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Keywords = total-IGF-binding protein-3

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22 pages, 12709 KiB  
Article
IGF2BP3 Modulates mRNA Splicing and Stability to Promote Trophoblast Progression via Interaction with PDE3A and Suppression by miR-196a-5p in Preeclampsia
by Chunyan Li, Pingpo Ming, Cuifang Fan, Jiao Chen and Jing Yang
Biomedicines 2025, 13(6), 1268; https://doi.org/10.3390/biomedicines13061268 - 22 May 2025
Viewed by 552
Abstract
Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of [...] Read more.
Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of AS in PE remain poorly understood. Methods: To elucidate AS-mediated regulatory pathways in PE, a total of 38 fresh-frozen placental samples, including 13 pre-eclampsia samples and 25 normal control samples, were collected from Renmin Hospital of Wuhan University between 1 February and 30 July 2022. We performed transcriptome sequencing of seven PE and seven normal placentas to identify differentially spliced events. After quality control and adapter trimming, raw sequencing reads were aligned to the human reference genome using STAR. Differential exon usage was analyzed using DEXSeq (version 1.36.0), and exons with an adjusted p-value < 0.05 and a fold change greater than 2 or less than 0.5 were considered significantly differentially spliced. Functional assays, including CCK8, colony formation, and cell cycle analyses, were conducted to assess trophoblast proliferation, whereas wound healing and Transwell assays were used to evaluate trophoblast migration and invasion using the HTR-8/SVneo cell line. RNA immunoprecipitation sequencing (RIP-seq) and RNA stability assays were employed to investigate mRNA interactions and stability. Results: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) emerged as a key RNA-binding protein associated with alternative splicing regulation, intersecting both AS-related candidate genes and known splicing factors, although it is not a classical splicing factor itself. IGF2BP3 overexpression markedly enhanced HTR-8/SVneo trophoblast proliferation, migration, and invasion while suppressing ROS activation. RNA-seq, RIP-seq, and RNA stability assays revealed that IGF2BP3 directly interacts with and enhances the stability of PDE3A mRNA. Functional rescue experiments confirmed that PDE3A knockdown partially abrogated IGF2BP3-mediated trophoblast progression. Furthermore, miR-196a-5p was identified as a negative regulator of IGF2BP3 via miRNA inhibitor/mimic transfection, qRT-PCR, and functional assays, confirming that miR-196a-5p overexpression downregulates IGF2BP3, thereby impairing trophoblast migration and proliferation. Notably, restoring IGF2BP3 expression reversed these inhibitory effects. Conclusions: Our findings reveal a previously unrecognized regulatory axis in PE in which miR-196a-5p suppresses IGF2BP3 expression, leading to PDE3A mRNA destabilization and impaired trophoblast function. This study offers mechanistic insights into PE pathogenesis and identifies IGF2BP3 as a potential therapeutic target. Full article
(This article belongs to the Section Cell Biology and Pathology)
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12 pages, 1293 KiB  
Article
Insulin-like Growth Factor-I Reduces Collagen Production by Hepatic Stellate Cells Through Stimulation of Collagen Degradation System via mTOR-Dependent Signaling Pathway
by Takako Nishikawa, Natsuko Ohtomo, Yukiko Inoue, Mami Takahashi, Hitoshi Ikeda, Kazuhiko Koike, Nobutake Yamamichi, Mitsuhiro Fujishiro and Tomoaki Tomiya
Biomedicines 2025, 13(3), 566; https://doi.org/10.3390/biomedicines13030566 - 24 Feb 2025
Viewed by 760
Abstract
Aim: The liver is the major source of circulating insulin-like growth factor (IGF)-I. Serum IGF-I levels are decreased in cirrhotic patients depending on severity. IGF-I administration was shown to improve liver function in patients and animal models of liver cirrhosis. However, controversy [...] Read more.
