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INTRODUCTION: Short stature is one of the main reasons for consultation in outpatient clinics and paediatric endocrinology departments and is defined as height below the 3rd centile or less than -2 standard deviations (SDs). MATERIAL AND METHODS: The study's overarching aim was to analyse the PAPP-A2 gene at mutation sites described to date and at exons 3, 4, and 5, which encode the fragment of the catalytic domain with the active site of the pregnancy-associated plasma protein A2 (PAPP-A2) protein. The secondary aims of the study were clinical and auxological analysis of a group of patients with idiopathic short stature and biochemical analysis of growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis parameters not assessed as part of the routine diagnosis of short stature, such as free IGF-1, insulin-like growth factor binding protein 5 (IGFBP-5), and acid-labile subunit (ALS) levels. Molecular analysis of the PAPP-A2 gene was performed using polymerase chain reaction (PCR) and direct sequencing. Biochemical analysis of free IGF-1, IGFBP-5, and ALS was performed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean height standard deviation score (HSDS) in the study group was -2.95. None of the patients exhibited previously described mutations in the PAPP-A2 gene or mutations in exons 3, 4, and 5 encoding the fragment of catalytic domain with the active site of the PAPP-A2 protein. In 4 patients, the known, non-pathogenic, heterozygotic polymorphism c.2328C>T(rs10913241) in exon 5 was found. CONCLUSIONS: Free IGF-1 levels correlate better with height and HSDS than total IGF-1 levels. The previously described mutations in the PAPP-A2 gene and mutations in exons 3, 4, and 5 encoding the fragment of catalytic domain with the active site of the PAPP-A2 protein were not detected; only the known and non-pathogenic, heterozygotic polymorphism c.2328C>T(rs10913241) in exon 5 of the PAPP-A2 gene was observed.

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PURPOSE: Physique athletes engage in rigorous competition preparation involving intense energy restriction and physical training to enhance muscle definition. This study investigates hormonal changes and their physiological and performance impacts during such preparation. METHODS: Participants included female (10 competing (COMP) and 10 non-dieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP participants were tested 23 weeks before (PRE), one week before (MID), and 23 weeks after the competition (POST). Non-dieting CTRL participants were tested at similar intervals. Measurements included body composition (DXA), muscle cross-sectional area (ultrasound), energy availability (EA) derived by subtracting exercise energy expenditure (EEE) from energy intake (EI) and dividing by fat-free mass (FFM), muscle strength, and various serum hormone concentrations (ACTH, cortisol, estradiol, FSH, IGF-1, IGFBP-3, insulin, and free and total testosterone and SHBG). RESULTS: During the diet, EA (p < 0.001), IGF-1 (p < 0.001), IGFBP-3 (p < 0.01), and absolute muscle strength (p < 0.01-0.001) decreased significantly in both sexes in COMP. Decreases in IGF-1 were also associated with higher loss in FFM. In males, testosterone (p < 0.01) and free testosterone (p < 0.05) decreased, while SHBG (p < 0.001) and cortisol (p < 0.05) increased. Insulin decreased significantly only in males (p < 0.001). Mood disturbances, particularly increased fatigue in males (p < 0.05), highlighted the psychological strain of competition preparation. All these changes were restored by increased EA during the post-competition recovery period. CONCLUSION: Significant reductions in IGF-1 and IGFBP-3 during competition preparation may serve as biomarkers for monitoring physiological stress. This study offers valuable insights into hormonal changes, muscle strength, and mood state during energy-restricted intense training.

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Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC). Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients. Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC. Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.

