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Neoplasic transformation is a continuous process that occurs in the body. Even before clinical signs, the immune system is capable of recognizing these aberrant cells and reacting to suppress them. However, transformed cells acquire the ability to evade innate and adaptive immune defenses through the secretion of molecules that inhibit immune effector functions, resulting in tumor progression. Hormones have the ability to modulate the immune system and are involved in the pathogenesis of autoimmune diseases, and cancer. Hormones can control both the innate and adaptive immune systems in men and women. For example androgens reduce immunity through modulating the production of pro-inflammatory and anti-inflammatory mediators. Women are more prone than men to suffer from autoimmune diseases such as systemic lupus erythematosus, psoriasis and others. This is linked to female hormones modulating the immune system. Patients with autoimmune diseases consistently have an increased risk of cancer, either as a result of underlying immune system dysregulation or as a side effect of pharmaceutical treatments. Epidemiological data on cancer incidence emphasize the link between the immune system and cancer. We outline and illustrate the occurrence of hormone-related cancer and its relationship to the immune system or autoimmune diseases in this review. It is obvious that some observations are contentious and require explanation of molecular mechanisms and validation. As a result, future research should clarify the molecular pathways involved, including any causal relationships, in order to eventually allocate information that will aid in the treatment of hormone-sensitive cancer and autoimmune illness. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease or Amyotrophic lateral sclerosis, but it is rather a determinant factor, which plays a pivotal role in the onset and progression of these disorders. Neuroinflammation can affect cells and processes in the central nervous system (CNS) as well as immune cells, and might precede protein aggregation, which is a hallmark of the neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation and delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), which represent potent vasoactive drugs used as a first-line treatment for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned PDE5 as a therapeutic target, and more specifically, PDE5is as potential alternative strategies for the treatment of a variety of neurological disorders. Indeed, PDE5is can limit neuroinflammation and enhance synaptic plasticity, with beneficial effects on cognitive function and memory. The aim of this review is to provide an overview of some of the main processes underlying neuroinflammation and neurodegeneration which may be potential targets for PDE5is, focusing on sildenafil, the most extensively studied. Current strategies using PDEis for the treatment of neurodegenerative diseases will be summarized. [ABSTRACT FROM AUTHOR]

Introduction: According to the Institute of Environmental Sciences, endocrine-disrupting chemicals (EDCs) are "natural or human-made chemicals that may mimic, block, or interfere with the body's hormones, associated with a wide array of health issues", mainly in the endocrine system. Recent studies have discussed the potential contribution of EDCs as risk factors leading to diabetes mellitus type 1 (T1DM), through various cellular and molecular pathways. Purpose: The purpose of this study was to investigate the correlation between the EDCs and the development of T1DM. Methodology: Thus, a 5-year systematic review was conducted to bring light to this research question. Using the meta-analysis and systematic review guideline protocol, a PRISMA flow diagram was constructed and, using the keywords (diabetes mellitus type 1) AND (endocrine-disrupting chemicals) in the databases PubMed, Scopus and ScienceDirect, the relevant data was collected and extracted into tables. Quality assessment tools were employed to evaluate the quality of the content of each article retrieved. Results: Based on the data collected and extracted from both human and animal studies, an association was found between T1DM and certain EDCs, such as bisphenol A (BPA), bisphenol S (BPS), persistent organic pollutants (POPs), phthalates and dioxins. Moreover, based on the quality assessments performed, using the Newcastle–Ottawa Scale and ARRIVE quality assessment tool, the articles were considered of high quality and thus eligible to justify the correlation of the EDCs and the development of T1DM. Conclusion: Based on the above study, the correlation can be justified; however, additional studies can be made focusing mainly on humans to understand further the pathophysiologic mechanism involved in this association. [ABSTRACT FROM AUTHOR]

A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed in the environment since these compounds are mass-produced for the manufacture of plastics and plasticizers. These compounds belong to a large group of substances termed endocrine-disrupting chemicals (EDC). It is well known that humans and living organisms are unavoidably and unintentionally exposed to BPA and phthalates from food packaging materials and many other everyday products. BPA and phthalates exert their effect by interfering with hormone synthesis, bioavailability, and action, thereby altering cellular proliferation and differentiation, tissue development, and the regulation of several physiological processes. In fact, these EDC can alter fetal programming at an epigenetic level, which can be transgenerational transmitted and may be involved in the development of various chronic pathologies later in the adulthood, including metabolic, reproductive and degenerative diseases, and certain types of cancer. In this review, we describe the most recent proposed mechanisms of action of these EDC and offer a compelling selection of experimental, epidemiological and clinical studies, which show evidence of how exposure to these pollutants affects our health during development, and their association with a wide range of reproductive, metabolic and neurological diseases, as well as hormone-related cancers. We stress the importance of concern in the general population and the urgent need for the medical health care system to closely monitor EDC levels in the population due to unavoidable and involuntary exposure to these pollutants and their impact on human health. Image 1 • Human clinical trials demonstrate that endocrine-disrupting chemicals impact human health at multisystemic level. • Epidemiological studies show strong evidence of endocrine disruption associated with bisphenol A and phthalate exposure. • Health policies and biomonitoring should guarantee human health protection from endocrine disruptor exposure. [ABSTRACT FROM AUTHOR]

