times; Lee index – by 6,6 % and 7,3 %; related visceral fat mass – by 38,5 %, respectively in compare with HCD. Animals without HCD which obtain melatonin did not change observed parameters, accept relative visceral fat mass (it was decreased in rely to control). The effects of different modes melatonin administration manifested in decrease weight gain rate, Lee index and relative visceral fat mass in rats with diet-induced obesity only after evening administration, as well as after delivery continuously with drinking water without any effect on food and water consumption.

http://biovestnik.com/index.php/problems/article/download/337/353

The effects of different mode of melatonin administration on the development of high-calorie diet-induced obesity in rats

This study aimed to evaluate changes in beige adipocytes at different times of melatonin administration, in the morning (ZT01) or in the evening (ZT11), at 30 mg/kg daily by gavage for 7 weeks or continuously with drinking water in the ter m of high-calorie diet-induced obesity (HCD). Melatonin received at ZT11 or with drinking water resulted in an increased area of the browning zone in the subcutaneous white adipose tissue (sWAT), even in rats with HCD (compared with Control or HCD, respectively). The b eige adipocyte and lipid droplet area after melatonin use were reduced compared to those with HCD and Control, in all administration modes (group ZT01 showed smaller changes compared to ZT11 or with drinking water groups). The fibrosis level decreased and significan tly differed in HCD ZT01, HCD ZT11, and HCD water compared to that in HCD; moreover, the lowest value determined in HCD water, reached the control parameters. Furthermore, the IL-1b and IL-8 level was decreased in the HCD groups under melatonin treatment at ZT11 or with drinking water compared to that in HCD. The obtained results suggest that melatonin promotes sWAT browning in rats with diet-induced obesity and influences morphological signs of normal rats depending on the time of administration. Different funct ional activity of beige adipocytes was observed after melatonin was used depending on the time of administration, resulting in heat p roduction and lipolysis (the relative mass of visceral fat was likewise diminished). More rapid browning was observed when melatonin trea tment was performed at 1 h before lights-off (ZT11) or continuously via drinking water. Melatonin acted on beige adipocytes of obese rats through changing some parameters such as the area of adipocytes and lipid drops, the number of lipid drops, the relative area b rowning of sWAT, and the level of tissue fibrosis.

https://scielo.conicyt.cl/pdf/ijmorphol/v38n3/0717-9502-ijmorphol-38-03-737.pdf

Variable Beige Adipocyte Morphology in Obese Rats by Different Times of Melatonin Administration

One of the prominent obesity-related changes is the development of systemic low-grade proinflammatory state. Brown adipose tissue (BAT) may serve as a potential target for activation by melatonin to facilitate heat  production and simultaneously stimulate lipolysis during obesity development. At the same time, melatonin is known to have immunomodulatory properties, which are performed via endocrine and paracrine signal pathways in variety cell types (including brown adipocytes)and change significantly during the day. Therefore, it can be used in a wide range of doses and at different times of the day (chronotherapeutic approach). Thus, the main goal of our research was to analyze the inflammation state of brown adipose tissue of rats during high-calorie diet induced-obesity development after different daily melatonin application in different regimes. Melatonin was administered by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (HCD ZT11, M ZT11, evening), or 1 h after lights-on (HCD ZT01, M ZT01, morning). Tissue collagen content and leukocyte infiltration levels in BAT, detected by Van Gieson trichrome staining, were used as markers for the assessment of BAT inflammation state BAT. Propagation of obesity resulted in the increase of BATfibrosis level (the relative area occupied by collagen fibers) and tissue leukocyte infiltration in comparison to control rats. BAT fibrosis level after melatonin administrations to obese rats of HCD ZT01 and HCD ZT11 groups decreased to control values. Similar effects were observedinBAT tissue leukocyte infiltration after both regimes (HCD ZT01 and HCD ZT11 groups) of melatonin intake: this parameter decreased significantly, comparing to obese rats, but was still elevated, comparing to controls. At the same time, melatonin treatmentin morning or evening regimes did not have any impact on BAT fibrosis propagation and leukocyte infiltration in animals that consumed standard diet (M ZT01 and M ZT11 groups). To sum up, we suggest corrective properties of melatonin in context of chronic low-grade inflammation in obese rats BAT and suppose its wide potential for the therapeutic use combined with virtually absent side effects on BAT histophysiology of non-obese rats.