Aim: The liver is the major source of circulating insulin-like growth factor (IGF)-I. Serum IGF-I levels are decreased in cirrhotic patients depending on severity. IGF-I administration was shown to improve liver function in patients and animal models of liver cirrhosis. However, controversy exists as to whether IGF-I stimulates or reduces fibrosis in the liver. The effects of IGF-I on collagen accumulation by hepatic stellate cells (HSCs) and its mechanisms were studied. Methods: A moderately activated HSC clone was used to determine the effect of IGF-I administration on the collagen production system, including its degradation. The intracellular signaling system was also studied in the cells stimulated by IGF-I. Results: IGF-I treatment reduced total amounts of collagen deposition in a dose-related manner, while DNA synthesis was stimulated by IGF-I. IGF-I treatment did not affect transforming growth factor-beta levels and type I procollagen mRNA expression. Expression of matrix metalloproteinase (MMP)-2 and -9 was upregulated, and tissue inhibitor of metalloproteinase (TIMP)-1 expression was downregulated by IGF-I treatment. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suppressed phosphorylation of 70 kDa ribosomal protein S6 kinase and eukaryotic initiation factor 4E-binding protein 1, and abrogated IGF-I-induced increase in MMP-2 and -9 expression and decrease in TIMP-1 expression. Conclusions: IGF-I has the ability to stimulate the collagen degradation system by HSCs through an mTOR-dependent pathway independent of modulation of the activation state of HSCs. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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14 pages, 1038 KiB  
Article
Profiling of snoRNAs in Exosomes Secreted from Cells Infected with Influenza A Virus
by Wojciech Rozek, Malgorzata Kwasnik, Wojciech Socha, Bartosz Czech and Jerzy Rola
Int. J. Mol. Sci. 2025, 26(1), 12; https://doi.org/10.3390/ijms26010012 - 24 Dec 2024
Viewed by 1151
Abstract
Small nucleolar RNAs (snoRNAs) are non-coding RNAs (ncRNAs) that regulate many cellular processes. Changes in the profiles of cellular ncRNAs and those secreted in exosomes are observed during viral infection. In our study, we analysed differences in expression profiles of snoRNAs isolated from [...] Read more.
Small nucleolar RNAs (snoRNAs) are non-coding RNAs (ncRNAs) that regulate many cellular processes. Changes in the profiles of cellular ncRNAs and those secreted in exosomes are observed during viral infection. In our study, we analysed differences in expression profiles of snoRNAs isolated from exosomes of influenza (IAV)-infected and non-infected MDCK cells using high-throughput sequencing. The analysis revealed 133 significantly differentially regulated snoRNAs (131 upregulated and 2 downregulated), including 93 SNORD, 38 SNORA, and 2 SCARNA. The most upregulated was SNORD58 (log2FoldChange = 9.61), while the only downregulated snoRNAs were SNORD3 (log2FC = −2.98) and SNORA74 (log2FC = −2.67). Several snoRNAs previously described as involved in viral infections were upregulated, including SNORD27, SNORD28, SNORD29, SNORD58, and SNORD44. In total, 533 interactors of dysregulated snoRNAs were identified using the RNAinter database with an assigned confidence score ≥ 0.25. The main groups of predicted interactors were transcription factors (TFs, 169 interactors) and RNA-binding proteins (RBPs, 130 interactors). Among the most important were pioneer TFs such as POU5F1, SOX2, CEBPB, and MYC, while in the RBP category, notable interactors included Polr2a, TNRC6A, IGF2BP3, and FMRP. Our results suggest that snoRNAs are involved in pro-viral activity, although follow-up studies including experimental validation would be beneficial. Full article
(This article belongs to the Special Issue Exosomes and Non-Coding RNA Research in Health and Disease)
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12 pages, 3104 KiB  
Article
Distinct Patterns of Smooth Muscle Phenotypic Modulation in Thoracic and Abdominal Aortic Aneurysms
by Chien-Jung Lin, Campbell Keating, Robyn Roth, Yasar Caliskan, Mustafa Nazzal, Vernat Exil, Richard DiPaolo, Divya Ratan Verma, Kishore Harjai, Mohamed Zayed, Chieh-Yu Lin, Robert P. Mecham and Ajay K. Jain
J. Cardiovasc. Dev. Dis. 2024, 11(11), 349; https://doi.org/10.3390/jcdd11110349 - 1 Nov 2024
Cited by 1 | Viewed by 1515
Abstract
Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk [...] Read more.
Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk RNA studies, these findings represent the totality of gene expression without regards to the differences in cellular composition. Single-cell RNA sequencing provides an opportunity to interrogate cell-type-specific transcriptomes. Single cell RNA sequencing datasets from mouse TAA (GSE153534) and AAA (GSE164678 and GSE152583) with respective controls were obtained from the Gene Expression Omnibus. Bioinformatic analysis was performed with the Seurat 4, clusterProfiler, and Connectome software packages (V1.0.1). Immunostaining was performed with standard protocols. Within normal and aneurysmal aortae, three unique populations of cells that express smooth muscle cell (SMC) markers were identified (SMC1, SMC2, and SMCmod). A greater proportion of TAA SMCs clustered as a unique population, SMCmod, relative to the AAA SMCs (38% vs. 10–12%). These cells exhibited transcriptional features distinct from other SMCs, which were characterized by Igfbp2 and Tnfrsf11b expression. Genes upregulated in TAA SMCs were enriched for the Reactome terms “extracellular matrix organization” and “insulin-like growth factor (IGF) transport and uptake by IGF binding proteins (IGFBPs)”, indicating a role for Igfbp2 in TAA pathogenesis. Regulon analysis revealed transcription factors enriched in TAAs and AAAs. Validating these mouse bioinformatic findings, immunostaining demonstrated that both IGFBP2 and TNFRSF11B proteins increased in human TAAs compared to AAAs. These results highlight the unique cellular composition and transcriptional signature of SMCs in TAAs and AAAs. Future studies are needed to reveal the pathogenetic pathways of IGFBP2 and TNFRSF11B. Full article
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24 pages, 10083 KiB  
Article
The Aqueous Extract of Hemerocallis citrina Baroni Improves the Lactation-Promoting Effect in Bovine Mammary Epithelial Cells through the PI3K-AKT Signaling Pathway
by Jiaxu Chen, Zhaoping Pan, Qili Li, Yanyang Wu, Xiaopeng Li, Xue Wang, Dandan Hao, Xiaoyu Peng, Lina Pan, Wei Li, Jiaqi Wang, Tao Li and Fuhua Fu
Foods 2024, 13(17), 2813; https://doi.org/10.3390/foods13172813 - 4 Sep 2024
Cited by 2 | Viewed by 1472
Abstract
Insufficient milk supply is a widespread issue faced by women globally and associated with a higher risk of health problems in infants and mothers. Hemerocallis citrina Baron, commonly known as daylily, is a perennial edible plant often used in traditional Asian cuisine to [...] Read more.
Insufficient milk supply is a widespread issue faced by women globally and associated with a higher risk of health problems in infants and mothers. Hemerocallis citrina Baron, commonly known as daylily, is a perennial edible plant often used in traditional Asian cuisine to promote lactation. However, the active compound(s) and mechanism of its lactation-promoting effect remain unclear. This study aimed to confirm the traditional use of daylily in promoting lactation and investigate its potential active components and underlying molecular mechanisms. Our results showed that the aqueous extracts of H. citrina Baroni (HAE) significantly enhanced milk production, and the serum levels of lactation-related hormones, and promoted mammary gland development in lactating rats, as well as increased the levels of milk components in bovine mammary epithelial cells (BMECs) (p < 0.05). UHPLC-Q-Exactive Orbitrap-MS analysis revealed that hexamethylquercetin (HQ) is the representative flavonoid component in HAE, accounting for 42.66% of the total flavonoids. An integrated network pharmacology and molecular docking analysis suggested that HQ may be the potential active flavonoid in HAE that promotes lactation, possibly supporting lactation by binding to key target proteins such as STAT5A, PIK3CA, IGF1R, TP53, CCND1, BCL2, INS, AR, and DLD. Cell experiments further demonstrated that HQ could promote cell proliferation and the synthesis of milk proteins, lactose, and milk fat in BMECs. Transcriptomic analysis combined with a quantitative reverse transcription polymerase chain reaction (RT-qPCR) revealed that both HAE and HQ exert a lactation-promoting function mainly through regulating the expression of key genes in the PI3K-Akt signaling pathway. Full article
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13 pages, 840 KiB  
Article
Differences in Bone Metabolism between Children with Prader–Willi Syndrome during Growth Hormone Treatment and Healthy Subjects: A Pilot Study
by Joanna Gajewska, Magdalena Chełchowska, Katarzyna Szamotulska, Witold Klemarczyk, Małgorzata Strucińska and Jadwiga Ambroszkiewicz
Int. J. Mol. Sci. 2024, 25(17), 9159; https://doi.org/10.3390/ijms25179159 - 23 Aug 2024
Cited by 2 | Viewed by 1638
Abstract
Despite therapy with growth hormone (GH) in children with Prader–Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children [...] Read more.
