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Reference intervals are among the most widely used decision-making tools in the medical field, and are invaluable in the interpretation of laboratory test results. Moreover, when several biochemical analytes are needed to diagnose the same condition, a multivariate reference region is necessary to take the correlations among the analytes into account. Traditionally, multivariate reference regions have been constructed as ellipsoidal in shape. Since such regions are difficult to interpret and cannot detect the outlyingness of a specific analyte, many authors prefer rectangular regions. Reference intervals and regions may also depend on covariates such as age and sex. The covariate values are often random quantities since they are typically not controlled in reference interval determination studies. In this study, we propose procedures to construct rectangular multivariate reference regions that incorporate random covariate information. The reference regions are computed in a multivariate normal setting, using a prediction region criterion. A parametric bootstrap approach is employed to compute the prediction factor. Numerical results show that the parametric bootstrap approach is quite accurate, with coverage probabilities close to the desired nominal value. Finally, we apply the proposed methods to real-life data from a study to compute covariate-dependent reference regions for insulin-like growth factors. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence and impact of acute kidney injury (AKI) following cardiac surgery, particularly coronary artery bypass grafting (CABG). It highlights the PROTECTION trial, which investigated the efficacy of intravenous amino acid therapy (Isopuramin 10%) in preventing AKI in patients undergoing elective cardiac surgery. The trial showed a statistically significant reduction in AKI incidence with amino acid infusion compared to a placebo, particularly in patients aged ≥75 years. While promising, further research is needed to explore the mechanisms and long-term benefits of amino acid infusions in preventing AKI, as well as to determine optimal dosing and timing for patient outcomes. [Extracted from the article]

Purpose: The present study aims to describe initial changes in muscle thickness and composition, muscle growth signaling mediators, and systemic inflammation in critically ill patients after major trauma. Methods: This observational study was carried out in a Level-I nonprofit trauma center. Thirty adults requiring mechanical ventilation were assessed within 24 h post-admission. Skeletal muscle wasting was evaluated using ultrasound for muscle thickness and echogenicity along with circulating insulin-like growth factor 1 (IGF-1) and inflammatory cytokines over five consecutive days. Changes over time were assessed using ANOVA repeated-measures analysis with a Bonferroni post-hoc test. Bivariate correlations were evaluated using Pearson or Spearman coefficients. Results: Over five days, a significant decrease (11%) in rectus femoris thickness (3.91 ± 0.86 to 3.47 ± 0.64, cm, p = 0.01) and an increase (29%) in echogenicity (62.1 ± 13.1 to 80.4 ± 17.3, AU, p < 0.01) were observed among the 30 patients included in this study. Circulating levels of IGF-1 exhibited a 38% reduction (68.8 ± 43.6 to 42.4 ± 29.4, ng/mL, p = 0.01). Furthermore, pro-inflammatory cytokine (IFN-y) increased by 17% (4.83 ± 1.39 to 5.66 ± 1.61, pg./mL, p = 0.02) from day 1 to day 5. Conclusions: These findings reveal substantial thickness and muscle composition alterations within 48 h post-admission, worsening over five days. Despite standard rehabilitation care, changes in IGF-1 and IFN-y levels suggest early declines in muscle growth stimulus and increased inflammation. [ABSTRACT FROM AUTHOR]

Background: Somatostatin receptor analogs (SRAs) and dopamine agonists (DAs) are the main medical treatments for patients with acromegaly who fail to achieve remission after surgery. We aimed to explore the potential role of select clinical, biochemical, and radiological factors in predicting biochemical and structural responses to medical therapy in a real-world setting. Methods: This retrospective cohort study included 58 patients with active acromegaly following surgery treated with Octreotide long-acting release (LAR) (± Cabergoline). Biochemical outcomes were defined as the tight biochemical response (TBR; normal insulin-like growth factor-1(IGF-1)) and biochemical control (BC; IGF-1 ≤ 1.2 upper limit of normal (ULN)). The structural response was defined as > 25% reduction in one dimension of the tumor at the last visit. Univariate and multivariate analyses assessed the predictors of biochemical and structural response. Results: The mean age of the participants was 41.5 ± 11.7 years. They were followed for a median of 27.6 (19.2–43.2) months. At the last visit, TBR and BC were achieved in 48.3% and 51.7% of the patients. Moreover, 51.4% of the patients showed a structural response. Applying the age-sex adjusted model, post-operative IGF-1 was inversely associated with TBR [OR 0.34, P = 0.006] and BC [OR 0.30, P = 0.004]. Moreover, Knosp grading < 3 compared to ≥ 3, and T2-hypointensity compared to the non-T2-hypointensity were associated with higher odds of TBR [OR 3.98, P = 0.04], [OR 27.63, P = 0.01], and BC [OR 5.80, P = 0.01], [OR 35.15, P = 0.01], respectively. Conclusions: Post-operative IGF-1, Knosp grading, and T2-hypointensity could be considered for an individualized treatment plan in acromegaly. Accordingly, we propose an individual multidisciplinary treatment approach for patients not achieving remission after surgery. [ABSTRACT FROM AUTHOR]

The 31st Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP) in 2024 in Santiago, Chile, featured abstracts on various clinical cases, including a pediatric case of non-metastatic abdominal paraganglioma with a new pathogenic variant in SDHB. Other cases discussed included hyperlipoproteinemia in a pediatric patient, ovotesticular sex differentiation disorder, and frontometaphyseal dysplasia type II. The research aimed to identify new candidate genes linked to delayed puberty in boys and girls with prepubertal sexual development, revealing rare loss-of-function variants in constraint genes. Liraglutide therapy showed promising results in managing hypothalamic obesity in young patients with craniopharyngioma-associated hypothalamic obesity, suggesting it as a potential treatment option. A study conducted at Nemours Children's Health in Jacksonville, Florida, focused on the positive effects of supervised home high-intensity interval training (HIIT) on metabolic control, physical fitness, and mental health in adolescents with type 1 diabetes. [Extracted from the article]

Metabolic changes are essential for axonal regeneration. Neurons may convert their inert metabolic state to an anabolic metabolism to support axon regrowth. Preconditioning injury in peripheral nerves endows neurons with a regenerative capacity associated with metabolic modification. Multiple growth factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF), promote axonal regeneration by stimulating the mechanistic target of rapamycin (mTOR) pathway and upregulating anabolic metabolism. Cellular metabolism and epigenetic modification are tightly interconnected and mutually regulated during axonal regeneration. Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function. [ABSTRACT FROM AUTHOR]

Background: The understanding of disease pathophysiology is pivotal for tailored treatments. The spatial distribution of brain damage relies on the regional antigen expression and the local balance of susceptibility and protective elements. Objective: As proof-of-concept, we investigated the spatial association between brain damage and gene expression in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD). Methods: In this multicenter cross-sectional study, 90 AQP4 + NMOSD patients and 94 age-matched healthy controls underwent a brain magnetic resonance imaging (MRI). We used T2-hyperintense lesion probability maps and white/gray matter atrophy as proxies of inflammation and neurodegeneration. The association with the expression of 266 candidate genes was obtained with the Multimodal Environment for Neuroimaging and Genomic Analysis platform. A functional-enrichment analysis investigated overrepresented biological processes. Results: In AQP4 + NMOSD, T2-hyperintense lesions were mainly periventricular; atrophy mostly involved the visual pathway. The expression of AQP4 and complement (C4a and C5) was associated with both inflammation and neurodegeneration. Complement activation and regulation/uptake of the insulin-like growth factor were the most relevant enriched pathways. Nonspecific pathways related to DNA synthesis and repair were associated with brain atrophy. Conclusions: Quantitative MRI and gene expression atlas identified the key elements of AQP4 + NMOSD pathophysiology. This analysis could help in understanding the pathophysiology of antibody-mediated autoimmune disorders. [ABSTRACT FROM AUTHOR]

Insulin receptor substrates (IRSs) are well-known mediators of the insulin and insulin-like growth factor (IGF)-I signaling pathways. We previously reported that the protein levels of IRS-2, a molecular species of IRS, were upregulated in the livers of rats fed a protein-restricted diet. This study aimed to elucidate the physiological role of IRS-2, whose level increases in response to protein restriction in cultured hepatocyte models. Hepatocyte-derived cell lines subjected to amino acid deprivation showed increased IRS2 mRNA and IRS-2 protein levels due to increased IRS2 transcription and translation, respectively. Amino acid deprivation markedly increased vascular endothelial growth factor-D (VEGF-D) secretion. Remarkably, the amino acid deprivation-induced VEGF-D secretion was suppressed by IRS-2 knockdown and enhanced by IRS-2 overexpression. These results suggest that IRS-2 is an intercellular signaling molecule that extracellularly transmits information on amino acid deprivation stress by regulating the secretion of growth factors such as VEGF-D. Moreover, this function of IRS-2 is distinct from its currently accepted function as a mediator of the insulin/IGF-I signaling pathways. This study demonstrates that IRS-2 can modulate protein secretion in an insulin-independent manner and greatly expands our understanding of the role of IRS-2, which is upregulated in response to amino acid deprivation. [ABSTRACT FROM AUTHOR]

