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Pancreatic cancer continues to be a deadly disease because of its delayed diagnosis and aggressive tumor biology. Oncogenes and risk factors are being reported to influence the signaling pathways involved in pancreatic embryogenesis leading to pancreatic cancer genesis. Although studies using rodent models have yielded insightful information, the scarcity of human pancreatic tissue has made it difficult to comprehend how the human pancreas develops. Transcription factors like IPF1/PDX1, HLXB9, PBX1, MEIS, Islet-1, and signaling pathways, including Hedgehog, TGF-β, and Notch, are directing pancreatic organogenesis. Any derangements in the above pathways may lead to pancreatic cancer. TP53: and CDKN2A are tumor suppressor genes, and the mutations in TP53 and somatic loss of CDKN2A are the drivers of pancreatic cancer. This review clarifies the complex signaling mechanism involved in pancreatic cancer, the same signaling pathways in pancreas development, the current therapeutic approach targeting signaling molecules, and the mechanism of action of risk factors in promoting pancreatic cancer. [ABSTRACT FROM AUTHOR]

Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects. [ABSTRACT FROM AUTHOR]

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to highlight the feasibility of an olfactory training program entirely monitored through online media in COVID-19 patients. Methods: Classic olfactory training was performed with a sample with olfactory loss due COVID-19 (n = 11). Participants were engaged on a weekly video call in order to improve adherence and collect information regarding the number of correct answers and the individuals' perception of olfactory function. The olfactory status after training was compared to two groups, one composed of participants who contracted COVID-19 but did not report olfactory loss (n = 11) and a sample composed of healthy participants (n = 11). Results: The experimental group showed improvements throughout the training period (TDI score on week 0 was 20.3 (5.6) and 24.6 (4.3) for week 12, and on week 24 was 25.4 (6.2) (F = 5.115, df = 2, 20, p = 0.016), and post hoc tests showed that participants significantly improved their TDI score in W12 compared to W0 (SMD = 0.869, p = 0.041) and in W24 compared to W0 (SMD = 0.859, p = 0.041). The experimental group showed lower scores when compared with both groups, and the no OT COVID-19 group showed lower scores than the healthy control group, even though they did not report olfactory alterations. Conclusions: Findings suggest that the strategies applied to improve adherence were successful since 100% of the sample completed the training adherence, offering a valuable framework for future olfactory training studies. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the usefulness and relevance of projective techniques such as house‐tree‐person (HTP) and family in individuals with Prader‐Willi syndrome (PWS), who have a limited ability to identify and verbalize emotions and express them often using behaviors. Methods: We included individuals with genetic confirmation of PWS immersed in a regular transdisciplinary treatment in an institution dedicated to rare diseases. All individuals were evaluated using the HTP and family projective techniques. These instruments are commonly administered to the general population and, in this case, to people with mild to moderate intellectual disabilities, including difficulties in their communication abilities. Results: A total of 25 individuals with PWS between 10 and 41 years old (15 men and 10 women) were included. We identified the presence of graphic indicators corresponding to the behavioral phenotype of individuals with PWS, such as anxiety, stubbornness, emotional lability, difficulty in achieving adequate externalization and identification of emotions, impulsivity, aggressive traits, poor social skills, need for support and interaction, low self‐concept, and compulsive behaviors. Conclusions: In the present study, we demonstrated the usefulness of graphic techniques to elucidate aspects of behavior, emotions, and thoughts that individuals with PWS cannot formulate due to expression and communication difficulties. [ABSTRACT FROM AUTHOR]