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Androgens exert their effects primarily by binding to the androgen receptor (AR), a ligand-dependent nuclear receptor. While androgens have anabolic effects on skeletal muscle, previous studies reported that AR functions in myofibers to regulate skeletal muscle quality, rather than skeletal muscle mass. Therefore, the anabolic effects of androgens are exerted via nonmyofiber cells. In this context, the cellular and molecular mechanisms of AR in mesenchymal progenitors, which play a crucial role in maintaining skeletal muscle homeostasis, remain largely unknown. In this study, we demonstrated expression of AR in mesenchymal progenitors and found that targeted AR ablation in mesenchymal progenitors reduced limb muscle mass in mature adult, but not young or aged, male mice, although fatty infiltration of muscle was not affected. The absence of AR in mesenchymal progenitors led to remarkable perineal muscle hypotrophy, regardless of age, due to abnormal regulation of transcripts associated with cell death and extracellular matrix organization. Additionally, we revealed that AR in mesenchymal progenitors regulates the expression of insulin-like growth factor 1 (Igf1) and that IGF1 administration prevents perineal muscle atrophy in a paracrine manner. These findings indicate that the anabolic effects of androgens regulate skeletal muscle mass via, at least in part, AR signaling in mesenchymal progenitors.

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OBJECTIVE: LIN28B and insulin-like growth factor-1 receptor (IGF-1R) play important roles in the growth and metastasis of colorectal cancer (CRC). The relationship between LIN28B and IGF-1R and their co-expression role in CRC is unknown. This study aims to assess whether the combined detection of LIN28B and IGF-1R is a better predictor of prognosis in CRC than either marker alone. METHODS: We used immunohistochemistry to detect LIN28B and IGF-1R protein. The correlation between LIN28B and IGF-1R expression in CRC was determined by the Spearman correlation analysis. The association between LIN28B/IGF-1R expression and clinicopathological features was analyzed, and overall survivals were also performed. RESULTS: The expression of LIN28B and IGF-1R in CRC tissues were significantly higher than that in non-cancerous tissues (P<0.001 and P<0.001, respectively). LIN28B over-expression positively correlated with IGF-1R over-expression (r=0.283, P=0.007). The increased expression of LIN28B and IGF-1R were both significantly correlated with TNM stage, lymph node metastasis and distant metastasis (all P<0.05). IGF-1R, not LIN28B, was significantly associated with vascular invasion (P=0.007). Overall survival appears to be lower in patients with high LIN28B expression or/and high IGF-1R expression than those with low LIN28B expression or/and low IGF-1R expression. In addition, the predictive sensitivity of LIN28B combined with IGF-1R was stronger than that of either one alone. CONCLUSIONS: The combined over-expression of LIN28B and IGF-1R in patients with colorectal cancer may provide a more powerful predictor for CRC prognosis.

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OBJECTIVES: We hypothesised that growth hormone (GH) deficiency (GHD) in children with attention deficit hyperactivity disorder (ADHD) is rare. This study aimed to determine any distinct clinical or biochemical parameters, including GH provocation testing, in children with ADHD on psychostimulants or idiopathic short stature (ISS). METHODS: Retrospective cross-sectional study of children who had GH provocative testing between 1998 and 2013 at one tertiary paediatric endocrine centre. Clinical data included age, sex, anthropometry, pubertal staging, bone age, diagnostic code as per the European Society Paediatric Endocrinology (ESPE), GH provocation test results, thyroid function tests, serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels. RESULTS: Four hundred ninety-three subjects underwent GH provocation testing for investigation of short stature to exclude GHD during the study period. Fifty-one children had a diagnosis of ADHD. In the remaining children, the diagnosis was Idiopathic short stature (n=240), GHD +/- hypopituitarism (n=60), and 142 subjects had other causes of short stature. Children with ADHD were older, had higher height and weight SDS and were GH-sufficient. All 51 children with ADHD had a normal serum IGFBP-3, while 20 out of these 51 subjects had a low serum IGF-1. CONCLUSIONS: GHD in children with ADHD on psychostimulant medication is rare. GH testing in children with ADHD may not be necessary, particularly if serum IGFBP-3 is in the normal range. We suggest IGFBP-3 could be used as a surrogate marker of GH sufficiency in children with ADHD. However, this needs to be confirmed with a larger study group.

