The Vitamin C Enantiomers Possess a Comparable Potency in the Induction of Oxidative Stress in Cancer Cells but Differ in Their Toxicity.

The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its high-dose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in KrasG12D-expressing mutant cancer cells as indicated by a substantial increase in reactive oxidative species (ROS) production and depolarization of mitochondria. To examine the L-VC and D-VC toxicity effects, we administered high doses of D-VC and L-VC to CD1 mice and carried out an evaluation of their toxic effects. The daily injections of L-VC at a dose of 9.2 g/kg for 18 days were lethal to mice, while 80% of mice remained alive following the similar high-dose administration of D-VC. Following the drug injection courses and histopathological studies, we determined that a natural form of VC (L-VC) is more harmful and toxic to mice when compared to the effects caused by the similar doses of D-VC. Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings.

The prevalence and risk factors of pressure ulcers among residents of long-term care institutions: a case study of Kazakhstan.

Limited information is available regarding the prevalence of pressure ulcers (PUs) in residential homes in Central Asia. Therefore, the aim of this study was to identify the prevalence rates and risk factors associated with PUs among residents of long-term care medical institutions in the Republic of Kazakhstan. This cross-sectional study was conducted in four long-term care institutions in Kazakhstan. The study sample consisted of 640 patients who were assessed for the presence of PUs and associated risk factors. The evaluation was performed using the International Prevalence Measurement of Care Quality (Landelijke Prevalentiemeting Zorgkwaliteit, LPZ), the Braden scale, and the Care Dependency Score (CDS). The overall prevalence of PUs, classified as categories I-IV, was found to be 37%. When excluding category I PUs, the prevalence decreased to 35.6%. The odds ratios (ORs) for presenting with PUs were as follows: history of stroke (OR 5.22), diseases of the digestive system (OR 10.01), presence of spinal cord lesions/paraplegia (OR 20.50), recent reported confusion within the last 7 days (OR 184.00), and limited extent dependency according to the CDS (OR 4.44; 95%CI 1.31-16.1). It is imperative to establish specialized training programs aimed at equipping medical personnel, relatives, and patients themselves with the necessary skills to provide optimal care for individuals affected by PUs.

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation.

This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.

Molecular and Cellular Mechanism of Action of Chrysotile Asbestos in MRC5 Cell Line.

Asbestos is a known carcinogen; however, the influence of chrysotile asbestos on the development of tumor-related diseases remains a subject of intense debate within the scientific community. To analyze the effect of asbestos, we conducted a study using the MRC5 cell line. We were able to demonstrate that chrysotile asbestos stimulated the production of reactive oxygen species (ROS), leading to cell death and DNA damage in the MRC5 cell line, using various techniques such as ROS measurement, comet assay, MTT assay, and qPCR. In addition, we found that chrysotile asbestos treatment significantly increased extracellular mitochondrial DNA levels in the culture medium and induced significant changes in the expression profile of several miRNAs, which was the first of its kind. Thus, our research highlights the importance of studying the effects of chrysotile asbestos on human health and reveals multiple adverse effects of chrysotile asbestos.

Worldwide Prevalence of Alcohol Use in Non-Fatally Injured Motor Vehicle Drivers: A Systematic Review and Meta-Analysis.

Drunk driving is an important risk factor significantly contributing to traffic accidents and their associated lethality. This meta-analysis of observational studies aims to provide the estimates of drunk driving prevalence in non-lethally injured motor vehicle drivers in relation to the world region, blood alcohol concentration (BAC), and quality of the primary study. A systematic search for observational studies that examined the prevalence of drunk driving in injured drivers was performed, and 17 studies comprising 232,198 drivers were included in the pooled analysis. The pooled prevalence of drunk driving in injured drivers was found to be 16.6% (95% CI: 12.8-20.3%; I2 = 99.87%, p < 0.001). In addition, the prevalence of alcohol use ranged from 5.5% (95% CI: 0.8-10.1%) in the Middle East, North Africa, and Greater Arabia region to 30.6% (95% CI: 24.6-36.5%) in the Asia region. As for the subgroups with different thresholds of BAC, the maximum value of 34.4% (95% CI: 28.5-40.3%) was found for a dose of 0.3 g/L. The prevalence of alcohol use reported by high-quality studies was 15.7% (95% CI: 11.1-20.3%), compared to 17.7% (95% CI: 11.3-24.2%) reported by studies of moderate quality. These findings could inform law enforcement efforts to promote road safety.

Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients.