Background: Anlotinib is a targeted therapy indicated for some malignancies, including advanced non-small cell lung cancer (NSCLC). However, noninvasive biomarkers for identifying patients who will benefit from this disease remain lacking. Methods: Here, we investigated the potential of small extracellular vesicle (sEV) microRNAs (miRNAs) as predictive biomarkers for anlotinib efficacy. A total of 20 advanced NSCLC patients were enrolled. Patients were classified as having stable disease (SD) or progressive disease (PD) after the initial efficacy assessment. Results: Seven differentially expressed miRNAs (DEMs) were identified. Among them, miR-941 was significantly upregulated in the PD group, while the others were downregulated. Furthermore, these six downregulated miRNAs (miR-30a-3p, miR-150-5p, miR-122-5p, miR-10b-5p, miR-92a-3p, and miR-150-3p) were more pronounced in nonsmoking patients. Conclusions: It was found that sEV miRNAs have the potential to predict the benefit of anlotinib. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have emerged as key players in intercellular communication, disease pathology, and therapeutic innovation. Initially overlooked as cellular debris, EVs are now recognized as vital mediators of cell-to-cell communication, ferrying a cargo of proteins, nucleic acids, and lipids, providing cellular resilience in response to stresses. This review provides a comprehensive overview of EVs, focusing on their role as biomarkers in disease diagnosis, their functional significance in physiological and pathological processes, and the potential of bioengineering for therapeutic applications. EVs offer a promising avenue for noninvasive disease diagnosis and monitoring, reflecting the physiological state of originating cells. Their diagnostic potential spans a spectrum of diseases, including cancer, cardiovascular disorders, neurodegenerative diseases, and infectious diseases. Moreover, their presence in bodily fluids such as blood, urine, and cerebrospinal fluid enhances their diagnostic utility, presenting advantages over traditional methods. Beyond diagnostics, EVs mediate crucial roles in intercellular communication, facilitating the transfer of bioactive molecules between cells. This communication modulates various physiological processes such as tissue regeneration, immune modulation, and neuronal communication. Dysregulation of EV-mediated communication is implicated in diseases such as cancer, immune disorders, and neurodegenerative diseases, highlighting their therapeutic potential. Bioengineering techniques offer avenues for manipulating EVs for therapeutic applications, from isolation and purification to engineering cargo and targeted delivery systems. These approaches hold promise for developing novel therapeutics tailored to specific diseases, revolutionizing personalized medicine. However, challenges such as standardization, scalability, and regulatory approval need addressing for successful clinical translation. Overall, EVs represent a dynamic frontier in biomedical research with vast potential for diagnostics, therapeutics, and personalized medicine. [ABSTRACT FROM AUTHOR]

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood–brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is a major global health concern affecting male individuals. Among its variants, androgen-independent prostate cancer exhibits slow progression and lacks effective treatment targets, rendering it insensitive to hormone therapy. Recent reports have highlighted the significance of Mortalin, an important oncogene, in tumor migration and invasion through various signaling pathways. Experimental evidence from in-vivo and in-vitro studies indicate upregulated expression of Mortalin in prostate cancer tissues. Moreover, it has been shown to regulate the epithelial-mesenchymal transition (EMT) process via the Wnt/β-catenin signaling pathway, thereby promoting prostate cancer proliferation and metastasis. These findings suggest that Mortalin may serve as a promising novel immunotherapeutic target for prostate cancer. [ABSTRACT FROM AUTHOR]

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Computational drug-repositioning technology is an effective tool for speeding up drug development. As biological data resources continue to grow, it becomes more important to find effective methods to identify potential therapeutic drugs for diseases. The effective use of valuable data has become a more rational and efficient approach to drug repositioning. The disease–drug correlation method (DDCM) proposed in this study is a novel approach that integrates data from multiple sources and different levels to predict potential treatments for diseases, utilizing support-vector regression (SVR). The DDCM approach resulted in potential therapeutic drugs for neoplasms and cardiovascular diseases by constructing a correlation hybrid matrix containing the respective similarities of drugs and diseases, implementing the SVR algorithm to predict the correlation scores, and undergoing a randomized perturbation and stepwise screening pipeline. Some potential therapeutic drugs were predicted by this approach. The potential therapeutic ability of these drugs has been well-validated in terms of the literature, function, drug target, and survival-essential genes. The method's feasibility was confirmed by comparing the predicted results with the classical method and conducting a co-drug analysis of the sub-branch. Our method challenges the conventional approach to studying disease–drug correlations and presents a fresh perspective for understanding the pathogenesis of diseases. [ABSTRACT FROM AUTHOR]