NREM parasomnias, also known as non-rapid eye movement sleep parasomnias, are a group of sleep disorders that occur during the deeper stages of NREM sleep. These parasomnias can lead to a range of behaviors, including sleepwalking, sleep talking, and night terrors. NREM parasomnias usually occur during the first third of the night and can last from a few seconds to 30 minutes or more. The person may appear to be awake and alert, but is actually in a state of deep sleep. People with NREM parasomnias may also engage in activities that are dangerous, such as leaving the house or driving a car. The causes are not well-understood, but it is believed that NREM parasomnias are related to disturbances in the normal sleep cycle. They can be caused by stress, sleep deprivation, or the use of certain medications or substances. Their treatment may include a combination of behavioral therapy and medication. Behavioral therapy can help the person to understand better their sleep patterns and develop strategies to reduce the occurrence of parasomnias. Medication can help regulate sleep cycles or manage any underlying medical conditions. A sleep specialist can help diagnose and treat NREM parasomnias and provide guidance on how to manage these disorders effectively. In conclusion, NREM parasomnias are a group of sleep disorders that can lead to a range of behaviors during deep NREM sleep. These disorders can disrupt daily life and can be dangerous if left untreated. Treatment for NREM parasomnias may include a combination of behavioral therapy and medication, and it is important to seek medical help if these disorders are suspected. [ABSTRACT FROM AUTHOR]

The article examines therapeutic strategies applied within the probation system for substance users in Romania. Recent events have highlighted the need for effective policies, and public debates have influenced legislative changes. The research focuses on the interventions of probation counselors, identifying three levels of action: compliance with court-imposed legal obligations, adaptation of interventions to individual needs, and case management. The methodology is qualitative, based on case studies and observations from professional practice. Data collected from the Bucharest Probation Service indicate a significant number of cases related to drug-related offenses, with their dynamics reflecting legislative changes over the past two decades. The research reveals the challenges and limitations faced by counselors, such as the lack of specific programs for drug users and communication difficulties with partner institutions. Improvement proposals include continuous training for counselors, diversifying treatment options, and strengthening inter-institutional collaboration. The article's conclusions highlight the need for an integrated and flexible approach to managing cases of substance users to ensure effective social reintegration and reduced recidivism [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family.

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues. Graphical Abstract

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.

• Computer simulations and the Lipinski rule evaluate the pharmacokinetic and toxicological aspects of methyl eugenol as a drug candidate. • Treatment with methyl eugenol (ME) during and after the initiation of acute respiratory distress syndrome (ARDS) can prevent the progression of acute inflammation. • In vivo and in silico tests indicate that ME oil is an orally bioavailable drug that exerts multifunctional cytoprotective activities. • ME oil can treat and prevent intestinal I/R-induced ARDS in rats. Acute respiratory distress syndrome (ARDS) is an inflammatory disease that affects the lungs with rupture of the alveolar-capillary barrier and loss of lung compliance, orchestrated by an intense inflammatory process mediated by neutrophils that culminates in diffuse alveolar data and tissue hypoxia. In this context, no specific drug has yet been applied to treat the syndrome. Therefore, finding new therapeutic targets that can treat the syndrome has become a research study. In view of this, methyl-eugenol (ME) has become the target of this study. The aim of this work was to carry out an in silico pharmacological and toxicological analysis with ADMET, as well as to determine, by means of molecular docking, the interaction affinity of the 5-LOX and COX-2 enzymes with ME and then the in vivo tests; in which male rats were distributed into five groups with five rats each, in which some groups were subjected to the process of ischemia and reperfusion (I/R). Groups G4 and G5 were treated by inhalation with ME (10 %). After completing these procedures, statistical analysis and lung histology were carried out. In the ADMET prediction, ME showed high intestinal absorption and a medium-permeability blood-brain barrier. ME had no violations of Lipinski's rule, demonstrating high potential as a drug candidate. Molecular docking showed that ME had the highest binding affinity with the 5-LOX enzyme. Finally, the statistical and histological analyses of the in vivo test showed acute and accentuated lung damage in the G1 group, while in the G4 and G5 groups, ME showed pharmacological efficacy, reducing the number of inflammatory cells, free macrophages and free radicals. The results indicate that ME oil is a favorable therapeutic approach in the treatment of ARDS. [ABSTRACT FROM AUTHOR]