BACKGROUND: Vitiligo is one of the most common hypomelanoses, in which the destruction of functioning melanocytes causes depigmentation of the skin, hair and mucous membranes. The genes encrypting brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) might be the conceivable contributors to the development of vitiligo. This study was aimed at investigation of the serum levels of BDNF and CRH as well as their selected single nucleotide polymorphisms (SNPs) in vitiligo patients in comparison with the healthy controls. METHODS: The cross-sectional study was carried out between October 2020 and June 2021 in 93 vitiligo patients (age range from 23 to 48 years) and 132 healthy controls (age range from 24 to 52 years). The psychological status of study participants was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) scale. Serum levels of BDNF and CRH were measured with the help of a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Genotyping for the rs11030094 polymorphism of the BDNF gene and for the rs242924 polymorphism of the corticotropin releasing hormone receptor 1 (CRH-R1) gene was performed by a real-time polymerase chain reaction (PCR). RESULTS: There was a significant relationship between the CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Moreover, serum levels of neurotransmitters differed significantly between vitiligo and control groups and were associated with the CRH-R1 rs242924 and BDNF rs11030094 SNPs. CONCLUSIONS: Our findings demonstrated the association between CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Further studies need to be carried out in vitiligo patients to confirm the results observed.

Associations between serum levels of brain-derived neurotrophic factor, corticotropin releasing hormone and mental distress in vitiligo patients.

Vitiligo is clinically characterized by the appearance of non-symptomatic depigmented macules, but the disorder is highly correlated with a wide range of psychiatric disorders and psychological problems. The aim of our study was to investigate serum brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) levels in vitiligo patients and healthy controls in relation to the observed symptoms of depression and anxiety disorders. This study comprised 96 vitiligo patients and 96 healthy controls who filled out the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Serum levels of BDNF and CRH were measured using enzyme-linked immunosorbent assay (ELISA) technique. There was a significant increase of depression and anxiety scores in vitiligo patients as compared with healthy controls (P < 0.05). The serum levels of BDNF were significantly lower in vitiligo patients than in healthy individuals (Z = 4.002; P < 0.001), while the serum levels of CRH were markedly higher in cases than those in controls (Z = 3.764; P < 0.001). The significant positive correlations between serum CRH levels and GAD-7, PHQ-9 scores were observed. However, the aforementioned psychometric scales did not correlate significantly with serum BDNF level. Vitiligo is associated with the depression and is closely linked with lower BDNF levels.

The Role of Mitochondrial miRNAs in the Development of Radon-Induced Lung Cancer.

MicroRNAs are short, non-coding RNA molecules regulating gene expression by inhibiting the translation of messenger RNA (mRNA) or leading to degradation. The miRNAs are encoded in the nuclear genome and exported to the cytosol. However, miRNAs have been found in mitochondria and are probably derived from mitochondrial DNA. These miRNAs are able to directly regulate mitochondrial genes and mitochondrial activity. Mitochondrial dysfunction is the cause of many diseases, including cancer. In this review, we consider the role of mitochondrial miRNAs in the pathogenesis of lung cancer with particular reference to radon exposure.

The level of free-circulating mtDNA in patients with radon-induced lung cancer.

OBJECTIVE: According to the World Health Organization, radon is the second leading cause of lung cancer after smoking. Cell free circulating mitochondrial DNA (cf mtDNA) have been used not only as a biomarker of carcinogenesis but also as a biomarker of exposure to radiation, but nothing is known about changes in the level of cf mtDNA following radon exposure. Therefore, the purpose of this study was to estimate the cf mtDNA copy number as a biomarker of the response to radon exposure in lung cancer pathogenesis. METHODS: 207 subjects were examined including 41 radon-exposed lung cancer patients, 40 lung cancer patients without radon exposure and 126 healthy controls exposed/not exposed to high level of radon. Total cell free circulating DNA from blood samples was extracted and used to detect cell free circulating mitochondrial DNA copy number by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our data indicate that the level of cf mtDNA in the radon-induced lung cancer patients was significantly higher than that of the other study participants. There was a significant difference in the level of cf mtDNA in the blood plasma of healthy volunteers exposed and not exposed to high doses of radon. Moreover, in healthy volunteers living in areas with high radon levels, the mtDNA copy number was higher than that in patients with lung cancer who were not exposed to high doses of radon. CONCLUSION: Our study provides evidence for a possible role of cf mtDNA as a promising biomarker of lung cancer induced by exposure to high dose of radon.

Involvement of Circulating Cell-Free Mitochondrial DNA and Proinflammatory Cytokines in Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer.