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests. We identify 9 genes; 5 with fetal-only effects on birth weight, 1 with maternal-only effects, 3 with both, and observe directionally concordant associations in an independent sample. Four of the genes were previously implicated by GWAS of birth weight. IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (fetal-acting) are involved in adipose tissue regulation, and the latter two also show associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG (fetal-acting) in adipocyte differentiation and placental angiogenesis. NOS3 (fetal and maternal-acting), NRK (fetal), and ADAMTS8 (maternal-acting) have been implicated in placental function and hypertension. To conclude, our analysis of rare coding variants identifies regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, and further evidence for the role of insulin-like growth factors. An exome-wide association study for fetal and maternal rare deleterious variants affecting the normal variation in birth weight identifies nine genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling. [ABSTRACT FROM AUTHOR]

The etiology of fetal growth restriction (FGR) is multifactorial, although many cases often involve placental insufficiency. Placental insufficiency is associated with inadequate trophoblast invasion, resulting in high resistance to blood flow, decreased availability of nutrients, and increased hypoxia. We have developed a nonviral, polymer-based nanoparticle that facilitates delivery and transient gene expression of human insulin-like 1 growth factor (hIGF1) in placental trophoblast for the treatment of placenta insufficiency and FGR. Using the established guinea pig maternal nutrient restriction (MNR) model of placental insufficiency and FGR, the aim of the study was to identify novel pathways in the subplacenta/decidua that provide insight into the underlying mechanism driving placental insufficiency and may be corrected with hIGF1 nanoparticle treatment. Pregnant guinea pigs underwent ultrasound-guided sham or hIGF1 nanoparticle treatment at midpregnancy, and subplacenta/decidua tissue was collected 5 days later. Transcriptome analysis was performed using RNA Sequencing on the Illumina platform. The MNR subplacenta/decidua demonstrated fewer maternal spiral arteries lined by trophoblast, shallower trophoblast invasion, and downregulation of genelists involved in the regulation of cell migration. hIGF1 nanoparticle treatment resulted in marked changes to transporter activity in the MNR + hIGF1 subplacenta/decidua when compared with sham MNR. Under normal growth conditions however, hIGF1 nanoparticle treatment decreased genelists enriched for kinase signaling pathways and increased genelists enriched for proteolysis, indicative of homeostasis. Overall, this study identified changes to the subplacenta/decidua transcriptome that likely result in inadequate trophoblast invasion and increases our understanding of pathways that hIGF1 nanoparticle treatment acts on to restore or maintain appropriate placenta function. NEW & NOTEWORTHY: Placental insufficiency at midpregnancy, established through moderate maternal nutrient restriction, is characterized with fewer maternal spiral arteries lined by trophoblast, shallower trophoblast invasion, and downregulation of genelists involved in the regulation of cell migration. Treatment of placenta insufficiency with a hIGF1 nanoparticle results in marked changes to transporter activity and increases our mechanistic understanding of how therapies designed to improve fetal growth may impact the placenta. [ABSTRACT FROM AUTHOR]

Fetal bovine serum (FBS) has long been the standard supplement in cell culture media, providing essential growth factors and proteins that support cell growth and differentiation. However, ethical concerns and rising costs associated with FBS have driven researchers to explore alternatives, particularly human platelet lysate (HPL). Among these alternatives, fibrinogen-depleted HPL (FD-HPL) has gained attention due to its reduced thrombogenicity, which minimizes the risk of clot formation in cell cultures and enhances the safety of therapeutic applications. This study investigates two preparation methods for FD-HPL from human platelet concentrates: the calcium chloride method and a mechanical approach. The concentrations of critical growth factors, including vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF), and keratinocyte growth factor (KGF), were evaluated for both methods. Additionally, the impact of FD-HPL on the proliferation and morphology of umbilical cord-derived mesenchymal stem cells (UC-MSCs) was assessed. The findings revealed that the calcium chloride method produced significantly higher concentrations of all measured growth factors compared to the mechanical method. Moreover, UC-MSCs cultured in calcium chloride-prepared FD-HPL exhibited enhanced cellular characteristics, including increased cell size, elongation, and improved overall morphology compared to those cultured in mechanically processed FD-HPL. These results indicate that the preparation method significantly influences the biological properties of HPL and the effectiveness of UC-MSC culture. The calcium chloride method emerges as a superior technique for producing FD-HPL, offering a promising alternative to FBS in regenerative medicine applications. This study underscores the importance of preparation methods in optimizing HPL for cell culture and therapeutic uses. [ABSTRACT FROM AUTHOR]

The purpose of this experiment was to assess the effects of the green macroalgae (Ulva intestinalis) on growth performance, immune parameters of serum and mucus, liver enzymes and the expression of genes related to growth (GH and IGF-1), and immunity (IL1-β and LYZ) in common carp (Cyprinus carpio). The test was carried out in eight weeks with the treatments supplemented with 0 (control), 0.25%, 0.5%, and 1% macroalgae and three replications for each group. At the end of the course, growth indices, serum and mucus total protein, total immunoglobulin, lysozyme, and liver enzymes including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were evaluated. Additionally, the expression of growth (GH and IGF-1) and immunity (IL1-β and LYZ) genes was evaluated using real-time PCR in the brain, liver, and intestine. Based on the results, a significant difference was observed in the levels of total protein, total immunoglobulin, and mucus lysozyme in the fish that received 1% U. intestinalis compared to the control group (P<0.05). In addition, the amount of total protein, total immunoglobulin, and lysozyme in the control group and the other treatments represented a significant difference (P<0.05). Although the initial weight did not show a significant difference among the treatments (P>0.05), the final growth parameters significantly varied in different treatments, with the highest final weight observed in fish fed with 0.25% algae (P<0.05). The results of the expression of immune genes lysozyme (LYZ) and interleukin-1 (IL-1) indicated a significant difference with the control group (P<0.05), representing an increasing pattern with the rising percentage of macroalgae (P<0.05). The supplement was also found effective in promoting the expression of growth hormone (GH) and insulin-like growth factor (IGF-1) compared to the control fish (P<0.05), revealing an increasing pattern for the IGF-1 gene with the elevated level of the supplement. In general, according to the results of the present study, U. intestinalis can be recommended in carp aquaculture, most preferably at the level of 1% of daily feed, as it could significantly enhance the growth and innate immunity of fish. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS. A Somascan proteomic analysis of 12 MMPs, three of their inhibitors (TIMP-1, 2, 3), two ADAMS (9, 12), five ADAMTS (1, 4, 5, 13, 15), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor-1 (IGF-1) was undertaken in a well-validated PCOS database of 143 women with PCOS and 97 controls. Women with PCOS had significantly higher levels of MMP-9 and lower levels of MMP-2, MMP-14, TIMP-2, IGFBP-1, and IGF-1 compared to the controls (p < 0.0001, p < 0.005, p < 0.04, p < 0.05, p < 0.0001, and p < 0.0001, respectively). No differences were observed for any other MMPs. The ADAMS or ADAMTS levels did not differ between groups. Body mass index (BMI) was correlated with MMP-9 (p < 0.01), MMP-1 (p < 0.05), MMP-2 (p < 0.05), MMP-10 (p < 0.005), MMP-12 (p < 0.005), ADAM-9 (p < 0.05), and IGFBP-1 (p < 0.0001), but only MMP-9 still differed after accounting for BMI. MMP-9/TIMP-1, MMP-9/TIMP-2, and MMP-9/TIMP-3 ratios were higher in the PCOS group (p < 0.01), whilst MMP-17/TIMP-1 and MMP-17/TIMP-2 were lower (p = 0.01). MMP-2/TIMP ratios showed no difference between groups. TIMP-2 was positively correlated with CRP (p < 0.01). MMP changes in PCOS are largely driven by BMI, though increased MMP-9 is BMI-independent, suggesting that any deleterious effects of MMP-9 would be potentially exacerbated by a concomitantly increased BMI. The significant increases in the MMP-9/TIMP ratios suggests MMP-9 overactivity in PCOS. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-binding proteins (IGFBPs) regulate insulin-like growth factor (IGF) signaling, but IGFBP-specific functions are not well characterized in fishes. A line of rainbow trout (Oncorhynchus mykiss) lacking a functional IGFBP-2b was produced using gene editing and subsequent breeding to an F2 generation. This loss-of-function model [IGFBP-2b knockout (2bKO)] was subjected to either continuous feeding or feed deprivation (3 wk) followed by refeeding (1 wk). During continuous feeding, the 2bKO line displayed faster specific growth rate for both body weight and fork length, higher feed intake, and reduced feed conversion ratio compared with a wild-type (WT) line. However, loss of IGFBP-2b did not affect the feed deprivation or refeeding response in terms of weight loss or weight gain, respectively. Several components of the IGF/IGFBP system were affected by loss of IGFBP-2b. Total serum IGF-1 in the 2bKO line was reduced to 0.5- to 0.8-fold of the WT line, although the concentration of free serum IGF-1 was not affected. Gene expression differences include reduced abundance of igfbp1a1, igfbp1b2, igfbp5b2, and igfbp6b1 transcripts and elevated igf2 and igfbp6b2 transcripts in liver of the 2bKO line. Collectively, these findings suggest that although IGFBP-2b is a carrier of circulating IGF-1 in salmonids, the presence of IGFBP-2a and compensatory responses of other IGF/IGFBP system components support an anabolic response that improved growth performance in the loss-of-function model. NEW & NOTEWORTHY: Knocking out IGFBP-2b in rainbow trout improved food intake, growth performance, and feed conversion ratio and reduced serum IGF-1 by 0.5- to 0.8-fold, without changes in the concentration of free serum IGF-1. Based on these findings, we propose that, in addition to IGFBP-2b, the 32-kDa IGFBP (putative IGFBP-2a) also serves as a major carrier of circulating IGF-1 in salmonids. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) is the most frequently occurring pituitary hormone deficiency. Lesions in the hypothalamo-pituitary region and their treatment, pituitary apoplexy, empty sella, Sheehan's syndrome, traumatic brain injury, infective, autoimmune, infiltrative, and genetic causes may contribute to the development of GHD. Diagnosis of GHD relies on serum insulin-like growth factor-1 (IGF-1) levels, which may be low based on age/gender reference levels. Insulin-like growth factor-1 may not be diagnostic alone, and stimulation tests may be needed. The insulin tolerance test is considered the gold standard, with the growth hormone-releasing hormone-arginine test and the glucagon stimulation test as primary alternatives. Recently, a novel test with high diagnostic accuracy, macimorelin, an oral growth hormone (GH) secretagogue receptor agonist and ghrelin-mimetic, has been used. Adult GHD does not have pathognomonic clinical features. Decreased energy, reduced quality of life, depressive mood, increased fat mass, dry skin, osteoporosis, hypertension, dysglycemia, dyslipidemia, and increased cardiovascular risks are the most commonly reported findings, which are all may be seen in several diseases. Recombinant human GH is an effective and safe treatment, beneficial for body composition, bone, lipid profile, and quality of life, but it is costly, and not all patients with GHD may require treatment. If there is no benefit after 6-12 months of treatment, it may be discontinued. The best follow-up parameters for GH treatment are clinical response and serum IGF-1 levels, which should be kept within the mid-normal range, adjusted for age and gender. In this review, we extensively discussed GHD in adults with current data. [ABSTRACT FROM AUTHOR]

