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Journal of Clinical Medicine Jun 2024Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper... (Review)
Review
Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional "PARP enzyme-inhibitor complex" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as (). Hence, identifying HR-deficiencies by genomic analysis-for instance, used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available analysis. In this review, we discuss [F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.
PubMed: 38929955
DOI: 10.3390/jcm13123426 -
Journal of Personalized Medicine Jun 2024Personalized sleep medicine represents a transformative shift in healthcare, emphasizing individualized approaches to optimizing sleep health, considering the... (Review)
Review
Personalized sleep medicine represents a transformative shift in healthcare, emphasizing individualized approaches to optimizing sleep health, considering the bidirectional relationship between sleep and health. This field moves beyond conventional methods, tailoring care to the unique physiological and psychological needs of individuals to improve sleep quality and manage disorders. Key to this approach is the consideration of diverse factors like genetic predispositions, lifestyle habits, environmental factors, and underlying health conditions. This enables more accurate diagnoses, targeted treatments, and proactive management. Technological advancements play a pivotal role in this field: wearable devices, mobile health applications, and advanced diagnostic tools collect detailed sleep data for continuous monitoring and analysis. The integration of machine learning and artificial intelligence enhances data interpretation, offering personalized treatment plans based on individual sleep profiles. Moreover, research on circadian rhythms and sleep physiology is advancing our understanding of sleep's impact on overall health. The next generation of wearable technology will integrate more seamlessly with IoT and smart home systems, facilitating holistic sleep environment management. Telemedicine and virtual healthcare platforms will increase accessibility to specialized care, especially in remote areas. Advancements will also focus on integrating various data sources for comprehensive assessments and treatments. Genomic and molecular research could lead to breakthroughs in understanding individual sleep disorders, informing highly personalized treatment plans. Sophisticated methods for sleep stage estimation, including machine learning techniques, are improving diagnostic precision. Computational models, particularly for conditions like obstructive sleep apnea, are enabling patient-specific treatment strategies. The future of personalized sleep medicine will likely involve cross-disciplinary collaborations, integrating cognitive behavioral therapy and mental health interventions. Public awareness and education about personalized sleep approaches, alongside updated regulatory frameworks for data security and privacy, are essential. Longitudinal studies will provide insights into evolving sleep patterns, further refining treatment approaches. In conclusion, personalized sleep medicine is revolutionizing sleep disorder treatment, leveraging individual characteristics and advanced technologies for improved diagnosis, treatment, and management. This shift towards individualized care marks a significant advancement in healthcare, enhancing life quality for those with sleep disorders.
PubMed: 38929819
DOI: 10.3390/jpm14060598 -
Life (Basel, Switzerland) Jun 2024In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While... (Review)
Review
In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While psoriasis primarily affects the skin, it is increasingly recognized as a systemic disease that can have effects beyond the skin. Obesity is associated with more severe forms of psoriasis and can potentially worsen the systemic inflammation and metabolic dysfunction seen in psoriatic patients. The exact mechanisms underlying the link between these two conditions are not fully understood, but it is believed that chronic inflammation and immune dysregulation play a role. In this review, we examine the existing body of knowledge regarding the intersection of pathogenic processes responsible for psoriasis and obesity. The ability of biological therapies to reduce systemic and obesity-related inflammation in patients with psoriasis will be also discussed.
PubMed: 38929716
DOI: 10.3390/life14060733 -
Medicina (Kaunas, Lithuania) Jun 2024Preterm-born children are susceptible to problems of adaptation in the early neonatal period, as well as the emergence of consequences due to the immaturity of the... (Review)
Review
Preterm-born children are susceptible to problems of adaptation in the early neonatal period, as well as the emergence of consequences due to the immaturity of the respiratory, cardiovascular, and especially cerebrovascular systems. The authors searched PubMed, Scopus, the Cochrane Library, and Web of Science for articles that were available in their entirety and published in English between 1990 and 2024 in peer-reviewed journals using keywords relevant to the manuscript topic. Analyzing the requested studies and manuscripts, adequate articles describing the stated problem were used. The last trimester of pregnancy is the most important period in brain development. Brain growth is at its most intense, and nerve cells are created, multiply, and migrate, creating numerous connections between them and receptors. During this period, the baby is protected from the influence of external environmental factors. When a baby is born, it leaves its protected environment and very often requires intensive treatment to survive. In these circumstances, the immature nervous system, which is in a sensitive stage of development, is overloaded with numerous external stimuli, continuous light, noise, inappropriate positioning, and repeated painful reactions due to necessary diagnostic and therapeutic procedures and the unavoidable absence of the mother and the family, which cause stress that threatens proper programmed development. Minimally invasive therapeutic procedures and the presence of parents during hospitalization play a significant role in reducing the consequences for a premature child.
Topics: Humans; Infant, Newborn; Premature Birth; Female; Pregnancy; Infant, Premature
PubMed: 38929631
DOI: 10.3390/medicina60061014 -
Children (Basel, Switzerland) May 2024Evidence has shown that parenting intervention programmes improve parental knowledge, attitudes, and practices, which helps in promoting child development. This study...
