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Capsaicinoids and capsinoids are bioactive compounds mostly found in peppers. Although preclinical studies have reported that these compounds can improve exercise performance due to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated thermogenesis, sympathetic modulation, and releasing calcium, it is still unclear how they affect exercise performance in humans as ergogenic supplements. Conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guide 2020, this systematic review examined the ergogenic effect of capsaicinoids and capsinoids on exercise performance in healthy adults. A total of 19 randomized placebo-controlled trials were included in the study. Studies were accessed by searching five databases (PubMed, Scopus, SPORTDiscus, Web of Science, and Cochrane Library). The quality of the studies was evaluated using the Cochrane risk-of-bias assessment tool. According to the study results, 10 studies examining the effect of capsaicinoid and capsinoid supplements on exercise performance reported positive effects. Also, the effect of capsaicinoids and capsinoids on exercise performance is more pronounced in resistance training. This difference, which varies according to the type of exercise, may be due to the correlation between capsaicin transient receptor potential vanilloid subtype 1 and insulin-like growth factor-1. [ABSTRACT FROM AUTHOR]

Functional impairments in the brain's insulin and insulin-like growth factor (IGF) signal transduction networks are recognized mediators of dysregulated energy metabolism, a major driver of the Alzheimer's disease (AD) neurodegeneration cascade. AD-associated insulin-deficient and insulin-resistant states mimic those of diabetes mellitus and affect all cell types in the brain. Besides accounting for abundant amyloid-β and hyperphosphorylated tau lesions in AD, insulin/IGF pathway dysfunctions cause cortical atrophy, loss of synaptic plasticity, white matter myelin/oligodendrocyte degeneration, astrocyte and microglial neuroinflammation and oxidative stress, deficits in energy metabolism, mitochondrial dysfunction, and microvascular disease. These same neuropathological processes have been linked to cognitive impairment in type 2 diabetes mellitus, Parkinson's disease, and vascular dementia. Strategies to address metabolic mediators of cognitive impairment have been borrowed from diabetes and other insulin-resistant diseases and leveraged on preclinical AD model data. The repurposing of diabetes drugs led to clinical trials with intranasal insulin, followed by insulin sensitizers including metformin and peroxisome-proliferator-activated receptor agonists, and then incretin mimetics primarily targeting GLP-1 receptors. In addition, other glucose-lowering agents have been tested for their efficacy in preventing cognitive declines. The strengths and limitations of these approaches are discussed. The main conclusion of this review is that we have now arrived at a stage in which it is time to address long-term deficits in trophic factor availability and receptor responsiveness, signaling abnormalities that extend beyond insulin and include IGFs and interconnected pathways, and the need for multi-pronged rather than single-pronged therapeutic targeting to remediate AD and other forms of neurodegeneration. [ABSTRACT FROM AUTHOR]

Infantile haemangioma (IH) – the most common vascular tumour of infancy – is comprised of diverse cell types, including endothelial cells, pericytes, fibroblasts and immune cells. IH is characterized by rapid proliferation followed by slow involution over 1–10 years. Most lesions regress spontaneously, but up to 10% can be disfiguring, with complications that require further medical treatment. Recent research has revealed the biological characteristics of IH, highlighting the involvement of angiogenesis and vasculogenesis during tumour formation. Gene expression profiling has provided vital insights into the underlying biological processes, with some of the key IH-related pathways identified, including vascular endothelial growth factor, the renin–angiotensin–aldosterone system, hypoxia-inducible factor 1α, Notch, platelet-derived growth factor, phosphoinositide 3-kinase/Akt/mammalian target of rapamycin, Janus kinase/signal transducers and activators of transcription, fibroblast growth factor, peroxisome proliferator-activated receptor-γ and insulin-like growth factor. Further evidence suggests extracellular matrix factors and hormone receptors regulate IH progression. In this review, we explore the molecular mechanisms involved in the proliferating, plateau and involuting phases of IH, identifying differentially expressed genes, targeted proteins and key signalling pathways. This knowledge will increase the broader understanding of vascular development, tissue remodelling and angiogenesis. [ABSTRACT FROM AUTHOR]

• This study compared the effect of intraperitoneal (IP) and intracerebroventricular (ICV) IGF1 on acute and chronic stroke. • ICV-IGF-1 initiated 4h after MCAo reduces infarct volume, improves sensory motor impairment, while IP-IGF-1 does not. • In contrast, IP-IGF1 reduces inflammatory cytokines and stroke induced cognitive impairment, while ICV-IGF-1 does not. • IP-IGF1 restores the gut epithelium and maintains normal gut microbial flora, while ICV-IGF1 does not. • Overall, these data support the hypothesis that repairing the gut can improve chronic stroke outcomes. Stroke results in immediate sensory or motor disability and increases the risk for long term cognitive-affective impairments. Thus, therapies are urgently needed to improve quality of life for stroke survivors, especially women who are at a greater risk for severe stroke after menopause. Most current research on stroke therapies target the central nervous system; however, stroke also impacts peripheral organ systems. Our studies using acyclic (estrogen-deficient) middle aged female Sprague Dawley rats show that this group not only displays worse outcomes after stroke as compared to adult females, but also has lower levels of the neuroprotective peptide Insulin-like Growth Factor (IGF1) in circulation. Intracerebroventricular (ICV) administration of IGF1 to this group decreases infarct volume and improves sensory motor performance in the acute phase. In this study, we show that, despite this neuroprotection, ICV-IGF1 did not reduce peripheral inflammation or improve post stroke cognitive impairment in the chronic phase. In view of the evidence that stroke induces rapid gut dysfunction, we tested whether systemic delivery of IGF1 (intraperitoneal, IP) would promote gut health and consequently improve long-term behavioral outcomes. Surprisingly, while IP-IGF1, delivered 4 h and 24 h after ischemic stroke, did not reduce infarct volume or acute sensory motor impairment, it significantly attenuated circulating levels of pro-inflammatory cytokines, and attenuated stroke-induced cognitive impairment. In addition, IP-IGF1 treatment reduced gut dysmorphology and gut dysbiosis. Our data support the conclusion that therapeutics targeting peripheral targets are critical for long-term stroke recovery, and that gut repair is a novel therapeutic target to improve brain health in aging females. [ABSTRACT FROM AUTHOR]

Context Rare patients with short stature and growth hormone (GH) resistance have dominant-negative variants in the GH receptor. We describe a patient with GH resistance due to elevated levels of GH binding protein and demonstrate the potential for a precision medicine intervention. Objective To determine whether high-dose GH can overcome GH resistance in this specific patient resulting in normal insulin-like growth factor (IGF)-1 levels and improved growth rates. Methods Single patient trial of ascending doses of GH followed by a dose stable phase: total 12 months of treatment. The patient has a heterozygous variant in the GH receptor resulting in elevated levels of GH binding protein manifesting as GH resistance and severe short stature. Daily subcutaneous GH was administered, starting at 50 µg/kg/day and escalating to 250 µg/kg/day until goal IGF-1 achieved. The subject continued on 250 µg/kg/day for a total treatment duration of 12 months. The primary outcome measure was the dose of GH required to achieve an IGF-1 level above the midpoint of the normal range. Secondary endpoints included height velocity and the change in height SDS during the first year of treatment. Results A dose of GH of 250 µg/kg/day achieved the target IGF-1 level. The patient's annualized height velocity was 8.7 cm/year, an increase of 3.4 cm/year from baseline, resulting in a 0.81 SD gain in height. Conclusion A precision medicine approach of extremely high dose GH was able to overcome GH resistance in a patient with a dominant-negative variant in the GH receptor resulting in elevated GH binding protein levels. [ABSTRACT FROM AUTHOR]