Objective: The influence of serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) on sperm parameters has been previously described in patients with acromegaly. However, the relationship between local GH/IGF-1 with systemic levels and sperm parameters in patients with acromegaly has not been established. In this study, we investigated the effects of seminal plasma hormone levels on sperm parameters in patients with acromegaly. Methods: This cross-sectional study was conducted on 24 patients with acromegaly in remission and 16 men without chronic disease and/or hypogonadism. Seminal plasma GH and IGF-1 were measured. Semen parameters and seminal plasma hormone levels were compared. Results: The acromegaly group had higher levels of serum GH (0.475 IQR (0.245-0.770) ng/mL) compared to the control group (0.08 IQR (0.03-0.159) ng/mL) (P < .001). Although seminal plasma GH levels were higher in the acromegaly (114 ± 82 pg/mL) than in the control group (61 ± 39 pg/mL) (P = .004), seminal plasma IGF-1 levels were similar (P = .203). Serum GH was positively correlated with seminal plasma GH (r = 0.489, P = .001) and negatively correlated with sperm count (r = -0.337, P = .039) and fast-forward motility (r = -0.360, P = .023). There was no correlation between seminal plasma hormone levels and semen parameters (P > .05 for all). Conclusion: The findings suggested that sperm count may be adversely affected in patients with acromegaly despite an intact hypot halam ic-pi tuita ry-go nadal axis and disease control. The seminal plasma hormone levels seemed not to be correlated with semen alterations. [ABSTRACT FROM AUTHOR]

Aim: Azithromycin (AZM) is widely used to treat mycoplasma infection in pregnancy. However, there is no adequate evaluation of its side effect on the placenta. In this study, using human placental syncytiotrophoblasts and a mouse model, we investigated whether AZM use in pregnancy might adversely affect placental function and pregnancy outcome. Results: Transcriptomic analysis of AZM-treated human placental syncytiotrophoblasts showed increased expression of endoplasmic reticulum (ER) stress-related genes and decreased expression of genes for hormone production and growth factor processing. Verification studies showed that AZM increased the abundance of ER stress mediators (phosphorylated eIF2α, activating transcription factor 4 [ATF4], and C/EBP Homologous Protein [CHOP]) and decreased the abundance of enzymes involved in progesterone and estradiol synthesis (STS, CYP11A1, and CYP19A1) and insulin-like growth factor binding protein (IGFBP) cleavage (PAPPA and ADAM12) in human placental syncytiotrophoblasts. Inhibition of ER stress blocked AZM-induced decreases in the expression of CYP19A1, CYP11A1, PAPPA, and ADAM12, suggesting that the inhibition of AZM on those genes' expression was secondary to AZM-induced ER stress. Further mechanism study showed that increased ATF4 in ER stress might repressively interact with C/EBPα to suppress the expression of those genes, including CEBPA itself. Mouse studies showed that AZM administration decreased fetal weights along with increased ER stress mediators and decreased levels of insulin-like growth factor, estrogen, and progesterone in the maternal blood, which could be alleviated by inhibition of ER stress. Innovation and Conclusion: These findings first support the fact that AZM, often used during pregnancy, may affect fetal growth by inhibiting crucial enzymes for estrogen and progesterone synthesis and disrupting crucial proteases for IGFBP cleavage via inducing ER stress in placental syncytiotrophoblasts. Antioxid. Redox Signal. 42, 16–35. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC), endometriosis (ENDO), and obesity (OBY) are interconnected conditions in women that may share underlying genetic pathways. This study aimed to identify shared genetic pathways and differential gene expressions across these conditions to uncover potential therapeutic targets. A bioinformatics pipeline was applied using gene expression datasets from the GEO database, incorporating differential expression analysis, functional and pathway enrichment, PPI network construction, survival analysis, and mutational profiling across 198 samples. The analysis revealed 26 shared differentially expressed genes (DEGs), with IGF-1, CREBBP, EP300, and PIAS1 identified as key hub genes. Elevated IGF-1 expression was significantly linked to poorer survival outcomes in EC patients (p <.05). Frequent mutations were observed in these hub genes, suggesting their critical role in disease mechanisms. This study highlights genetic links among EC, ENDO, and OBY, emphasizing high IGF-1 expression as a potential prognostic marker in EC and recurrent alterations in hub genes as promising therapeutic targets. These findings provide insights into the shared genetic underpinnings of these conditions and present new avenues for targeted therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic conditions such as obesity, diabetes, and insulin resistance, combined with hormonal imbalances, can disrupt the body's natural growth regulation systems, including the insulin-like growth factor-1 (IGF1) pathway. These disruptions significantly increase the risk of endometrial cancer (EC), a cancer that develops in the lining of the uterus. This review delves into the roles of IGF1 and its variants; IGF1-Ea, IGF1-Eb, and IGF1-Ec, and their interactions with hormones like oestrogen in driving tumour growth and spread. By unravelling these connections, we aim to identify innovative strategies for preventing and treating this cancer, bringing hope for improved patient outcomes and advancing research in hormone-driven cancers. Endometrial cancer (EC) is a common gynaecological malignancy associated with metabolic dysfunctions such as obesity, diabetes and insulin resistance, as well as hormonal imbalances, particularly involving oestrogen and progesterone. These factors disrupt normal cellular metabolism, heightening the risk of developing endometrioid EC (EEC), the most prevalent subtype of EC. The insulin-like growth factor-1 (IGF1) pathway, a key regulator of growth, metabolism, and organ function, is implicated in EC progression. Recent research highlights the distinct roles of IGF1 isoforms, including IGF1-Ea, IGF1-Eb, and IGF1-Ec, in promoting tumour growth, metastasis, and hormone signalling interactions, particularly with oestrogen. This review examines the function and clinical significance of IGF-1 isoforms, emphasising their mechanisms in gynaecological physiology and their contributions to EC pathogenesis. Evidence from other cancers further underscores the relevance of IGF1 isoforms in driving tumour behaviours, offering valuable insights into their potential as biomarkers and therapeutic targets. Understanding these mechanisms provides opportunities for novel approaches to the prevention, diagnosis, and treatment of EC, improving patient outcomes and advancing the broader field of hormone-driven cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: In chronic lymphocytic leukemia (CLL), abnormal B lymphocytes accumulate in the bone marrow (BM) and secondary lymphoid tissues. The BM and lymph nodes support angiogenesis and increased vascularization. Although certain drugs approved by the US Food and Drug Administration improve clinical outcomes, some patients do not respond and others relapse. Interactions between CLL cells and the tissue microenvironment favor leukemic cell trafficking, survival, and proliferation via the production of soluble factors. Some of these factors exhibit pro-angiogenic properties. This review summarizes the biology of these molecules with survival/pro-angiogenic value, and provides a summary of new, selective inhibitors targeting these molecules (and their receptors) currently under evaluation in preclinical and clinical studies. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogenic factors in CLL. A number of other CLL factors might have pro-angiogenic activity: fibroblast growth factor-2, certain chemokines (such as CXCL-12 and CXCL-2), tumor necrosis factor-α, insulin-like growth factor-1, neutrophil gelatinase-associated lipocalin, and progranulin. All these molecules contribute to the survival, proliferation, and migration of CLL cells. Here, we review the literature on these factors' respective expression profiles and roles in CLL. We also summarize the main results of preclinical and clinical trials of novel agents targeting most of these molecules in a CLL setting. Through the eradication of leukemic cells and the inhibition of angiogenesis, these therapeutic approaches might alter the course of CLL. [ABSTRACT FROM AUTHOR]