Despite therapy with growth hormone (GH) in children with Prader–Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children with PWS undergoing GH therapy and a low-energy dietary intervention. Twenty-four children with PWS and 30 healthy children of the same age were included. Serum concentrations of bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), periostin, osteopontin, osteoprotegerin (OPG), sclerostin, C-terminal telopeptide of type I collagen (CTX-I), and insulin-like growth factor-I (IGF-I) were determined using immunoenzymatic methods. OC levels and the OC/CTX-I ratios were lower in children with PWS than in healthy children (p = 0.011, p = 0.006, respectively). Glu-OC concentrations were lower (p = 0.002), but Gla-OC and periostin concentrations were higher in patients with PWS compared with the controls (p = 0.005, p < 0.001, respectively). The relationships between IGF-I and OC (p = 0.013), Gla-OC (p = 0.042), and the OC/CTX-I ratio (p = 0.017) were significant after adjusting for age in children with PWS. Bone turnover disorders in children with PWS may result from impaired bone formation due to the lower concentrations of OC and the OC/CTX-I ratio. The altered profile of OC forms with elevated periostin concentrations may indicate more intensive carboxylation processes of VKDPs in these patients. The detailed relationships between the GH/IGF-I axis and bone metabolism markers, particularly VKDPs, in children with PWS requires further research. Full article
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19 pages, 1608 KiB  
Article
Association between IGF-1 and IGFBPs in Blood and Follicular Fluid in Dairy Cows Under Field Conditions
by Christina Schiffers, Idil Serbetci, Kirsten Mense, Ana Kassens, Hanna Grothmann, Matthias Sommer, Christine Hoeflich, Andreas Hoeflich, Heinrich Bollwein and Marion Schmicke
Animals 2024, 14(16), 2370; https://doi.org/10.3390/ani14162370 - 15 Aug 2024
Viewed by 1740
Abstract
Insulin-like growth factor 1 (IGF-1) regulates dairy cow reproduction, while the paracrine IGF system locally influences fertility. In both systems, IGF-1 bioactivity is regulated through binding proteins (IGFBPs) inhibiting IGF-1 binding to its receptor (IGF1R). This study aimed to investigate a possible transfer [...] Read more.
Insulin-like growth factor 1 (IGF-1) regulates dairy cow reproduction, while the paracrine IGF system locally influences fertility. In both systems, IGF-1 bioactivity is regulated through binding proteins (IGFBPs) inhibiting IGF-1 binding to its receptor (IGF1R). This study aimed to investigate a possible transfer between this endocrine and paracrine system. Therefore, blood and follicular fluid (FF) from postpartum dairy cows were analysed for ß-hydroxybutyrate (BHB), IGF-1, IGFBP-2, -3, -4, -5, and an IGFBP fragment in two study parts. The mRNA expression of IGFBP-2, IGFBP-4, IGF1R, and the pregnancy-associated plasma protein A (PAPP-A) in granulosa cells was measured. The results showed correlations between plasma and FF for IGF-1 (r = 0.57, p < 0.001) and IGFBP-2 (r = −0.57, p < 0.05). Blood BHB negatively correlated with IGF-1 in blood and FF and IGFBP-3, -5 and total IGFBP in blood (IGF-1 plasma: r = −0.26, p < 0.05; FF: r = −0.35, p < 0.05; IGFBP-3: r = −0.64, p = 0.006; IGFBP-5: r = −0.49, p < 0.05; total IGFBP: r = −0.52, p < 0.05). A negative correlation was found between IGFBP-2 expression and IGF-1 concentration in FF (r = −0.97, p = 0.001), while an IGFBP fragment positively correlated with IGF1R-mRNA in FF (r = 0.82, p = 0.042). These findings suggest a transfer and local regulation between the somatotropic axis and the follicular IGF system, linking the metabolic status with local effects on dairy cow fertility. Full article
(This article belongs to the Section Cattle)
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28 pages, 3251 KiB  
Article
Insulin-like Growth Factor-Binding Protein 2 in Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Gender-Based Perspective
by Elke Boxhammer, Vera Paar, Kristen Kopp, Sarah X. Gharibeh, Evelyn Bovenkamp-Aberger, Richard Rezar, Michael Lichtenauer, Uta C. Hoppe and Moritz Mirna
Int. J. Mol. Sci. 2024, 25(15), 8220; https://doi.org/10.3390/ijms25158220 - 27 Jul 2024
Viewed by 1314
Abstract
Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease [...] Read more.
Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease mechanisms and therapeutic targets for these conditions. A total of 102 patients (46 female, 56 male) with severe AS undergoing a transcatheter aortic valve replacement (TAVR) in a single-center study were classified using echocardiography tests to determine systolic pulmonary artery pressure (sPAP) and the presence (sPAP ≥ 40 mmHg) or absence (sPAP < 40 mmHg) of PH. Additionally, serial laboratory determinations of IGF-BP2 before, and at 24 h, 96 h, and 3 months after intervention were conducted in all study participants. Considering the entire cohort, patients with PH had significant and continuously higher serum IGF-BP2 concentrations over time than patients without PH. After subdivision by sex, it could be demonstrated that the above-mentioned results were only verifiable in males, but not in females. In the male patients, baseline IGF-BP2 levels before the TAVR was an isolated risk factor for premature death after intervention and at 1, 3, and 5 years post-intervention. The same was valid for the combination of male and echocardiographically established PH patients. The predictive role of IGF-BP2 in severe AS and concurrent PH remains unknown. A more profound comprehension of IGF-BP2 mechanisms, particularly in males, could facilitate the earlier consideration of the TAVR as a more effective and successful treatment strategy. Full article
(This article belongs to the Special Issue Novel Biomarkers for Cardiovascular Diseases)
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17 pages, 4250 KiB  
Article
Effect of IGFBP-4 during In Vitro Maturation on Developmental Competence of Bovine Cumulus Oocyte Complexes
by Adriana Raquel Camacho de Gutiérrez, Oguz Calisici, Christine Wrenzycki, Juan Carlos Gutiérrez-Añez, Christine Hoeflich, Andreas Hoeflich, Árpád Csaba Bajcsy and Marion Schmicke
Animals 2024, 14(5), 673; https://doi.org/10.3390/ani14050673 - 21 Feb 2024
Viewed by 1948
Abstract
Insulin-like growth factors (IGFs) are essential for oocyte maturation. Their bioavailability is regulated by their respective binding proteins (IGFBPs) and proteases. IGFBP-4 blocks the biological effects of IGFs. High IGFBP-4 expression has been associated with follicle atresia. We hypothesized that IGFBP-4 affects oocyte [...] Read more.
Insulin-like growth factors (IGFs) are essential for oocyte maturation. Their bioavailability is regulated by their respective binding proteins (IGFBPs) and proteases. IGFBP-4 blocks the biological effects of IGFs. High IGFBP-4 expression has been associated with follicle atresia. We hypothesized that IGFBP-4 affects oocyte developmental competence during maturation. Therefore, the aim of this study was to examine the effect of IGFBP-4 on the developmental rate of bovine cumulus–oocyte complexes (COCs) during in vitro embryo production. Abattoir-derived COCs were matured with rbIGFBP-4 (2000, 540, and 54 ng/mL) compared to a control. Cumulus expansion, oocyte maturation, cleavage, blastocyst, and hatching rates were evaluated. Furthermore, blastocyst gene expression of SOCS2, STAT3, SLC2A1, SLCA3, BAX, and POU5F1 transcripts were quantified using RT-qPCR. No statistical differences were detected among the groups for cumulus expansion, maturation, cleavage, blastocyst rates, or all gene transcripts analyzed. However, at day 8 and 9, the number of total hatching and successfully hatched blastocysts was lower in 2000 ng/mL rbIGFBP-4 compared to the control (day 8: total hatching: 17.1 ± 0.21 vs. 31.2 ± 0.11%, p = 0.02 and hatched blastocyst 6.7 ± 0.31 vs. 21.5 ± 0.14%, p = 0.004; day 9 total hatching 36.4 ± 0.18 vs. 57.7 ± 0.10%, p = 0.009 and hatched blastocyst 18.2 ± 0.21 vs. 38.1 ± 0.11%, p = 0.004). We concluded that high concentrations of rbIGFBP-4 might negatively affect the subsequent ability of the embryo to hatch and possibly compromise further elongation. Full article
(This article belongs to the Special Issue Advances in In Vitro Oocyte Development in Domestic Animals)
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16 pages, 2832 KiB  
Article
Upregulation of Anti-Angiogenic miR-106b-3p Correlates Negatively with IGF-1 and Vascular Health Parameters in a Model of Subclinical Cardiovascular Disease: Study with Metformin Therapy
by Sherin Bakhashab, Josie O’Neill, Rosie Barber, Catherine Arden and Jolanta U. Weaver
Biomedicines 2024, 12(1), 171; https://doi.org/10.3390/biomedicines12010171 - 12 Jan 2024
Cited by 4 | Viewed by 1669
Abstract
Well-controlled type 1 diabetes mellitus (T1DM) is regarded as a model of subclinical cardiovascular disease (CVD), characterized by inflammation and adverse vascular health. However, the underlying mechanisms are not fully understood. We investigated insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels, their [...] Read more.