Evidence has shown that parenting intervention programmes improve parental knowledge, attitudes, and practices, which helps in promoting child development. This study aims to examine the effectiveness of parenting intervention in improving child behaviours. This is a secondary analysis of data from a cluster-randomised controlled trial with depressed mothers aged 18-44 years with a child aged 0 to 36 months. This paper reports findings from the dataset of participants with a child aged between 24 and 36 months. Villages ( = 120) were randomised into either of two arms: learning through play plus (LTP Plus) or treatment as usual (TAU). LTP Plus is a 10-session, group parenting intervention integrated with cognitive behaviour therapy, delivered over 3 months. This secondary analysis reports findings on the Eyberg Child Behaviour Inventory (ECBI) and the Home Observation for Measurement of the Environment (HOME). Findings show a significant improvement in child behaviour (ECBI) scores ( < 0.011) and HOME scores ( < 0.001) in the intervention group compared to TAU at 3-month follow-up. In a low-resource setting, low-cost group parenting intervention delivered by community health workers has the potential to improve child behaviours and quality of the home environment. Parenting interventions aimed at improving child behavioural problems can have significant implications for the child, family, and broader societal outcomes. Addressing behavioural problems in early years, parenting interventions can potentially reduce long-term consequences and costs associated with untreated child behavioural issues.
PubMed: 38929226
DOI: 10.3390/children11060646 -
International Journal of Molecular... Jun 2024MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important...
MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle.
Topics: MicroRNAs; Tissue Engineering; Humans; Tissue Scaffolds; Cell Differentiation; Adipose Tissue; Blood Vessels; Gene Expression Regulation; Neovascularization, Physiologic; Stem Cells; Cell Proliferation; Signal Transduction
PubMed: 38928467
DOI: 10.3390/ijms25126762 -
International Journal of Molecular... Jun 2024Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have... (Review)
Review
Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; MicroRNAs; Lung Neoplasms; Immune Checkpoint Inhibitors; Microbiota; Gastrointestinal Microbiome; Prognosis; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Animals
PubMed: 38928392
DOI: 10.3390/ijms25126685 -
International Journal of Molecular... Jun 2024Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review... (Review)
Review
Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential therapeutic applications of these compounds. The results of ex vivo and in vivo preclinical data indicate that cannabinoids can both inhibit and stimulate gut peristalsis, depending on various factors. Endocannabinoids affect peristalsis in a cannabinoid (CB) receptor-specific manner; however, there is also an important interaction between them and the transient receptor potential cation channel subfamily V member 1 (TRPV1) system. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact gut motility mainly through the CB1 receptor. They were also found to improve intestinal barrier integrity, mainly through CB1 receptor stimulation but also via protein kinase A (PKA), mitogen-associated protein kinase (MAPK), and adenylyl cyclase signaling pathways, as well as by influencing the expression of tight junction (TJ) proteins. The anti-inflammatory effects of cannabinoids in GIT disorders are postulated to occur by the lowering of inflammatory factors such as myeloperoxidase (MPO) activity and regulation of cytokine levels. In conclusion, there is a prospect of utilizing cannabinoids as components of therapy for GIT disorders.
Topics: Humans; Cannabinoids; Gastrointestinal Motility; Animals; Gastrointestinal Diseases; Permeability; Intestinal Mucosa; Endocannabinoids
PubMed: 38928387
DOI: 10.3390/ijms25126682 -
International Journal of Molecular... Jun 2024The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are...
The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.
Topics: Animals; Bone Morphogenetic Protein 2; Osteocytes; Calcium Phosphates; Mice; Recombinant Proteins; Disease Models, Animal; Bisphosphonate-Associated Osteonecrosis of the Jaw; Humans; Bone Regeneration; Male; Tooth Extraction; Transforming Growth Factor beta; Alveolar Process
PubMed: 38928355
DOI: 10.3390/ijms25126648 -
International Journal of Molecular... Jun 2024Hepatic ischemia/reperfusion injury (IRI) is an important factor affecting liver regeneration and functional recovery postoperatively. Many studies have suggested that...
Hepatic ischemia/reperfusion injury (IRI) is an important factor affecting liver regeneration and functional recovery postoperatively. Many studies have suggested that mesenchymal stem cells (MSCs) contribute to hepatic tissue repair and functional recovery through paracrine mechanisms mediated by exosomes. Minipigs exhibit much more similar characteristics of the liver to those of humans than rodents. This study aimed to explore whether exosomes from adipose-derived MSCs (ADSCs-exo) could actively promote liver regeneration after hepatectomy combined with HIRI in minipigs and the role they play in the cell proliferation process. This study also compared the effects and differences in the role of ADSCs and ADSCs-exo in the inflammatory response and liver regeneration. The results showed that ADSCs-exo suppressed histopathological changes and reduced inflammatory infiltration in the liver; significantly decreased levels of ALT, TBIL, HA, and the pro-inflammatory cytokines TNF-α, IL-6, and CRP; increased levels of the anti-inflammatory cytokine IL-10 and the pro-regeneration factors Ki67, PCNA, CyclinD1, HGF, STAT3, VEGF, ANG1, ANG2; and decreased levels of the anti-regeneration factors SOCS3 and TGF-β. These indicators above showed similar changes with the ADSCs intervention group. Indicating that ADSCs-exo can exert the same role as ADSCs in regulating inflammatory responses and promoting liver regeneration. Our findings provide experimental evidence for the possibility that ADSCs-exo could be considered a safe and effective cell-free therapy to promote regeneration of injured livers.
Topics: Animals; Swine; Mesenchymal Stem Cells; Swine, Miniature; Exosomes; Liver Regeneration; Adipose Tissue; Liver; Cell Proliferation; Reperfusion Injury; Hepatectomy; Cytokines; Male
PubMed: 38928308
DOI: 10.3390/ijms25126604