Context Insulin-like growth factor (IGF) signaling is known to affect human ovarian follicular function during growth and development. However, the role of the IGF system is unknown during the ovulatory peak, which is characterized by profound changes in granulosa cell (GCs) mitosis and function. Objective How is the IGF system expressed and regulated during the midcycle surge in women? Methods Follicular fluid (FF) and GCs were collected during the ovulatory peak from 2 specific time points. One sample was obtained before oocyte pickup (OPU): before ovulation trigger (OT) (T = 0 hours) or at 12, 17, or 32 hours after OT, and 1 sample was obtained at OPU 36 hours after OT. Fifty women undergoing ovarian stimulation at a university hospital were included. Gene expression profiles were assessed by microarray analysis of GCs. IGF-related proteins in the FF were assessed by immunoassay or by determination of activity with a proteinase assay. Results Gene expression of proteins promoting IGF activity (ie, IGF2, PAPP-A, and IRS1) together with proliferation markers were downregulated on a transcriptional level in GCs after OT, whereas proteins inhibiting the IGF signal (ie, IGFBPs, IGF2, and STC1) were upregulated. STC1 gene expression and protein levels were greatly upregulated after OT with a parallel steep downregulation of PAPP-A proteolytic activity. Conclusion These data suggest that downregulation of IGF signaling mediated by increased STC1 expression is instrumental for the sudden cessation in GC proliferation and onset of differentiation during the ovulatory peak. [ABSTRACT FROM AUTHOR]

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]

Background: Acromegaly is a disease with high morbidity and mortality rates. The role of primary care physicians is very important in the early diagnosis of acromegaly. The present study aims to determine the knowledge and attitudes of primary care physicians about acromegaly in different countries worldwide. Methods: The survey consisted of 33 questions prepared in English and Turkish and was administered to a total of 396 primary care physicians, 280 of whom were from Turkey, 84 from European countries, 28 from Asian countries, and 4 from Nigeria. Mostly, the survey was administered via Google Forms sent to social media groups of primary care physicians. Some of the surveys were administered in person. The survey included 12 questions about the clinical manifestations, six questions about the diagnosis, 12 questions about the comorbidities, one question about the treatment, and two questions about the prognosis of acromegaly. Data of acromegaly knowledge and the attitudes of physicians were evaluated using the chi-square test. Results: The presence of acral findings in acromegaly was better known by Turkish physicians (96.8%) compared to Asian/African (84.4%) and European (84.5%) physicians (p < 0.001). The presence of generalized visceromegaly and excessive sweating was better known by Asian/African physicians (p = 0.01 and p = 0.009, respectively). The rate of correct answers to the question "Old photographs can be informative in patients suspected to have acromegaly" was higher in the Turkish and Asian/African groups (p < 0.001). Only 36.1% of the Turkish physicians, 29.8% of the European physicians, and 31.3% of the Asian/African physicians knew that serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were diagnostic indicators for acromegaly. Colon cancer and goitre incidences were increased in acromegaly patients. These comorbidities were better known by Asian/African primary care physicians than by Turkish and European primary care physicians (p < 0.001 and p = 0.032, respectively). Only 18.6% of Turkish and 13% of European physicians knew that surgery was the treatment of choice for acromegaly patients. The rate of correct answers to this question was higher for Asian/African physicians (59.4%) (p = 0.003). Conclusion: Knowledge of primary care physicians regarding acromegaly should be increased through workshops, seminars, and subject-focused courses. [ABSTRACT FROM AUTHOR]

The demand for cartilage reconstruction in the head and neck region arises frequently due to trauma, malignancies, and hereditary diseases. Traditional tissue engineering produces cartilage from a small biopsy by combining biomaterials and expanded cells. However, this top-down approach is associated with several limitations, including the non-uniform distribution of cells, lack of physiological cell-cell and cell-matrix interactions, and compromised mechanical properties and tissue architecture. The capacity of cells to aggregate into microtissues enables an alternative bottom-up approach to producing cartilage with or without further scaffolding support. Here we explored the optimal conditions for obtaining small spheroids from head and neck cartilage tissues. We used chondrocytes (CCs) and chondroprogenitors (CPCs) isolated from auricular and nasoseptal cartilage to prepare spheroids using ultra-low attachment (ULA) plates or micromass cultures. Different cell densities were tested to estimate the minimal cell number required for optimal spheroid formation. Furthermore, we evaluated the influence of key chondrogenic cytokines, such as transforming growth factor (TGF)-β, connective tissue growth factor (CTGF), and insulin-like growth factor (IGF)-1, on spheroid morphology and the production of cartilage extracellular matrix (ECM) components. Spheroids expressing cartilage markers were formed with 2.5 × 104 cells in a commercially available chondrogenic differentiation medium on ULA plates but not in conventional micromass cultures. Differences were seen in auricular and nasal spheroids with respect to growth patterns and response to cytokine composition. Auricular spheroids were larger and showed size increase in culture, whereas nasal aggregates tended to shrink. Cytokines differentially influenced spheroid growth, and ECM structure and composition. Under all tested conditions, both spheroid types generated one or more cartilage ECM components, including elastin, which was also found in nasal spheroids despite their hyaline origin. Our results suggest that spheroid cultures can offer a viable approach to generating mature cartilage tissue without a biomaterial scaffold. Furthermore, nasal CCs and CPCs can be used to generate elastic cartilage. The findings of the study provide technical insights toward the goal of obtaining cartilage microtissues that can be potentially used for reconstructive procedures of HNC cartilage defects. [ABSTRACT FROM AUTHOR]

Background: Tuina is an effective treatment for the decrease of skeletal muscle atrophy after peripheral nerve injury. However, the underlying mechanism of action remains unclear. This study aimed to explore the underlying mechanisms of tuina in rats with sciatic nerve injury (SNI). Methods: We established an SNI rat model. After Tuina intervention, curative effects were evaluated by behavioral assessment, nerve function index, and muscle atrophy index (MAI). Pathological changes were observed by transmission electron microscopy and immunofluorescence. Insulin-like growth factor 1 (IGF-1), forkhead box O (FoxO) and p-FoxO levels were detected using enzyme-linked immunosorbent assay. Western blotting was performed to detect the expression of proteins involved in the PI3K/AKT signaling pathway. Result: Behavioral assessment, nerve function index, and MAI revealed that the tuina had significantly improved muscle atrophy after SNI compared with the SNI model group. Transmission electron microscopy showed that tuina improved muscle ultramicrostructure. CD31 immunofluorescence revealed that tuina improved microcirculation. Furthermore, we observed that tuina differentially regulated the levels of IGF-1, FoxO and p-FoxO, and the protein expression of p-Phosphoinositide 3-kinase (p-PI3K), p-AKT, and vascular endothelial growth factor in the anterior tibial muscle and soleus muscles. Conclusion: Tuina could effectively inhibit skeletal muscle atrophy via the microcirculation pathway in a rat model of SNI by regulating the expression of IGF-1 and FoxO. The underlying mechanism of action may involve the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The insulin-like growth factor (IGF) system plays a vital role in regulating gonadotropin-releasing hormone (GnRH), whether the IGF2 can act on the GnRH neurons during the pubertal period is unclear. Methods: Central precocious puberty (CPP) rats were induced by danazol, and when the rats met the first diestrus, they were euthanized and tissues were collected. GT1-7 cells were cultured and treated with 0, 1, 10 ng/mL IGF2 for 4 hours and the changes in GnRH were measured. Mice were injected intracerebroventricularly with IGF2 (15 ng/g, 5 µL) or with the same dose of phosphate buffered saline (PBS), after eight hours, they were euthanized and tissues collected. Results: CPP rats had increased expression of IGF2 and GnRH mRNA and their respective proteins in the preoptic area (POA) of the hypothalamus. Treatment of GT1-7 cells with 10 ng/mL of IGF2 increased GnRH mRNA and protein expression, and GnRH concentration in the culture medium. Injection of IGF2 protein into the lateral ventricle of mice increased the expression of GnRH mRNA and protein in the POA. Conclusions: IGF2 may upregulate the synthesis of GnRH during the pubertal period, and may also take part in the pathology of CPP. [ABSTRACT FROM AUTHOR]