Introduction: The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC) and is considered a promising therapeutic target. EOC is an immunosuppressive disease, although there are limited data about the involvement of the IGF1R system in the anti-tumor immune response in the EOC microenvironment. Methods: In the current study, we hypothesized that IGF 1 receptor (IGF1R) involvement in the maturation of dendritic cells (DC) with the co-inhibition of IGF1R and PD-1 would affect the EOC microenvironment. Results: We found that DC pretreated with IGF1R inhibitor resulted in fewer EOC cells. Moreover, in vivo experiments conducted with an EOC mouse model, with anti-PD-1/IGF1R combined, resulted in lower tumor weight compared to individual treatments. Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1. The combined treatment increased CD8+ T-cell levels compared to AEW-541 alone. RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone. Discussion: These findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations. [ABSTRACT FROM AUTHOR]

Aims: To explore the predictive value of the IGF-1/IGFBP-3 ratio for the presence of thyroid nodules in patients with type 2 diabetes mellitus (T2DM). Methods: This observational study prospectively enrolled patients with T2DM at the Second Hospital of Jilin University between May 2021 and January 2022. Thyroid nodule (TN) status was determined by ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the serum IGF-1/IGFBP-3 molar ratio for TNs. Multivariable logistic regression analysis was conducted to identify risk factors for thyroid nodules in patients with T2DM. Results: A total of 122 patients (mean age ± standard deviation: 52.57 ± 11.71 years; 74 males) were enrolled. 37.7% (n=46) of patients did not have TNs, while 62.3% (n=76) had TNs. The duration of diabetes, age, and HDL-C level were significantly higher in the T2DM group with TNs compared to the group without TNs (all P < 0.05). The area under the ROC curve (AUC) for the combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio in predicting TNs in T2DM patients was 0.619 (P < 0.001). Additionally, multivariable logistic regression analysis revealed that the duration of diabetes, age, fasting plasma glucose (FPG), fasting insulin (FINS), thyroid-stimulating hormone (TSH), IGF-1, and IGFBP-3 levels were independent risk factors for thyroid nodules, while the serum IGF-1/IGFBP-3 molar ratio level was an independent protective factor for thyroid nodules in patients with T2DM (all P < 0.05). Conclusion: The combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio may have a better predictive value for TNs in T2DM patients than using any single marker alone. The duration of diabetes, age, FPG, FINS, TSH, IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio levels were independently associated with thyroid nodules in patients with T2DM. [ABSTRACT FROM AUTHOR]

Chronic tympanic membrane (TM) perforation is a tubotympanic disease caused by either traumatic injury or inflammation. A recent study demonstrated significant progress in promoting the regeneration of chronic TM perforations through the application of nanofibers with radially aligned nanostructures and controlled release of growth factors. However, radially aligned nanostructures with stem cell-stimulating factors have never been used. In this study, insulin-like growth factor binding factor 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. The IRA-NFPs were prepared by electrospinning 8 wt% polycaprolactone in trifluoroethanol and acetic acid (9:1). Random nanofibers (RFs) and aligned nanofibers (AFs) were successfully fabricated using a flat plate and a custom-designed circular collector, respectively. The presence of IGFBP2 was confirmed via Fourier transform infrared spectroscopy and the release of IGFBP2 was sustained for up to 20 days. In vitro studies revealed enhanced cellular proliferation and migration on AFs compared to RFs, and the incorporation of IGFBP2 further promoted these effects. Quantitative real-time PCR revealed mRNA downregulation, correlating with accelerated migration and increased cell confluency. In vivo studies showed IGFBP2-loaded RF and AF patches increased regeneration success rates by 1.59-fold and 2.23-fold, respectively, while also reducing healing time by 2.5-fold compared to the control. Furthermore, IGFBP2-incorporated AFs demonstrated superior efficacy in healing larger perforations with enhanced histological similarity to native TMs. This study, combining stem cell stimulating factors and aligned nanostructures, proposes a novel approach potentially replacing conventional surgical methods for chronic TM perforation regeneration. Chronic otitis media (COM) affects approximately 200 million people worldwide due to inflammation, inadequate blood supply, and lack of growth factors. Current surgical treatments have limitations like high costs and anesthetic risks. Recent research explored the use of nanofibers with radially aligned nanostructures and controlled release of growth factors to treat chronic tympanic membrane (TM) perforations. In this study, insulin-like growth factor binding protein 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. We assessed their properties and efficacy through in vitro and in vivo studies. IRA-NFPs showed promising healing capabilities with chronic TM perforation models. This innovative approach has the potential to improve COM management, reduce surgery costs, and enhance patient safety. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Beyond the signature amyloid-beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been shown to exhibit dysregulated metabolic signaling through insulin and insulin-like growth factor (IGF) networks that crosstalk with the mechanistic target of rapamycin (mTOR). Its broad impact on brain structure and function suggests that mTOR is likely an important therapeutic target for AD. Objective: This study characterizes temporal lobe (TL) mTOR signaling abnormalities in a rat model of sporadic AD neurodegeneration. Methods: Long Evans rats were given intracerebroventricular injections of streptozotocin (ic-STZ) or saline (control), and 4 weeks later, they were administered neurobehavioral tests followed by terminal harvesting of the TLs for histopathological study and measurement of AD biomarkers, neuroinflammatory/oxidative stress markers, and total and phosphorylated insulin/IGF-1-Akt-mTOR pathway signaling molecules. Results: Rats treated with ic-STZ exhibited significantly impaired performance on Rotarod (RR) and Morris Water Maze (MWM) tests, brain atrophy, TL and hippocampal neuronal and white matter degeneration, and elevated TL pTau, AbPP, Ab, AChE, 4-HNE, and GAPDH and reduced ubiquitin, IL-2, IL-6, and IFN-g immunoreactivities. In addition, ic-STZ reduced TL pY1135=1136-IGF-1R, Akt, PTEN, pS380-PTEN, pS2448-mTOR, p70S6K, pT412-p70S6K, p/T-pT412-p70S6K, p/T-Rictor, and p/T-Raptor. Conclusion: Experimental ic-STZ-induced sporadic AD-type neurodegeneration with neurobehavioral dysfunctions associated with inhibition of mTOR signaling networks linked to energy metabolism, plasticity, and white matter integrity. [ABSTRACT FROM AUTHOR]