For decades, oxybutynin hydrochloride has been prescribed to improve bladder control in cases of incontinence and excessive urination frequency. This review summarizes synthetic methods enabling the preparation of the racemic drug and, in a detailed manner, preparation of (S)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid, a key intermediate in the synthesis of (S)-oxybutynin. The mode of action and metabolism are briefly addressed in order to explain the main adverse effects associated with its use and to justify the evolution observed in the diverse commercial formulations. Repositioning opportunities are discussed in terms of clinical trials for the management of hyperhidrosis, hot flashes, and obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy. [ABSTRACT FROM AUTHOR]

To investigate FDA-approved drugs prescribed for unrelated diseases or conditions that promote remission in subjects diagnosed with opioid use disorder (OUD). This was a retrospective observational study utilizing the TriNetX electronic medical record data. Subjects between 18 and 65 years old were included in this study. First, a drug screen was employed to identify medications used for chronic illness that are associated with OUD remission. Based on Fisher's exact test for significance, 28 of 101 medications were selected for further analysis. Positive (buprenorphine/methadone) and negative controls (benazepril) were included in the analysis. Medications were analyzed in the absence and presence of buprenorphine or methadone, two medications used to treat OUD, to identify the likelihood of OUD remission up to one year following the index event. We identify 8 medications (prazosin, propranolol, lithium carbonate, olanzapine, quetiapine, bupropion, citalopram, and escitalopram) that may be useful for increasing remission in OUD in the absence of buprenorphine or methadone. Additionally, our results identify psychiatric medications that when taken alongside buprenorphine and methadone improve remission rates. These results provide medication options that may be useful in treating OUD as well as integrated therapies to treat comorbid mental illness. [ABSTRACT FROM AUTHOR]

Cancer stem cells exhibit self-renewal, tumorigenesis, and a high differentiation potential. These cells have been detected in every type of cancer, and different signaling pathways can regulate their maintenance and proliferation. Androgen receptor signaling plays a relevant role in the pathophysiology of prostate cancer, promoting cell growth and differentiation processes. However, in the case of prostate cancer stem cells, the androgen receptor negatively regulates their maintenance and self-renewal. On the other hand, there is evidence that androgen receptor activity positively regulates the generation of cancer stem cells in other types of neoplasia, such as breast cancer or glioblastoma. Thus, the androgen receptor role in cancer stem cells depends on the cellular context. We aimed to analyze androgen receptor signaling in the maintenance and self-renewal of different types of cancer stem cells and its action on the expression of transcription factors and surface markers associated with stemness. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) remains a difficult breast cancer subtype to treat as it exhibits a particularly aggressive behavior. The dysregulation of distinct signaling pathways underlies this aggressive behavior, with an overactivation of MAP kinase interacting kinases (MNKs) promoting tumor cell behavior, and driving proliferation and migration. Therefore, MNK1 is an excellent target to impair the progression of TNBC and indeed, an MNK1-specific aptamer has proved to be efficient in inhibiting TBNC cell proliferation in vitro. Although polyethyleneimine-coated iron oxide nanoparticles (PEI–IONPs) have been used as transfection and immunomodulating agents, no study has yet addressed the benefits of using these nanoparticles as a magnetic carrier for the delivery of a functional aptamer. Results: Here, we tested the antitumor effect of a PEI–IONP complexed to the functional MNK1b-specific aptamer in vitro and in vivo. We demonstrated that these apMNKQ2@PEI–IONP nanoconjugates delivered three times more apMNKQ2 to MDA-MB-231 cells than the aptamer alone, and that this enhanced intracellular delivery of the aptamer had consequences for MNK1 signaling, reducing the amount of MNK1 and its target the phospho(Ser209)-eukaryotic initiation factor 4E (eIF4E). As a result, a synergistic effect of the apMNKQ2 and PEI–IONPs was observed that inhibited MDA-MB-231 cell migration, probably in association with an increase in the serum and glucocorticoid-regulated kinase-1 (SGK1) and the phospho(Thr346)-N-myc down-regulated gene 1 (NDRG1). However, intravenous administration of the apMNKQ2 alone did not significantly impair tumor growth in vivo, whereas the PEI–IONP alone did significantly inhibit tumor growth. Significantly, tumor growth was not inhibited when the apMNKQ2@PEI–IONP nanocomplex was administered, possibly due to fewer IONPs accumulating in the tumor. This apMNKQ2-induced reversion of the intrinsic antitumor effect of the PEI–IONPs was abolished when an external magnetic field was applied at the tumor site, promoting IONP accumulation. Conclusions: Electrostatic conjugation of the apMNKQ2 aptamer with PEI–IONPs impedes the accumulation of the latter in tumors, which appears to be necessary for PEI–IONPs to exert their antitumor activity. [ABSTRACT FROM AUTHOR]