Well-controlled type 1 diabetes mellitus (T1DM) is regarded as a model of subclinical cardiovascular disease (CVD), characterized by inflammation and adverse vascular health. However, the underlying mechanisms are not fully understood. We investigated insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels, their correlation to miR-106b-3p expression in a subclinical CVD model, and the cardioprotective effect of metformin. A total of 20 controls and 29 well-controlled T1DM subjects were studied. Plasma IGF-1, IGFBP-3 levels, and miR-106b-3p expression in colony-forming unit-Hills were analyzed and compared with vascular markers. miR-106b-3p was upregulated in T1DM (p < 0.05) and negatively correlated with pro-angiogenic markers CD34+/100-lymphocytes (p < 0.05) and IGF-1 (p < 0.05). IGF-1 was downregulated in T1DM (p < 0.01), which was associated with increased inflammatory markers TNF-α, CRP, and IL-10 and reduced CD34+/100-lymphocytes. IGFBP-3 had no significant results. Metformin had no effect on IGF-1 but significantly reduced miR-106b-3p (p < 0.0001). An Ingenuity Pathway analysis predicted miR-106b-3p to inhibit PDGFA, PIK3CG, GDNF, and ADAMTS13, which activated CVD. Metformin was predicted to be cardioprotective by inhibiting miR-106b-3p. In conclusion: Subclinical CVD is characterized by a cardio-adverse profile of low IGF-1 and upregulated miR-106b-3p. We demonstrated that the cardioprotective effect of metformin may be via downregulation of upregulated miR-106b-3p and its effect on downstream targets. Full article
(This article belongs to the Special Issue Adult Stem Cells and Endothelial Progenitor Cells in Diseases)
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11 pages, 277 KiB  
Article
Association Study of IGF-1 rs35767 and rs6214 Gene Polymorphisms with Cancer Susceptibility and Circulating Levels of IGF-1, IGFBP-2, and IGFBP-3 in Colorectal Cancer Patients
by Maryam H. Alrashid, Ahmad E. Al-Serri, Rubina F. Hussain, Suzanne A. Al-Bustan and Jasem Al-Barrak
Biomedicines 2023, 11(12), 3166; https://doi.org/10.3390/biomedicines11123166 - 28 Nov 2023
Viewed by 1911
Abstract
Early detection of colorectal cancer (CRC) increases the 5-year survival rate by 90%; therefore, non-invasive biomarkers such as measurable circulating proteins for early detection and prognosis are crucial. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and apoptosis. IGF [...] Read more.
Early detection of colorectal cancer (CRC) increases the 5-year survival rate by 90%; therefore, non-invasive biomarkers such as measurable circulating proteins for early detection and prognosis are crucial. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and apoptosis. IGF binding proteins (IGFBPs) bind and inhibit the activity of IGF-1. It was inconsistently reported that high IGF-1 and IGFBP-2 and low IGFBP-3 circulating levels are associated with high cancer risk, poor prognosis, and tumor metastasis in several cancers. A total of 175 patients with CRC and 429 controls were enrolled in this study. We genotyped for IGF-1 rs35767 and rs6214 gene polymorphisms and assessed their association with circulating levels of IGF-1 and/or the risk for CRC. We also determined plasma levels of IGF-1, IGFBP-2, and IGFBP-3. Neither rs35767 nor rs2614 were associated with cancer risk or IGF-1 levels in our study cohort. IGF-1 and IGFBP-3 levels were higher in controls than in patients, whereas IGFBP-2 was higher in patients than in controls. Only IGFBP-2 was associated with increased tumor grade but not stage. Therefore, IGF-1, IGFBP-2, and IGFBP-3 may be useful as early detection and prognostic biomarkers in CRC. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
21 pages, 1722 KiB  
Article
Replacing Fish Meal with Hydrolyzed Collagen Derived from Fish By-Products Improved Muscle Quality and Glycolipid Metabolism of Triploid Crucian Carp
by Fangle Tong, Jinhai Bai, Zhongtian Tang, Chunyan Li, Shaojun Liu and Zehong Wei
Foods 2023, 12(6), 1235; https://doi.org/10.3390/foods12061235 - 14 Mar 2023
Cited by 5 | Viewed by 3076
Abstract
Fish by-products are rich in collagen. Hydrolyzed collagen derived from fish by-products was used to replace fish meal to evaluate the effects on muscle quality and glycolipid metabolism of juvenile triploid crucian carp. A total of 240 juvenile fish with body weight of [...] Read more.