• Tenascin-C is highly expressed in cancer generating immune suppressive niches. • Tenascin-C is used as tumor biomarker and as zip code for delivery of therapeutic agents. • Tenascin-C is targeted by a huge arsenal of versatile molecular tools. • Numerous clinical trials are supporting tenascin-C targeting as clinical option. • Targeting tenascin-C immune suppression offer novel targeting opportunities. Tenascin-C (TNC) is a matricellular and multimodular glycoprotein highly expressed under pathological conditions, especially in cancer and chronic inflammatory diseases. Since a long time TNC is considered as a promising target for diagnostic and therapeutic approaches in anti-cancer treatments and was already extensively targeted in clinical trials on cancer patients. This review provides an overview of the current most advanced strategies used for TNC detection and anti-TNC theranostic approaches including some advanced clinical strategies. We also discuss novel treatment protocols, where targeting immune modulating functions of TNC could be center stage. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response to injury, quiescent CFs become activated and adopt a collagen-secreting phenotype highly contributing to cardiac fibrosis. In recent years, studies have been focused on the exploration of molecular and cellular mechanisms implicated in the activation process of CFs, which allow the development of novel therapeutic approaches for the treatment of cardiac fibrosis. Transcriptomic analyses using single-cell RNA sequencing (RNA-seq) have helped to elucidate the high cellular diversity and complex intercellular communication networks that CFs establish in the mammalian heart. Furthermore, a significant body of work supports the critical role of epigenetic regulation on the expression of genes involved in the pathogenesis of cardiac fibrosis. The study of epigenetic mechanisms, including DNA methylation, histone modification, and chromatin remodeling, has provided more insights into CF activation and fibrotic processes. Targeting epigenetic regulators, especially DNA methyltransferases (DNMT), histone acetylases (HAT), or histone deacetylases (HDAC), has emerged as a promising approach for the development of novel anti-fibrotic therapies. This review focuses on recent transcriptomic advances regarding CF diversity and molecular and epigenetic mechanisms that modulate the activation process of CFs and their possible clinical applications for the treatment of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive decline in cognitive ability and behavior which eventually disrupts daily activities. AD has no cure and the progression rate varies unlikely. Among various causative factors, heavy metals are reported to be a significant hazard in AD pathogenesis. Metal‐induced neurodegeneration has been focused globally with thorough research to unravel the mechanistic insights in AD. Recently, heavy metals suggested to play an important role in epigenetic alterations which might provide evidential results on AD pathology. Epigenetic modifications are known to play towards novel therapeutic approaches in treating AD. Though many studies focus on epigenetics and heavy metal implications in AD, there is a lack of research on heavy metal influence on epigenetic toxicity in neurological disorders. The current review aims to elucidate the plausible role of cadmium (Cd), iron (Fe), arsenic (As), copper (Cu), and lithium (Li) metals on epigenetic factors and the increase in amyloid beta and tau phosphorylation in AD. Also, the review discusses the common methods of heavy metal detection to implicate in AD pathogenesis. Hence, from this review, we can extend the need for future research on identifying the mechanistic behavior of heavy metals on epigenetic toxicity and to develop diagnostic and therapeutic markers in AD. [ABSTRACT FROM AUTHOR]

Breast cancer, the most prevalentmalignant tumor among women globally, is significantly influenced by the Wnt/β-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/β-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/β-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM. [ABSTRACT FROM AUTHOR]

