Deoxyribonucleic Acid Synthesis Research Articles

Use of antiviral drugs and incidence of Parkinson's disease in Taiwan.

Patients infected with herpes zoster might be at risk for Parkinson's disease (PD). However, antiviral drugs may impede viral deoxyribonucleic acid (DNA) synthesis. This study aimed to determine whether the currently observed association between herpes zoster and PD is consistent with previous findings, and whether antiviral drug use is associated with PD. This retrospective cohort study used the Longitudinal Generation Tracking Database. We included patients aged 40 years and above and applied propensity score matching at 1:1 ratio for study comparability. PD risk was evaluated using Cox proportional hazards regression methods. A total of 234,730 people were analyzed. The adjusted hazard ratio (aHR) for PD in patients with herpes zoster was 1.05. Furthermore, the overall incidence of PD was lower in those treated with antiviral drugs than in the untreated ones (3.17 vs. 3.76 per 1,000 person-years); the aHR was 0.84. After stratifying for sex or age, a similar result was observed. In conclusion, herpes zoster may increase the risk of PD, particularly among females, but receiving antiviral treatment reduces the risk by 16%. Therefore, using antiviral drugs may help prevent PD. However, additional research is required to determine the underlying mechanism(s).

Theoretical Study on The Effect of Metal Ions on The Structural Properties of Base

Metal ions play an important role in living organisms, for example Mg2+ is a cofactor for many biological enzymes (including DNA and RNA synthesis), Ca2+ is an important component of bone composition, and metal ions such as Fe, Co, Zn, Ni and Cu also play an important role in the normal functioning of living organisms. One of the main targets of metal ions in living organisms is deoxyribonucleic acid (DNA), which is an important carrier of information stored and transmitted by organisms. The direct interaction between DNA base pairs and metal ions have a significant impact on the structure and function of DNA base pairs, which is demonstrated as following: the binding of metals to bases usually breaks the hydrogen bonds of the base pairs. The N7 atom of a purine residue or the N3 atom of a pyrimidine residue, as well as the outer ring O atom and the phosphate oxygen atom, are the preferred sites for metal binding. The binding of metals to DNA and RNA also indirectly affects the conformation of the sugar ring. REDOX active metal ions have the ability to bind to DNA and can mediate oxidative DNA damage by reacting with endogenous oxidants. According to studies of antioxidants in the field of metal-mediated oxidative DNA damage, metal ion coordination also plays a key role in the mechanism of some antioxidants. Also, metal-DNA interactions are the basis for many anti-cancer drugs, anti-viral drugs and anti-bacterial agents. Metal-mediated oxidative DNA damage is associated with a variety of diseases and conditions, and understanding the binding interactions and subsequent reactivity can facilitate the management or prevention of oxidative damage. It can be seen that the study of the effect of metal ions on the structural properties of DNA bases has far-reaching implications, providing a theoretical basis for the development of novel anticancer drugs, DNA-based metal nanodevice technologies and the fabrication of spectroscopic and reactive probes.

HIF1α Contribution to the NHEJ DNA Repair Pathway Through Decreased Expression of XRCC4

Background: Hypoxia-inducible factor 1α (HIF1α), a key transcription factor activated during low oxygen levels, influences cell cycle and metastasis. Hypoxia induces double-strand breaks (DSBs), a highly carcinogenic process. Objectives: This study aimed to elucidate the impact of HIF1α down-regulation on the expression of XRCC4 and XRCC7, key components of the non-homologous end joining (NHEJ) pathway crucial for DSB repair. Methods: HeLa and [human embryonic kidney (HEK)293] cells underwent culture, transfection with HIF1α small interfering ribonucleic acid (siRNA), and viability assessment after 48 hours. Subsequent examination included cell cycle alterations. Ribonucleic acid extraction, complementary deoxyribonucleic acid (cDNA) synthesis, and RT-qPCR were performed to compare the fold-change in HIF1α, XRCC4, and XRCC7 gene expression, followed by statistical analyses. Results: Downregulating HIF1α using siRNA resulted in reduced viability and increased apoptosis in both HeLa and HEK293 cells 48 hours after transfection. The findings also indicated a significant decrease in XRCC4 expression; nevertheless, XRCC7 expression remained unchanged in both cell lines. Conclusions: This study underscores that HIF1α potentially modulates the NHEJ pathway through XRCC4, presenting itself as a plausible target for cancer therapy.

