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Microorganisms May 2024Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small... (Review)
Review
Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive (pks+ ) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.
PubMed: 38930493
DOI: 10.3390/microorganisms12061111 -
Materials (Basel, Switzerland) Jun 2024The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition...
The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition of copper onto the wool fibers. The WO-Cu material was subjected to physio-chemical and biological investigations. The physio-chemical investigations included the elemental analysis of materials (C, N, O, S, and Cu), their microscopic analysis, and surface properties analysis (specific surface area and total pore volume). The biological investigations consisted of the antimicrobial activity tests of the WO-Cu materials against colonies of Gram-positive () bacteria, Gram-negative () bacteria, and fungal mold species (). Biochemical-hematological tests included the evaluation of the activated partial thromboplastin time and pro-thrombin time. The tested wool-copper demonstrated the ability to interact with the DNA in a time-dependent manner. These interactions led to the DNA's breaking and degradation. The antimicrobial and antifungal activities of the WO-Cu materials suggest a potential application as an antibacterial/antifungal material. Wool-copper materials may be also used as customized materials where the blood coagulation process could be well controlled through the appropriate copper content.
PubMed: 38930247
DOI: 10.3390/ma17122878 -
Journal of Clinical Medicine Jun 2024Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper... (Review)
Review
Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional "PARP enzyme-inhibitor complex" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as (). Hence, identifying HR-deficiencies by genomic analysis-for instance, used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available analysis. In this review, we discuss [F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.
PubMed: 38929955
DOI: 10.3390/jcm13123426 -
Life (Basel, Switzerland) Jun 2024Atmospheric nonthermal plasma (ANTP) has rapidly evolved as an innovative tool in biomedicine with various applications, especially in treating skin diseases. In...
Atmospheric nonthermal plasma (ANTP) has rapidly evolved as an innovative tool in biomedicine with various applications, especially in treating skin diseases. In particular, the formation of reactive oxygen species (ROS) and nitrogen species (RNS), which are generated by ANTP, plays an important role in the biological signaling pathways of human cells. Unfortunately, excessive amounts of these reactive species significantly result in cellular damage and cell death induction. To ensure the safe application of ANTP, preclinical in vitro studies must be conducted before proceeding to in vivo or clinical trials involving humans. Our study aimed to investigate adverse effects on genetic substances in murine fibroblast cells exposed to ANTP. Cell viability and proliferation were markedly reduced after exposing the cells with plasma. Both extracellular and intracellular reactive species, especially RNS, were significantly increased upon plasma exposure in the culture medium and the cells. Notably, significant DNA damage in the cells was observed in the cells exposed to plasma. However, plasma was not classified as a mutagen in the Ames test. This suggested that plasma led to the generation of both extracellular and intracellular reactive species, particularly nitrogen species, which affect cell proliferation and are also known to induce genetic damage in fibroblast cells. These results highlight the genotoxic and mutagenic effects of ANTP, emphasizing the need for the cautious selection of plasma intensity in specific applications to avoid adverse side effects resulting from reactive species production.
PubMed: 38929742
DOI: 10.3390/life14060759 -
Medicina (Kaunas, Lithuania) Jun 2024Infertility is a prevalent global issue affecting approximately 17.5% of adults, with sole male factor contributing to 20-30% of cases. Oxidative stress (OS) is a... (Review)
Review
Infertility is a prevalent global issue affecting approximately 17.5% of adults, with sole male factor contributing to 20-30% of cases. Oxidative stress (OS) is a critical factor in male infertility, disrupting the balance between reactive oxygen species (ROS) and antioxidants. This imbalance detrimentally affects sperm function and viability, ultimately impairing fertility. OS also triggers molecular changes in sperm, including DNA damage, lipid peroxidation, and alterations in protein expression, further compromising sperm functionality and potential fertilization. Diagnostic tools discussed in this review offer insights into OS markers, antioxidant levels, and intracellular ROS concentrations. By accurately assessing these parameters, clinicians can diagnose male infertility more effectively and thus tailor treatment plans to individual patients. Additionally, this review explores various treatment options for males with OS-associated infertility, such as empirical drugs, antioxidants, nanoantioxidants, and lifestyle modifications. By addressing the root causes of male infertility and implementing targeted interventions, clinicians can optimize treatment outcomes and enhance the chances of conception for couples struggling with infertility.
Topics: Humans; Male; Oxidative Stress; Infertility, Male; Antioxidants; Reactive Oxygen Species; Spermatozoa
PubMed: 38929625
DOI: 10.3390/medicina60061008 -
Antioxidants (Basel, Switzerland) Jun 2024Affecting millions of people worldwide, chronic kidney disease is a serious medical problem. It results in a decrease in glomerular filtration rate below 60 mL/min/1.73... (Review)
Review
Affecting millions of people worldwide, chronic kidney disease is a serious medical problem. It results in a decrease in glomerular filtration rate below 60 mL/min/1.73 m, albuminuria, abnormalities in urine sediment and pathologies detected by imaging studies lasting a minimum of 3 months. Patients with CKD develop uremia, and as a result of the accumulation of uremic toxins in the body, patients can be expected to suffer from a number of medical consequences such as progression of CKD with renal fibrosis, development of atherosclerosis or increased incidence of cardiovascular events. Another key element in the pathogenesis of CKD is oxidative stress, resulting from an imbalance between the production of antioxidants and the production of reactive oxygen species. Oxidative stress contributes to damage to cellular proteins, lipids and DNA and increases inflammation, perpetuating kidney dysfunction. Additionally, renal fibrogenesis involving the accumulation of fibrous tissue in the kidneys occurs. In our review, we also included examples of forms of therapy for CKD. To improve the condition of CKD patients, pharmacotherapy can be used, as described in our review. Among the drugs that improve the prognosis of patients with CKD, we can include: GLP-1 analogues, SGLT2 inhibitors, Finerenone monoclonal antibody-Canakinumab and Sacubitril/Valsartan.