Purpose. This study aimed to investigate the potential mechanism underlying the therapeutic effect of sildenafil in combination with islet transplantation for diabetic peripheral neuropathy. Methods. A streptozotocin-induced diabetic mouse model was established to evaluate the effects of islet transplantation and sildenafil intervention. The mice were subjected to different interventions for 6 weeks, and histopathological staining and immunohistochemistry techniques were employed to examine the pathological changes and protein expressions of BDNF, MBP, and cleaved caspase-3 in the sciatic nerve tissue. Moreover, RSC96 cells were cocultured with islet cells and sildenafil under high glucose conditions to investigate the potential involvement of the mTOR/S6K1 pathway, BDNF, and MBP proteins. Western blotting was used to detect protein expression in each group. Results. The results showed that islet transplantation can restore sciatic nerve injury in diabetic mice, and sildenafil can enhance the therapeutic effect of islet transplantation. In addition, the combination of sildenafil and islet cells significantly upregulated the expression levels of mTOR/S6K1, BDNF, and MBP in RSC96 cells under high glucose conditions. Conclusions. Islet transplantation can reverse sciatic nerve injury in diabetic mice, and islet cells exhibit a protective effect on RSC96 cells under high glucose conditions via the activation of the mTOR/S6K1 pathway. Sildenafil enhances the therapeutic effect of islet transplantation, which may represent a potential treatment strategy for diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment. [ABSTRACT FROM AUTHOR]

The development of packaging technology has become a crucial part of the food industry in today's modern societies, which are characterized by technological advancements, industrialization, densely populated cities, and scientific advancements that have increased food production over the past 50 years despite the lack of agricultural land. Various types of food-packaging materials are utilized, with plastic being the most versatile. However, there are certain concerns with regards to the usage of plastic packaging because of unreacted monomers' potential migration from the polymer packaging to the food. The magnitude of monomer migration depends on numerous aspects, including the monomer chemistry, type of plastic packaging, physical–chemical parameters such as the temperature and pH, and food chemistry. The major concern for the presence of packaging monomers in food is that some monomers are endocrine-disrupting compounds (EDCs) with a capability to interfere with the functioning of vital hormonal systems in the human body. For this reason, different countries have resolved to enforce guidelines and regulations for packaging monomers in food. Additionally, many countries have introduced migration testing procedures and safe limits for packaging monomer migration into food. However, to date, several research studies have reported levels of monomer migration above the set migration limits due to leaching from the food-packaging materials into the food. This raises concerns regarding possible health effects on consumers. This paper provides a critical review on plastic food-contact materials' monomer migration, including that from biodegradable plastic packaging, the monomer migration mechanisms, the monomer migration chemistry, the key factors that affect the migration process, and the associated potential EDC human health risks linked to monomers' presence in food. The aim is to contribute to the existing knowledge and understanding of plastic food-packaging monomer migration. [ABSTRACT FROM AUTHOR]

Curcumin is a polyphenol extracted from the rhizome of turmeric, and our previous research showed that curcumin inhibited cholesterol absorption and had cholesterol‐lowering effect. Bisphenol A (BPA), a common plasticizer, is widely used in the manufacture of food packaging and is associated with non‐alcoholic fatty liver disease (NAFLD). We hypothesized that curcumin could protect against BPA‐induced hepatic steatosis by inhibiting cholesterol absorption and synthesis. Male CD‐1 mice fed BPA‐contaminated diet with or without curcumin for 24 weeks were used to test our hypothesis. We found that chronic low‐dose BPA exposure significantly increased the levels of serum triglyceride (TG), total cholesterol (TC), and low‐density lipoprotein cholesterol and the contents of liver TG and TC, resulting in liver fat accumulation and hepatic steatosis while curcumin supplementation could alleviate BPA‐induced dyslipidemia and hepatic steatosis. Moreover, the anti‐steatosis and cholesterol‐lowering effects of curcumin against BPA coincided with a significant reduction in intestinal cholesterol absorption and liver cholesterol synthesis, which was modulated by suppressing the expression of sterol regulatory element‐binding protein‐2 (SREBP‐2), Niemann–Pick C1‐like 1 (NPC1L1), and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCR) in the small intestine and liver. In addition, the expression levels of liver lipogenic genes such as liver X receptor alpha (LXRα), SREBP‐1c, acetyl‐CoA carboxylase 1 (ACC1), and ACC2 were also markedly down‐regulated by curcumin. Overall, our findings indicated that curcumin inhibited BPA‐induced intestinal cholesterol absorption and liver cholesterol synthesis by suppressing SREBP‐2, NPC1L1, and HMGCR expression, subsequently reducing liver cholesterol accumulation and fat synthesis, thereby preventing hepatic steatosis and NAFLD. [ABSTRACT FROM AUTHOR]