Bombesin-like receptor 3 expression induced by bisphenol A is likely associated with reduced cell proliferation by inhibiting DNA synthesis and inducing inflammation in liver cells.

Bisphenol A (BPA) is an exogenous endocrine disruptor mimicking hormones closely associated with health complications, such as cancer progression. BPA is also related to an increase in the prevalence of obesity-related diseases due to its obesogenic action. Bombesin-like receptor 3 (BRS3) is an important factor that should be considered in the adipogenic gene network, as depletion of this gene alters adiposity. Therefore, the present study aimed to investigate the messenger ribonucleic acid (mRNA) expression of BRS3 in human liver THLE-2 cells post-BPA treatment by real-time polymerase chain reaction. The effects of BPA on the levels of pro-inflammatory proteins, interleukin 6 (IL6) and CC motif chemokine ligand 2 (CCL2), in conditioned media of BPA-treated THLE-2 cells and deoxyribonucleic acid (DNA) synthesis in replicating BPA-treated THLE-2 cells during the cell cycle were also examined by enzyme-linked immunosorbent assay(ELISA) and flow cytometry, respectively. The study found that the mRNA expression of BRS3 was increased in THLE-2 cells treated with BPA. The study also showed that the expression levels of IL6 and CCL2 reached an optimum level in the conditioned media of BPA-treated THLE-2 cells after 48h of treatment. Subsequently, the DNA synthesis analysis showed that bromodeoxyuridine/propidium iodide(BrdU/PI) stained positive cells were decreased in BPA-treated THLE-2 cells at 72h of treatment. The study demonstrates that BRS3 expression induced by BPA is likely associated with reduced cell proliferation by inhibiting DNA synthesis and inducing cellular inflammation in liver cells.

High-throughput DNA synthesis for data storage.

With the explosion of digital world, the dramatically increasing data volume is expected to reach 175 ZB (1 ZB = 1012 GB) in 2025. Storing such huge global data would consume tons of resources. Fortunately, it has been found that the deoxyribonucleic acid (DNA) molecule is the most compact and durable information storage medium in the world so far. Its high coding density and long-term preservation properties make itself one of the best data storage carriers for the future. High-throughput DNA synthesis is a key technology for "DNA data storage", which encodes binary data stream (0/1) into quaternary long DNA sequences consisting of four bases (A/G/C/T). In this review, the workflow of DNA data storage and the basic methods of artificial DNA synthesis technology are outlined first. Then, the technical characteristics of different synthesis methods and the state-of-the-art of representative commercial companies, with a primary focus on silicon chip microarray-based synthesis and novel enzymatic DNA synthesis are presented. Finally, the recent status of DNA storage and new opportunities for future development in the field of high-throughput, large-scale DNA synthesis technology are summarized.

Regucalcin Is a Potential Regulator in Human Cancer: Aiming to Expand into Cancer Therapy.

Regucalcin, a calcium-binding protein lacking the EF-hand motif, was initially discovered in 1978. Its name is indicative of its function in calcium signaling regulation. The rgn gene encodes for regucalcin and is situated on the X chromosome in both humans and vertebrates. Regucalcin regulates pivotal enzymes involved in signal transduction and has an inhibitory function, which includes protein kinases, protein phosphatases, cysteinyl protease, nitric oxide dynthetase, aminoacyl-transfer ribonucleic acid (tRNA) synthetase, and protein synthesis. This cytoplasmic protein is transported to the nucleus where it regulates deoxyribonucleic acid and RNA synthesis as well as gene expression. Overexpression of regucalcin inhibits proliferation in both normal and cancer cells in vitro, independent of apoptosis. During liver regeneration in vivo, endogenous regucalcin suppresses cell growth when overexpressed. Regucalcin mRNA and protein expressions are significantly downregulated in tumor tissues of patients with various types of cancers. Patients exhibiting upregulated regucalcin in tumor tissue have shown prolonged survival. The decrease of regucalcin expression is linked to the advancement of cancer. Overexpression of regucalcin carries the potential for preventing and treating carcinogenesis. Additionally, extracellular regucalcin has displayed control over various types of human cancer cells. Regucalcin may hold a prominent role as a regulatory factor in cancer development. Supplying the regucalcin gene could prove to be a valuable asset in cancer treatment. The therapeutic value of regucalcin suggests its potential significance in treating cancer patients. This review delves into the most recent research on the regulatory role of regucalcin in human cancer development, providing a novel approach for treatment.

