Neuroprotective properties of taurine

Taurine is the most abundant non-proteinogenic sulphur amino acid in humans, and its level decreases dramatically with aging. In humans, the highest levels of taurine are present in retina, leukocytes, heart, skeletal muscles and brain. Taurine is necessary to ensure proper homeostasis and recent research in animals (for example mice and monkeys) have shown that it significantly increases life expectancy and improves health. At the cellular level, taurine is involved in a number of processes such as osmoregulation, modulation of calcium levels and stabilization of cell membranes. Moreover, it has an inhibitory effect on the central nervous system and has antioxidant, anti-apoptotic and anti-inflammatory activity. The development of neurodegenerative diseases is associated with improper functioning of mitochondria, oxidative stress, development of inflammation, excessive activation of ionotropic and metabotropic glutamate receptors and neuronal apoptosis. In vitro and in vivo studies have shown that taurine inhibits the above-mentioned pathological processes and has neuroprotective properties. The antioxidant effect of taurine results from neutralizing hypochlorous acid, a strong oxidant that is produced by neutrophils at the site of the inflammation. Taurine chloramine (Tau-Cl) produced in this reaction reduces oxidative stress and inhibits the production of pro-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6), nitric oxide (NO) and prostaglandin E2. Moreover, this compound stimulates the expression of antioxidant enzymes (e.g. peroxiredoxin 1, thioredoxin-1, hemooxygenase-1, glutathione peroxidase, catalase). Within the nervous tissue, the anti-inflammatory and antioxidant effect of taurine is related to reduced expression of IL-1α, IL-1β, TNF-α, IFN-γ, IL-6 and GM-CSF, and increase in the activity of antioxidant enzymes (peroxidase-, reductase- and S- glutathione transferase, superoxide dismutase) and glutathione concentration. Taurine is necessary for the proper functioning of mitochondria. Its deficiency blocks the synthesis of taurine-modified leucine tRNA (τm5U-tRNALeu), which results in inhibition of the synthesis of NADH-ubiquinone oxidoreductase, improper functioning of complex I of the respiratory chain and increase in oxidative stress. Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases and can lead to neuronal apoptosis. Taurine deficiency increases the accumulation of misfolded cellular proteins and induces ER stress. Taurine supplementation reduces neuronal ER stress by inhibiting ATF6- and IRE-1-dependent signalling pathways. Moreover, taurine inhibits apoptosis of neuronal cells by increasing the expression of Bcl-2, decreasing the expression of p53, CHOP and Bax and reducing the activity of caspase-3. In the central nervous system, taurine also serves as an inhibitory neurotransmitter due to binding with γ-aminobutyric acid and glycine receptors (GABAA and GlyR, respectively). Such interactions causes an increased influx of chloride ions into neurons, hyperpolarization of the cell membrane and, consequently, inhibition of glutamatergic neurotransmission and excitotoxicity induced by glutamic acid. The neuroprotective activity of taurine is due to its pleiotropic effects related to the inhibition of apoptosis, oxidative stress, ER stress, and also to its anti-inflammatory activity and inhibition of neuronal excitability

Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience

This article belongs to the Special Issue Novel Insights into Prenatal Genetic Testing.Background: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. Methods: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. Results: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. Conclusions: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.This research was funded by the Ministry of Health, granted to the Center of Postgradu- ate Medical Education, Poland, grant number Minigrant-501-1-106-44-20/MG4 to J.B., and by the National Science Centre, Poland, grant number Miniatura 2—Dec2018/02/X/NZ2/00709 to D.M.info:eu-repo/semantics/publishedVersio

Vitamin K Contribution to DNA Damage—Advantage or Disadvantage? A Human Health Response

Vitamin K is the common name for a group of compounds recognized as essential for blood clotting. The group comprises phylloquinone (K1)—a 2-methyl-3-phytyl-1,4-naphthoquinone; menaquinone (K2, MK)—a group of compounds with an unsaturated side chain in position 3 of a different number of isoprene units and a 1,4-naphthoquinone group and menadione (K3, MD)—a group of synthetic, water-soluble compounds 2-methyl-1,4-naphthoquinone. However, recent epidemiological studies suggest that vitamin K has various benefits that go beyond blood coagulation processes. A dietary intake of K1 is inversely associated with the risk of pancreatic cancer, K2 has the potential to induce a differentiation in leukemia cells or apoptosis of various types of cancer cells, and K3 has a documented anti-cancer effect. A healthy diet rich in fruit and vegetables ensures an optimal supply of K1 and K2, though consumers often prefer supplements. Interestingly, the synthetic form of vitamin K—menadione—appears in the cell during the metabolism of phylloquinone and is a precursor of MK-4, a form of vitamin K2 inaccessible in food. With this in mind, the purpose of this review is to emphasize the importance of vitamin K as a micronutrient, which not only has a beneficial effect on blood clotting and the skeleton, but also reduces the risk of cancer and other pro-inflammatory diseases. A proper diet should be a basic and common preventive procedure, resulting in a healthier society and reduced burden on healthcare systems

The Antioxidant Potential of Commercial Manuka Honey from New Zealand—Biochemical and Cellular Studies

Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive and antioxidant substances such as polyphenols that contribute to its protective effects against oxidative stress. In this study, commercially available Manuka honey was tested for its total polyphenol content and DPPH radical scavenging ability. It was then tested in vitro on human fibroblast cells exposed to UV radiation to assess its potential to protect cells against oxidative stress. The results showed that the honey itself significantly interfered with cell metabolism, and its presence only slightly alleviated the effects of UV exposure. This study also suggested that the MGO content has a minor impact on reducing oxidative stress in UV-irradiated cells and efficiency in scavenging the DPPH radical