Reference ranges are invaluable in laboratory medicine, as these are indispensable tools for the interpretation of laboratory test results. When assessing measurements on a single analyte, univariate reference intervals are required. In many cases, however, measurements on several analytes are needed by medical practitioners to diagnose more complicated conditions such as kidney function or liver function. For such cases, it is recommended to use multivariate reference regions, which account for the cross-correlations among the analytes. Traditionally, multivariate reference regions (MRRs) have been constructed as ellipsoidal regions. The disadvantage of such regions is that they are unable to detect component-wise outlying measurements. Because of this, rectangular reference regions have recently been put forward in the literature. In this study, we develop methodologies to compute rectangular MRRs that incorporate covariate information, which are often necessary in evaluating laboratory test results. We construct the reference region using tolerance-based criteria so that the resulting region possesses the multiple use property. Results show that the proposed regions yield coverage probabilities that are accurate and are robust to the sample size. Finally, we apply the proposed procedures to a real-life example on the computation of an MRR for three components of the insulin-like growth factor system. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is a severe and common neurological disorder, yet its precise physiological mechanisms remain unclear. The IGF1/IGF1r signaling pathway plays a crucial role in pain modulation. Studies have shown that IGF1, by binding to its receptor IGF1r, activates a series of downstream signaling cascades involved in neuronal survival, proliferation, autophagy and functional regulation. The activation of these pathways can influence nociceptive transmission. Furthermore, alterations in IGF1/IGF1r signaling are closely associated with the development of various chronic pain conditions. Therefore, understanding the specific mechanisms by which this pathway contributes to pain is of significant importance for the development of novel pain treatment strategies. In this study, we investigated the role of IGF1/IGF1r and its potential mechanisms in a mouse model of chronic migraine. Methods: Chronic migraine was induced in mice by repeated intraperitoneal injections of nitroglycerin. Mechanical and thermal hypersensitivity responses were assessed using Von Frey filaments and radiant heat, respectively. To determine the role of IGF1/IGF1r in chronic migraine (CM), we examined the effects of the IGF1 receptor antagonist ppp (Picropodophyllin) on pain behaviors and the expression of calcitonin gene-related peptide (CGRP) and c-Fos. Result: In the nitroglycerin-induced chronic migraine model in mice, neuronal secretion of IGF1 is elevated within the trigeminal nucleus caudalis (TNC). Increased phosphorylation of the IGF1 receptor occurs, predominantly co-localizing with neurons. Treatment with ppp alleviated basal mechanical hypersensitivity and acute mechanical allodynia. Furthermore, ppp ameliorated autophagic dysfunction and reduced the expression of CGRP and c-Fos. Conclusion: Our findings demonstrate that in the chronic migraine (CM) model in mice, there is a significant increase in IGF1 expression in the TNC region. This upregulation of IGF1 leads to enhanced phosphorylation of IGF1 receptors on neurons. Targeting and inhibiting this signaling pathway may offer potential preventive strategies for mitigating the progression of chronic migraine. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention. [ABSTRACT FROM AUTHOR]

As our population ages, the medical challenges it faces become increasingly acute, with chronic kidney disease (CKD) becoming more prevalent among older adults. Frailty is alarmingly more common in CKD patients than in the general populace, putting the elderly at high risk of both physical and cognitive decline. CKD not only accelerates physical deterioration, but also heightens vascular dysfunction, calcification, arterial rigidity, systemic inflammation, oxidative stress, and cognitive impairment. Cognitive frailty, a distinct syndrome marked by cognitive deficits caused by physiological causes (excluding Alzheimer's and other dementias), is a critical concern. Although cognitive impairment has been well-studied, the molecular mechanisms driving cognitive frailty remain largely uncharted. Comprehensive interventions, including cutting-edge pharmaceuticals and lifestyle changes, are pivotal and effective, especially in the early stages of CKD. Recent research suggests that systematic exercise could counteract cognitive decline by improving brain blood flow, boosting neuroplasticity through the brain-derived neurotrophic factor (BDNF), and by triggering the release of neurotrophic factors such as insulin-like growth factor (IGF-1). This review delves into the molecular pathways of cognitive frailty in CKD, identifies key risk factors, and highlights therapeutic approaches, particularly the potent role of exercise in enhancing cognitive health. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11–13 weeks of gestation were quantified using liquid chromatography–multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6–40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE. [ABSTRACT FROM AUTHOR]

Purpose: To investigate serum levels of VEGF, IGF-1 and FGF-2, and relationships with several clinical characteristics in children and adolescents with autism spectrum disorder (ASD) with and without bipolar disorder (BD). Method: 40 subjects with ASD + BD as study group, and 40 subjects with ASD as control group were included. Serum levels of VEGF, IGF-1, and FGF-2 were measured using commercial enzyme-linked immunosorbent assay kits. Results: The study group was significantly higher than the control group in terms of ASD severity, self-harming behavior and sleep disturbance. Serum VEGF and FGF-2 levels were significantly higher in the ASD + BD group than in the control group. There was no significant difference in serum IGF-1 levels between the two groups. There was no correlation between VEGF, IGF-1 and FGF-2 serum levels and ASD severity in the study group. However there was a negative correlation between VEGF levels and age at first diagnosis of BD, and a positive correlation between IGF-1 levels and the number of bipolar episodes in the study group. Conclusion: Growth factors like VEGF and FGF-2 may be potential biomarkers of bipolar disorder in young subjects with ASD. Given the difficulty of clinical management of BD in young subjects with ASD, potential biomarkers would help clinicians in the diagnosis and follow up of BD in this special population. Further research is needed whether VEGF and FGF-2 can be potential biomarkers in the clinical management of young subjects with ASD and BD. [ABSTRACT FROM AUTHOR]

Fermented red ginseng (FRG) enhances the bioactivity and bioavailability of ginsenosides, which possess various immunomodulatory, antiaging, anti-obesity, and antidiabetic properties. However, the effects of FRG extract on muscle atrophy and the underlying molecular mechanisms remain unclear. This study aimed to elucidate the effects of FRG extract on muscle atrophy using both in vitro and in vivo models. In vitro experiments used dexamethasone (DEX)-induced C2C12 myotubes to assess cell viability, myotube diameter, and fusion index. In vivo experiments were conducted on hind limb immobilization (HI)-induced mice to evaluate grip strength, muscle mass, and fiber cross-sectional area (CSA) of the gastrocnemius (GAS), quadriceps (QUA), and soleus (SOL) muscles. Molecular mechanisms were investigated through the analysis of key signaling pathways associated with muscle protein synthesis, energy metabolism, and protein degradation. FRG extract treatment enhanced viability of DEX-induced C2C12 myotubes and restored myotube diameter and fusion index. In HI-induced mice, FRG extract improved grip strength, increased muscle mass and CSA of GAS, QUA, and SOL muscles. Mechanistic studies revealed that FRG extract activated the insulin-like growth factor 1/protein kinase B (Akt)/mammalian target of rapamycin signaling pathway, promoted muscle energy metabolism via the sirtuin 1/peroxisome proliferator-activated receptor gamma-coactivator-1α pathway, and inhibited muscle protein degradation by suppressing the forkhead box O3a, muscle ring-finger 1, and F-box protein (Fbx32) signaling pathways. FRG extract shows promise for ameliorating muscle atrophy by modulating key molecular pathways associated with muscle protein synthesis, energy metabolism, and protein degradation, offering insights for future drug development. [ABSTRACT FROM AUTHOR]

Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This study investigated changes in the secretome of perirenal ASC (prASC) under different conditions: normoxia, cytokine exposure, high glucose, hypoxia, and hypoxia with high glucose. Using mass spectrometry and enrichment clustering analysis, we found that normoxia enriched pathways related to extracellular matrix (ECM) organization, platelet degranulation, and insulin-like growth factor (IGF) transport and uptake. Cytokine exposure influenced metabolism, vascular development, and protein processing pathways. High glucose affected the immune system, metabolic processes, and IGF transport and uptake. Hypoxia impacted immune and metabolic processes and protein processing. Combined hypoxia and high glucose influenced the immune system, IGF transport and uptake, and ECM organization. Our findings highlight the potential of manipulating culturing conditions to produce secretomes with distinct protein and functional profiles, tailoring therapeutic strategies accordingly. [ABSTRACT FROM AUTHOR]

Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P—hospitalized patients with confirmed or suspected COVID-19; I—use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C—placebo or no placebo (standard of care); O—mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T—phase III RCTs. Results: While studying these drugs' respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Microalgae such as Spirulina platensis and essential oils derived from Citrus limon have potential growth-promoting, antimicrobial, antioxidant, and immunostimulant effects for several fish species. This manuscript spotlights Spirulina platensis and Citrus limon essential oil and their roles in improving the performance and health of Nile tilapia. Our results indicate that Spirulina platensis and/or lemon essential oil can be used as natural feed additives during aquafeed formulation to improve fish welfare through nutritional management. The dietary presence of feed additives is crucial for boosting fish growth and immunity. Accordingly, this feeding trial aimed to investigate the effects of the separate and concurrent dietary supplementation of Spirulina platensis (SP) and bitter lemon (Citrus limon) peel essential oil (LEO) on the growth, immunity, antioxidant capacity, and intestinal health of Nile tilapia (Oreochromis niloticus). Four groups of male Nile tilapia were employed. The first group (control) was given the basal diet, while the second and third groups received the basal diet supplemented with LEO extract (1%) and SP (1 g/kg diet), respectively. The fourth group received the basal diet supplemented with a mix of LEO (1%) and SP at 1 g/kg. After two months of feeding, using LEO or/and SP improved the overall growth and immunological parameters, with their combination yielding the best outcomes. The supplementation of LEO or/and SP improved the Nile tilapia's growth metrics and transcriptomic levels of growth-regulating genes such as (oligo-peptide transporter 1 (Pep1), growth hormone receptors 1 (GHR1), and insulin-like growth factor (IGF1). The improved growth performance was linked to significant increases in the expression levels of mucin and fat metabolism-related genes. Moreover, fish supplemented with LEO, SP, or their combination showed enhanced non-specific immunological measures, including phagocytic and lysozyme activities and the mRNA copies of its regulating genes. Additionally, remarkable increases in the antioxidant enzyme activities and the mRNA levels of their related genes were detected. The complement (C3) gene's transcriptomic level was also significantly increased. Furthermore, the dietary supplementation of LEO, SP, or their combination improved the histological structures of the spleen, hepatopancreas, and intestine. The enhanced effects of LEO, SP, or their combination on fish immunity and growth are suggested to be due to their contents of bioactive compounds with anti-inflammatory, antioxidant, and antimicrobial properties. Thus, using the LOE and SP blends as feed additives is recommended for better growth and immunity of Nile tilapia. [ABSTRACT FROM AUTHOR]

Background: Diabetes (primarily type 2) is linked to a higher risk of breast cancer. Insulin-like growth factor (IGF) is one of the most important factors that affects mitosis and thus inhibits apoptosis. The purpose of this study was to compare the pre-treatment insulin-like growth factor (IGF) levels in breast cancer against normal population. Methods: In this case-control study, 60 patients with breast cancer and 60 healthy controls were enrolled in 2017 and 2018 at Tehran's Shahid-Modarres Hospital. In this study, the blood sugar of the patients was examined before entering the study, and the age of the patients was also within the age limit of 18 to 70 years. They were studied to determine the relationship between insulin-like growth factor (ELISA method) and breast cancer. Results: Both groups have similar IGF-1 levels (Ctrl and Case) (P= 0.188). But, IGF-2 levels were significantly higher in breast cancer patients (373.4 vs. 317.3 ng/ml), (P=0.0001). Conclusion: According to our study, IGF-2 may serve as a prognostic biomarker and potential therapeutic target for breast cancer. However, further investigation is needed to validate this claim. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) is considered as a pathogenic factor contributing to sebaceous gland dysfunction, which leads to acne vulgaris. Paeoniflorin (Pae), a bioactive monomer derived from total glycosides of paeony, has shown potential in treating various diseases. However, its anti-acne effects on human sebocytes are not well understood. In this study, we investigated the effects of Pae on acne development induced by IGF-1 in SZ95 sebocytes. Following IGF-1 stimulation, SZ95 sebocytes were exposed to Pae and then determined for proliferation, cell cycle, apoptosis, lipogenesis and pro-inflammatory cytokine secretion. We also analyzed the expression of proteins involved in the PI3K/Akt/FoxO1 and JAK2/STAT3 pathways. In vitro experiments demonstrated that Pae significantly inhibited colony formation, induced G1/S cell cycle arrest, promoted apoptosis, inhibited lipogenesis and cytokine synthesis in IGF-1-treated SZ95 sebocytes. Furthermore, Pae suppressed the phosphorylation of Akt, FoxO1, JAK2, and STAT3. Importantly, the sebo-suppressive and anti-inflammatory effects of Pae were enhanced by blocking PI3K and JAK2. In summary, our findings suggest that Pae has potent anti-proliferative and pro-apoptotic effects in SZ95 sebocytes. Additionally, Pae effectively protects against IGF-1-induced lipogenesis and inflammation by targeting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways. [ABSTRACT FROM AUTHOR]

Background: A decreased glomerular filtration rate (GFR), estimated using creatinine (Cr– eGFR), is often found at the initial presentation of anorexia nervosa (AN). Its pathophysiology has been explained mainly by dehydration, and chronic hypokalemia is also thought to be a cause. However, because we have often experienced cases of AN with decreased Cr-eGFR without these conditions, we must consider different etiologies. The focus of this paper is on low free triiodothyronine (FT3) syndrome. We also discuss the utility of eGFR, estimated using cystatin-C (CysC-eGFR), for these patients. Methods: The data of 39 patients diagnosed with AN between January 2005 and December 2023 was available for study. The characteristics of patients at the lowest and highest body mass index standard deviation score (BMI-SDS) were examined. Data on the parameters Cr-eGFR, CysC-eGFR, dehydration markers, potassium (K), and hormonal data and BMI-SDS were assessed during the treatment course to evaluate the correlations in these parameters. Blood hematocrit, uric acid (UA), blood urine nitrogen (BUN) level, and urine specific gravity were adopted as dehydration markers; FT3, free thyroxine, thyroid stimulating hormone, and insulin-like growth factor were adopted as hormonal data. Cr-eGFR and simultaneously evaluated dehydration markers, K, or hormonal data were extracted and correlations associated with the changes in BMI-SDS were examined. Furthermore, Cr-eGFR and simultaneously assessed CysC-eGFR were compared. Results: When the BMI-SDS was at the lowest value, low-FT3 syndrome was shown. Severe hypokalemia was not found in our study. A linear relation was not found between Cr-eGFR and BMI-SDS. A statistically significant correlation was found between Cr-eGFR and FT3 (p = 0.0025). Among the dehydration markers, statistically significant correlations were found between Cr-eGFR and BUN or UA. The difference between Cr-eGFR and CysC-eGFR was prominent, and CysC-eGFR showed much higher values. Conclusions: Our data indicates that low-FT3 syndrome and dehydration were related to the renal function of our patients with AN. Furthermore, our data suggest that caution is needed in the interpretation of kidney function evaluation when using CysC-eGFR in cases of AN. [ABSTRACT FROM AUTHOR]