Neuroinflammation is the precursor for several neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Targeting neuroinflammation has emerged as a promising strategy to address a wide range of CNS pathologies. These NDDs still present significant challenges in terms of limited and ineffective diagnosis and treatment options, driving the need to explore innovative and novel therapeutic alternatives. Aptamers are single-stranded nucleic acids that offer the potential for addressing these challenges through diagnostic and therapeutic applications. In this review, we summarize diagnostic and therapeutic aptamers for inflammatory biomolecules, as well as the inflammatory cells in NDDs. We also discussed the potential of short nucleotides for Aptamer-Based Targeted Brain Delivery through their unique features and modifications, as well as their ability to penetrate the blood-brain barrier. Moreover, the unprecedented opportunities and substantial challenges of using aptamers as therapeutic agents, such as drug efficacy, safety considerations, and pharmacokinetics, are also discussed. Taken together, this review assesses the potential of aptamers as a pioneering approach for target delivery to the CNS and the treatment of neuroinflammation and NDDs. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The carcinogenesis of CRC is indeed complex, and there are many different mechanisms and pathways that contribute to the development of malignancy and the progression from primary to metastatic tumors. The OCT4A, encoded by the POU5F1 gene, is a transcription factor responsible for the phenotype of stem cells, maintaining pluripotency and regulation of differentiation. The POU5F1 gene is made up of five exons that can create numerous isoforms through alternative promoter or alternative splicing. In addition to OCT4A, other isoforms called OCT4B are also translated into protein; however, their role in cells has been unclear. The aim of our work was to investigate the expression patterns of OCT4 isoforms in primary and metastatic CRC, providing us with useful information about their role in the development and progression of CRC. Methods: Surgical specimens from a total of 78 patients were collected and isolated from primary tumors (n = 47) and metastases (n = 31). The relative gene expression of OCT4 isoforms was investigated using the RT-qPCR method together with the TaqMan probes for particular OCT4 isoforms. Results: Our results suggest significantly downregulated expression of the OCT4A and OCT4Bs isoforms in both primary (p = 0.0002 and p < 0.0001, respectively) and metastatic tumors (p = 0.0006 and p = 0.00051, respectively) when compared with the control samples. We also observed a correlation between reduced expression of all OCT4 isoforms and both primary and leftsided tumors (p = 0.001 and p = 0.030, respectively). On the other hand, the expression of all OCT4 isoforms was significantly upregulated in metastases compared with primary tumors (p < 0.0001). Discussion: Unlike previous reports, we found out that the expression of OCT4A, OCT4Bs, and all OCT4 isoforms was significantly reduced in primary tumors and metastases compared with control samples. On the other hand, we supposed that the expression rate of all OCT4 isoforms may be related to the cancer type and side, as well as to liver metastases. However, further studies are required to investigate the detailed expression patterns and significance of individual OCT4 isoforms in carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Phthalates are non-persistent chemicals largely used as plasticizers and considered ubiquitous pollutants with endocrine disrupting activity. The exposure during sensible temporal windows as pregnancy and early childhood, may influence physiological neurodevelopment. Aims and Scope: The aim of this study is to analyze the relationship between the urinary levels of phthalate metabolites in newborn and infants and the global development measured by the Griffiths Scales of Children Development (GSCD) at six months. Methods: Longitudinal cohort study in healthy Italian term newborn and their mothers from birth to the first 6 months of life. Urine samples were collected at respectively 0 (T0), 3 (T3), 6 (T6) months, and around the delivery for mothers. Urine samples were analyzed for a total of 7 major phthalate metabolites of 5 of the most commonly used phthalates. At six months of age a global child development assessment using the third edition of the Griffith Scales of Child Development (GSCD III) was performed in 104 participants. Results: In a total of 387 urine samples, the seven metabolites analyzed appeared widespread and were detected in most of the urine samples collected at any time of sampling (66-100%). At six months most of the Developmental Quotients (DQs) falls in average range, except for the subscale B, which presents a DQ median score of 87 (85-95). Adjusted linear regressions between DQs and urinary phthalate metabolite concentrations in mothers at T0 and in infants at T0, T3 and T6 identified several negative associations both for infants' and mothers especially for DEHP and MBzP. Moreover, once stratified by children's sex, negative associations were found in boys while positive in girls. Conclusions: Phthalates exposure is widespread, especially for not regulated compounds. Urinary phthalate metabolites were found to be associated to GSCD III scores, showing inverse association with higher phthalate levels related to lower development scores. Our data suggested differences related to the child's sex. [ABSTRACT FROM AUTHOR]