Background: To study effect of pregnancy on obese women's maternal cardiometabolic biomarkers as a signature for maternal morbidity and complications. Methods: This cross-sectional cohort study involved pregnant Emirati women who had regular menstrual cycles and had normal blood pressure. Pre-pregnancy body mass index was calculated using height and weight measurements recorded within three months before current pregnancy. Average systolic and diastolic blood pressure measurements were calculated from each visit. Blood samples were collected randomly once and following cardiometabolic biomarkers were measured. Results: We enrolled 178 pregnant women, with a mean age ± standard deviation of cohort was 29.9 ± 4.97 years and Pre-pregnancy body mass index 28.11 ± 6.58 kg/m2. None of blood pressure measurements or biomarkers serum concentrations were statistically different across Pre-pregnancy body mass index groups except for soluble intercellular cytoadhesive molecule-1levels which were the highest in underweight women. Pregnant women with pre-gestational obesity had higher systolic and diastolic blood pressure levels compared to women with normal or overweight. All variables were statistically significantly different by trimesters except systolic blood pressure, random blood glucose, lipoprotein-A, and high-sensitivity C-Reactive Protein. After adjusting, in a multivariate linear regression model, for maternal age, trimester of pregnancy, education level, parity and smoking, none of biomarkers or blood pressure were found to be significantly associated with Pre-pregnancy body mass index. In a multivariate linear regression model adjusting for maternal age, Pre-pregnancy body mass index, education level, parity and smoking, gamma-glutamyl transferase, total cholesterol, high density lipoprotein, low-density lipoprotein, triglycerides, apolipoprotein A & B, interleukin-6, tumor necrosis factor-alpha and insulin-like growth factor-1 concentrations remained significantly associated with advancing trimester of pregnancy. There was a significant interaction between Pre-pregnancy body mass index and trimester of pregnancy for serum gamma-glutamyl transferase and soluble intercellular cytoadhesive molecule-1concentration. Conclusion: This study emphasizes how pregnancy has a significant impact on cardiometabolic markers in obese women, indicating both hyperlipidemic status of pregnancy and diabetogenic tendency in obese patients who are not diabetics. These findings may suggest that pregnancy in obese patients increases risk of developing metabolic syndrome in future, therefore more attention is recommended of pregnant obese women and further study of establishing specific cardiometabolic biomarkers screening program. Plain Language Summary: The World Health Organization (WHO) has recommended a prevention strategy to reduce the maternal complications of obese pregnant women. This study assesses the effect of pregnancy on obese women's maternal cardiometabolic biomarkers (CMBs) as risk of increase maternal morbidity and complications. The women Pre-pregnancy body mass index (pBMI) was calculated and their blood pressure measured. Blood samples were collected randomly once during maternal clinical visits and the cardiometabolic biomarkers were analyzed. Many variables were significantly different by pregnancy trimesters that emphasizes the negative impact of pregnancy on cardiometabolic markers in obese women. These findings may suggest that pregnancy in obese patients increases the risk of developing metabolic syndrome in the future. [ABSTRACT FROM AUTHOR]

Hip fractures are associated with high morbidity and mortality. Sarcopenia is a significant factor contributing to poor prognosis; however, the clinical diagnosis of sarcopenia remains difficult in surgical patients. This systematic review aims to identify the biomarkers of sarcopenia as diagnostic and predictive tools in patients admitted for hip fracture surgery. A systematic search was conducted in the MEDLINE, EMBASE, and Google Scholar databases according to the PRISMA guidelines. Biomarker study quality was assessed using the BIOCROSS score. A total of 7 studies met the inclusion criteria and 515 patients were included, of whom 402 (78%) were female and 113 (22%) were male. The mean age of the participants was 83.1 years (SD: 5.9). Skeletal muscle biopsies were used for biomarker assessment in 14% (1/7) of studies and venous blood samples were used in the remaining 86% (6/7). The highlighted sarcopenia biomarkers included the low expression of insulin-like growth factor (IGF-I) and tumor necrosis factor-α (TNF-α), along with high serum myostatin and low serum vitamin D levels. Overall, the BIOCROSS score was satisfactory, with all studies obtaining at least a score of 13/20. The orthopedic literature is limited; however, the highlighted biomarkers in this review could be used as adjuncts in the diagnosis of sarcopenia in surgical patients. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most diagnosed cancers worldwide. The insulin-like growth factor (IGF) system promotes proliferation and survival in breast cancer cells and is regulated by 6 insulin-like growth factor binding proteins (IGFBPs). The IGFBPs sequester IGFs to prolong their half-life and attenuate binding to insulin-like growth factor 1 receptor (IGF1R). While IGFBP-6 has been studied in some cancers it has not been studied extensively in hormone receptor positive breast cancer. Survival analysis using available databases indicated that high IGFBP-6 levels improve overall survival in progesterone receptor positive breast cancers. IGFBP-6 is transcriptionally induced by progesterone in T47D breast cancer cells resulting in increased intracellular and extracellular IGFBP-6 protein. Knockdown of IGFBP-6 resulted in reduced proliferative antagonism when estradiol stimulated T47D cells were cotreated with progesterone and protein levels of both progesterone receptor isoforms (PR-A and PR-B) were decreased following knockdown of IGFBP-6. P21(Cip1/Waf1), which is progesterone responsive, was not induced in response to progesterone following knockdown of IGFBP-6. Cyclin E2, a cell cycle regulator, is induced by progesterone only when IGFBP-6 is knocked down. Stable overexpression of IGFBP-6 in MCF-7 cells resulted in an increase in Epidermal Growth Factor Receptor (EGFR) and this expression was further enhanced when cells were cotreated with progesterone and estradiol. These results indicate that IGFBP-6 is a regulator of progesterone action, and that PR is required for the observed protective effects of IGFBP-6 in breast cancer. [ABSTRACT FROM AUTHOR]

Microglia, the brain immune cells, support neurons by producing several established neurotrophic molecules including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). Modern analytical techniques have identified numerous phenotypic states of microglia, each associated with the secretion of a diverse set of substances, which likely include not only canonical neurotrophic factors but also other less-studied molecules that can interact with neurons and provide trophic support. In this review, we consider the following eight such candidate cytokines: oncostatin M (OSM), leukemia inhibitory factor (LIF), activin A, colony-stimulating factor (CSF)-1, interleukin (IL)-34, growth/differentiation factor (GDF)-15, fibroblast growth factor (FGF)-2, and insulin-like growth factor (IGF)-2. The available literature provides sufficient evidence demonstrating murine cells produce these cytokines and that they exhibit neurotrophic activity in at least one neuronal model. Several distinct types of neurotrophic activity are identified that only partially overlap among the cytokines considered, reflecting either their distinct intrinsic properties or lack of comprehensive studies covering the full spectrum of neurotrophic effects. The scarcity of human-specific studies is another significant knowledge gap revealed by this review. Further studies on these potential microglia-derived neurotrophic factors are warranted since they may be used as targeted treatments for diverse neurological disorders. [ABSTRACT FROM AUTHOR]

Numerous studies have explored alternative protein sources to fishmeal (FM) to enhance fish diets, yet limited research exists on their effects on maturation. This study assessed the impact of replacing FM with soy protein concentrate (SPC) supplemented with lysine and methionine on growth and gonadal development in olive flounder (Paralichthys olivaceus). Three diets were tested: a control (Con) diet with 60% FM and two diets replacing FM with 25% (LF1) and 50% (LF2) SPC. Fish were fed to apparent satiation twice daily for 12 months. Growth performance and feed intake were not significantly different between groups. However, the gonadosomatic index varied with diet. Muscle composition and amino acid levels were similar across treatments, though n-3 fatty acids were higher in Con. Spermatogonia was increased, and spermatogenesis was impaired in SPC groups. At 12 months, oocytes in Con diets had absorbed yolk globules, whereas this was absent in SPC groups. Growth-related genes in the brain (growth hormones and insulin-like growth factor) were increased with higher SPC, while follicle-stimulating and luteinizing hormones decreased. Estrogen receptor α levels were elevated in SPC groups. Vitellogenin gene expression in gonads was highest in Con, while liver expression peaked in LF2. The expression of digestive enzymes, chymotrypsin2, and trypsin2 was highest in LF2, while lipase genes were lower. In summary, up to 50% FM replacement with SPC, with amino acid supplementation, supported growth performance and muscle composition without adverse effects on growth in olive flounder but influenced gonadal development. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor binding-protein 7 (IGFBP7) gene is one of the potential genes related to meat quality. The objective of the current study was to evaluate polymorphism of the IGFBP7 gene (g.72351183A>C) and its association with meat quality traits in the Javanese thin-tailed (JTT) sheep. A comprehensive analysis was conducted on 88 JTT male sheep to examine their fatty acid composition, carcass characteristics, carcass retail cuts, and the physical properties of lamb meat. The polymorphism was detected using the PCR-RFLP technique. The association between the IGFBP7 gene polymorphism and the observed variables of meat quality was evaluated using one-way analysis of variance (ANOVA). The study results indicated that the IGFBP7 gene was polymorphic in JTT sheep population, with the allele distribution conforming to Hardy-Weinberg equilibrium. The AA genotype was found to be predominant. The IGFBP7 gene variants were associated (p<0.05) with erucic acid, linoleic acid, eicosapentaenoic acid, and total polyunsaturated fatty acid (PUFA). Sheep possesing the CC genotype exhibited the highest levels of linoleic acid, eicosapentaenoic acid, and total PUFA in comparison to those with AA and AC genotypes. However, the IGFBP7 gene polymorphism was not associated with carcass characteristics, carcass retail cuts, and physical properties of meat. These findings suggest that the IGFBP7 gene is a promising candidate marker for improving fatty acid composition in JTT sheep. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) is the main driver of growth during prenatal life and acts through IGF-1 receptor (IGF1R). Patients with IGF1R defects exhibit variable phenotypic features. A 10.9-year-old boy presented with severe short stature, microcephaly, minor dysmorphic features and mental retardation. Genetic analysis for IGF1R revealed heterozygous deletion of the complete IGF1R. At the age of 12.3 years, daily subcutaneous recombinant human growth hormone (rhGH) was started and continued for a total of 5.7 years in two courses with improvement of height velocity as well as final height. Puberty was delayed and eventually he did not achieve full puberty, suggesting partial hypogonadotropic hypogonadism. Hypothyroidism initially developed during rhGH therapy. However, low T4 levels persisted after cessation of rhGH therapy and thus central hypothyroidism is a likely diagnosis. rhGH has partial effect for induction of growth in cases with IGF1R defects. However, long-term treatment with an early initiation may have more beneficial effects. In addition, patients with IGF1R defects should be followed for delayed puberty-hypogonadism, and hypothyroidism. [ABSTRACT FROM AUTHOR]