Background: The choroid plexus (CP) is an understudied tissue in the central nervous system and is primarily implicated in cerebrospinal fluid (CSF) production. CP also produces numerous neurotrophic factors (NTF) which circulate to different brain regions. Regulation of NTFs in the CP during natural aging is largely unknown. Here, we investigated the age and gender-specific transcription of NTFs along with the changes in the tight junctional proteins (TJPs) and the water channel protein Aquaporin (AQP1). Methods: Male and female mice were used for our study. Age-related transcriptional changes were analyzed using quantitative PCR at three different time points: mature adult, middle-aged, and aged. Transcriptional changes during aging were further confirmed with digital droplet PCR. Additionally, we used immunohistochemical analysis (IHC) for the evaluation of in vivo protein expression. We further investigated the cellular phenotype of these NTFS, TJP, and water channel proteins in the mouse CP by co-labeling them with the classical vascular marker, Isolectin B4, and epithelial cell marker, Plectin. Results: Aging significantly altered NTF gene expression in the CP. Brain-derived neurotrophic factor (BDNF), Midkine (MDK), VGF, Insulin-like growth factor (IGF1), IGF2, Klotho (KL), Erythropoietin (EPO), and its receptor (EPOR) were reduced in the aged CP of males and females. Vascular endothelial growth factor (VEGF) transcription was gender-specific; in males, gene expression was unchanged in the aged CP, while females showed an age-dependent reduction. Age-dependent changes in VEGF localization were evident, from vasculature to epithelial cells. IGF2 and klotho localized in the basolateral membrane of the CP and showed an age-dependent reduction in epithelial cells. Water channel protein AQP1 localized in the tip of epithelial cells and showed an age-related reduction in mRNA and protein levels. TJP's JAM, CLAUDIN1, CLAUDIN2 and CLAUDIN5 were reduced in aged mice. Conclusions: Our study highlights transcriptional level changes in the CP during aging. The age-related transcriptional changes exhibit similarities as well as gene-specific differences in the CP of males and females. Altered transcription of the water channel protein AQP1 and TJPs could be involved in reduced CSF production during aging. Importantly, reduction in the neurotrophic factors and longevity factor Klotho can play a role in regulating brain aging. [ABSTRACT FROM AUTHOR]

Background: Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality. This study aimed to investigate the association of plasma proteins with all-cause and cause-specific mortality among individuals with and without baseline type 2 diabetes (T2D) and evaluate their impact on the prediction of all-cause mortality in two prospective Cooperative Health Research in the Region of Augsburg (KORA) studies. Methods: The discovery cohort comprised 1545 participants (median follow-up 15.6 years; 244 with T2D: 116 total, 62 cardiovascular, 31 cancer-related and 23 other-cause deaths; 1301 without T2D: 321 total, 114 cardiovascular, 120 cancer-related and 87 other-cause deaths). The validation cohort comprised 1031 participants (median follow-up 6.9 years; 203 with T2D: 76 total, 45 cardiovascular, 19 cancer-related and 12 other-cause deaths; 828 without T2D: 169 total, 74 cardiovascular, 39 cancer-related and 56 other-cause deaths). We used Cox regression to examine associations of 233 plasma proteins with all-cause and cause-specific mortality and Lasso regression to construct prediction models for all-cause mortality stratifying by baseline T2D. C-index, category-free net reclassification index (cfNRI), and integrated discrimination improvement (IDI) were conducted to evaluate the predictive performance of built prediction models. Results: Thirty-five and 62 proteins, with 29 overlapping, were positively associated with all-cause mortality in the group with and without T2D, respectively. Out of these, in the group with T2D, 35, eight, and 26 were positively associated with cardiovascular, cancer-related, and other-cause mortality, while in the group without T2D, 55, 41, and 47 were positively associated with respective cause-specific outcomes in the pooled analysis of both cohorts. Regulation of insulin-like growth factor (IGF) transport and uptake by IGF-binding proteins emerged as a unique pathway enriched for all-cause and cardiovascular mortality in individuals with T2D. The combined model containing the selected proteins (five and 12 proteins, with four overlapping, in the group with and without T2D, respectively) and clinical risk factors improved the prediction of all-cause mortality by C-index, cfNRI, and IDI. Conclusions: This study uncovered shared and unique mortality-related proteins in persons with and without T2D and emphasized the role of proteins in improving the prediction of mortality in different T2D subgroups. [ABSTRACT FROM AUTHOR]

Background: Malignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group. Results: CR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased. Conclusions: The combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) is an autologous blood-derived product utilized nowadays as a treatment for various non-hemostatic, orthopedic, and muscular injuries. Although the exact mechanism of PRP use and effectivity is not yet fully understood, PRP applications are extensively developing and expanding. PRP, as the name implies, contains mostly platelets; thus, platelets are the main players in this therapeutic management for numerous tissue disorders and conditions. Platelets are known to facilitate wound healing and tissue repair through the various growth factors present in their granules. The growth factors in platelets also act on cells found in tissues other than those involved in wound repair, resulting in an increased interest in PRP use as a regenerative therapy for various disorders. In this paper, we discussed platelets and its morphology, and the various growth factors present within the platelet granules. The effects of these growth factors on tissue recovery are highlighted. PRP components, preparation considerations and classifications are presented here to showcase PRP differences and complexity. [ABSTRACT FROM AUTHOR]

Background: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. Methods: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. Results: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. Conclusions: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity. [ABSTRACT FROM AUTHOR]

Background: Bronchopulmonary dysplasia (BPD) is the most common long-term complication of extreme preterm birth. It is associated with lifelong multisystemic consequences. Advances in neonatal care have not reduced the incidence of BPD and no new breakthrough therapy has been successfully translated into the clinic in recent decades. Summary: Current evidence demonstrates benefit of new modalities of first-line noninvasive positive pressure ventilation, selected strategies of postnatal corticosteroid administration, alternative surfactant delivery methods, and caffeine. Promising emerging therapies that are being translated from bench to bedside include mesenchymal stromal cells (MSCs), insulin-like growth factor 1/binding protein-3 (IGF-1/IGFBP-3), and interleukin 1 receptor (IL-1R) antagonist (anakinra). Strong preclinical data support efficacy of MSCs in attenuating neonatal lung injury. Early-phase clinical trials have already demonstrated safety and feasibility in preterm infants. Phase II studies that aimed at demonstrating efficacy are currently underway. Both IGF-1/IGFBP-3 and IL-1R antagonist present with biological plausibility and animal data of efficacy. Phase I/II clinical trials are currently recruiting patients. Key Messages: Early noninvasive respiratory support, late systemic dexamethasone, less invasive surfactant administration, and caffeine are proven strategies in reducing the risk of BPD. Potentially disruptive therapies – MSCs, IGF-1/IGFBP-3, and anakinra – are being advanced to clinical trials and their efficacy in remains to be demonstrated. Continued research efforts are needed in the growing population of extremely preterm infants at risk of developing BPD. [ABSTRACT FROM AUTHOR]

Objective: Mixed gonadal dysgenesis (MGD) is an uncommon chromosomal Disorder of Sexual Development (DSD). There is insufficient information regarding clinical findings and growth patterns. This study aimed to provide more information about mixed gonadal dysgenesis, which has not yet been sufficiently defined. Materials and Methods: Data from 10 patients diagnosed with mixed gonadal dysgenesis were retrospectively reviewed. Clinical presentations, complaints at admission, imaging, genetic results, and treatments received by the patients were examined. Gonadal status and the gender of the patients were reared and evaluated by a multidisciplinary council decision. If received, growth hormone treatment doses and height gains were examined. Results: The patients’ ages at admission range from 6 months to 17.5 years. The median height SDS of the patients was −0.75 (2.73), the mean body weight SDS was −0.49 (±1.46), and the mean body mass index (BMI) SDS was 0.26 (±0.97). The complaints at admission varied, including ambiguous genitalia, short stature, and absence of menstruation. Some patients are completely in the female phenotype, while some are inadequately virilized male phenotype. External Masculinization Score (EMS) ranges from 1 to 6.5. The decision to raise 6 patients as female and 4 patients as male was made by a multidisciplinary council. Growth hormone treatment was administered to patients raised as female and diagnosed with short stature. The height SDS gain in treated patients was 0.42 (±0.49). Conclusion: Due to its rarity and varied clinical presentation, our knowledge about mixed gonadal dysgenesis is limited. Therefore, early diagnosis and individualized treatment plans are crucial for this patient group. [ABSTRACT FROM AUTHOR]