PubMed: 38929126
DOI: 10.3390/antiox13060687 -
Antioxidants (Basel, Switzerland) May 2024Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in...
Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon genes (STING) signaling pathway has been suggested to not only facilitate inflammatory responses and the production of type I interferons (IFN), but also activate other cellular processes, such as apoptosis. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by statin treatment in human colorectal cancer cells. In this study, we reported that lovastatin impaired mitochondrial function, including the depolarization of mitochondrial membrane potential, reduction of oxygen consumption, mitochondrial DNA (mtDNA) integrity, and mtDNA abundance in human colorectal cancer HCT116 cells. The mitochondrial dysfunction markedly induced ROS production in mitochondria, whereas the defect in mitochondria respiration or depletion of mitochondria eliminated reactive oxygen species (ROS) production. The ROS-induced oxidative DNA damage by lovastatin treatment was attenuated by mitochondrial-targeted antioxidant mitoquinone (mitoQ). Upon DNA damage, mtDNA was released into the cytosol and bound to DNA sensor cGAS, thus activating the cGAS-STING signaling pathway to trigger a type I interferon response. This effect was not activated by nuclear DNA (nuDNA) or mitochondrial RNA, as the depletion of mitochondria compromised this effect, but not the knockdown of retinoic acid-inducible gene-1/melanoma differentiation-associated protein 5 (RIG-I/MDA5) adaptor or mitochondrial antiviral signaling protein (MAVS). Moreover, lovastatin-induced apoptosis was partly dependent on the cGAS-STING signaling pathway in HCT116 cells as the knockdown of cGAS or STING expression rescued cell viability and mitigated apoptosis. Similarly, the knockdown of cGAS or STING also attenuated the antitumor effect of lovastatin in the HCT116 xenograft model in vivo. Our findings suggest that lovastatin-induced apoptosis is at least partly mediated through the cGAS-STING signaling pathway by triggering mtDNA accumulation in the cytosol in human colorectal cancer HCT116 cells.
PubMed: 38929118
DOI: 10.3390/antiox13060679 -
Antioxidants (Basel, Switzerland) May 2024Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular... (Review)
Review
The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect.
Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson-Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions.
PubMed: 38929116
DOI: 10.3390/antiox13060678 -
Antioxidants (Basel, Switzerland) May 2024Oxidative stress, an imbalance between reactive oxygen species (ROS) and endogenous antioxidants, plays an important role in the development of neurodegenerative... (Review)
Review
Oxidative stress, an imbalance between reactive oxygen species (ROS) and endogenous antioxidants, plays an important role in the development of neurodegenerative diseases, including Parkinson's. The human brain is vulnerable to oxidative stress because of the high rate of oxygen that it needs and the high levels of polyunsaturated fatty acids, which are substrates of lipid peroxidation. Natural antioxidants inhibit oxidation and reduce oxidative stress, preventing cancer, inflammation, and neurodegenerative disorders. Furthermore, in the literature, it is reported that antioxidants, due to their possible neuroprotective activity, may offer an interesting option for better symptom management, even Parkinson's disease (PD). Natural antioxidants are usually found in several foods, such as fruits, vegetables, meat, fish, and oil, and in food wastes, such as seeds, peels, leaves, and skin. They can help the system of endogenous antioxidants, protect or repair cellular components from oxidative stress, and even halt lipid, protein, and DNA damage to neurons. This review will examine the extent of knowledge from the last ten years, about the neuroprotective potential effect of natural antioxidants present in food and food by-products, in in vivo and in vitro PD models. Additionally, this study will demonstrate that the pool of dietary antioxidants may be an important tool in the prevention of PD and an opportunity for cost savings in the public health area.
PubMed: 38929084
DOI: 10.3390/antiox13060645 -
Antioxidants (Basel, Switzerland) May 2024Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless,...
Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment. Both rat photothrombotic (PT) stroke and in vitro oxygen-glucose deprivation (OGD)-induced vascular endothelial injury models were utilized. We demonstrated that treatment with PBMT (808 nm, 350 mW/cm, 2 min/day) for 7 days significantly reduced PT-stroke-induced vascular permeability. Additionally, PBMT inhibited the levels of endothelial senescence markers (senescence green and p21) and antiangiogenic factor (endostatin), while increasing the phospho-eNOS (Ser1177) in the peri-infarct region following PT stroke. In vitro study further indicated that OGD increased p21, endostatin, and DNA damage (γH2AX) levels in the brain endothelial cell line, but they were reversed by PBMT. Intriguingly, the beneficial effects of PBMT were attenuated by a NOS inhibitor. In summary, these findings provide novel insights into the role of eNOS in PBMT-mediated protection against cerebrovascular senescence and endothelial dysfunction following ischemia. The use of PBMT as a therapeutic is a promising strategy to improve endothelial function in cerebrovascular disease.
PubMed: 38929072
DOI: 10.3390/antiox13060633