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Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction have primary importance in obesity. Large quantity of macrophages is accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway promotes more macrophage accumulation into the obese adipose tissue. However, obesity-induced changes in adipose tissue macrophage density are mainly dependent on increases in the triple-positive cluster of differentiation (CD)11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. As epigenetic regulators, microRNAs (miRNAs) are one of the most important mediators of obesity. miRNAs are expressed by adipocytes as well as macrophages and regulate inflammation with the expression of target genes. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-α) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1ß) by macrophages; both adipocyte and macrophage induction by toll-like receptor-4 (TLR4) through nuclear factor-kappaB (NF-κB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in mutual message transmission between adipocyte and macrophage and in the development of adipose tissue inflammation. Thus, the metabolic status of adipocytes and their released exosomes are important determinants of macrophage inflammatory output. However, old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. As a single miRNA can be able to regulate a variety of target genes and signaling pathways, reciprocal transfer of miRNAs between adipocytes and macrophages via miRNA-loaded exosomes reorganizes the different stages of obesity. Changes in the expression of circulating miRNAs because of obesity progression or anti-obesity treatment indicate that miRNAs could be used as potential biomarkers. Therefore, it is believed that targeting macrophage-associated miRNAs with anti-obesity miRNA-loaded nano-carriers may be successful in the attenuation of both obesity and adipose tissue inflammation in clinical practice. Moreover, miRNA-containing exosomes and transferable mitochondria between the adipocyte and macrophage are investigated as new therapeutic targets for obesity-related metabolic disorders.

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BACKGROUND: Acrylamide (ACR), a common industrial chemical, is a strong neurotoxic material. The hippocampus is a brain area of interest mostly affected by Alzheimer's disease. Mesenchymal stem cells (MSCs) usefulness in various neurological diseases including Alzheimer's is being debated. In this work, the authors aim to explore the role of MSCs in ACR-induced hippocampal neurodegeneration and elucidate the mediating mechanism. MATERIALS AND METHODS: For this purpose, ten rats served as control, another ten were injected ACR (i.p. 50 mg/kg/day for 2 weeks), and the last ten rats were injected ACR in addition to MSCs (i.p. 1 × 107 MSCs single injection). RESULTS: ACR induced neurodegenerative histopathological hippocampal changes and adversely altered hippocampal oxidative stress markers SOD, MDA, and GSH. ACR had induced hippocampal demyelination as detected by silver staining. ACR significantly (P < 0.05) up-regulated the ELISA hippocampal TNF-alpha and IL-6 and produced microglial & astrocyte activation (as tracked by Iba1 & GFAP immunohistochemistry respectively). ACR significantly reduced hippocampal PCR gene expression of IGF 1 (insulin growth factor-1), BDNF (brain-derived neurotrophic factor), and NGF (nerve growth factor). MSCs administration had mitigated all the previous deleterious changes. CONCLUSIONS: Acrylamide caused detrimental effects on the hippocampus and demonstrably altered the hippocampal architecture. Bone marrow mesenchymal stem cells offered a promising therapeutic role against these neurotoxic effects of acrylamide, presumably through modulation of IGF 1, BDNF, and NGF gene expressions.

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Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling.

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Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced fecundity and gamete quality. Conversely, reduced IIS confers germ cell resilience to HSF-1 depletion-induced protein folding defects and various proteotoxic stresses. Surprisingly, this effect was not mediated by an enhanced stress response, which underlies longevity in low IIS conditions, but by reduced ribosome biogenesis and translation rate. We found that IIS activates the expression of intestinal peptide transporter PEPT-1 by alleviating its repression by FOXO/DAF-16, allowing dietary proteins to be efficiently incorporated into an amino acid pool that fuels germline protein synthesis. Our data suggest this non-cell-autonomous pathway is critical for proteostasis regulation during gametogenesis.