REM parasomnias, or rapid eye movement sleep parasomnias, are a group of sleep disorders that occur during the REM stage of sleep. These parasomnias can lead to a range of behaviors including vivid and intense dreams, nightmares, sleep paralysis and REM behavior disorder (RBD). RBD is a particularly dangerous form of REM parasomnias, in which the person physically acts out their dreams during REM sleep. This can lead to injuries to themselves or a sleeping partner. REM parasomnias can be caused by a variety of factors, including medications, substance use, and underlying medical conditions. They may also be associated with sleep deprivation and high stress levels. Their treatment may include a combination of behavioral therapy and medication. Behavioral therapy can help the person develop strategies to reduce the occurrence of parasomnias. Medication can help regulate sleep cycles or manage any underlying medical conditions. These disorders can disrupt daily life and can be dangerous if left untreated. In conclusion, REM parasomnias are a group of sleep disorders that can lead to a range of behaviors during REM sleep, including vivid and intense dreams, nightmares, sleep paralysis, and RBD. RBD is a dangerous form of REM parasomnias. Treatment for REM parasomnias may involve a combination of behavioral therapy and medication, and it is important to seek medical help if these disorders are suspected. [ABSTRACT FROM AUTHOR]

Copyright of Religación: Revista de Ciencias Sociales y Humanidades is the property of Religacion: Revista de Ciencias Sociales y Humanidades and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pancreatic cancer continues to be a deadly disease because of its delayed diagnosis and aggressive tumor biology. Oncogenes and risk factors are being reported to influence the signaling pathways involved in pancreatic embryogenesis leading to pancreatic cancer genesis. Although studies using rodent models have yielded insightful information, the scarcity of human pancreatic tissue has made it difficult to comprehend how the human pancreas develops. Transcription factors like IPF1/PDX1, HLXB9, PBX1, MEIS, Islet-1, and signaling pathways, including Hedgehog, TGF-β, and Notch, are directing pancreatic organogenesis. Any derangements in the above pathways may lead to pancreatic cancer. TP53: and CDKN2A are tumor suppressor genes, and the mutations in TP53 and somatic loss of CDKN2A are the drivers of pancreatic cancer. This review clarifies the complex signaling mechanism involved in pancreatic cancer, the same signaling pathways in pancreas development, the current therapeutic approach targeting signaling molecules, and the mechanism of action of risk factors in promoting pancreatic cancer.

Obesity represents a serious medical condition and has nowadays reached pandemic proportions. Comorbidities associated with obesity are severe, and affect almost all organ systems. Adipose tissue has several important functions: to provide energy storage, maintain body temperature through the process of thermogenesis, and maintain balance in a variety of metabolic patterns. Adipose tissue is an endocrine organ with numerous biochemical roles, and in obese individuals adipose tissue becomes either hypertrophic or hyperplastic, with impaired function. The immune system activity and metabolic regulation in adipose tissue are extremely related processes. A loss of balance on this axis causes numerous disorders associated with obesity, and the basis of these disorders is insulin resistance, which is a hallmark of obesity. Hormones that are almost exclusively produced in adipocytes and studied in various biochemistry processes are leptin, adiponectin and resistin. Successful treatment of obesity nowadays involves lifestyle and diet modification, pharmacotherapy, mainly with glucagon-like peptide-1 agonists, and bariatric surgery, which remains the most effective treatment method for the selected population of severely obese individuals. Positive effects of bariatric surgery are reflected not only in a restriction of food intake, but in hormonal changes, especially those of gut hormones responsible for hunger regulation and energy metabolism.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice. [ABSTRACT FROM AUTHOR]

Obesity or excessive weight gain is identified as the most important and significant risk factor in the development and progression of type 2 diabetes mellitus (DM) in all age groups. It has reached pandemic dimensions, making the treatment of obesity crucial in the prevention and management of type 2 DM worldwide. Multiple clinical studies have demonstrated that moderate and sustained weight loss can improve blood glucose levels, insulin action and reduce the need for diabetic medications. A combined approach of diet, exercise and lifestyle modifications can successfully reduce obesity and subsequently ameliorate the ill effects and deadly complications of DM. This approach also helps largely in the prevention, control and remission of DM. Obesity and DM are chronic diseases that are increasing globally, requiring new approaches to manage and prevent diabetes in obese individuals. Therefore, it is essential to understand the mechanistic link between the two and design a comprehensive approach to increase life expectancy and improve the quality of life in patients with type 2 DM and obesity. This literature review provides explicit information on the clinical definitions of obesity and type 2 DM, the incidence and prevalence of type 2 DM in obese individuals, the indispensable role of obesity in the pathophysiology of type 2 DM and their mechanistic link. It also discusses clinical studies and outlines the recent management approaches for the treatment of these associated conditions. Additionally, in vivo studies on obesity and type 2 DM are discussed here as they pave the way for more rigorous development of therapeutic approaches. [ABSTRACT FROM AUTHOR]