Effect of endometrial biopsy method on ribonucleic acid quality and gene expression analysis in patients with leiomyoma

To compare ribonucleic acid (RNA) quantity and purity in tissue collected with different endometrial sampling methods to establish the optimal tool for use in endometrial gene expression studies. Observational study. University hospital. Fourteen patients with submucosal leiomyomas. Unguided biopsies were obtained using a low-pressure suction device before hysteroscopy from 14 patients with submucosal leiomyomas followed by guided biopsy with a resectoscope loop. Fifty-seven samples were collected: 25 obtained using a suction device and 32 with a loop. Total biopsy weight, RNA purity, and RNA yield for each collection method. After complementary deoxyribonucleic acid synthesis, HOXA10 expression was measured by quantitative polymerase chain reaction in the endometrium overlying and remote from the leiomyoma, as similar expression throughout the cavity was a prerequisite for the use of unguided biopsy method. The median weight of the samples was significantly larger when obtained with the low-pressure suction device than with the resectoscope loop (153 vs. 20 mg). The RNA yield was similar (suction curette, 1,625 ng/mg; resectoscope loop, 1,779 ng/mg). The A260-to-A280 ratio was satisfactory for 94.7 % of the samples, with no difference between the groups. The endometrial expression of HOXA10 was similar in areas overlying the leiomyoma compared with that in remote endometrial sites (2-ΔCt = 0.0224 vs. 0.0225). Low-pressure endometrial suction devices provide tissue samples with acceptable RNA purity and quantity for gene expression studies. The expression of HOXA10 did not differ between endometrial sampling sites even in the presence of leiomyomas.

The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial

BackgroundVitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. ObjectivesThe study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. MethodsThe study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 –11 mo, who were supplemented with 2 μg (2–3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. ResultsLTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (–0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. ConclusionsProviding daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL.This trial was registered at clinicaltrials.gov as NCT02272842.

Differential Expression of miR-21-5p, miR-20a-5p, TGF-β1, and TGF-β Receptor 2 in Skin, Serum, and Lung Samples Exposed to Sulfur Mustard.

Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA (miR) transcript levels are found in pulmonary diseases and even inflammation. Therefore, we evaluated the expression levels of miR-20a-5p, miR-21-5p, and two target transcripts (transforming growth factor-beta [TGF-β1] and TGF-β receptor 2 [TGFR2]) in lung, serum, and skin samples from patients exposed to SM. Total RNA was extracted from lung, serum, and skin samples of patients with moderate (n=10) and high (n=10) SM exposure, as well as 10 healthy subjects. Following the synthesis of complementary deoxyribonucleic acid using real-time polymerase chain reaction, we determined the expression levels of miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 transcripts. Furthermore, we evaluated the sensitivity and specificity of the chosen miRs by employing receiver operating characteristic (ROC) curves and calculating the area under the ROC curve. The results showed that miR-20a-5p and miR-21-5p expressions in the groups with moderate and high SM exposure were significantly lower than the normal controls. The expression analysis demonstrated that TGFR2 was significantly less expressed in skin samples exposed to SM in both groups of patients compared with healthy controls. Furthermore, the TGF-β1 expression in the skin samples of the group with moderate SM exposure was lower than that of the normal control group. Our findings suggest that miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 expressions could be used as potential biomarkers for discriminating SM-exposed patients from healthy individuals.

T helper type 9 cell response and its role in the neurological clinic of patients with Human T-lymphotropic virus 1