Fish by-products are rich in collagen. Hydrolyzed collagen derived from fish by-products was used to replace fish meal to evaluate the effects on muscle quality and glycolipid metabolism of juvenile triploid crucian carp. A total of 240 juvenile fish with body weight of 10.01 ± 0.02 g were divided into four groups and fed four diets for 66 days: fish meal (FM) replaced with hydrolyzed collagen (HC) in 0% (Control), 2% (2% HC), 4% (4% HC), and 6% (6% HC), respectively. The results were as follows: The increased proportion of fish meal replaced with hydrolyzed collagen linearly and quadratically decreased the specific growth rate (SGR) of triploid crucian carp (p < 0.05). Compared with the control group, the SGR and intestinal α-amylase, trypsin and lipase activities in the 4% and 6% HC groups significantly decreased (p < 0.05), while there was no significant difference between the control and 2% HC groups (p > 0.05). Total umami amino acids content, chewiness and myofiber density of muscle in the 4% and 6% HC groups, as well as the essential fatty acids content in all HC groups increased significantly (p < 0.05). All HC groups significantly increased the serum glutathione peroxidase (GSH-Px) activity and decreased the serum malondialdehyde (MDA) content (p < 0.05). When the replacement amount reached 4%, the serum glucose and liver glycogen content, the liver and serum triglyceride (TG) content, and serum total cholesterol (T-CHO) content were significantly reduced (p < 0.05). In addition, the expression levels of insulin-like growth factor-1 (IGF-1) of the liver in all HC groups and lipolysis-related genes (lipoprotein lipase (LPL), carnitine O-palmitoyltransferase 1 (CPT 1) and hydroxyacyl-coenzyme A dehydrogenase (HADH)) of the liver in the 6% of HC group increased significantly (p < 0.05), and the expression levels of lipogenesis-related genes (fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP 1)) of the liver in the 4% HC and 6% HC groups decreased significantly (p < 0.05). In conclusion, the replacement of 2% fish meal with hydrolyzed collagen had no negative effects on the growth of triploid crucian carp, while the replacement of 4% fish meal with hydrolyzed collagen decreased SGR, but improved the muscle quality and decreased glycolipid levels. The maximum proportion of hydrolyzed collagen replacing fish meal should not exceed 4%. Full article
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14 pages, 966 KiB  
Article
Circulating Levels of Nesfatin-1 and Spexin in Children with Prader-Willi Syndrome during Growth Hormone Treatment and Dietary Intervention
by Joanna Gajewska, Katarzyna Szamotulska, Witold Klemarczyk, Magdalena Chełchowska, Małgorzata Strucińska and Jadwiga Ambroszkiewicz
Nutrients 2023, 15(5), 1240; https://doi.org/10.3390/nu15051240 - 1 Mar 2023
Cited by 4 | Viewed by 2273
Abstract
Background: Despite observable improvement in the treatment outcomes of patients with Prader-Willi syndrome (PWS), adequate weight control is still a clinical problem. Therefore, the aim of this study was to analyze the profiles of neuroendocrine peptides regulating appetite—mainly nesfatin-1 and spexin—in children with [...] Read more.
Background: Despite observable improvement in the treatment outcomes of patients with Prader-Willi syndrome (PWS), adequate weight control is still a clinical problem. Therefore, the aim of this study was to analyze the profiles of neuroendocrine peptides regulating appetite—mainly nesfatin-1 and spexin—in children with PWS undergoing growth hormone treatment and reduced energy intake. Methods: Twenty-five non-obese children (aged 2–12 years) with PWS and 30 healthy children of the same age following an unrestricted age-appropriate diet were examined. Serum concentrations of nesfatin-1, spexin, leptin, leptin receptor, total adiponectin, high molecular weight adiponectin, proinsulin, insulin-like growth factor-I, and total and functional IGF-binding protein-3 concentrations were determined using immunoenzymatic methods. Results: The daily energy intake in children with PWS was lower by about 30% (p < 0.001) compared with the controls. Daily protein intake was similar in both groups, but carbohydrate and fat intakes were significantly lower in the patient group than the controls (p < 0.001). Similar values for nesfatin-1 in the PWS subgroup with BMI Z-score < −0.5 and the control group, while higher values in the PWS subgroup with BMI Z-score ≥ −0.5 (p < 0.001) were found. Spexin concentrations were significantly lower in both subgroups with PWS than the controls (p < 0.001; p = 0.005). Significant differences in the lipid profile between the PWS subgroups and the controls were also observed. Nesfatin-1 and leptin were positively related with BMI (p = 0.018; p = 0.001, respectively) and BMI Z-score (p = 0.031; p = 0.027, respectively) in the whole group with PWS. Both neuropeptides also correlated positively in these patients (p = 0.042). Conclusions: Altered profiles of anorexigenic peptides—especially nesfatin-1 and spexin—in non-obese children with Prader-Willi syndrome during growth hormone treatment and reduced energy intake were found. These differences may play a role in the etiology of metabolic disorders in Prader-Willi syndrome despite the applied therapy. Full article
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21 pages, 7904 KiB  
Article
Prognostic Value and Immune Infiltration of HPV-Related Genes in the Immune Microenvironment of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma
by Qiyu Gan, Luning Mao, Rui Shi, Linlin Chang, Guozeng Wang, Jingxin Cheng and Rui Chen
Cancers 2023, 15(5), 1419; https://doi.org/10.3390/cancers15051419 - 23 Feb 2023
Cited by 4 | Viewed by 2659
Abstract
Mounting evidence has highlighted the immune environment as a critical feature in the development of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the relationship between the clinical characteristics of the immune environment and CESC remain unclear. Therefore, the aim of this [...] Read more.