Hormones and its regulation plays vital role in causing breast, prostate, ovarian and endometrial cancers collectively known as hormone-sensitive cancers. This review discusses the various functions of the sex hormones and the biological pathways involved in causing hormone-associated cancer under differential regulation. We have also attempted to explore the biomarkers associated with the cancers and the current therapeutic availability to treat such cancers. Among various sex hormones such as estrogen, progesterone and androgen, estrogen the female sex hormone and its receptor had a major contribution in causing cancer and hence are considered a predominant target in treating the associated cancers. Other hormones and receptors such a androgen, progesterone, and their respective receptors were also reported to have a significant correlation in causing cancers. Apart from these receptors certain enzymes that act as precursors or as promoters are also targeted for treatment strategies. The drugs commonly used belong to the selective drug classes such as selective estrogen receptor modulators and selective progesterone receptor modulators. In the case of androgen regulation androgen deprivation therapies are practiced. It is also suggested that the use of natural substances to treat cancer could prevent resistance and reduce side effects. Identification of significant targets and the discovery of many efficient drugs shall be possible in the future with better understanding of hormone regulation and its influence on cancer causative mechanisms. [ABSTRACT FROM AUTHOR]

Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011–2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit (assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution Test (DSST)) and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 (quartile 3 (Q3)), 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF, and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR7-phthalates: 1.56 and WQS OR8-phthalates: 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand-receptor interaction pathway and activating the cytokine-cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation, and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of drugs based on nucleic acids is a promising direction in antitumor therapy. Some modified oligonucleotide analogs, such as antisense oligonucleotides, have been developed and used as innovative therapeutic agents in some areas of medicine. Many ways to build DNA nanomaterials with predefined shape and function characteristics have been designed. Thus, molecules of potent antitumor drugs, including doxorubicin, therapeutic oligonucleotides, and complex nanoparticles, have been loaded into or conjugated with DNA-based nanomaterials. It was found that DNA-based nanomaterials can increase the efficiency of drug uptake by cells. In this review, we would like to draw attention to some DNA-based nanomaterials, such as tetrahedrons, origami, DNA nanotubes, and aptamers, that have been used as carriers, drugs or target molecules for anticancer drug delivery. DNA nanotechnology has significantly advanced and might be used in biomedical applications, drug delivery, and cancer treatment during the past few decades. DNA nanomaterials are widely used in biomedical research involving biosensing, bioimaging, and drug delivery since they are remarkably addressable and biocompatible. Gradually, modified nucleic acids have begun to be employed to construct multifunctional DNA nanostructures with a variety of architectural designs. Aptamers are single-stranded nucleic acids (both DNAs and RNAs) capable of self-pairing to acquire secondary structure and of specifically binding with the target. Diagnosis and tumor therapy are prospective fields in which aptamers can be applied. Many DNA nanomaterials with three-dimensional structures have been studied as drug delivery systems for different anticancer medications or gene therapy agents. Different chemical alterations can be employed to construct a wide range of modified DNA nanostructures. Chemically altered DNA-based nanomaterials are useful for drug delivery because of their improved stability and inclusion of functional groups. In this work, the most common oligonucleotide nanomaterials were reviewed as modern drug delivery systems in tumor cells. [ABSTRACT FROM AUTHOR]

Environmental pollutants are involved in the development and progression of numerous cancers, including cervical cancer (CC). One possible explanation for this is the ability of several pollutants to mimic natural hormones. This study aimed to evaluate the urinary concentrations of monoesters of phthalates and bisphenol A (BPA) in women with CC. A total of 45 women were included: 15 in the control group, 12 with CC diagnosis classified in early stages IA-IIB, and 18 in late stages III-IV. Urine samples were analyzed for BPA, mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono 2-ethylhexyl phthalate (MEHP) using high-performance liquid chromatography coupled to a tandem mass detector. The detection rate of environmental pollutants was 100%, with a median concentration in the control group and early-, and late-stage groups of 10.4, 9.2, 4.3, 38.4, and 12.9 µg L−1; 3.1, 3.1, 151.1, 54.5, and 30.4 µg L−1 and 1.9, 92.8, 3.6, 31.0, and 9.3 µg L−1 for BPA, MEHP, MBzP, MBP, and MiBP, respectively This study reveals high levels of phthalates, particularly MEHP, in urine samples of women with CC associated with human papillomavirus (HPV) infection. Further studies are needed to evaluate the possible role of phthalates in synergy with HPV in progression to CC. [ABSTRACT FROM AUTHOR]