Human T-lymphotropic virus 1 (HTLV-1) affects 5–10 million individuals worldwide. Most of those infected with this virus remain asymptomatic; however, 0.25%–4% of individuals develop HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), while 2%–4% develop adult T-cell leukemia/lymphoma (ATLL). Understanding the immune response inherent in this infection is extremely important. The role of T helper type 1 (Th1) and Th2 cells in HTLV-1 infection is well known; however, exploring the different subtypes of immune responses is also necessary. The role of Th9 cells in HTLV-1 infection and the mechanisms involved in their interference in the pathophysiological process of HAM/TSP is poorly understood. This study aimed to evaluate the expression profiles of PU.1, interferon regulatory factor 4 (IRF-4), and cytokine interleukin-9 (IL-9) during the induction of peripheral immune response and their role in the HTLV-1-infected patients’ neurological symptoms. This analytical cross-sectional study was carried out at the Laboratory of Clinical and Epidemiology of Endemic Diseases and the Laboratory of Immunopathology, both from the Tropical Medicine Center at the Federal University of Pará. Assessment of neurological parameters was performed (gait, Expanded Kurtzke Disability State Scale (EDSS) score, upper and lower limb reflexes, Hoffman’s sign, Babinski reflex, and clonus reflex). For Th9 cell analysis, peripheral blood samples were collected from HTLV-1-infected patients; then, the lymphomononuclear cells were separated followed by the isolation of messenger ribonucleic acid (mRNA). Complementary deoxyribonucleic acid (cDNA) synthesis each sample was carried out. The gene expression levels of PU.1, IRF-4, and IL-9 as well as those of constitutive genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β-actin) were quantified by real-time polymerase chain reaction (qPCR). This study included 81 HTLV-1-infected patients, of whom 47 were asymptomatic, 13 were mono/oligosymptomatic (MOS), and 21 developed HAM/TSP. IL-9 was the least expressed gene among the three studied groups. The MOS group showed the lowest expression levels of PU.1, IRF-4, and IL-9. HAM/TSP patients showed lower IL-9 protein quantification. Negative correlations were found between IL and 9 and EDSS in MOS patients and between PU.1, EDSS, IRF-4, and EDSS in the HAM/TSP group. An association was found between IL and 9 and Babinski reflex in the HAM/TSP group, suggesting that this gene was more highly expressed in patients who did not have this pathological sign. Th9 cells may interfere with the neurological progression of HAM/TSP and act as a protective factor.

Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report

BackgroundNitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature.Case reportA 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected.ConclusionThis case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.

Review on Food Insecurity and its Relationship with Iron and Vitamin B12 Status Among Children

Iron and vitamin B12 are essential micronutrients needed for the growth and development of children. Iron is critical for erythropoiesis, notably in haemoglobin synthesis whereby haemoglobin transports oxygen to cells, which is essential for cellular metabolism and energy production. Meanwhile, vitamin B12 is required for deoxyribonucleic acid synthesis, intracellular metabolism, and blood cells formation and maturation. Lack of these essential micronutrients can lead to nutritional deficiency and anaemia, especially among children. Food insecurity is a condition where there is a lack of or uncertain availability of acquiring acceptable food. Food insecurity is associated with lower nutrient intake and micronutrient deficiencies including iron and vitamin B12, which can subsequently lead to poor health outcomes. Various determinants are associated with iron and vitamin B12 deficiency, and food insecurity, such as socio-economic factors, environmental factors, and dietary intake. This review will explore the possible relationship between iron, vitamin B12, and anaemia with food insecurity among children.

Study Based on the Alliance Between Serum Magnesium Levels and Preterm Labor: An Inclusive Review.

Preterm labor, regarded as the onset of labor before 37 weeks of gestation, is a highly prevalent issue in obstetrics with repercussions for neonatal health. This review article presents an in-depth analysis of the alliance between serum magnesium levels and preterm labor. The review explores the physiological roles of magnesium right through pregnancy, including its significance for energy metabolism, smooth muscle contraction, deoxyribonucleic acid (DNA), and protein synthesis. It addresses cellular transport and the homeostasis of magnesium. The pathophysiological processes encompassing inflammation, oxidative stress, calcium regulation, smooth muscle contractility, and neuroendocrine pathways are investigated. The review evaluates epidemiological studies investigating the alliance between serum magnesium levels and preterm labor. The review incorporates an assortment of study varieties, such as observational studies, case-control studies, prospective cohort studies, and meta-analyses. In the course of reviewing the prognostic relevance of serum magnesium levels in premature labor, therapeutic implications involving diagnostic precision, prognostic significance, and therapeutic response assessment have additionally been addressed. Therapeutic interventions targeting magnesium levels, such as magnesium supplementation, tocolytic therapy, and the role of magnesium in antenatal corticosteroid administration, are explored. This review provides an in-depth evaluation of the correlation between serum magnesium levels and preterm labor, stressing its therapeutic significance and repercussions for future research and treatment strategies.