Inflammation features of brown adipose tissue of rats with diet-induced obesity development after different regimes of melatonin administration

Objectives: To identify the obstacles and issues that hinder effective cancer prevention efforts in Ukraine. The study aims to provide a comprehensive assessment of the barriers to cancer prevention, including both infrastructure and behavioral factors, and identify potential solutions to address these challenges. Study Design: Comprehensive literature review. Methods: The following databases were searched: National Center for Biotechnology Information (NCBI) and PubMed (U.S. National Library of Medicine at the National Institutes of Health). The keywords used in the search included “Cervical Cancer”, “Human Papillomavirus Vaccination (HPV)”, “Ukraine”, “Eastern Europe”, “Healthcare Infrastructure in Disasters”, “Cervical Cancer Prevention”, “Pap Smear”, and “HPV Testing”. Results: A total of 3500 articles were screened. A total of 65 articles met the inclusion criteria. Limited public awareness and limited access to vaccination and screening, combined with inadequate treatment facilities lead to higher rates of cervical cancer. The COVID pandemic, war with Russia, and the Chernobyl disaster are significant factors for the low level of vaccination in Ukraine. Conclusion: The prevention and treatment of cervical cancer in Ukraine face significant challenges due to the inadequate HPV vaccination rates and screening by cytology. Efforts to improve funding and increase education of both the population and health care providers are necessary to increase interventions such as HPV vaccination, cervical cytology, and HPV testing to reduce cervical cancer rates in Ukraine. 

http://www.scirp.org/journal/PaperDownload.aspx?paperID=125932

Cervical Cancer Prevention Challenges and Barriers to Cervical Cancer Screening and HPV Vaccinations in Ukraine and Eastern Europe

Recently, numerous studies have indicated that melatonin, the hormone of pineal gland, affects the processes of differentiation of many cells, including preadipocytes into brown, beige and white adipocytes. Therefore, it is important to study the possibilities of using melatonin as a factor for the differentiation of preadipocytes to control the adipose tissue functional activity in the treatment of various diseases, including obesity. THE AIM of the study was to evaluate the morphology and functional status of brown adipose tissue at the different time of melatonin administration. MATERIALS AND METHODS. Outbred rats were divided into 3 experimental groups: control, administration of melatonin 1 hour after light-on ZT01 (Zeitgeber time), administration of melatonin 1 hour before light-off ZT11. Melatonin was administered by gavage daily for 7 weeks at a standard exposure to day-night light (12:12). RESULTS. The application of melatonin affects the morphology and functional state of brown adipocytes independently of the administration time: the nuclear-cytoplasmic ratio increases due to an increase in the area of the nucleus against the unchanging cell area. The number of lipid drops increases in each adipocyte, but their size is decreased. The effect of different time of melatonin administration was manifested in the increase of brown adipose tissue weight, in the terms of evening administrations. CONCLUSION. The effects of different times of melatonin administration at the cytological level are manifested almost identically in the brown adipocytes functional state in all experimental groups. However, at the organism level in terms of evening administrations, an increase in the relative mass of brown adipose tissue is observed, but the size of brown adipocytes do not change, which may indicate the activation of the differentiation of brown adipocytes from the progenitor cells.

/pdf/the-effects-of-different-time-of-melatonin-administration-on-4jjrqyfval.pdf

The effects of different time of melatonin administration on differentiation and functional status of the brown adipocytes in vivo

The Covid-19 pandemic and ongoing war in Ukraine caused unprecedented disruption in healthcare, including cytopathology activities. This paper elucidates the effect of two consecutive disasters-the COVID-19 pandemic followed by the war-on cytopathology practice in Ukraine through a single-centre retrospective study. Total testing volumes, geographic distribution, and indicators of laboratory operations were assessed during three periods of 3 months each: the first 3 months of the acute phase of the war (March-May 2022, period 1); summer (June-August 2022, period 2); and the fall (September-November 2022, period 3, associated with massive attacks on the energy infrastructure in Ukraine). These data were compared with the corresponding periods in 2020, during the COVID-19 pandemic, and in 2021, the post-lockdown period. The ongoing war in Ukraine has caused a dramatic disruption in routine health maintenance and cytological practice. A net decline in both PAP testing and non-gynaecological pathology was associated with a geographic redistribution of cytopathological testing, and an increase in the rate of abnormal sample reporting. Despite these challenges, cytopathology practice in Ukraine demonstrates resilience, allowing for maintaining the healthcare system and addressing the needs of the civil population during the war. The ongoing war in Ukraine heavily affected cytological practice. The decline in PAP testing during the early period of the war was associated with an increase in the abnormal sample rate. Further study of the war's impact on the cervical pathology rate and the health of the population in the next decades is needed.

The detrimental consequences of two consecutive disasters impacting cytopathology in Ukraine: COVID followed by the war.

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The effects of different time of melatonin administration on differentiation and functional status of the brown adipocytes in vivo

The detrimental consequences of two consecutive disasters impacting cytopathology in Ukraine: COVID followed by the war.