The quandary known as the Intracytoplasmic Sperm Injection (ICSI) paradox is found at the juncture of Assisted Reproductive Technology (ART) and 'andrological ignorance' - a term coined to denote the undervalued treatment and comprehension of male infertility. The prevalent use of ICSI as a solution for severe male infertility, despite its potential to propagate genetically defective sperm, consequently posing a threat to progeny health, illuminates this paradox. We posit that the meteoric rise in Industrial Revolution 4.0 (IR 4.0) and Artificial Intelligence (AI) technologies holds the potential for a transformative shift in addressing male infertility, specifically by mitigating the limitations engendered by 'andrological ignorance.' We advocate for the urgent need to transcend andrological ignorance, envisaging AI as a cornerstone in the precise diagnosis and treatment of the root causes of male infertility. This approach also incorporates the identification of potential genetic defects in descendants, the establishment of knowledge platforms dedicated to male reproductive health, and the optimization of therapeutic outcomes. Our hypothesis suggests that the assimilation of AI could streamline ICSI implementation, leading to an overall enhancement in the realm of male fertility treatments. However, it is essential to conduct further investigations to substantiate the efficacy of AI applications in a clinical setting. This article emphasizes the significance of harnessing AI technologies to optimize patient outcomes in the fast-paced domain of reproductive medicine, thereby fostering the well-being of upcoming generations.
- MeSH
- asistovaná reprodukce MeSH
- intracytoplazmatické injekce spermie * MeSH
- lidé MeSH
- mužská infertilita * diagnóza genetika terapie MeSH
- sperma MeSH
- umělá inteligence MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- dopisy MeSH
Recent advancements in the understanding of how sperm develop into offspring have shown complex interactions between environmental influences and genetic factors. The past decade, marked by a research surge, has not only highlighted the profound impact of paternal contributions on fertility and reproductive outcomes but also revolutionized our comprehension by unveiling how parental factors sculpt traits in successive generations through mechanisms that extend beyond traditional inheritance patterns. Studies have shown that offspring are more susceptible to environmental factors, especially during critical phases of growth. While these factors are broadly detrimental to health, their effects are especially acute during these periods. Moving beyond the immutable nature of the genome, the epigenetic profile of cells emerges as a dynamic architecture. This flexibility renders it susceptible to environmental disruptions. The primary objective of this review is to shed light on the diverse processes through which environmental agents affect male reproductive capacity. Additionally, it explores the consequences of paternal environmental interactions, demonstrating how interactions can reverberate in the offspring. It encompasses direct genetic changes as well as a broad spectrum of epigenetic adaptations. By consolidating current empirically supported research, it offers an exhaustive perspective on the interwoven trajectories of the environment, genetics, and epigenetics in the elaborate transition from sperm to offspring.
- MeSH
- epigeneze genetická MeSH
- fenotyp MeSH
- lidé MeSH
- náchylnost k nemoci MeSH
- rozmnožování genetika MeSH
- sperma * MeSH
- spermie * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.
- MeSH
- alkaloidy * terapeutické užití MeSH
- hormony terapeutické užití MeSH
- insulinu podobný růstový faktor I MeSH
- lidé MeSH
- nádory tračníku * farmakoterapie metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- časopisecké články MeSH
Confluence of environmental, genetic, and lifestyle variables is responsible for deterioration of human fecundity. Endocrine disruptors or endocrine disrupting chemicals (EDCs) may be found in a variety of foods, water, air, beverages, and tobacco smoke. It has been demonstrated in experimental investigations that a wide range of endocrine disrupting chemicals have negative effects on human reproductive function. However, evidence on the reproductive consequences of human exposure to endocrine disrupting chemicals is sparse and/or conflicting in the scientific literature. The combined toxicological assessment is a practical method for assessing the hazards of cocktails of chemicals, co-existing in the environment. The current review provides a comprehensive overview of studies emphasizing the combined toxicity of endocrine disrupting chemicals on human reproduction. Endocrine disrupting chemicals interact with each other to disrupt the different endocrine axes, resulting in severe gonadal dysfunctions. Transgenerational epigenetic effects have also been induced in germ cells, mostly through DNA methylation and epimutations. Similarly, after acute or chronic exposure to endocrine disrupting chemicals combinations, increased oxidative stress (OS), elevated antioxidant enzymatic activity, disrupted reproductive cycle, and reduced steroidogenesis are often reported consequences. The article also discusses the concentration addition (CA) and independent action (IA) prediction models, which reveal the importance of various synergistic actions of endocrine disrupting chemicals mixtures. More crucially, this evidence-based study addresses the research limitations and information gaps, as well as particularly presents the future research views on combined endocrine disrupting chemicals toxicity on human reproduction.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Male infertility is a global public health concern. Teratozoospermia is a qualitative anomaly of spermatozoa morphology, contributing significantly to male infertility, whereas azoospermia is the complete absence of spermatozoa in the ejaculate. Thus, there is a serious need for unveiling the common origin and/or connection between both of these diseases, if any. This study aims to identify common potential biomarker genes of these two diseases via an in silico approach using a meta-analysis of microarray data. In this study, a differential expression analysis of genes was performed on four publicly available RNA microarray datasets, two each from teratozoospermia (GSE6872 and GSE6967) and azoospermia (GSE145467 and GSE25518). From the analysis, 118 DEGs were found to be common to teratozoospermia and azoospermia, and, interestingly, sperm autoantigenic protein 17 (SPA17) was found to possess the highest fold change value among all the DEGs (9.471), while coiled-coil domain-containing 90B (CCDC90B) and coiled-coil domain-containing 91 (CCDC91) genes were found to be common among three of analyses, i.e., Network Analyst, ExAtlas, and GEO2R. This observation indicates that SPA17, CCDC90B, and CCDC91 genes might have significant roles to play as potential biomarkers for teratozoospermia and azoospermia. Thus, our study opens a new window of research in this area and can provide an important theoretical basis for the diagnosis and treatment of both these diseases.