Polyamine, 1,3-diaminopropane, regulates defence responses on growth, gas exchange, PSII photochemistry and antioxidant system in wheat under arsenic toxicity

The metalloid arsenic (As) is extremely hazardous to all living organisms, including plants. Pollution with As is very detrimental to the photosynthetic machinery, cell division, energy generation, and redox status. In order to cope with stress, the use of growth regulators such as polyamines (PA), which strengthen the antioxidant system of plants, has become widespread in recent years. PAs can modulate the plant growth through basic mechanisms common to all living organisms, such as membrane stabilization, free radical scavenging, deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein synthesis, enzyme activities and second messengers. However, the effect of 1,3- diaminopropane (Dap), which is a product of PA catabolism, is not clear enough in plants exposed to As toxicity. In the current study, the different concentrations of 1,3-diaminopropane (0.1, 0.5 and 1 mM Dap) were hydroponically treated to wheat (Triticum aestivum) under arsenic stress (100 μM As) and then relative growth rate (RGR), relative water content (RWC), proline content (Pro), gas exchange parameters, PSII photochemistry, chlorophyll fluorescence kinetics, antioxidant activity and lipid peroxidation were assessed. RGR, RWC, osmotic potential and Pro content decreased in As-applied plants. The inhibition of these parameters could be reversed by Dap treatments. Besides, Dap applications mitigated the As toxicity-induced suppression on chlorophyll fluorescence (Fv/Fm, Fv/Fo and Fo/Fm) and the performance of PSII photochemistry. As impaired the balance on antioxidant capacity by decreased activities of catalase (CAT), peroxidase (POX), glutathione peroxidase (GPX), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and the contents of ascorbate (AsA) and glutathione (GSH) and then lipid peroxidation (TBARS content) increased. In the presence of Dap under As stress, the plants exhibited an increase in superoxide dismutase (SOD), POX, and GPX. Dap treatments contributed to the maintenance of cellular redox state (AsA/DHA and GSH/GSSG) by regulating the activities/contents of enzyme/non-enzyme involved in the AsA-GSH cycle. After Dap applications against stress, ROS accumulation (H2O2 content) and lipid peroxidation (TBARS) were effectively reduced. The findings showed that by eliminating As-induced oxidative damage and protecting the biochemical processes of photosynthesis, Dap treatments have a substantial potential to give resistance to wheat.

Homocysteine, Vitamin B12 and Folate Level: Possible Risk Factors in the Progression of Chronic Heart and Kidney Disorders.

Cobalamin is an essential molecule for humans; it is exceptionally important for various body functions, including deoxyribonucleic acid synthesis and cellular energy production. Vegans are more vulnerable to vitamin B12 deficiency than natives with moderate consumption of animal dietary supplements or people with inadequate nutritional patterns. However, the long-term effects of sub-medical deficiency have not been thoroughly studied, but they may have a negative impact on the cardiovascular system, pregnancy outcomes, and vascular, renal, cognitive, bone, and eye health. Alongside the statin remedy, that is a powerful approach for CVD prevention. Another approach is related to the B nutrition substitution remedy with folic acid, and vitamins B6 and B12 are extensively practised nowadays. There is a tremendous interest in plasma homocysteine (tHcy) as a cardiovascular hazard factor. However, current research in the field of its prevention is more inclined toward confirming the benefit of tHcy-reducing remedy with vitamin B12. Thus, while folic acid fortification is primarily aimed at reducing neural-tube defects, it may also play a significant role in the primary prevention of CVD by lowering tHcy. Folate and B-vitamins play important roles in CVD prevention and nutrition policy implementation. Patients affected with Chronic Kidney Disease (CKD) or end-stage Stage Renal Disease (ESRD) experience a tremendous cardiovascular threat that may also further lead to death. As a result, routine monitoring of vitamin B12 levels is likely to be beneficial for the early detection and treatment of metabolic vitamin B12 deficiency, as well as the prevention of heart-related diseases.

