The glycoprotein clusterin (CLU) is involved in cell proliferation and DNA damage repair and is highly expressed in tumor cells. Here, we aimed to investigate the effects of CLU dysregulation on two human astrocytic cell lines: CCF-STTG1 astrocytoma cells and SV-40 immortalized normal human astrocytes. We observed that suppression of CLU expression by RNA interference inhibited cell proliferation, triggered the DNA damage response, and resulted in cellular senescence in both cell types tested. To further investigate the underlying mechanism behind these changes, we measured reactive oxygen species, assessed mitochondrial function, and determined selected markers of the senescence-associated secretory phenotype. Our results suggest that CLU deficiency triggers oxidative stress-mediated cellular senescence associated with pronounced alterations in mitochondrial membrane potential, mitochondrial mass, and expression levels of OXPHOS complex I, II, III and IV, indicating mitochondrial dysfunction. This report shows the important role of CLU in cell cycle maintenance in astrocytes. Based on these data, targeting CLU may serve as a potential therapeutic approach valuable for treating gliomas.
- MeSH
- Astrocytes * metabolism pathology MeSH
- Clusterin * metabolism genetics MeSH
- Humans MeSH
- Membrane Potential, Mitochondrial * physiology MeSH
- Mitochondria * metabolism MeSH
- Cell Line, Tumor MeSH
- Oxidative Stress physiology MeSH
- Oxidative Phosphorylation MeSH
- DNA Damage MeSH
- Cell Proliferation * MeSH
- Reactive Oxygen Species metabolism MeSH
- Cellular Senescence * physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.
- MeSH
- Antioxidants metabolism MeSH
- Bioaccumulation MeSH
- Environmental Pollutants toxicity MeSH
- Humans MeSH
- Oxidative Stress * drug effects MeSH
- Metals, Heavy * toxicity MeSH
- Environmental Exposure adverse effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.
- MeSH
- Antioxidants * metabolism MeSH
- Glutathione metabolism MeSH
- Humans MeSH
- Metabolic Diseases metabolism MeSH
- Oxidative Stress * MeSH
- Reactive Oxygen Species metabolism MeSH
- Vitamin E metabolism MeSH
- Fatty Liver metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.
Present study was aimed to develop an efficient microbial consortium for combating Alternaria blight disease in cumin. The research involved isolating biocontrol agents against Alternaria burnsii, characterizing their biocontrol and growth promotion traits, and assessing compatibility. A pot experiment was conducted during rabi season of 2022-2023 to evaluate the bioefficacy of four biocontrol agents (1F, 16B, 31B, and 223B) individually and in consortium, focusing on disease severity, plant growth promotion, and defense responses in cumin challenged with A. burnsii. Microbial isolates 1F, 16B, 31B, and 223B significantly inhibited A. burnsii growth in dual plate assays (~ 86%), displaying promising biocontrol and plant growth promotion activities. They were identified as Trichoderma afroharzianum 1F, Aneurinibacillus aneurinilyticus 16B, Pseudomonas lalkuanensis 31B, and Bacillus licheniformis 223B, respectively. The excellent compatibility was observed among all selected biocontrol agents. Cumin plants treated with consortia of 1F + 16B + 31B + 223B showed least percent disease index (32.47%) and highest percent disease control (64.87%). Consortia of biocontrol agents significantly enhanced production of secondary metabolites (total phenol, flavonoids, antioxidant, and tannin) and activation of antioxidant-defense enzymes (POX, PPOX, CAT, SOD, PAL, and TAL) compared to individual biocontrol treatment and infected control. Moreover, consortium treatments effectively reduced electrolyte leakage over the individual biocontrol agent and infected control treatment. The four-microbe consortium significantly enhanced chlorophyll (154%), carotenoid content (88%), plant height (78.77%), dry weight (72.81%), and seed yield (104%) compared to infected control. Based on these findings, this environmentally friendly four-microbe consortium may be recommended for managing Alternaria blight in cumin.
- MeSH
- Alternaria * growth & development physiology MeSH
- Biological Control Agents MeSH
- Cuminum * microbiology immunology growth & development MeSH
- Microbial Consortia * MeSH
- Plant Diseases * microbiology prevention & control immunology MeSH
- Disease Resistance MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers. MATERIALS AND METHODS: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant ́s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure. RESULTS: Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 μg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen. CONCLUSIONS: This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.