Epigenetic modifications are inherited differences in cellular phenotypes, such as cell gene expression alterations, that occur during somatic cell divisions (also, in rare circumstances, in germ line transmission), but no alterations to the DNA sequence are involved. Histone alterations, polycomb/trithorax associated proteins, short non-coding or short RNAs, long non-coding RNAs (lncRNAs), & DNA methylation are just a few biological processes involved in epigenetic events. These various modifications are intricately linked. The transcriptional potential of genes is closely conditioned by epigenetic control, which is crucial in normal growth and development. Epigenetic mechanisms transmit genomic adaptation to an environment, resulting in a specific phenotype. The purpose of this systematic review is to glance at the roles of Estrogen signalling, polycomb/trithorax associated proteins, DNA methylation in breast cancer progression, as well as epigenetic mechanisms in breast cancer therapy, with an emphasis on functionality, regulatory factors, therapeutic value, and future challenges.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Nanomaterials or nanoparticles are commonly used in the cosmetics, medicine, and food industries. Many researchers studied the possible side effects of several nanoparticles including aluminum oxide (Al2O3-nps) and zinc oxide nanoparticles (ZnO-nps). Although, there is limited information available on their direct or side effects, especially on the brain, heart, and lung functions. This study aimed to investigate the neurotoxicity, cardiotoxicity, and lung toxicity induced by Al2O3-nps and ZnO-nps or in combination via studying changes in gene expression, alteration in cytokine production, tumor suppressor protein p53, neurotransmitters, oxidative stress, and the histological and morphological changes. Obtained results showed that Al2O3-nps, ZnO-nps and their combination cause an increase in 8-hydroxy-2 ́-deoxyguanosine (8-OHdG), cytokines, p53, oxidative stress, creatine kinase, norepinephrine, acetylcholine (ACh), and lipid profile. Moreover, significant changes in the gene expression of mitochondrial transcription factor-A (mtTFA) and peroxisome proliferator activator receptor-gamma-coactivator-1alpha (PGC-1alpha) were also noted. On the other hand, a significant decrease in the levels of antioxidant enzymes, total antioxidant capacity (TAC), reduced glutathione (GSH), paraoxonase 1 (PON1), neurotransmitters (dopamine - DA, and serotonin - SER), and the activity of acetylcholine esterase (AChE) in the brain, heart, and lung were found. Additionally, these results were confirmed by histological examinations. The present study revealed that the toxic effects were more when these nanoparticle doses are used in combination. Thus, Al2O3-nps and ZnO-nps may behave as neurotoxic, cardiotoxic, and lung toxic, especially upon exposure to rats in combination.
- MeSH
- acetylcholin farmakologie MeSH
- antioxidancia farmakologie MeSH
- kovové nanočástice * toxicita MeSH
- krysa rodu rattus MeSH
- mozek metabolismus MeSH
- nanočástice * toxicita MeSH
- oxid hlinitý toxicita MeSH
- oxid zinečnatý * toxicita MeSH
- oxidační stres MeSH
- plíce metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Reactive nitrogen species (RNS), like reactive oxygen species (ROS), are useful for sustaining reproductive processes such as cell signaling, the regulation of hormonal biosynthesis, sperm capacitation, hyperactivation, and acrosome reaction. However, endogenous levels of RNS beyond physiological limits can impair fertility by disrupting testicular functions, reducing gonadotropin production, and compromising semen quality. Excessive RNS levels cause a variety of abnormalities in germ cells and gametes, particularly in the membranes and deoxyribonucleic acid (DNA), and severely impair the maturation and fertilization processes. Cell fragmentation and developmental blockage, usually at the two-cell stage, are also connected with imbalanced redox status of the embryo during its early developmental stage. Since high RNS levels are closely linked to male infertility and conventional semen analyses are not reliable predictors of the assisted reproductive technology (ART) outcomes for such infertility cases, it is critical to develop novel ways of assessing and treating oxidative and/or nitrosative stress-mediated male infertility. This review aims to explicate the physiological and pathological roles of RNS and their relationship with male reproduction.
- MeSH
- analýza spermatu MeSH
- DNA metabolismus MeSH
- lidé MeSH
- mužská infertilita * metabolismus MeSH
- oxidační stres fyziologie MeSH
- reaktivní formy dusíku * metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rozmnožování fyziologie MeSH
- sperma metabolismus MeSH
- spermie metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