The present study tested the symbiotic effects of dietary multi-strain Bacillus probiotics (MSB) (Bacillus licheniformis, B. pumilus, and B. subtilis) in Nile tilapia (Oreochromis niloticus) exposed to Aspergillus flavus infection. Furthermore, this study investigated water quality, growth performance, blood metabolites, histological morphology, immune regulatory genes, and resistance to A. flavus infection. For 70 days, fish (n = 240) were divided into four groups in triplicate: T0 (control group; MSB0), T1 (1 g/kg, MSB1), T2 (2 g/kg, MSB2), and T3 (3 g/kg, MSB3). The immune response was then assessed by challenging all fish groups with the A. flavus pathogen. The results showed that the rearing water quality, fish growth, and blood parameters, as well as total proteins, albumin, globulins, and amylase activity were significantly (P < 0.05) increased in all MSB-treated groups with the best results in MSB2 and MSB3 groups. Meanwhile, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and glucose levels were significantly (P < 0.05) modulated, particularly at higher concentrations of the probiotic mixture (MSB3 group). Fish fed with various levels of MSB showed a maintained histological structure of the hepatopancreas, intestine, and spleen tissues. The mRNA expression of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor receptor-1 (IGF-1R), and interleukin-8 (IL-8) were increased in a dose-dependent manner due to MSB dietary inclusion (P < 0.05). Conversely, the mRNA expression of interleukin-1β (IL-1β) gene was significantly decreased in MSB groups compared to untreated group (P < 0.05). Surprisingly, supplemented groups in Bacillus spp. probiotics exhibited significant modulations in all computed parameters. MSB supplementation improved the pathogenic tolerance of tilapia after change with A. flavus. The integration of growth performance, biochemical, and transcriptomic results confirms that the dietary intervention of multi-strain Bacillus spp. is symbiotic and enhances the benefits for the maintenance of O. niloticus' health, growth, and digestion. This is achieved by supporting growth genes, reducing inflammatory genes, and enhancing immune-antioxidant resistance to combat A. flavus infection. [ABSTRACT FROM AUTHOR]

The brain and liver of mandarin fish (Siniperca chuatsi) produce essential hormones for their growth and development. However, the mechanisms underlying the interplay of these hormones remain unclear. This study aimed to assess the slow – and fast-growing traits, including body weight and length of mandarin fish reared in a single pond. To compare the differentially expressed genes (DEGs) in slow – and fast-growing fishes, we performed RNA sequencing analysis. After assembling the clean reads, 192,280 transcripts and 100,416 unigenes were obtained. 344 and 845 DEGs in the brain and liver in the fast-and slow-growing group were annotated respectively. These DEGs were associated with signaling pathways involved in growth and development, such as AGE-RAGE, Transforming growth factor-β/Smad, Mitogen-activated protein kinase, Wingless/Integrated, and Insulin-like growth factor (IGF) 1. Furthermore, our fasting experiment revealed a concurrent decrease in body weight and the expression levels of genes related to the growth hormone (GH)/IGF system, alongside an increase in the insulin-like growth factor binding protein gene IGFBP3 expression. These findings suggest the GH/IGF system regulates body weight during fasting periods. The vast amount of transcriptome data generated in this study substantially expands the existing gene and genome resources for the growth traits of mandarin fish. [ABSTRACT FROM AUTHOR]

Background: Granulosa cells are somatic cells within the ovarian follicle. As the primary site of estradiol production, they are critical regulators of several aspects of female reproduction. This review aims to provide an overview of the physiology of mammalian granulosa cells and their importance for female fertility. Methods: the literature about the function and regulation of granulosa cells was reviewed. Results: a comprehensive summary and discussion of the role of granulosa cells on ovarian steroidogenesis and folliculogenesis, as well as factors that control granulosa cells function, are presented. Conclusion: The functions of granulosa cells are regulated by a plethora of intra- and extra-ovarian factors via autocrine, paracrine, and endocrine pathways, which creates a complex regulatory network. A comprehensive understanding of granulosa cells' physiology is vital for the development of innovative strategies to enhance reproductive outcomes in several species. [ABSTRACT FROM AUTHOR]

The rising global incidence of uterine cancer has been linked to the escalating prevalence of obesity. Obesity results in insulin resistance which alters the IGF system, thereby driving cancer progression via increased cell proliferation and the inhibition of apoptosis, although the precise mechanisms remain unclear. In a previous study, we compared the levels of IGF1 and IGF2 between fifty endometrial cancer patients (study group) and fifty age-matched non-cancer patients with benign gynaecological conditions (control group), identifying a correlation with menopause. Building on these data, we now report that IGF levels in pre-menopausal women were significantly lower in the study group compared to the control group, a pattern not observed in post-menopausal women. We undertook the receiver operating characteristic (ROC) curve analysis for calculating the potential of IGF1 and IGF2 to effectively distinguish pre-menopausal women with endometrial cancer from those without it. For pre-menopausal women, the area under ROC curve values were 0.966 for IGF1 and 0.955 for IGF2, both with significant p-values, indicating that IGF1 and IGF2 levels have the potential to be diagnostic biomarkers for distinguishing pre-menopausal women with endometrial cancer from those without it. In summary, our findings emphasise the importance of considering menopausal status in the context of IGF level assessments and suggest that IGF1 and IGF2 could play a crucial role in the early diagnosis of endometrial cancer in pre-menopausal women. [ABSTRACT FROM AUTHOR]

Simple Summary: One serious limitation of the efficacy of anticancer chemotherapy is the inevitable injury of non-malignant tissues. Side effects of 5-fluorouracil (5-FU), a drug widely used in treatment regimens for decades, are not an exception. Severe damage of the internal gut milieu, a state generally described by the term 'mucositis', is most unfavorable for the patient. This study presents an animal model for the analysis of molecular events attributable to the pathogenesis of 5-FU-induced gut mucositis. Our experiments and bioinformatics calculations indicated that this state is associated with a plethora of time-dependent changes in the intestine and the colon. These changes are directed at the coordination of the damage-related massive proteolysis combined with compensatory catabolic processes. Our findings uncovered new and counterintuitive mechanisms relevant to the rational design of pharmacological gut protectors during antitumor chemotherapy. Background/Objectives. Damage of the gastrointestinal mucosa is a major side effect of the anticancer drug 5-fluorouracil (5-FU). Insight into the molecular pathogenesis of 5-FU-induced gut mucositis is expected to justify the strategies of prophylaxis. Methods. We analyzed intestinal specimens obtained from Balb/c mice treated with 70 mg/kg 5-FU daily for up to 6 days. Results. Manifestations of mucositis in the ileum and the colon included diarrhea, weight loss, and morphological lesions. The proteomic analysis revealed dozens of differentially expressed proteins governed by a set of master regulator proteins that regulated downstream pathways culminating in the complexes of specific transcription factors. Among the most important mechanisms of 5-FU-induced gut damage predicted by bioinformatics tools was stimulation of insulin-like growth factor 1 concomitant with inhibition of insulin receptor substrate 1, suggesting an involvement of the insulin pathway. Furthermore, the levels of 14-3-3γ protein and epinephrin B2 tyrosine kinase were interpreted as key inhibitory effects of 5-FU. These changes were detectable in the ileum as well as in the colon, pointing to the commonality of 5-FU responses across the gut. Conclusion. These results demonstrated a hierarchical network of gut injury mechanisms differentially regulated in the course of the emergence of 5-FU-induced mucositis. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the impact of polyethylene glycol - conjugated recombinant human growth hormone (PEG - rhGH) treatment on immune function in children with growth hormone deficiency (GHD), by analyzing changes in lymphocyte subsets, immunoglobulin levels, and T helper cell (Th1/Th2) cytokines before and after treatment. Methods: Fifty - five children diagnosed with GHD were enrolled as study participants from May 2022 to June 2023 at the Department of Pediatrics of Huai' an First People's Hospital and Hongze District People's Hospital. According to the preferences of the participants, they were allocated into a control group (n=25) and a PEG-rhGH group (n=30) . The control group received guidance on exercise, diet, and sleep, while the PEG-rhGH group received PEG-rhGH treatment in addition to these interventions. Measurements of height, bone age, BMI, insulin-like growth factor -1 (IGF -1), lymphocyte subsets, Th1/Th2 cytokines, and immunoglobulin (Ig) levels were conducted at baseline and 3 months post-treatment. The changes in various parameters before and after the intervention were compared. Results: Before treatment, there were no significant differences in the baseline levels of the various indicators between the two groups. After 3 months of treatment, the standard deviation of height, growth rate, and serum IGF - 1 level in the PEG - rhGH group significantly increased compared to pre - treatment levels and were notably higher than those in the control group. After treatment, the PEG - rhGH group demonstrated a significantly higher proportion of CD3+, CD4+ and CD4+ /CD8+ as well as elevated levels of IgA, IgM, and IgG compared to the control group, while the proportion of CD8+ cells was notably lower in the PEG-rhGH group than in the control group, There were no significant differences in the proportion of CD19 + and CD3- CD16 + CD56 + cells between the two groups. Additionally, the levels of Th1/Th2 cytokines, interleukin (IL) -2, IL-6, and tumor necrosis factor-α (TNF-α) in the PEG-rhGH group were significantly lower after treatment compared to before, and were significantly lower than those in the control group. There were still no significant differences in the levels of IL-4 and interferon-γ (IFN-γ) between the two groups. Conclusion: PEG-rhGH treatment not only improves the height of GHD children but also affects their cellular immunity and humoral immunity. [ABSTRACT FROM AUTHOR]