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Insulin-like Growth Factor-1 (IGF-1) is a crucial mitogenic factor with important functions in the mammary gland, mainly through its interaction with the IGF-1 receptor (IGF-1R). This interaction activates a complex signaling network that promotes cell proliferation, epithelial to mesenchymal transition (EMT) and inhibits apoptosis. Despite extensive research, the precise molecular pathways and intracellular mechanisms activated by IGF-1, in cancer, remain poorly understood. Recent evidence highlights the essential roles of IGF-1 and its isoforms in breast cancer (BC) development, progression, and metastasis. The peptides that define the IGF-1 isoforms-IGF-1Ea, IGF-1Eb, and IGF-1Ec-act as key points of convergence for various signaling pathways that influence the growth, metastasis and survival of BC cells. The aim of this review is to provide a detailed exami-nation of the role of the mature IGF-1 and its isoforms in BC biology and their potential use as possible therapeutical targets.

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Despite the International Federation of Horseracing Authorities (IFHA) regulation associated with heavy sanctions, the abuse of prohibited substances must be identified and deterred throughout horses' athletic careers, such as the administration of recombinant growth hormone (rGH). GH is naturally produced in mammal organisms to stimulate growth. Thus, rGH administration can enhance the performance of horses by expanding some physical abilities. As measuring endogenous GH levels is complex, an indirect strategy is to monitor GH-associated biomarkers in plasma as insulin-like growth factor 1 (IGF-1) levels. To prevent these misuses, the Equine Biological Passport (EBP) has been designed in France (GIE LCH) and Australia (ARFL-Racing NSW) to profile specific biological and chemical parameters in selected racehorses. In this study, we investigated individual limits as a complementary tool to a single limit to supervise the stability of IGF-1 profile over a racing season. The aim is to design custom limits based on the horse's history to detect any deviation below the single limit. The method was assessed using experimental data and then tested on EBP data from three thoroughbreds and three French trotters. Finally, individual limits have been added to the French EBP for IGF-1 monitoring.

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As a new therapeutic method, extracorporeal shock wave (ESW) has shown remarkable efficacy in the treatment of temporomandibular joint disorder syndrome. Numerous studies have shown that it has the advantages of noninvasiveness, short treatment time, etc. It can effectively relieve pain and improve symptoms such as joint mobility and opening degree. In clinical practice, through accurate diagnosis and positioning of different patients, appropriate treatment parameters such as therapeutic transducer, frequency and pressure can be selected to significantly improve the efficacy. At the same time, follow-up evaluation after treatment, including temporomandibular joint disorder index and visual analogue score, is also helpful to fully understand the rehabilitation of patients. Extracorporeal shock wave therapy (ESWT) brings new hope to patients with temporomandibular joint disorder syndrome and has a broad application prospect.

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Thyroid stimulating hormone-secreting pituitary neuroendocrine tumor (TSH-PitNET) is a rare disease in which pituitary adenomas secrete excessive amounts of TSH, and TSH is not suppressed despite high blood levels of thyroid hormone. Somatostatin analogs (SSAs) like lanreotide are used to control TSH secretion and manage symptoms in cases where surgery is not fully effective or feasible. The treatment of choice for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer is generally chemotherapy and anti-HER2 therapy. A 52-year-old woman was diagnosed with Graves' disease 26 years ago and stopped going to the hospital after several years of treatment with thiamazole. She had a right breast mass two years prior and visited the Department of Breast and Endocrine Surgery in our hospital one year prior, where she was diagnosed with T3N3M1, stage 4 breast cancer with a mass 52 mm in diameter in the right breast and metastasis in the 12th thoracic vertebra. Breast cancer receptor status was negative for the estrogen receptor, negative for the progesterone receptor, and positive for HER2. She was also found to have an enlarged thyroid gland, palpitations, inappropriate TSH secretion, and a 6 mm nodule on the pituitary gland, which was diagnosed as a TSH-PitNET. She was treated for breast cancer with trastuzumab deruxtecan therapy and for TSH-PitNET with lanreotide. One month after starting lanreotide, pituitary, and thyroid function improved to normal, and four months later, the breast mass was significantly reduced to 16 mm in diameter and a mastectomy was performed. The size of the pituitary adenoma remained unchanged during observation. Remarkably, the mastectomy specimen was free of cancer cells and showed a pathologically complete response. Needle biopsy specimens at the time of breast cancer diagnosis were positive for somatostatin receptor 2 (SSTR2) and insulin-like growth factor 1 receptor (IGF-1R) immunostaining. However, both were negative in the mastectomy specimen. Recently, SSTR2 and IGF-1R were reported to be expressed in breast cancer, and several clinical trials of SSAs for breast cancer have been conducted. SSAs are effective in improving pituitary and thyroid functions against TSH-PiTNET, and in combination with chemotherapy, they may have synergistic antitumor effects in patients with SSTR2-positive breast cancer.