- MeSH
- Antioxidants analysis MeSH
- Biomarkers * analysis MeSH
- Breath Tests MeSH
- Adult MeSH
- Glutathione analysis MeSH
- Inhalation Exposure * adverse effects analysis MeSH
- Thiobarbituric Acid Reactive Substances analysis MeSH
- Humans MeSH
- Nanocomposites * chemistry MeSH
- Nitric Oxide analysis metabolism MeSH
- Oxidative Stress * MeSH
- Occupational Exposure * analysis adverse effects MeSH
- Dentists MeSH
- Dental Materials MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Male infertility is a multifactorial condition contributing to approximately 50% of all cases of couple infertility. In recent years, significant advances have been made in both diagnostics and treatment. This review summarizes key developments from 2019 to 2024 with direct relevance to routine clinical practice in Czech urology and andrology. Particular attention is paid to the updated semen analysis standards (World Health Organisation 6th edition, 2021), sperm DNA fragmentation testing, genetic evaluation (karyotyping, Y chromosome microdeletions, and exome sequencing), surgical management of varicocele, and sperm retrieval techniques for azoospermia, including microdissection testicular sperm extraction (micro-TESE). The article also discusses pharmacological options (gonadotropins, selective estrogen receptor modulators, antioxidants), the impact of lifestyle factors, and the importance of interdisciplinary collaboration with assisted reproduction centers. Future perspectives, including the role of preventive strategies in male reproductive health, are also addressed. The aim is to provide a comprehensive and clinically applicable overview of current recommendations and therapeutic approaches in andrology, with a focus on their implementation in the Czech urological setting.
- MeSH
- Semen Analysis methods MeSH
- Antioxidants pharmacology therapeutic use MeSH
- Reproductive Techniques, Assisted MeSH
- Genetic Testing methods MeSH
- Gonadotropins therapeutic use MeSH
- Humans MeSH
- Infertility, Male * diagnosis etiology therapy MeSH
- Sperm Retrieval MeSH
- Selective Estrogen Receptor Modulators pharmacology therapeutic use MeSH
- Varicocele surgery MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Publication type
- Systematic Review MeSH
Given the high incidence of diet-related diseases, including type 2 diabetes and cancer, there is a growing need to explore new strategies for their prevention. Although polyphenols are known to reduce starch digestibility and lower the in vitro glycemic index, their antioxidant capacity and cytotoxic properties, when complexed with starches, remain underexplored. Therefore, this study aimed to investigate the antioxidant activity, total polyphenol content, and cytotoxic potential of polyphenol-starch complexes formed using common dietary polyphenols-(+)-catechin, epigallocatechin gallate, hesperidin, naringenin, trans-ferulic acid, p-coumaric acid, quercetin, and kaempferol-and widely consumed starches from wheat, rice, potato, and maize. Antioxidant activity (FRAP and DPPH) together with the total polyphenols content (Folin-Ciocalteu) were tested: (1) before (undigested) enzymatic hydrolysis of the tested sample; (2) after (digested) enzymatic hydrolysis of the tested sample and (3) after hydrolysis of the sample and its centrifugation (supernatant). Cytotoxicity against colon cancer (Caco-2, HT29) and normal colon (CCD 841CoN) cell lines were determined in vitro by the MTT method. In undigested samples, the highest antioxidant activity was obtained with the addition of quercetin to wheat, rice, and maize starch (6735.8 μmol Fe2+/g d.m., 678.8, 539.4 μmol Trolox/g d.m., respectively), and epigallocatechin gallate to wheat, rice, potato, and maize starch (692.1, 538.0, 625.8, 573.6 μmol Trolox/g d.m., respectively). In digested samples, the highest antioxidant activity was obtained with the addition of quercetin to wheat and rice starch (2104.5 μmol Fe2+/g d.m., 742.1 μmol Trolox/g d.m., respectively). In the case of the natant of the digested samples, the highest value was recorded for the addition of (+)-catechin to potato starch and trans-ferulic acid to maize starch (823.7 μmol Fe2+/g d.m., 245.1 μmol Trolox/g d.m., respectively). The addition of quercetin to wheat and rice starch and (+)-catechin to potato starch (0.239, 0.151, 0.085 g gallic acid/g d.m., respectively) resulted in the highest total polyphenol content. Furthermore, quercetin demonstrated the most significant level of cytotoxic activity against the tumor cell line Caco-2 (IC50 = 275.6 μg/mL; potato starch). Overall, quercetin was identified as the most significant or one of the most significant for all parameters evaluated.