Immature sacrococcygeal teratoma represents a histological form with rapid tumor growth, a risk of premature birth, an enhanced rate of complications, an increased risk of recurrence, and a higher mortality rate than the mature type. Thus, prenatal diagnosis of immature forms would significantly improve the prognosis of these cases. To this end, we performed an extensive literature review on the diagnosis, therapeutic management, and follow-up of immature teratomas. Regarding this medical conduct, we also presented our case. In conclusion, the early identification of immature sacrococcygeal teratomas with or without other associated structural abnormalities and their correct therapeutic approach are basic principles for a favorable evolution of these cases. [ABSTRACT FROM AUTHOR]

Background: Nurses are faced with the sexual behavior of the patients. These behaviors do not mean that the patient cannot meet their sexual needs. It is not known how often nurses encounter such behaviors, how nurses' approach sexual patient behaviors, and whether nurses have a therapeutic approach. Purpose: This study was carried out in order to reveal how often nurses encounter sexual behaviors of patients and to determine whether nurses show a therapeutic approach to sexual patient behaviors. Methods: The cross-sectional study was conducted with 276 nurses. The data were collected by using a Questionnaire Form. Data were analyzed using descriptive and chi-square test. Results: The mean age of the nurses participating in the study was 31.12 ± 7.26. 93.8% of them were women, 61.6% were married, 57.2% were undergraduate graduates and the average duration of working life was 9.24±7.11. Compared with the nurses in the other groups, the older nurses, the married ones, those with distant education undergraduate degree, those with 13 years or more working experience and those working in intensive care units were more likely to expose to inappropriate sexual behaviors of the patients (p < .05). Nurses stated that 42.4% of them were exposed to the patients with inappropriate sexual behaviors. The types of inappropriate sexual behaviors that the nurses were exposed to were as follows; "verbal or written" (51.1%), "nonverbal" (37.6%), "physical" (11.3%). The approaches of the nurses towards these patients were "non-therapeutic" (68.1%). Conclusion: It was determined that almost half of the nurses encountered sexual patient behaviors and had difficulty in approaching patients who behaved sexually, and most of the nurses had non-therapeutic approaches to patients who behaved sexually. [ABSTRACT FROM AUTHOR]

Neurological disorders have become severe and dreadful issues around the globe that are rarely directly mediated because of the blood-brain barrier (BBB). Despite the various therapeutic strategies, including the utilization of cholinesterase inhibitors, metal chelators, molecular chaperones, and anti-body treatment that have been put forth, drug delivery to the brain has remained a problem in the treatment of neurodegenerative disorders (NDD). Chitosan, one of nature's multifunctional polymers, is acknowledged as a useful chemical in the medical and pharmaceutical industries due to its distinctive and flexible biological characteristics. By using Chitosan and its derivatives as drug delivery methods, it is possible to give medications in a sustained and regulated way, increase their stability, and lessen the likelihood of adverse drug reactions. In the current review, we have concentrated on the significance of Chitosan and its derivatives to become a hotspot in drug delivery, particularly for NDDs. This review also explains their properties as drug delivery vectors and their ability to cross the BBB, which is a significant obstacle to medication administration in NDDs. In conclusion, this review suggests that expanding the scope of such research would make it possible to develop NDD drug delivery systems that are more efficient.