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Objective: Reduced IGF-1 signalling is an evolutionarily conserved mediator of longevity, yet the magnitude of this effect is substantially larger in organisms retaining a common insulin and IGF-1 receptor. Whether this reflects the failure to simultaneously reduce IGF-1 and insulin signalling in mammalian model systems remains unexplored, as is the associated impact on markers of healthy ageing. We set out to address these uncertainties. Methods: We compared the duration of healthy life (healthspan) in male mice with haploinsufficiency of the insulin receptor (IRKO), IGF-1 receptor (IGF-1RKO), or both (DKO), versus wildtype (WT) littermates. Cognitive performance was defined using nesting studies at 3- and 24-months of age. Brain transcriptome was characterised at 3- and 18-months of age using RNA-seq. Results: Healthspan was longer in DKO versus WT, with IRKO and IGF-1RKO being intermediate. At 2 years of age, DKO also exhibited preserved nesting behaviour in contrast with all other genotypes. Differential insulin sensitivity or weight gain during ageing did not explain the preserved healthspan of DKO, since these were comparable to IRKO littermates. Brain transcriptomics at 18 months of age revealed lower expression of canonical ageing-associated genes in DKO versus WT, although many of these findings were replicated in IRKO versus WT or IGF-1RKO vs WT. Conclusions: Reduced insulin and IGF-1 receptor expression have both common and synergistic effects upon elements of healthy mammalian ageing, suggesting future ageing studies should consider targeting both insulin and IGF-1 signalling.

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Vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor-1 (IGF-1) may help the brain resist both functional and structural neurodegeneration, which is critical for maintaining cognitive and neurological health in older adults. This meta-analysis and meta-regression seek to elucidate the impact of physical activity on these biomarker levels in healthy seniors, as well as to examine the influence of several moderator factors, including age, sex, period length, and time, for the first time. The standardized mean effect metric was used to assess the influence of weights, which reflected each group's relative importance in comparison to baseline data. The study looked at potential moderating factors including age, gender, and physical activity levels. The analysis of 11 studies indicated no significant effect of physical activity on VEGF levels [0.328, CI 95 % (-0.871 to 1.52); I2 = 0.00; p = 0.592; Q = 4.14]. Physical activity had a substantial impact on brain-derived neurotrophic factor (0.827, 95 % confidence interval: 0.487 to 1.16; I2 = 0.00; p = 0.00; Q = 78.46), with females showing particularly notable effects (Tau2 = 0.327, Tau = 0.571, I2 = 80.90 %, Q = 68.05, df = 15, p = 0.00). Physical activity also had a substantial effect on insulin-like growth factor 1 (0.276, 95 % confidence interval: 0.065 to 0.487; I2 = 0.00; p = 0.10; Q = 8.35), indicating that it positively influences IGF-1 levels. Overall, while physical exercise has a significant effect on BDNF and IGF-1, more research is needed to fully understand its impact on vascular endothelial growth factor and to investigate how individual characteristics may influence exercise outcomes.