- MeSH
- Antioxidants * pharmacology chemistry MeSH
- HT29 Cells MeSH
- Caco-2 Cells MeSH
- Catechin analogs & derivatives MeSH
- Zea mays chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Polyphenols * chemistry pharmacology MeSH
- Oryza chemistry MeSH
- Starch * chemistry pharmacology MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Posterior fossa syndrome (PFS) is a serious postoperative complication that primarily affects children following resection of posterior fossa tumors. Although its complex pathophysiology, involving disruption of cerebellar structures and the dentato-thalamo-cortical pathway, is increasingly being elucidated, effective treatments remain limited. This perspective explores acetyl-DL-leucine (ADLL) and its active L-enantiomer, N-acetyl-L-leucine (NALL), as promising therapeutic candidates for PFS. Emerging mechanistic, preclinical, and clinical evidence suggests that both compounds might alleviate PFS symptoms through neuroprotective and neurorestorative mechanisms, including neuronal membrane stabilization, metabolic enhancement, antioxidant and anti-inflammatory effects, and dopaminergic modulation. NALL, which has greater neurotherapeutic potential than ADLL, might particularly support recovery through its multimodal effects on neuronal function, thereby enhancing perioperative resilience. Further translational research into these acetylated leucine analogues is warranted.
- MeSH
- Infratentorial Neoplasms * surgery MeSH
- Leucine * analogs & derivatives therapeutic use pharmacology MeSH
- Humans MeSH
- Neuroprotective Agents * pharmacology therapeutic use MeSH
- Postoperative Complications * drug therapy MeSH
- Syndrome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Food hydrocolloids, derived from natural sources such as plants, algae, and microbes, possess bioactive properties that significantly contribute to cardiovascular health. This review focuses on six key hydrocolloids: alginate, astragalus polysaccharides, carrageenan, fucoidan, lunasin, and psyllium, while also considering other important natural hydrocoloids such as short chain fatty acids (SCFAs), plant-derived food hydrocolloids, plant-derived gums, plant-derived mucilages, pectin, modified citrus pectin, inulin, naringenin, chia seeds, gelatine, whey protein, casein, microbial exopolysaccharides and gums, ulvan, and laminarin. Alginate, from brown seaweed, aids in cardiac tissue regeneration and repair. Astragalus polysaccharides, from the Astragalus plant, provide antioxidant, anti-inflammatory, and immunomodulatory benefits. Carrageenan, sourced from red seaweed, supports lipid profile balance and heart health. Fucoidan, another brown seaweed derivative, offers antihypertensive and lipid-lowering effects. Lunasin, a peptide found in soybeans, oats, and barley, is known for its cholesterol-lowering properties and anti-inflammatory effects. Psyllium, rich in soluble fiber, helps lower LDL cholesterol and improve overall cardiovascular function. These hydrocolloids, along with other mentioned compounds, are utilized in drug formulations, cosmetics, processed foods, and dietary supplements, enhancing food texture and stability while delivering health benefits. Upon consumption, they can be absorbed into the bloodstream or metabolized by gut microbiota into bioactive metabolites. This review examines their effects on cardiovascular function, highlighting their mechanisms in regulating vascular tone, blood pressure, vascular inflammation, and cardiac function. It consolidates current research, emphasizing the potential of these hydrocolloids and related compounds in the prevention and management of cardiovascular diseases (CVDs).
- MeSH
- Alginates * chemistry pharmacology MeSH
- Carrageenan * chemistry pharmacology MeSH
- Cardiovascular Diseases * prevention & control MeSH
- Cardiovascular System * drug effects MeSH
- Colloids chemistry pharmacology MeSH
- Humans MeSH
- Polysaccharides * chemistry pharmacology MeSH
- Psyllium * chemistry pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