Urinary retention due to the impossibility of evacuation of bladder contents and the secondary pathophysiologic processes, which it entails, as well as by inducing mental discomfort or a perpetual state of restlessness, represents a medical emergency in pets. The etiology of urinary retention is represented by: mechanical urinary retention, retention caused by obstruction or occlusion, urethral but also extraurethral; paralytic urinary retention, which occurs secondary to spinal cord lesions, or in geriatric patients due to proliferative processes or degeneration of the spinal column. Retention of spastic origin is characterized by the occurrence of sphincter spasm which is frequently produced by sympathetic irritation resulting in increased tonicity of the bladder sphincter, consequence of pelvic plexus irritation or the presence of diseases such as colic or peritonitis. A good therapeutic management influences both the evolution and the well-being of the patient, therefore an early identification of the specific clinical signs of urinary retention is essential in all types of urinary retention. [ABSTRACT FROM AUTHOR]

Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects.

Purpose: This study aims to highlight the feasibility of an olfactory training program entirely monitored through online media in COVID-19 patients. Methods: Classic olfactory training was performed with a sample with olfactory loss due COVID-19 (n = 11). Participants were engaged on a weekly video call in order to improve adherence and collect information regarding the number of correct answers and the individuals’ perception of olfactory function. The olfactory status after training was compared to two groups, one composed of participants who contracted COVID-19 but did not report olfactory loss (n = 11) and a sample composed of healthy participants (n = 11). Results: The experimental group showed improvements throughout the training period (TDI score on week 0 was 20.3 (5.6) and 24.6 (4.3) for week 12, and on week 24 was 25.4 (6.2) (F = 5.115, df = 2, 20, p = 0.016), and post hoc tests showed that participants significantly improved their TDI score in W12 compared to W0 (SMD = 0.869, p = 0.041) and in W24 compared to W0 (SMD = 0.859, p = 0.041). The experimental group showed lower scores when compared with both groups, and the no OT COVID-19 group showed lower scores than the healthy control group, even though they did not report olfactory alterations. Conclusions: Findings suggest that the strategies applied to improve adherence were successful since 100% of the sample completed the training adherence, offering a valuable framework for future olfactory training studies.

Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response to injury, quiescent CFs become activated and adopt a collagen-secreting phenotype highly contributing to cardiac fibrosis. In recent years, studies have been focused on the exploration of molecular and cellular mechanisms implicated in the activation process of CFs, which allow the development of novel therapeutic approaches for the treatment of cardiac fibrosis. Transcriptomic analyses using single-cell RNA sequencing (RNA-seq) have helped to elucidate the high cellular diversity and complex intercellular communication networks that CFs establish in the mammalian heart. Furthermore, a significant body of work supports the critical role of epigenetic regulation on the expression of genes involved in the pathogenesis of cardiac fibrosis. The study of epigenetic mechanisms, including DNA methylation, histone modification, and chromatin remodeling, has provided more insights into CF activation and fibrotic processes. Targeting epigenetic regulators, especially DNA methyltransferases (DNMT), histone acetylases (HAT), or histone deacetylases (HDAC), has emerged as a promising approach for the development of novel anti-fibrotic therapies. This review focuses on recent transcriptomic advances regarding CF diversity and molecular and epigenetic mechanisms that modulate the activation process of CFs and their possible clinical applications for the treatment of cardiac fibrosis.

Immature sacrococcygeal teratoma represents a histological form with rapid tumor growth, a risk of premature birth, an enhanced rate of complications, an increased risk of recurrence, and a higher mortality rate than the mature type. Thus, prenatal diagnosis of immature forms would significantly improve the prognosis of these cases. To this end, we performed an extensive literature review on the diagnosis, therapeutic management, and follow-up of immature teratomas. Regarding this medical conduct, we also presented our case. In conclusion, the early identification of immature sacrococcygeal teratomas with or without other associated structural abnormalities and their correct therapeutic approach are basic principles for a favorable evolution of these cases.