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Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and endocrine fashion. The aim of this intervention study was to investigate if massage therapy affects circulating myokine levels. A total of 46 healthy, normal-weight subjects (15 men) aged 18-35 were recruited. Forty-five minutes of massage Swedish therapy was applied to the back and hamstrings. Blood samples via cannula were taken at the baseline, during the massage (30 min), end of the massage (45 min), and 30 min and 1 h after the massage. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) were measured as surrogate markers by ELISAs. There was a significant increase in IL-6 from 1.09 pg/mL to 1.85 pg/mL over time (Wilks' Lambda Value 0.545, p < 0.000; repeated measures ANOVA). Pair-wise comparisons showed a significant increase after 1 h of massage. No significant increase was observed in IGF-1 levels. The change in myokine levels was not correlated with muscle mass (p = 0.16, 0.74). The increase in IL-6 suggests that there might be anti-inflammatory effects, affecting glucose and lipid metabolism pathways via IL-6 signaling to muscles, fat tissue, and the liver.

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Prostate enlargement due to benign prostate hyperplasia (BPH) is a common, progressive disorder in elderly males with increasing prevalence. It causes devastating lower urinary tract symptoms with no satisfactory medication. Asiatic acid (AA), a natural pentacyclic triterpenoid, is known to have antiproliferative, antioxidant, and anti-inflammatory activities. The aim of this study was to evaluate the possible preventive activities of AA against BPH induced by testosterone in rats. Finasteride (0.5 mg/kg) was used as a reference drug. AA (10 or 20 mg/kg) administration inhibited the rise in prostatic weight and index induced by testosterone. Histopathological staining proved that AA mitigated the pathological features of BPH induced by testosterone, which was reflected as lower glandular epithelial in AA-treated groups. Also, the administration of AA along with testosterone restored the redox valance by inhibiting lipid peroxidation, and MDA production, and restoring the activities of superoxide dismutase (SOD) and catalase (CAT) activities. Also, AA reduced prostate interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein expression. In addition, AA modulated mRNA expression of Bax and Bcl-2 in favor of apoptosis. The effects of AA (20 mg/kg) were comparable to those of finasteride. Further, AA ameliorated the rise in insulin-like growth factor 1 receptor (IGF-1R) mRNA expression. This was associated with the enhancement of the prostatic content of PPAR-γ. It can be concluded that AA mitigated the features of BPH induced by testosterone in rats. This involves antioxidant, anti-inflammatory and pro-apototic activities of AA as well as its ability to down-regulate IGF-1R expression and enhance PPAR-γ concentration in prostatic tissues.

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Aging-related muscle atrophy/sarcopenia is the most common type of muscle impairment that affects the quality of life. In the current study, we examined the effect of a functional food mixture of amla, turmeric, black pepper, cinnamon, and ginger on D-galactose-induced muscle alterations in rats. Wistar rats were randomly divided into three groups: Control (C), D-galactose (G), and D-galactose + functional food mixture intervention (G + I). Rats in group-G and -G + I were injected with D-galactose (300 mg/kg/day) for 90 days. After 3 months of the experimental period, the rats were sacrificed to collect gastrocnemius muscle. Group-G rats showed elevated levels of inflammatory cytokines (TNFα and NF-kB), atrogenes (atrogin-1 and MuRF1), decreased insulin/IGF1 signaling (decreased AKT phosphorylation), altered mitochondrial dynamics (increased fission and decreased fusion proteins), increased apoptotic mediators (Bax/Bcl-2, and caspase-3), and decreased muscle cell cross-sectional area when compared with group-C (p < 0.05). Interestingly, supplementation with the functional food mixture prevented galactose-induced alterations in the muscle. The observed anti-inflammatory, insulin-sensitizing, mitochondria-protective, and antiapoptotic effects of the functional food could be the underlying mechanisms in displaying positive effects against galactose-induced muscle atrophy and, hence, may be useful for the prevention of age-related muscle disorders.