This non-randomized controlled trial aimed to compare the effect of the 5:2 diet on insulin levels as a primary outcome and markers of insulin secretion (connecting peptide (C-peptide) and insulin-like growth factor binding protein-1 (IGFBP-1)) and sensitivity (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), as well as body composition as secondary outcomes in overweight/obese individuals with and without type 2 diabetes (T2D). Ninety-seven participants (62% women), 35 with T2D and 62 BMI- and waist-matched controls without T2D, followed the 5:2 diet (two days per week of fasting) for six months with a 12-month follow-up. At six months, there was no loss to follow-up in the T2D group, whereas four controls discontinued this study. Overall, 82% attended the 12-month follow-up. After the intervention, insulin levels decreased in the control group and glucose decreased in the T2D group, while C-peptide, HOMA-IR, waist circumference, BMI, trunk, and total fat% decreased in both groups. Furthermore, low IGFBP-1, indicating hyperinsulinemia, improved in the T2D group. The changes in fasting glucose and waist measurement were significantly more improved in the T2D group than in the controls. Persistent positive effects were observed at the 12-month follow-up. The 5:2 diet for six months was feasible and efficient to reduce markers of insulin secretion and resistance and therefore holds promise as management of overweight/obesity in subjects with and without T2D. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) poses significant challenges due to its complex biological characteristics and high recurrence rate. The high recurrence rate of LUAD is closely associated with cellular dormancy, which enhances resistance to chemotherapy and evasion of immune cell destruction. Using single-cell RNA sequencing (scRNA-seq) data from LUAD patients, we categorized the cells into two subclusters: dormant and active cells. Utilizing high-density Weighted Gene Co-expression Network Analysis (hdWGCNA) and pseudo-time cell trajectory, aberrant expression of genes involved in protein O-glycosylation was detected in dormant cells, suggesting a crucial role for O-glycosylation in maintaining the dormant state. Intercellular communication analysis highlighted the interaction between fibroblasts and dormant cells, where the Insulin-like Growth Factor (IGF) signaling pathway regulated by O-glycosylation was crucial. By employing Gene Set Variation Analysis (GSVA) and machine learning, a risk score model was developed using hub genes, which showed high accuracy in determining LUAD prognosis. The model also demonstrated robust performance on the training dataset and excellent predictive capability, providing a reliable basis for predicting patient clinical outcomes. The group with a higher risk score exhibited a propensity for adverse outcomes in the tumor microenvironment (TME) and tumor mutational burden (TMB). Additionally, the 50% inhibitory concentration (IC50) values for chemotherapy exhibited significant variations among the different risk groups. In vitro experiments demonstrated that EFNB2, PTTG1IP, and TNFRSF11A were upregulated in dormant tumor cells, which also contributed greatly to the diagnosis of LUAD. In conclusion, this study highlighted the crucial role of O-glycosylation in the dormancy state of LUAD tumors and developed a predictive model for the prognosis of LUAD patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Wilms tumor is the most common pediatric primary renal malignancy globally but exhibits significant variations in epidemiological, clinical, and molecular aspects among different populations. Wilms tumor has been shown to occur at lower incidences, younger ages, and earlier stages of disease with higher incidences of favorable histology among Asians compared to Caucasians. Despite a worldwide convergence between the two main management approaches, it is not known if these are generalizable to all ethnic populations. This paper summarizes the current literature on the inter-ethnic variations in the clinical, pathological, and molecular characteristics of Wilms tumor. Wilms tumor is the commonest primary renal malignancy in children and demonstrates substantial inter-ethnic variation in clinical, pathological, and molecular characteristics. Wilms tumor occurs at a lower incidence and at a younger age in Asians compared to Caucasians and Africans. Asians also present at an earlier stage of disease, with a higher incidence of favorable histology tumors and a lower incidence of perilobar nephrogenic rests compared to Caucasians, while African children present with more advanced disease. Studies have implicated population differences in the incidence of WT1 mutations, loss of imprinting of the IGF2 locus, and loss of heterozygosity of 1p/16q, or 1q gain as possible bases for epidemiological differences in the disease profile of Wilms tumors in various ethnic groups. Yet, evidence to support these associations is confounded by differences in treatment protocols and inequalities in the availability of treatment resources and remains limited by the quality of population-based data, especially in resource-limited settings. [ABSTRACT FROM AUTHOR]

Cancer is a global health concern influenced by genetics, environment and lifestyle choices. Recent research shows that a ketogenic diet (KD) might ease cancer symptoms and reduce tumour size. We hypothesised that the KD could result in improvements in cancer‐related variables. Therefore, this study aims to perform a systematic review and meta‐analysis to assess the KD's efficacy for patients with cancer. The databases PubMed (MEDLINE), Web of Science, CINAHL and Open Grey were utilised for conducting a systematic review and meta‐analysis. The analysis was limited to randomised controlled trials with adult participants aged 18 years and above. Levels of glucose, cholesterol, insulin‐like growth factor 1, weight and quality of life were evaluated following the KD. After identifying 596 articles in the initial search, eight studies, lasting between 4 and 16 weeks, were included in the systematic review and seven in the meta‐analysis. The KD led to decreased glucose levels in patients with cancer but did not show significant improvements in cholesterol, insulin‐like growth factor 1, weight or quality of life. Based on the results of this systematic review and meta‐analysis, there is insufficient evidence to establish a definitive link between the KD and cancer‐related parameters. While some studies suggest potential benefits in terms of some outcomes and tumour size reduction, further research is required to fully comprehend the effects of this diet. [ABSTRACT FROM AUTHOR]

Context Prader-Willi syndrome (PWS) is associated with impaired growth hormone (GH) secretion and decreased insulin-like growth factor (IGF)-I levels. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implication in PWS is unknown. Objective We determined serum levels of PAPP-As and STCs in association with IGF axis components in prepubertal and pubertal patients with PWS, also analyzing the effect of GH treatment. Methods Forty children and adolescents with PWS and 120 sex- and age-matched controls were included. The effect of GH was evaluated at 6 months of treatment in 11 children. Results Children with PWS had lower levels of total IGF-I, total and intact IGFBP-3, acid-labile subunit, intact IGFBP-4, and STC-1, and they had higher concentrations of free IGF-I, IGFBP-5, and PAPP-A. Patients with PWS after pubertal onset had decreased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4 levels, and had increased total IGFBP-4, and STCs concentrations. GH treatment increased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4, with no changes in PAPP-As, STCs, and free IGF-I levels. Standardized height correlated directly with intact IGFBP-3 and inversely with PAPP-As and the free/total IGF-I ratio. Conclusion The increase in PAPP-A could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability in children with PWS. Further studies are needed to establish the relationship between growth, GH resistance, and changes in the IGF axis during development and after GH treatment in these patients. [ABSTRACT FROM AUTHOR]

The present work investigates the potential role of metformin nanoparticles (MTF-NPs) as a radio-protector against cardiac fibrosis and inflammation induced by gamma radiation via CXCL1/TGF-β pathway. Lethal dose fifty of nano-metformin was determined in mice, then 21 rats (male albino) were equally divided into three groups: normal control (G1), irradiated control (G2), and MTF-NPs + IRR (G3). The possible protective effect of MTF-NPs is illustrated via decreasing cardiac contents of troponin, C-X-C motif Ligand 1 (CXCL1), tumor growth factor β (TGF-β), protein kinase B (AKT), and nuclear factor-κB (NF-κB). Also, the positive effect of MTF-NPs on insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) in heart tissues using immunohistochemical technique is illustrated in the present study. Histopathological examination emphasizes the biochemical findings. The current investigation suggests that MTF-NPs might be considered as a potent novel treatment for the management of cardiac fibrosis and inflammation in patients who receive radiotherapy or workers who may be exposed to gamma radiation. [ABSTRACT FROM AUTHOR]