• Tumor-associated macrophages (TAMs) exert profound influences on cancer progression. • The review delves into the impact of TAM-derived exosomes on fundamental cancer hallmarks, elucidating their involvement in promoting cancer. • miRNAs, such as miR-155, miR-196a-5p, and miR-221-3p, are highlighted for their pivotal roles in mediating TAM-derived exosomal communication. Tumor-associated macrophages (TAMs) exert profound influences on cancer progression, orchestrating a dynamic interplay within the tumor microenvironment. Recent attention has focused on the role of TAM-derived exosomes, small extracellular vesicles containing bioactive molecules, in mediating this intricate communication. This review comprehensively synthesizes current knowledge, emphasizing the diverse functions of TAM-derived exosomes across various cancer types. The review delves into the impact of TAM-derived exosomes on fundamental cancer hallmarks, elucidating their involvement in promoting cancer cell proliferation, migration, invasion, and apoptosis evasion. By dissecting the molecular cargo encapsulated within these exosomes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and proteins, the review uncovers key regulatory mechanisms governing these effects. Noteworthy miRNAs, such as miR-155, miR-196a-5p, and miR-221-3p, are highlighted for their pivotal roles in mediating TAM-derived exosomal communication and influencing downstream targets. Moreover, the review explores the impact of TAM-derived exosomes on the immune microenvironment, particularly their ability to modulate immune cell function and foster immune evasion. The discussion encompasses the regulation of programmed cell death ligand 1 (PD-L1) expression and subsequent impairment of CD8 + T cell activity, unraveling the immunosuppressive effects of TAM-derived exosomes. With an eye toward clinical implications, the review underscores the potential of TAM-derived exosomes as diagnostic markers and therapeutic targets. Their involvement in cancer progression, metastasis, and therapy resistance positions TAM-derived exosomes as key players in reshaping treatment strategies. Finally, the review outlines future directions, proposing avenues for targeted therapies aimed at disrupting TAM-derived exosomal functions and redefining the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Unlike classical protein kinase A, with separate catalytic and regulatory subunits, EPACs are single chain multi-domain proteins containing both catalytic and regulatory elements. The importance of cAMP-Epac-signaling as an energy provider has emerged over the last years. However, little is known about Epac1 signaling in chronic kidney disease. Here, we examined the role of Epac1 during the progression of glomerulonephritis (GN). We first observed that total genetic deletion of Epac1 in mice accelerated the progression of nephrotoxic serum (NTS)-induced GN. Next, mice with podocyte-specific conditional deletion of Epac1 were generated and showed that NTS-induced GN was exacerbated in these mice. Gene expression analysis in glomeruli at the early and late phases of GN showed that deletion of Epac1 in podocytes was associated with major alterations in mitochondrial and metabolic processes and significant dysregulation of the glycolysis pathway. In vitro, Epac1 activation in a human podocyte cell line increased mitochondrial function to cope with the extra energy demand under conditions of stress. Furthermore, Epac1-induced glycolysis and lactate production improved podocyte viability. To verify the in vivo therapeutic potential of Epac1 activation, the Epac1 selective cAMP mimetic 8-pCPT was administered in wild type mice after induction of GN. 8-pCPT alleviated the progression of GN by improving kidney function with decreased structural injury with decreased crescent formation and kidney inflammation. Importantly, 8-pCPT had no beneficial effect in mice with Epac1 deletion in podocytes. Thus, our data suggest that Epac1 activation is an essential protective mechanism in GN by reprogramming podocyte metabolism. Hence, targeting Epac1 activation could represent a potential therapeutic approach., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: A Consensus document on the management of patients with neurogenic detrusor overactivity (NDO) was published in 2018. The present document aims to update its recommendations regarding treatment considering the new evidence available, and to contribute to the standardization of the management of this disorder., Methods: The methodology used was based on a systematic review and the Nominal Group Technique. The clinical coordinator (CC) and the Consensus update group (CUG) defined the questions to be updated and carried out a systematic review to identify the new available evidence. After being evaluated by the expert panel, the relevant recommendations were updated and agreed in a consensus meeting., Results: A total of 3210 publications were identified and 26 publications that met the inclusion criteria were included. The CUG updated 18 recommendations on the therapeutic approach to NDO. Unanimous consensus was reached on all of them., Conclusions: Previous recommendations need to be revised due to the availability of new drugs, the increasing evidence on the use of botulinum toxin or neuromodulation procedures, and new surgical options., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Breast cancer, the most prevalent malignant tumor among women globally, is significantly influenced by the Wnt/β-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/β-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/β-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Zhang, Zhao, Ge, Sun, Fu and Li.)

Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations., (© 2024. The Author(s).)

• Conventional youth justice facilities are typically highly restrictive, complicating the relationships between staff and young people. • Relational security recognises the importance of collaborative relationships between staff and young people. • This research puts forward key considerations for establishing relational security in conventional youth justice detention. • Staff workloads, high turnover, and procedural inflexibility form some of the main challenges. • Trust and respect, being adaptable to young people's needs, and maintaining professional boundaries are key. Constructive relationships between staff and young people in youth justice detention are a vital component of a therapeutic youth justice approach, which extends to the maintenance of a safe environment (i.e. relational security). However, there is a dearth of research on relational security and how it can be implemented and operationalized in conventional youth justice settings. Our aim was to understand custodial officers' views on, and approaches to, establishing a relational approach with young people, while maintaining safety and security. We conducted semi-structured interviews with 26 staff at a youth justice detention facility in Victoria, Australia. Thematic analysis using a framework analysis approach. Four main themes were derived: Staff roles, maintaining a safe environment, establishing a constructive relationship, and staffing challenges. These findings shed light on how relational security principles can provide a way to balance the care and support of young people with a need for safety and security in a conventional youth justice detention setting in Australia, as well as challenges of current procedures and arrangements. We argue that a relational security approach should inform staff recruitment, training, support, and management strategies, as well as decisions about the design and use of space in youth justice detention settings. [ABSTRACT FROM AUTHOR]

The popularity and usage of synthetic cannabinoids (SCs) are increasing due to their easy accessibility and psychoactive effects worldwide. Studies on cannabinoids on leukemic stem cells (LSC) and hematopoietic stem cells (HSCs), which are the precursors of leukemia cells, generally depend on the natural cannabinoid delta-9-THC. As there is only a limited number of studies focusing on the results of SC applications, the reflections upon LSCs have to be clarified. In this study, biological responses and antileukemic effects of JWH-018-one of the first produced and widely used SCs-were evaluated upon leukemia cells. Whether JWH-018 exhibited a preventive effect on both leukemic and HSCs was evaluated by presenting a therapeutic approach for the first time in the literature. Cells were analyzed in case of cell proliferation, apoptosis, and transcriptional expression profiling of some significant JAK/STAT and AKT/mTOR pathways, apoptotic, cell cycle regulation, and epigenetic chromatin remodeling-related genes following JWH-018 treatment. In conclusion, however, further studies are still needed upon both HSCs and LSCs to illuminate the effects of SCs on leukemogenesis on chronic myeloid leukemia (CML) more clearly; we consider that the JWH-018 can provide a therapeutic effect on the pathogenesis of leukemia and particularly upon LSCs and SCs might have therapeutic potential in addition to current therapy.

Though the book's journey into The Hidden World of Protein Aggregation has come to an end, the search for knowledge, the development of healthier lives, and the discovery of nature's mysteries continue, promising new horizons and discoveries yet to be discovered. The intricacies of protein misfolding and aggregation remain a mystery in cellular biology, despite advances made in unraveling them. In this chapter, we will summarize the specific conclusions from the previous chapters and explore the persistent obstacles and unanswered questions that motivate scientists to pursue exploration of protein misfolding and aggregation., (Copyright © 2024. Published by Elsevier Inc.)