RHODIOLA ROSEA AND FERULIC ACID ACTIVATE EXPRESSION OF GENES RELATED TO AUTOPHAGY AND RESISTANCE TO HEAT SHOCK IN MICE OF DIFFERENT AGE

The aim of our study was testing whether R. rosea extract and ferulic acid activate expression of targets of FoxO, regulators of energy metabolism and autophagy in livers of young and old mice, and to what extent the effects of R. rosea extract and ferulic acid on the genes studied coincide. Methods. . C57BL/6J mice were reared at 22 ± 2 °С, 50-60% humidity, and 12/12 hour light/dark cycle. All groups were reared on a standard chow (4,8% fats, 21,8% protein, and 3,9% fibre). Experimental groups consumed water, supplemented with either sodium ferulate or R. rosea during 12 weeks prior sacrificing. The amounts of ferulate and R. rosea were adjusted to provide 4 mg of phenol-containing substances per 100 g weight, for a mouse, for 24 hours. We tested three-month-old (“young”) and twelve-month-old males (“old”). The levels of messenger ribonucleic acid (mRNA) were assessed using AriaMx real-time polymerase chain reaction (RT-PCR) instrument (Agilent). Ribonucleic acid was purified using the Monarch Miniprep kit (New England BioLabs (NEB), T2010), complementary deoxyribonucleic acid synthesis was performed using the ProtoScript II kit (NEB, E6560), and quantitative RT-PCR (qRT-PCR) was performed using the Luna Universal kit (NEB, E3003). The expression of genes ATG5 (an autophagy marker), HSPB8 (a small heat shock protein, an FoxO target), UCP2 (uncoupling protein 2, a senescence marker), CDKN2 (cell cycle regulator, a senescence marker), PDK2 and PDK4 (pyruvate dehydrogenase kinases 2 and 4, regulators of oxidative metabolism), and TFEB (transcription factor EB, a transcriptional regulator of autophagy) was evaluated. Results. Livers of young mice that consumed food supplemented with either sodium ferulate or R. rosea extract had 3.2-fold and 3.6-fold higher levels of mRNA of the small heat shock protein HspB8 than control mice, respectively. In old mice, the levels of mRNA for this protein were 3.3-fold higher in mice reared on the diet containing R. rosea extract as compared with the control. However, there was no significant difference between control mice and those that consumed ferulate-supplemented food. In young mice, ferulate and R. rosea extract induced synthesis of mRNA of PDK4 by 4.3 and 6.6 times from the control level, respectively. Ferulate and R. rosea extract also affected the levels of mRNA of ATG5 and PDK2 in the livers of old mice. The levels of PDK2 were 1.5-fold higher in the livers of mice that consumed ferulate-supplemented food than in control mice. Conclusions. Both, R. rosea extract and one of its active components – ferulic acid – promote increasing in the levels of mRNA for genes HSPB8 and PDK4, coding for small heat shock protein and pyruvate dehydrogenase kinase 4, respectively. In old mice, R. rosea promote expression of HSPB8, ATG5, PDK2, and PDK4. Thus, ferulic acid and R. rosea exert similar effects on gene expression by supposed activation of heat shock response and autophagy, and concomitant inhibition of mitochondrial metabolism via boosting expression of PDK2 and PDK4.

Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three-Dimensional Pathological Model.

An incomplete understanding of the cellular functions and underlying mechanisms of zinc ions released from zinc-based stents in atherosclerosis (AS) therapy is one of the major obstacles to their clinical translation. The existing evaluation methodology using cell monolayers has limitations on accurate results due to the lack of vascular architectures and pathological features. Herein, the authors propose a 3D biomimetic AS model based on a multi-layer vascular structure comprising endothelial cells and smooth muscle cells with hyperlipidemic surroundings and inflammatory stimulations as AS-prone biochemical conditions to explore the biological functions of zinc ions in AS therapy. Concentration-dependent biphasic effects of zinc ions on cell growth are observed both in cell monolayers and 3D AS models. Nevertheless, the cells within 3D AS model exhibit more accurate biological assessments of the zinc ions, as evidenced by augmented pathological features and significantly higher half-maximal inhibitory concentration values against zinc ions. Based on such a developed 3D biomimetic AS model, the inhibitory effects on the deoxyribonucleic acid (DNA) synthesis, significantly influenced biological processes like cell motility, proliferation, and adhesion, and several potential bio-targets of zinc ions of cells are revealed.