OBJECTIVE: Circulating cell-free mitochondrial DNA (cf-MtDNA) has been reported in patients with chronic obstructive pulmonary disease (COPD) and lung cancers. However, inter-relationships among the three biological events have not been well-characterized. Therefore, our investigation was conducted to better understand the role of cf-MtDNA on pathogenesis of the two diseases. METHODS: Plasma samples were collected from 64 non-small cell lung cancer (NSCLC) patients (before therapy), 45 patients with COPD and 62 healthy individuals. cf-MtDNA copy numbers were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and cytokines were determined using a human ELISA kit. RESULTS: Our data indicate that smoking statuses of the patients and controls were significantly associated with increased cf-MtDNA in plasma samples. Furthermore, NSCLC patients had significantly higher cf-MtDNA copy numbers than COPD patients (p < 0.03) and normal controls (p < 0.02), together with elevated proinflammatory cytokines over the controls (p < 0.05). Our  study shows that the copy numbers for the NSCLC patients were positively associated with their subsequent metastasis but inversely associated with their overall survival.  Conclusion: Our study indicates certain lung injury (e.g., from cigarette smoking) was responsible for the release of cf-MtDNA and proinflammatory cytokines into plasmas among our patients and controls. The increase in cf-MtDNA copy numbers was significantly associated with the development of both COPD and NSCLC, with increase in interleukin 6, and from our 5-year follow-up, with poor prognosis among the NSCLC patients. Therefore, with further validation, cf-MtDNA can be considered for use as diagnostic and prognostic biomarkers for NSCLC.

Role of microRNAs in Lung Carcinogenesis Induced by Asbestos.

MicroRNAs are a class of small noncoding endogenous RNAs 19-25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.

Vitiligo and anxiety: A systematic review and meta-analysis.

BACKGROUND: Vitiligo is an acquired depigmenting skin disease which is often accompanied by mental distress. There are numerous studies dedicated to local and global prevalence of depression in patients with vitiligo but anxiety has not been recognized as a major mental problem within named population. We aimed to evaluate the prevalence of anxiety among patients with vitiligo from different countries and to compare it with patients suffering from eczema, psoriasis, and acne. METHODS: In November 2019, we conducted a systematic search for observational studies that examined the prevalence of anxiety in vitiligo patients. Fifteen studies comprising 1176 patients with vitiligo were included to our systematic review. RESULTS: The general prevalence of anxiety among vitiligo patients was equal to 35.8%. Statistically significant difference in anxiety rates was found among female and male patients (47.32% vs 42.4%) (P = 0.03), but the clinical relevance of this issue remains arguable. In addition, the pooled odds ratio among vitiligo and non-vitiligo patients did not indicate a statistical significance among patients coming from different continents. CONCLUSIONS: The pooled prevalence of anxiety among vitiligo patients worldwide was comparable to other severe skin disorders. This finding accentuates the necessity of anxiety awareness in management of patients with skin diseases.

miR-19 in blood plasma reflects lung cancer occurrence but is not specifically associated with radon exposure.

Radon is one of the most powerful carcinogens, particularly in terms of lung cancer onset and development. miRNAs may be considered not only as markers of the ongoing tumorigenesis but also as a hallmark of exposure to radiation, including radon and its progeny. Therefore, the purpose of the present study was to estimate the value of plasma miR-19b-3p level as the prospective marker of the response to radon exposure in lung cancer pathogenesis. A total of 136 subjects were examined, including 49 radon-exposed patients with lung cancer, 37 patients with lung cancer without radon exposure and 50 age/sex matched healthy controls. Total RNA from blood samples was extracted and used to detect miR-19b-3p expression via reverse transcription quantitative-polymerase chain reaction. The 2-ΔΔCq method was used to quantify the amount of relative miRNA. The plasma level of p53 protein was determined using a Human p53 ELISA kit. Plasma miR-19b-3p level was significantly higher in the patients with lung cancer groups, compared with the healthy control group (P<0.0001). No other statistically significant differences were determined in the expression level of plasma miR-19b-3p between patients diagnosed with lung cancer exposed to radon and not exposed to radon. The expression level of free circulating miR-19b-3p was higher in the group of non-smoking patients with lung cancer, compared with smokers with lung cancer. The miR-19b-3p was 1.4-fold higher in non-smokers than in smokers (P<0.05). No association between plasma levels of p53 protein and miR-19b-3p freely circulating in patients with lung cancer was observed. No other statistically significant differences were determined in the plasma p53 protein level between patients diagnosed with lung cancer exposed and not exposed to radon. These results indicated that detection of miR-19b-3p levels in plasma potentially could be exploited as a noninvasive method for the lung cancer diagnostics. However, this miRNA is not suitable as the precise marker for radon impact.