The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study

The 5′,8-cyclo-2′-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered—the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5′-end side of cdPu than on its 3′-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded

The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study

The 5′,8-cyclo-2′-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered—the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5′-end side of cdPu than on its 3′-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded

Nutrition Can Help DNA Repair in the Case of Aging

Micronutrients such as vitamins and trace elements are crucial for maintaining the health of all organisms. Micronutrients are involved in every cellular/biochemical process. They play roles in proper heart and brain functioning, influence immunological responses, and antioxidant defense systems. Therefore, prolonged deficiency in one or more micronutrients leads to cardiovascular or neurodegenerative disorders. Keeping micronutrients at adequate levels is especially important for seniors. They are prone to deficiencies due to age-associated functional decline and often to a diet poor in nutrients. Moreover, lack of micronutrients has an indirect impact on the genome. Their low levels reduce the activity of antioxidant enzymes, and therefore inhibit the efficiency of defense against free radicals which can lead to the formation of DNA lesions. The more DNA damage in the genetic material, the faster aging at the cellular level and a higher risk of pathological processes (e.g., carcinogenesis). Supplementation of crucial antioxidative micronutrients such as selenium, zinc, vitamin C, and vitamin E seems to have the potential to positively influence the condition of an aging organism, including minimizing inflammation, enhancing antioxidative defense, and limiting the formation of DNA lesions. In consequence, it may lead to lowering the risk and incidence of age-related diseases such as cardiovascular diseases, neurodegenerative diseases, and malnutrition. In this article, we attempt to present the synergistic action of selected antioxidant micronutrients (vitamin C, vitamin E, selenium, and zinc) for inhibiting oxidative stress and DNA damage, which may impede the process of healthy aging

The Usefulness of Autoradiography for DNA Repair Proteins Activity Detection in the Cytoplasm towards Radiolabeled Oligonucleotides Containing 5′,8-Cyclo-2′-deoxyadenosine

Autoradiography of 32P-radiolabeled oligonucleotides is one of the most precise detection methods of DNA repair processes. In this study, autoradiography allowed assessing the activity of proteins in the cytoplasm involved in DNA repair. The cytoplasm is the site of protein biosynthesis but is also a target cellular compartment of synthetic therapeutic oligonucleotide (STO) delivery. The DNA-based drugs may be impaired by radiation-induced lesions, such as clustered DNA lesions (CDL) and/or 5′,8-cyclo-2′-deoxypurines (cdPu). CDL and cdPu may appear in the sequence of STO after irradiation and subsequently impair DNA repair, as shown in previous studies. Hence, the interesting questions are (1) is it safe to combine STO treatment with radiotherapy; (2) are repair proteins active in the cytoplasm; and (3) is their activity different in the cytoplasm than in the nucleus? This unique study examined whether the proteins involved in the DNA repair are affected by the CDL while they are still present in the cytoplasm of xrs5, BJ, and XPC cells. Double-stranded oligonucleotides with bi-stranded CDL were used (containing AP site in one strand and a (5′S) or (5′R) 5′,8-cyclo-2′-deoxyadenosine (cdA) in the other strand located 1 or 4 bp in both directions). The results have shown that the proteins involved in the repair were active in the cytoplasm, but less than in the nucleus. The general trends aligned for cytoplasm and nucleus—lesions located in the 5′-end direction inhibited the course of DNA repair. The combination of STO with radiotherapy should be applied carefully, as unrepaired lesions within STO may impair their therapeutic efficiency

The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System

Mitochondria emerged from bacterial ancestors during endosymbiosis and are crucial for cellular processes such as energy production and homeostasis, stress responses, cell survival, and more. They are the site of aerobic respiration and adenosine triphosphate (ATP) production in eukaryotes. However, oxidative phosphorylation (OXPHOS) is also the source of reactive oxygen species (ROS), which are both important and dangerous for the cell. Human mitochondria contain mitochondrial DNA (mtDNA), and its integrity may be endangered by the action of ROS. Fortunately, human mitochondria have repair mechanisms that allow protecting mtDNA and repairing lesions that may contribute to the occurrence of mutations. Mutagenesis of the mitochondrial genome may manifest in the form of pathological states such as mitochondrial, neurodegenerative, and/or cardiovascular diseases, premature aging, and cancer. The review describes the mitochondrial structure, genome, and the main mitochondrial repair mechanism (base excision repair (BER)) of oxidative lesions in the context of common features between human mitochondria and bacteria. The authors present a holistic view of the similarities of mitochondria and bacteria to show that bacteria may be an interesting experimental model for studying mitochondrial diseases, especially those where the mechanism of DNA repair is impaired

Analysis of the dedusting process in a rectangular chamber filter

Purifying air from dust is a very important, current topic. There are many methods to minimize the amount of dust, one of them being chamber filters. This paper presents the research results of a newly designed rectangular chamber filter. The efficiency of the dedusting process is influenced by contamination properties, but also by the construction of the apparatus, inlet, and outlet location, the ratio of certain dimensions, and the gas flow rate. The airflow containing solid particles is a multi-phase, difficult-to-describe issue, therefore an attempt to determine the trajectory of particle movement in the apparatus was carried out using the PIV method. A decrease in the dedusting efficiency was observed with the increase of the gas flow rate, as well as for smaller diameters of the solid particles. The obtained values of the efficiency of the apparatus are comparable with the values obtained for the constructions discussed in other papers