With over 95% of bisphenol‐A (BPA) used in the production of polycarbonate (PC) and epoxy resins, termed here as BPA‐based plastic materials, components, and products (MCPs), an investigation of human exposure to BPA over the whole lifecycle of BPA‐based plastic MCPs is necessary. This mini‐review unpacks the implications arising from the long‐term human exposure to BPA and its potential accumulation across the lifecycle of BPA‐based plastics (production, use, and management). This investigation is timely and necessary in promoting a sustainable circular economy model. Restrictions of BPA in the form of bans and safety standards are often specific to products, while safety limits rely on traditional toxicological and biomonitoring methods that may underestimate human health implications and therefore the "safety" of BPA exposure. Controversies in regards to the: (a) dose–response curves; (b) the complexity of sources, release mechanisms, and pathways of exposure; and/or (c) the quality and reliability of toxicological studies, appear to currently stifle progress toward the regulation of BPA‐based plastic MCPs. Due to the abundance of BPA in our MCPs production, consumption, and management systems, there is partial and inadequate evidence on the contribution of BPA‐based plastic MCPs to human exposure to BPA. Yet, the production, use, and end‐of‐life management of plastic MCPs constitute the most critical BPA source and potential exposure pathways that require further investigation. Active collaboration among risk assessors, government, policy‐makers, and researchers is needed to explore the impacts of BPA in the long term and introduce restrictions to BPA‐based MCPs. Integr Environ Assess Manag 2023;19:45–62. © 2022 SETAC KEY POINTS: Bisphenol‐A (BPA) is still a widely used additive in various plastic materials, components, and products (MCPs).BPA can be leached and/or migrated into food and beverages and/or be dispersed in all environmental media.There is still incomplete information on BPA's transferability pathways from a wider range of plastic MCPs to humans.The potential release of BPA could lead to its uptake (via inhaling, or ingesting contaminated food and/or beverage) and bioaccumulation. [ABSTRACT FROM AUTHOR]

This article reviews the recent publications on the effects of micro and nano plastics being bioaccumulated, inhaled, ingested, digested, absorbed, or excreted in models and humans. Also, the retention of microplastics and nano plastics in the blood and lymphatic circulation, and their possible toxic effects on tissues at the cellular and biomolecular level is discussed. [ABSTRACT FROM AUTHOR]

Aptamers are synthetic single-stranded oligonucleotides (such as RNA and DNA) evolved in vitro using Systematic Evolution of Ligands through Exponential enrichment (SELEX) techniques. Aptamers are evolved to have high affinity and specificity to targets; hence, they have a great potential for use in therapeutics as delivery agents and/or in treatment strategies. Aptamers can be chemically synthesized and modified in a cost-effective manner and are easy to hybridize to a variety of nano-particles and other agents which has paved a way for targeted therapy and diagnostics applications such as in breast tumors. In this review, we systematically explain different aptamer adoption approaches to therapeutic or diagnostic uses when addressing breast tumors. We summarize the current therapeutic techniques to address breast tumors including aptamer-base approaches. We discuss the next aptamer-based therapeutic and diagnostic approaches targeting breast tumors. Finally, we provide a perspective on the future of aptamer-based sensors for breast therapeutics and diagnostics. In this section, the therapeutic applications of aptamers will be discussed for the targeting therapy of breast cancer. [ABSTRACT FROM AUTHOR]

The occurrence of litter in natural areas is nowadays one of the major environmental challenges. The uncontrolled dumping of solid waste in nature not only threatens wildlife on land and in water, but also constitutes a serious threat to human health. The detection and monitoring of areas affected by litter pollution is thus of utmost importance, as it allows for the cleaning of these areas and guides public authorities in defining mitigation measures. Among the methods used to spot littered areas, aerial surveillance stands out as a valuable alternative as it allows for the detection of relatively small such regions while covering a relatively large area in a short timeframe. In this study, remotely piloted aircraft systems equipped with multispectral cameras are deployed over littered areas with the ultimate goal of obtaining classification maps based on spectral characteristics. Our approach employs classification algorithms based on random forest approaches in order to distinguish between four classes of natural land cover types and five litter classes. The obtained results show that the detection of various litter types is feasible in the proposed scenario and the employed machine learning algorithms achieve accuracies superior to 85% for all classes in test data. The study further explores sources of errors, the effect of spatial resolution on the retrieved maps and the applicability of the designed algorithm to floating litter detection. [ABSTRACT FROM AUTHOR]

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer–siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers. [ABSTRACT FROM AUTHOR]