Background: Graves' orbitopathy (GO) is an autoimmune condition that causes serious ocular symptoms; its treatment strategies are limited. Physalin A is a phytosterol that has shown various therapeutic properties, including anti-inflammatory and anti-fibrotic effects. In this study, we investigated whether physalin A could inhibit inflammation, fibrosis, hyaluronan (hyaluronic acid) production, and adipogenesis, which are crucial to the pathogenesis of GO. Methods: Orbital tissue explants were obtained from patients with GO during orbital decompression surgery and healthy controls. Orbital fibroblasts (OFs) were isolated and treated with different concentrations of physalin A. Using western blot and ELISA analyses, we determined the effects of physalin A on OFs. Results: Physalin A treatment suppressed the production of interleukin (IL)-1β-induced prostaglandin E2 (PGE2) and pro-inflammatory molecules, including cyclooxygenase (COX)-2, IL-6, IL-8, and intercellular adhesion molecule (ICAM)-1. We discovered that physalin A attenuated hyaluronan production induced by IL-1β or insulin-like growth factor (IGF)-1. Moreover, physalin A reduced lipid droplet formation and production of peroxisome proliferator activator (PPAR) γ, CCAAT-enhancer-binding protein (C/EBP) α, C/EBP β, sterol regulatory element binding protein (SREBP)-1, leptin, and adiponectin proteins. Physalin A suppressed the phosphorylation of extracellular signal-related kinase (ERK), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and suppressor of mothers against decapentaplegic (SMAD) 2 signaling protein. Conclusions: Our study suggests that the major mechanisms by which physalin A suppresses GO include reducing inflammation, fibrosis, hyaluronan production, and adipogenesis in OFs. The findings of this study provide evidence of the therapeutic effect of physalin A in GO. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has recently been renamed metabolic dysfunction–associated fatty liver disease (MAFLD) by international consensus. Both MAFLD and osteoporosis are highly prevalent metabolic diseases. Recent evidence indicates that NAFLD increases the risk of low bone mineral density and osteoporosis, likely mediated by obesity. NAFLD has a close association with obesity and other metabolic disorders. Although obesity was previously thought to protect against bone loss, it now heightens osteoporotic fracture risk. This overview summarizes current clinical correlations between obesity, NAFLD, and osteoporosis, with a focus on recent insights into potential mechanisms interconnecting these three conditions. This study reviewed the scientific literature on the relationship between obesity, nonalcoholic fatty liver disease, and osteoporosis as well as the scientific literature that reveals the underlying pathophysiologic mechanisms between the three. Emerging evidence suggests obesity plays a key role in mediating the relationship between NAFLD and osteoporosis. Accumulating laboratory evidence supports plausible pathophysiological links between obesity, NAFLD, and osteoporosis, including inflammatory pathways, insulin resistance, gut microbiota dysbiosis, bone marrow adiposity, and alterations in insulin-like growth factor-1 signaling. Adiposity has important associations with NAFLD and osteoporosis, the underlying pathophysiologic mechanisms between the three may provide new therapeutic targets for this complex patient population. [ABSTRACT FROM AUTHOR]

Context Proptosis in thyroid eye disease (TED) can result in facial disfigurement and visual dysfunction. Treatment with insulin-like growth factor I receptor (IGF-IR) inhibitors has been shown to be effective in reducing proptosis but with side effects. Objective To test the hypothesis that inhibition of IGF-IR indirectly and more selectively with PAPP-A inhibitors attenuates IGF-IR signaling in TED. Informed consent was obtained from patients with TED undergoing surgery, and retro-orbital tissue was collected for fibroblast isolation and culture. Operations were performed in Mayo Clinic operating suites. Cell culture was performed in a sterile tissue culture facility. Retro-orbital tissue was collected from 19 patients with TED. Methods Treatment of TED fibroblasts with proinflammatory cytokines. Flow separation of CD34− and CD34+ orbital fibroblasts, the latter representing infiltrating fibrocytes into the orbit in TED. PAPP-A expression and proteolytic activity, IGF-I stimulation of phosphatidylinositol 3 kinase/Akt pathway, and inhibition by immuno-neutralizing antibodies against PAPP-A, CD34+ status, and associated PAPP-A and IGF-IR expression were measured. Results Proinflammatory cytokines markedly increased PAPP-A expression in TED fibroblasts. IGF-IR expression was not affected by cytokine treatment. Inhibition of PAPP-A's proteolytic activity suppressed IGF-IR activation in orbital fibroblasts from patients with TED. TED fibroblasts that were CD34+ represented ∼80% of the cells in culture and accounted for ∼70% of PAPP-A and IGF-IR–expressing cells. Conclusion These results support a role for PAPP-A in TED pathogenesis and indicate the potential for novel therapeutic targeting of the IGF axis. [ABSTRACT FROM AUTHOR]

Context Few data exist about the clinical course of acromegaly, surgical and medical outcomes in patients with GH- and prolactin cosecreting pituitary adenomas (GH&PRL-PAs). Nevertheless, some series described a more aggressive clinic-radiological behavior than in growth hormone–secreting pituitary adenomas (GH-PAs). Objective This work aims to evaluate differences in clinical presentation and in surgical outcomes between GH-PAs and GH&PRL-PAs. Methods A multicenter retrospective study was conducted of 604 patients with acromegaly who underwent pituitary surgery. Patients were classified into 2 groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal (ULN) and IHC for GH and PRL was positive or PRL levels were greater than 100 ng/dL and PRL IHC was not available (n = 130) and b) GH-PA patients who did not meet the previously mentioned criteria (n = 474). Results GH&PRL-PAs represented 21.5% (n = 130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P <.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs 77.4%; P =.001) and tended to be more invasive (33.6% vs 24.7%; P =.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (odds ratio 2.8; 95% CI, 1.83-4.38). Insulin-like growth factor ULN levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [interquartile range (IQR) 1.73-3.29] vs 2.7 [IQR 1.91-3.67]; P =.023). There were no differences in the immediate (41.1% vs 43.3%; P =.659) or long-term postsurgical acromegaly biochemical cure rate (53.5% vs 53.1%; P =.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs 2.4%; P =.011) in GH&PRL-PA patients. Conclusion GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger, and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with a systemic inflammatory state that contributes to neuroinflammation and increases the risk of stroke at an early age. Stroke is the third leading cause of death worldwide and the leading cause of permanent disability. This work aimed to assess whether obesity-induced neuroinflammation can be a prognostic stroke factor that can be improved with oral administration of silymarin, an anti-inflammatory and neuroprotective drug. Methods: Male C57/Bl6 mice were used to establish an obesity model through a high-fat diet (HFD) for 12 weeks. Cerebral ischemia was performed with photothrombosis in the left motor cortex at the end of the diet. Following the induction of ischemia, silymarin (100 mg/kg) was administered orally for 14 days. Levels of pro-inflammatory (IL1β, TNFα, and MCP1) and anti-inflammatory markers (IL4, IL10), neurotrophic factors (IGF1, BDNF), and CX3CL1 were assessed in the cortex and striatum using ELISA. Results: Mice on the HFD gained significantly more weight than control subjects and exhibited altered glucose metabolism, which was improved after silymarin treatment. The survival rate was significantly lower in HFD mice (52.2%) compared to control mice (86%). Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%). Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences. Conclusion: Our findings suggest that silymarin improves glucose metabolism, possibly impacting post-stroke survival in obese mice. The increased levels of neurotrophic factors BDNF and IGF1, along with microglial regulatory factor CX3CL1, may contribute to the improved survival observed. These results indicate that silymarin could be a potential therapeutic option for managing neuroinflammation and enhancing post-stroke outcomes in obese individuals. [ABSTRACT FROM AUTHOR]