ROS-Induced DNA-Damage and Autophagy in Oral Squamous Cell Carcinoma by Usnea barbata Oil Extract—An In Vitro Study

Oxidative stress is associated with aging, cancers, and numerous metabolic and chronic disorders, and phenolic compounds are well known for their health-promoting role due to their free-radical scavenging activity. These phytochemicals could also exhibit pro-oxidant effects. Due to its bioactive phenolic secondary metabolites, Usnea barbata (L.) Weber ex. F.H. Wigg (U. barbata) displays anticancer and antioxidant activities and has been used as a phytomedicine for thousands of years. The present work aims to analyze the properties of U. barbata extract in canola oil (UBO). The UBO cytotoxicity on oral squamous cell carcinoma (OSCC) CLS-354 cell line and blood cell cultures was explored through complex flow cytometry analyses regarding apoptosis, reactive oxygen species (ROS) levels, the enzymatic activity of caspase 3/7, cell cycle, nuclear shrinkage (NS), autophagy (A), and synthesis of deoxyribonucleic acid (DNA). All these studies were concomitantly performed on canola oil (CNO) to evidence the interaction of lichen metabolites with the constituents of this green solvent used for extraction. The obtained data evidenced that UBO inhibited CLS-354 oral cancer cell proliferation through ROS generation (316.67 × 104), determining higher levels of nuclear shrinkage (40.12%), cell cycle arrest in G0/G1 (92.51%; G0 is the differentiation phase, while during G1 phase occurs preparation for cell division), DNA fragmentation (2.97%), and autophagy (62.98%) than in blood cells. At a substantially higher ROS level in blood cells (5250.00 × 104), the processes that lead to cell death-NS (30.05%), cell cycle arrest in G0/G1 (86.30%), DNA fragmentation (0.72%), and autophagy (39.37%)-are considerably lower than in CLS-354 oral cancer cells. Our work reveals the ROS-mediated anticancer potential of UBO through DNA damage and autophagy. Moreover, the present study suggests that UBO pharmacological potential could result from the synergism between lichen secondary metabolites and canola oil phytoconstituents.

EFFECT OF DIURNAL VARIATION ON THE MEASUREMENT OF SERUM IRON AND TIBC LEVELS IN HEALTHY POPULATION

Background: It is well-known that deciency or over exposure to various elements has noticeable effects on human health. The effect of an element is determined by several characteristics, including absorption, metabolism, and degree of interaction with physiological processes. Iron is an essential element for almost all living organisms as it participates in a wide variety of metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and electron transport. The Study was Conducted Material and Methods: in department of Biochemistry Guru Gobind Singh Medical College Faridkot. Ethical clearance was taken from institutional ethical committee. Proper informed consent was taken from all the participitants. Out of 60 healthy patients, 30 were males and 30 females. The Correlation between iron in three time Result: intervals on the same day (Morning – Evening and Morning – Afternoon )for morning – afternoon values, the p value was <0.001 and the r value was 0.920. For morning – evening, the p value was <0.001 and r value was 0.928, which shows statistically highly signicant correlation. Conclusion: It was conducted that Iron levels showed signicant diurnal variations on same day samples. The variation was statistically non signicant for TIBC. Also no consistant pattern has observed for iron variation. So the time of day for Iron &TIBC estimation does not hold much value and only a fasting sample is required.

Medicatiefouten met methotrexaat: casuïstiek en opportuniteiten door de bril van de ziekenhuisapotheker

Medication errors with methotrexate: new insights into an old drug Methotrexate (MTX) was first used in 1948 to treat childhood leukaemia. Nowadays, it is used for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis and inflammatory bowel disease. MTX is a folic acid antagonist that binds dihydrofolate reductase and thereby inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins. As an incontestable cornerstone in the treatment of RA, MTX should be started as soon as RA is diagnosed. The primary goal of the treatment is rapid and effective disease control to prevent long-term damage to the joints. For the treatment of patients with RA, the usual starting dose of MTX is 7.5-10 mg per week. Based on the clinical response, the dose could be increased to reach the optimal dose. The most common adverse drug events of MTX therapy are gastro-intestinal intolerance, haematological abnormalities, alopecia, hepatotoxicity and pulmonary toxicity. Overall, MTX is well tolerated. However, fatal cases of MTX intoxication have been reported in literature, mainly due to the daily intake and thus overdose of MTX. Despite the widespread experience with MTX, medication errors still occur with a risk of potentially severe adverse drug events. Clinical pharmacy interventions aim to detect these medication errors in inpatients. Based on a case series within a hospital population, the most common medication errors with MTX are presented. Subsequently, specific interventions to optimize medication safety with MTX therapy are described. The implementation of a specific chemotherapy module in the computerized physician order entry and clinical pharmacy interventions, such as medication reconciliation, the engagement of clinical pharmacists on hospital wards as part of the interdisciplinary team and prescription validation based on clinical rules, can contribute to a safer use of MTX.