Objective: Bisphenol A and phthalate are known endocrine disruptors and capable of inducing epigenetic changes in the human population. However, their impact on the placenta is less well studied. Our objective was to measure the effect of exposure to bisphenol A and benzyl butyl phthalate in first-trimester HTR8-SVneo and third-trimester 3A-sub E trophoblast cells by profiling the DNA methylation pattern of the imprinting control region of the IGF2 (insulin-like growth factor) and H19 genes. Methods: Human placental HTR8-SVneo and 3A-sub E cell lines were treated with two sub-lethal concentrations of bisphenol A and benzyl butyl phthalate. Demethylating agent, 5-azacytidine, was used as a positive control. Cells were harvested on post-treatment days 1 and 4. The methylation profile of six CpG dinucleotide sites, part of the CTCF 6 binding site of the IGF2/H19 imprinting control region, was determined by pyrosequencing. Results: In the first-trimester HTR8-SVneo cell line, we observed a significant increased methylation of the CpG sites 3, 4 when treated with a high concentration of bisphenol A or benzyl butyl phthalate while increased methylation at site 6 for both high and low dose treatment on day 4. Demethylation of the CpG sites 1, 4, and 6 was observed when treated with 5-azacytidine on day 4. In the third-trimester 3A-sub E cell line, no significant changes in the methylation profile were observed under any treatment conditions. Conclusions: The results of this study demonstrate the capability of epigenetic changes in human placenta cells induced by bisphenol A and benzyl butyl phthalate. The observed methylation changes only in the first-trimester HTR8-SVneo cells phthalate may reflect a window of epigenetic susceptibility related to these environmental toxicants. [ABSTRACT FROM AUTHOR]

Background: Doege-Potter syndrome is a rare paraneoplastic phenomenon associated with solitary fibrous tumors of the pleura (SFTPs). It is characterized by the presence of severe, sustained, and treatment-refractory hypoglycemia. Hypoglycaemia, which may be the sole symptom at disease onset, is mediated by the secretion of high-molecular-weight insulin-like growth factor (IGF-2). Most tumors exhibit benign behavior, with a 100% survival rate at 5 years. However, 10% of these tumors may display aggressive behavior with local or metastatic recurrence. We present a clinical case of a patient with a benign solitary fibrous tumor of the pleura who presented with symptomatic hypoglycemia and required pulmonary and pleural surgical resection to control the paraneoplastic phenomenon. Case presentation: A Hispanic 46-year-old man presented with a 15-day history of transient alterations in consciousness worsened by fasting. The relevant medical history included obstructive sleep apnea treated with continuous positive air pressure (CPAP) and previous smoking. In-hospital studies revealed noninsulinemic hypoglycemia and a benign SFTP. Complete surgical resection was performed while the patient received dextrose fluids and corticosteroids perioperatively for hypoglycemia. Subsequently, the hypoglycemia resolved, and the patient was followed-up without disease recurrence. Conclusion: Doege-Potter syndrome is challenging to recognize. However, effective treatment can be achieved with a high survival rate. Raising awareness among healthcare professionals about the recognition of this paraneoplasic syndrome patients will improve diagnostic suspicion, biochemical confirmation, the development of diagnostic and therapeutic guidelines, and the creation of predictive indices for aggressive presentations requiring closer monitoring. [ABSTRACT FROM AUTHOR]

One of the most vital processes of the body is the cardiovascular system's proper operation. Physiological processes in the heart are regulated by the balance of cardioprotective and pathological mechanisms. The insulin-like growth factor system (IGF system, IGF signaling pathway) plays a pivotal role in regulating growth and development of various cells and tissues. In myocardium, the IGF system provides cardioprotective effects as well as participates in pathological processes. This review summarizes recent data on the role of IGF signaling in cardioprotection and pathogenesis of various cardiovascular diseases, as well as analyzes severity of these effects in various scenarios. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with an urgent unmet clinical need for new therapies. Using a combination of in vitro assays and in vivo preclinical models we demonstrate that therapeutic inhibition of the IGF signalling axis promotes the accumulation of CD8+ cytotoxic T cells within the tumour microenvironment of PDAC tumours. Mechanistically, we show that IGF blockade promotes macrophage and fibroblast production of the chemokines CXCL9 and CXCL10 to facilitate CD8+ T cell recruitment and trafficking towards the PDAC tumour. Exploring this pathway further, we show that IGF inhibition leads to increased STAT1 transcriptional activity, correlating with a downregulation of the AKT/STAT3 signalling axis, in turn promoting Cxcl9 and Cxcl10 gene transcription. Using patient derived tumour explants, we also demonstrate that our findings translate into the human setting. PDAC tumours are frequently described as "immunologically cold", therefore bolstering CD8+ T cell recruitment to PDAC tumours through IGF inhibition may serve to improve the efficacy of immune checkpoint inhibitors which rely on the presence of CD8+ T cells in tumours. [ABSTRACT FROM AUTHOR]