Bisphenol analogs (BPs) are widely used in industrial and commercial products and have been detected in surface water, sediment, sewage, and sludge. The presence of BPs in the natural environment poses threats to the aquatic ecosystem and human health. The concentration, distribution, seasonal variation, and risk assessment of BPA and BPA structural analogs including BPB, BPF, BPS, BPZ, BPAF, and BPAP in surface water and sediment during dry season and flood season in Luoma Lake and its inflow rivers in Jiangsu Province, China, were investigated in this study. The detection frequency of BPA and BPF was 100%. Although the use of BPA is restricted, BPA is still the dominant BPs in surface water and sediment. The concentration of BPs in surface water during flood season was higher than that in dry season. The concentrations of BPs in Fangting River, Zhongyun River, and Bulao River were higher than those in Luoma Lake. The average concentrations of BPs in surface water were in the order of BPA > BPF> BPS> BPB > BPZ > BPAF> BPAP. Compared with other studies, the concentration of BPs in Luoma Lake was moderate. There is no significant spatial distribution and difference in seasonal variation of BPs concentration in sediment (p > 0.05). Compared with other studies, the contamination of BPs in sediment of Luoma Lake was relatively low. Risk quotient (RQ) was used to evaluate the ecological risk of BPs in water environment, and the 17β estradiol equivalent (EEQ) method was used to estimate the estrogenic activity of BPs. The risk assessment showed no high ecological risk (RQ < 1.0) and estrogenic risk (EEQ < 1.0 ng/L) in dry season and flood season. The estimated RQ and EEQt indicated that the ecological and human health impacts were negligible in the short term. [ABSTRACT FROM AUTHOR]

Background: Experimental evidence has revealed that phosphodiesterase five inhibitors (PDE5is) increase epithelial barrier function and suppress intestinal carcinogenesis. Few epidemiological studies have investigated the role of PDE5i in increasing the risk of colorectal cancer (CRC); however, these studies have proffered varying conclusions. We therefore aimed to perform a comprehensive review and meta-analysis to investigate whether PDE5i use is associated with the incidence of CRC. Methods: Databases, namely, PubMed, Scopus, Embase, and Web of Science, were used for literature search. Observational studies (published until January 31, 2021) that assessed the association of PDE5i use with CRC incidence were considered. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model. Results: We identified four retrospective studies that involved 965,044 participants and 3,518 CRC cases detected during a mean follow-up of 12.7 years. Pooled results indicated a significantly reduced CRC risk among all PDE5i users (RR, 0.85; 95% CI, 0.76–0.95; P = 0.004, I2 = 63%). Moreover, continuous use of PDE5i was associated with a significantly reduced risk of CRC (RR, 0.63; 95% CI, 0.59–0.68; P < 0.001, I2 = 0.0%). However, the type of PDE5i exhibited no association with the risk of CRC (RR, 1.00; 95% CI, 0.98–1.02; I2 = 84.7%). Conclusion: Our findings suggest that continuous use of PDE5i was associated with a significantly reduced risk of CRC development. Future studies with a longitudinal design and adequate control of confounding factors are required to clarify whether a longer duration of PDE5i use alters the risk of CRC. [ABSTRACT FROM AUTHOR]

The cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers responsible for translating extracellular signals to intracellular biological responses in both normal and tumor cells. When these signals are aberrant or missing, cells may undergo neoplastic transformation or become resistant to chemotherapy. cGMP-hydrolyzing phosphodiesterases (PDEs) are attracting tremendous interest as drug targets for many diseases, including cancer, where they regulate cell growth, apoptosis and sensitization to radio- and chemotherapy. In breast cancer, PDE5 inhibition is associated with increased intracellular cGMP levels, which is responsible for the phosphorylation of PKG and other downstream molecules involved in cell proliferation or apoptosis. In this review, we provide an overview of the most relevant studies regarding the controversial role of PDE inhibitors as off-label adjuvants in cancer therapy. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the relationship between the level of bisphenol A (BPA) in the blood and follicular fluid, the polymorphism of the detoxification system genes, and the outcomes of IVF cycles. The data of 300 infertile patients with fresh IVF-ET cycles were analyzed. The level of BPA in the blood and follicular fluid was determined by HPLC-MRM-MS/MS. Determination of genotypes of the detoxification system genes was carried out by the real-time PCR. The threshold level for determining BPA was 0.1 ng/mL. BPA was detected in 92.3% (277/300) blood and in 16.8% (49/292) follicular fluid (FF) samples. There was no correlation between BPA level in the blood and FF. In patients with the absence of the A allele of the SULT1A1 gene, BPA was detected in FF significantly more often (22.6% vs. 13.5%, p = 0.0341). There was an association (not statistically significant) between the level of BPA in the blood and the presence of the G allele of the GSTP1 gene (rs1695) and the C allele in the GSTP1 gene (rs1138272). Our data suggests the role of detoxification system genes in the metabolism of BPA in the human body. The influence of BPA and detoxification system genes on the IVF outcomes requires further research. [ABSTRACT FROM AUTHOR]

Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates. [ABSTRACT FROM AUTHOR]