Background: Previous researches on the effect of low-fat diet (LF) on insulin-like growth factor-1 (IGF-1), and its binding proteins (IGFBPs) did not reach a consensus result, and there is no study summarizing these findings. Thus, this systematic review and meta-analysis of randomized control trials (RCTs) was performed to pool available evidence and answer the question whether dietary fat can affect IGF-1 and IGFBPs or not. Methods: PubMed, Scopus, ISI Web of Science, Google, Google scholar, ProQuest, and the Cochrane Library were searched without language restrictions until July 2, 2024 to retrieve related studies. Weighted mean difference and the corresponding variance were considered as the effect size. Standard tools were applied to assess the quality of the studies and evidence. Results: Pooling data of the eligible studies showed no significant effect of LF diet on IGF-1 (six studies; participants = 1029.; pooled mean = 1.63 ng/ml, 95% CI= [-1.34, 4.59], P = 0.28, I2 = 0.00%), and IGFBP-3 (five studies; participants = 969; pooled mean = 65.24 ng/ml, 95% CI= [-169.53, 300.00], P = 0.59, I2 = 0.0%). The results of subgroup analysis for IGF-1 and IGFBP-3 also demonstrated no significant findings. For IGFBP-1, available evidence is insufficient since only two studies have been performed yet and their results are contradictory. Conclusions: This study indicated no significant effect of LF diet on IGF-1, and IGFBP-3 concentrations. Low certainty of evidence indicates that available evidence cannot support to draw a firm conclusion and future researches may change the estimates. [ABSTRACT FROM AUTHOR]

Introduction: Insulin-like growth factor binding protein-3 (IGFBP-3) exerts varying effects on estrogen receptor alpha (ERα)-positive and triple-negative breast cancer (TNBC) cells. In ERα-positive cells, IGFBP-3 is antiproliferative and proapoptotic. In contrast, IGFBP-3 stimulates proliferation in triple-negative breast cancer (TNBC) cells via EGFR activation. Methods: To identify potential mechanisms that underlie the opposing effects of IGFBP-3 on these two breast cancer subtypes, IGFBP-3 expression was determined in cell line models of both ERα-positive breast cancer and TNBC, and cells were treated with antiestrogens tamoxifen and fulvestrant. Results and discussion: MCF-7 and T-47D cells expressed low levels of IGFBP-3 when compared to MDA-MB-231 and MDA-MB-468 cells. MCF-7 cells with acquired resistance to the selective estrogen receptor degrader fulvestrant expressed high IGFBP-3 and MCF-7 cells with constitutive IGFBP-3 expression were fulvestrant resistant. IGFBP-3 expression was increased in all cell lines upon treatment with fulvestrant or the selective estrogen receptor modulator tamoxifen and both fulvestrant and tamoxifen increased TNBC cell proliferation. Further, IGFBP-3 expression was increased by treatment with the GPER1 agonist G-1 and attenuated upon treatment with P17, a YAP/TAZ inhibitor. These data suggest that IGFBP-3 modulates breast cancer cells and is a mediator of breast cancer cell response to fulvestrant and tamoxifen. Graphical abstract of proposed mechanism of IGFBP-3 induction by GPER1 agonists. Antiestrogens tamoxifen (Tam) and fulvestrant (Ful) inhibit the actions of estrogen receptor alpha (ERα) but activate the g-protein coupled estrogen receptor (GPER1), similar to G-1, the selective GPER1 agonist. GPER1 activates transcriptional coactivators YAP and TAZ, which induce the expression of IGFBP-3. Once induced, IGFBP-3 promotes survival and proliferation in triple-negative breast cancer cells. While Tam and Ful both induced IGFBP-3, YAP/TAZ were not involved in Ful-induced IGFBP-3 expression, suggesting alternative signaling pathways that induce IGFBP-3 expression in response to Ful. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that calcium plus vitamin D supplementation during adolescent pregnancy reduces the magnitude of transient postpartum bone mass loss. In the present post hoc analysis, we further investigated the effect of calcium plus vitamin D supplementation during pregnancy in hip geometry throughout one year postpartum in Brazilian adolescents with low daily calcium intake (∼600 mg/d). Pregnant adolescents (14–19 years) were randomly assigned to receive calcium (600 mg/d) plus vitamin D3 (200 μg/d) or a placebo from 26 weeks of gestation until parturition. Dual-energy X-ray absorptiometry images were obtained at 5 (n 30 and 26 for calcium plus vitamin D and placebo, respectively), 20 (n 26 and 21) and 56 (n 18 and 12) weeks postpartum, and hip geometry parameters were analysed by Advanced Hip Assessment software. The effects of the intervention, time point and their interaction were assessed using repeated-measures mixed-effects models. No significant intervention effects or intervention × time interactions were observed on hip geometry parameters (P > 0·05). Time effects were observed in cross-sectional area, cross-sectional moment of inertia and section modulus parameters with decreases from the 5th to the 20th week postpartum followed by recovery from the 20th to the 56th week (P < 0·05). Our findings indicate that the postpartum period is associated with transient changes in the hip geometry of lactating adolescent mothers, regardless of the low calcium intake and the supplementation offered during pregnancy, suggesting that a physiological adaptation of these adolescents to low calcium intake is at play. [ABSTRACT FROM AUTHOR]

• Protein chip tech screened 2 expressed Pr in VE group. CTSL up, Fractalkine down. • CSF cytokines like CTSL, MIF, etc. can be cand biomks for VE diag & prog. • These cytokines may involve in VE pathog via inflam response, BBB destruction, etc. • It shows potential in viral enceph research using protein chip and cytokines. • The findings provide insights into viral enceph through CSF cytokine analysis. To extensively identify cerebrospinal fluid (CSF) cytokine profiles related to the occurrence, development and prognosis of viral encephalitis (VE) patients by using a high-throughput proteomic approach. We measured 80 cytokines in the CSF of acute-phase VE patients (n = 11) using high-throughput protein chip technology, comparing them to controls (n = 6). ELISA validated these findings and assessed additional cytokines from prior literature in a larger cohort (15 VE patients, 15 controls). Correlations between biomarkers and clinical characteristics were also examined. In the initial stage, we identified two differentially expressed cytokines: cathepsin-L (CTSL), which was up-regulated, and Fractalkine, which was down-regulated. Functional enrichment analysis revealed that these proteins are linked to inflammation, apoptosis, autophagy, and blood-brain barrier disruption. In stage2, the elevations of cathepsin-L (CTSL), fractalkine, interleukin-6 (IL-6), IL-1β, macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), insulin-like growth factor Ⅱ (IGF-2) and CXC chemokine ligand 10 (CXCL10) in VE were validated by ELISA. The results of linear regression indicated that these cytokines was positively correlated with CSF reactive lesions (p < 0.05). In this study, some biomarkers related with CSF level changes and prognosis were obtained. Although these cytokines are not specific, they may be related to the occurrence and development of VE. CTSL, MIF, IL-1β, TNF-α and CXCL10 can be used as VE potential biomarkers. These cytokines may participate in the pathogenesis of VE through inflammatory response, cell apoptosis, autophagy, blood-brain barrier disruption and cytokine-cytokine receptor interaction pathway. [ABSTRACT FROM AUTHOR]

In sub-Saharan Africa, children with severe malnutrition (SM) and HIV have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. Biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi, and Burkina Faso examined effect of HIV on six months post-discharge growth among children with SM and those at risk of malnutrition, assessed proteomic signatures associated with HIV in these children, and investigated how these systemic processes impact post-discharge growth in children with SM. Using SomaScanTM assay, 7335 human plasma proteins were quantified. Linear mixed models identified HIV-associated biological processes and their associations with post-discharge growth. Using structural equation modelling, we examined directed paths explaining how HIV influences post-discharge growth. Here, we show that at baseline, HIV is associated with lower anthropometry. Additionally, HIV is associated with protein profiles indicating increased complement activation and decreased insulin-like growth factor signalling and bone mineralisation. HIV indirectly affects post-discharge growth by influencing baseline anthropometry and modulating proteins involved in bone mineralisation and humoral immune responses. These findings suggest specific biological pathways linking HIV to poor growth, offering insights for targeted interventions in this vulnerable population. Here the authors show in a case-control study with more than 800 children that HIV indirectly affects early post-discharge growth in children recovering from severe malnutrition by impacting baseline anthropometry and altering proteins key to bone mineralisation, growth signalling, and humoral immune response. [ABSTRACT FROM AUTHOR]