The hypothalamic‐pituitary‐somatotropic (HPS) axis controls many physiological and pathophysiological processes. The phenomenon of insensitivity to growth hormone resistance (GHres) was previously reported to be due to the development of inflammation. Therefore, the primary aim of the study was to determine the impact of inflammation caused by lipopolysaccharides (LPS) on the secretory activity of the HPS axis in sheep. The further goal was to determine the effect of inflammatory factors on individual components involved in intracellular signal transduction to GH via the GH receptor (GHR). The research was carried out on 24 seasonal sheep kept under a short‐day photoperiod, randomly divided into two groups. Before the experiment, the sheep estrous cycles were synchronized. The results of the current study in a sheep model showed that inflammation impairs the activity of the somatotropic axis. On the one hand, LPS injection stimulated (p < 0.01) GH secretion, and on the other hand, it reduced the liver's sensitivity to this hormone by directly reducing (p < 0.01) GHR expression and activating the GHR inhibitory signal transduction mechanism. A symptom of such an inhibitory postreceptor signaling pathway may be due to an increase in SOCS3 expression (p < 0.01). The effect of various inhibition pathways is a significant reduction in the expression of the main transcription activator IGF1‐STAT5B (p < 0.05). The action of GHres in the liver resulted in the inhibition of IGF1 secretion, which in the long term may have negative consequences for growth and development. Our study suggests that disruption of the GH cell signaling pathway may be one of the important elements of the pathophysiology of inflammation. It can suppress growth and hepatic metabolism to spare energy expenditure. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints. Lymphoplasmacytic lymphoma is a B-cell low-grade lymphoma with no approved standard therapy. Here the authors report a non-randomized phase 1 clinical trial performing early intervention with personalized neoantigen vaccines in asymptomatic patients and associating clinical efficacy with successful perturbation of the tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the relationship between the tri-ponderal mass index (TMI), a new indirect measure of fat mass, and insulin-like growth factor (IGF)-I/ IGF binding protein (IGFBP)-3. Methods: The study included 1,630 children and adolescents who visited Jeonbuk National University Children's Hospital. Each patient’s medical record was retrospectively reviewed for age, sex, height, weight, body mass index (BMI), TMI, and IGF-1 and IGFBP-3 levels. Study participants were divided by sex and then categorized by age, BMI, and TMI. Finally, the correlations of TMI with IGF-1 level, IGF-1 standard deviation score (SDS), IGFBP-3 level, IGFBP-3 SDS, and IGF-1/IGFBP-3 ratio were investigated. Results: All participants were <19 years of age. BMI correlated with IGF-1 and IGFBP-3 levels in both sexes; however, the relationship with TMI differed by sex. TMI correlated with IGF-1 and IGFBP-3 SDS in boys and with IGF-1, IGFBP-3, and IGFBP-3 SDS in girls across all ages. In boys, BMI and TMI significantly correlated with IGF-1, IGF-1 SDS, IGFBP-3, IGFBP-3 SDS, and the IGF-1/IGFBP-3 ratio in the normal-weight group. TMI also correlated with IGF-1, IGFBP-3, and IGFBP-3 SDS in the overweight group. In girls, BMI significantly correlated with IGF-1, IGF-1 SDS, IGFBP-3, IGFBP-3 SDS, and the IGF-1/IGFBP-3 ratio in the normal-weight group and with IGFBP-3 and IGFBP-3 SDS in the overweight group, while TMI correlated with IGF-1, IGF-1 SDS, and the IGF-1/IGFBP-3 ratio in the normal-weight group; with IGF-1, IGFBP-3, and IGFBP-3 SDS in the overweight group; and with IGFBP-3 SDS in the obese group. Conclusion: TMI may more strongly correlate with IGFBP-3 level than BMI in overweight boys and with IGFBP-3 SDS in overweight and obese girls. The correlation of IGFBP-3 SDS with TMI may be helpful for evaluating weight status in adolescent girls. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere with IGF-1 immunoassays urged the implementation of various techniques to moderate this issue and provide accurate IGF-1 results. Additionally, in response to the limitations associated with IGF-1 immunoassays and the occurrence of discordant IGF-1 results, modern mass spectrometric methods were developed to facilitate the quantification of IGF-1 levels. Taking advantage of their ability to minimize the interference caused by IGF-1 variants, mass spectrometric methods offer the capacity to deliver robust, reliable, and accurate IGF-1 results, relying on the precision of mass measurements. This also enables the potential detection of pathogenic mutations through protein sequence analysis. However, despite the analytical challenges, the discordance in IGF-1 reference intervals can be attributed to a multitude of factors, potentially leading to distinct interpretations of results. The establishment of reference intervals for each assay is a demanding task, and it requires nationwide multicenter collaboration among laboratorians, clinicians, and assay manufacturers to achieve this common goal in a cost-effective and resource-efficient manner. In this comprehensive review, we examine the challenges associated with the standardization of IGF-1 measurement methods, the minimization of pre-analytical factors, and the harmonization of reference intervals. Particular emphasis will be placed on the development of IGF-1 measurement techniques using "top-down" or "bottom-up" mass spectrometric methods. [ABSTRACT FROM AUTHOR]

The article discusses the need for reliable biomarkers to detect pulmonary congestion in patients with heart failure (HF) in order to prevent hospitalizations and improve patient outcomes. The current biomarkers used in clinical practice, B-type natriuretic peptides (NPs), have limitations such as being affected by comorbidities and having inconsistent measurement intervals. The article presents the BioMEMS study, which aims to identify alternative biomarkers that accurately reflect worsening congestion and can be easily measured. The study collects blood samples from HF patients and analyzes them using the Olink Cardiovascular III panel to evaluate the relationship between biomarkers and pulmonary artery pressures. The ultimate goal is to develop a biomarker-based management strategy for HF patients that is decentralized, manageable, and economically sustainable. [Extracted from the article]

Background and Purpose: Excessive fibrogenesis is associated with adverse cardiac remodelling and heart failure. The myofibroblast, primarily derived from resident fibroblast, is the effector cell type in cardiac fibrosis. Megakaryocytic leukaemia 1 (MKL1) is considered the master regulator of fibroblast–myofibroblast transition (FMyT). The underlying transcriptional mechanism is not completely understood. Our goal was to identify novel transcriptional targets of MKL1 that might regulate FMyT and contribute to cardiac fibrosis. Experimental Approach: RNA sequencing (RNA‐seq) performed in primary cardiac fibroblasts identified insulin‐like growth factor binding protein 5 (IGFBP5) as one of the genes most significantly up‐regulated by constitutively active (CA) MKL1 over‐expression. IGFBP5 expression was detected in heart failure tissues using RT‐qPCR and western blots. Key Results: Once activated, IGFBP5 translocated to the nucleus to elicit a pro‐FMyT transcriptional programme. Consistently, IGFBP5 knockdown blocked FMyT in vitro and dampened cardiac fibrosis in mice. Of interest, IGFBP5 interacted with nuclear factor of activated T‐cell 4 (NFAT4) to stimulate the transcription of microfibril‐associated protein 5 (MFAP5). MFAP5 contributed to FMyT and cardiac fibrosis by enabling sterol response element binding protein 2 (SREBP2)‐dependent cholesterol synthesis. Conclusions and Implications: Our data unveil a previously unrecognized transcriptional cascade, initiated by IGFBP5, that promotes FMyT and cardiac fibrosis. Screening for small‐molecule compounds that target this axis could yield potential therapeutics against adverse cardiac remodelling. [ABSTRACT FROM AUTHOR]

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) exhibit multipotency, self-renewal, and immune-modulatory properties, making them promising in regenerative medicine, particularly in cardiovascular treatments. However, optimizing the MSC source and induction method of cardiac differentiation is challenging. This study compares the cardiomyogenic potential of bone marrow (BM)-MSCs and adipose-derived (AD)-MSCs using 5-Azacytidine (5-Aza) alone or combined with low doses of Fibroblast Growth Factor (FGF) and Insulin-like Growth Factor (IGF). BM-MSCs and AD-MSCs were differentiated using two protocols: 10 μmol 5-Aza alone and 10 μmol 5-Aza with 1 ng/mL FGF and 10 ng/mL IGF. Morphological, transcriptional, and translational analyses, along with cell viability assessments, were performed. Both the MSC types exhibited similar morphological changes; however, AD-MSCs achieved 70–80% confluence faster than BM-MSCs. Surface marker profiling confirmed CD29 and CD90 positivity and CD45 negativity. The differentiation protocols led to cell flattening and myotube formation, with earlier differentiation in AD-MSCs. The combined protocol reduced cell mortality in BM-MSCs and enhanced the expression of cardiac markers (MEF2c, Troponin I, GSK-3β), particularly in BM-MSCs. Immunofluorescence confirmed cardiac-specific protein expression in all the treated groups. Both MSC types exhibited the expression of cardiac-specific markers indicative of cardiomyogenic differentiation, with the combined treatment showing superior efficiency for BM-MSCs. [ABSTRACT FROM AUTHOR]

(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case–control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor binding protein 7 (IGFBP7) serves as a crucial extracellular matrix protein, exerting pivotal roles in both physiological and pathological processes. This comprehensive review meticulously delineates the structural attributes of IGFBP7, juxtaposing them with other members within the IGFBP families, and delves into the expression patterns across various tissues. Furthermore, the review thoroughly examines the multifaceted functions of IGFBP7, encompassing its regulatory effects on cell proliferation, apoptosis, and migration, elucidating the underlying mechanistic pathways. Moreover, it underscores the compelling roles in tumor progression, acute kidney injury, and reproductive processes. By rigorously elucidating the diverse functionalities and regulatory networks of IGFBP7 across various physiological and pathological contexts, this review aims to furnish a robust theoretical framework and delineate future research trajectories for leveraging IGFBP7 in disease diagnosis, therapeutic interventions, and pharmaceutical innovations. [ABSTRACT FROM AUTHOR]