Mounting evidence has highlighted the immune environment as a critical feature in the development of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the relationship between the clinical characteristics of the immune environment and CESC remain unclear. Therefore, the aim of this study was to further characterize the relationship between the tumor and immune microenvironment and the clinical features of CESC using a variety of bioinformatic methods. Expression profiles (303 CESCs and three control samples) and relevant clinical data were obtained from The Cancer Genome Atlas. We divided CESC cases into different subtypes and performed a differential gene expression analysis. In addition, gene ontology (GO) and gene set enrichment analysis (GSEA) were performed to identify potential molecular mechanisms. Furthermore, data from 115 CESC patients from East Hospital were used to help identify the relationship between the protein expressions of key genes and disease-free survival using tissue microarray technology. Cases of CESC (n = 303) were divided into five subtypes (C1–C5) based on their expression profiles. A total of 69 cross-validated differentially expressed immune-related genes were identified. Subtype C4 demonstrated a downregulation of the immune profile, lower tumor immune/stroma scores, and worse prognosis. In contrast, the C1 subtype showed an upregulation of the immune profile, higher tumor immune/stroma scores, and better prognosis. A GO analysis suggested that changes in CESC were primarily enriched nuclear division, chromatin binding, and condensed chromosomes. In addition, GSEA demonstrated that cellular senescence, the p53 signaling pathway, and viral carcinogenesis are critical features of CESC. Moreover, high FOXO3 and low IGF-1 protein expression were closely correlated with decreased clinical prognosis. In summary, our findings provide novel insight into the relationship between the immune microenvironment and CESC. As such, our results may provide guidance for developing potential immunotherapeutic targets and biomarkers for CESC. Full article
(This article belongs to the Section Tumor Microenvironment)
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17 pages, 740 KiB  
Article
Impact of Dietary Administration of Seaweed Polysaccharide on Growth, Microbial Abundance, and Growth and Immune-Related Genes Expression of The Pacific Whiteleg Shrimp (Litopenaeus vannamei)
by Eman M. Abbas, Ahmed Said Al-Souti, Zaki Z. Sharawy, Ehab El-Haroun and Mohamed Ashour
Life 2023, 13(2), 344; https://doi.org/10.3390/life13020344 - 27 Jan 2023
Cited by 48 | Viewed by 4683
Abstract
This work aims to determine the impact of dietary supplementation of polysaccharide, extracted from brown seaweeds Sargassum dentifolium on growth indices, feed utilization, biochemical compositions, microbial abundance, expressions of growth and immunity-related genes, and stress genes of the Pacific Whiteleg shrimp Litopenaeus vannamei [...] Read more.
This work aims to determine the impact of dietary supplementation of polysaccharide, extracted from brown seaweeds Sargassum dentifolium on growth indices, feed utilization, biochemical compositions, microbial abundance, expressions of growth and immunity-related genes, and stress genes of the Pacific Whiteleg shrimp Litopenaeus vannamei. A total of 360 post-larvae of L. vannamei were randomly distributed into a 12-glass aquarium (40 L of each) at a stocking density of 30 shrimp with an initial weight of (0.0017 ± 0.001 g). During the 90-day experiment trial, all shrimp larvae were fed their respective diets at 10% of total body weight, three times a day. Three experimental diets were prepared with different seaweed polysaccharide (SWP) levels. The basal control diet had no polysaccharide level (SWP0), while SWP1, SWP2, and SWP3 contained polysaccharides at concentrations of 1, 2, and 3 g kg−1 diet, respectively. Diets supplemented with polysaccharide levels showed significant improvements in weight gain and survival rate, compared to the control diet. Whole-body biochemical composition and the microbial abundance (the total count of heterotrophic bacteria and Vibrio spp.) of L. vannamei showed significant differences among polysaccharide-treated diets compared to the control. At the end of the feeding experiment, the dietary supplementation of polysaccharide levels enhanced the expression of growth-related genes (Insulin-like growth factors (IGF-I, IGF-II), immune-related genes (β -Glucan-binding protein (β-Bgp), Prophenoloxidase (ProPO), Lysozyme (Lys), and Crustin), and stress genes (Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) in the muscle tissue of L. vannamei. However, the current study concluded that the inclusion rate of 2 g kg–1 of polysaccharide as a dietary additive administration enhanced both weight gain and survival rate of L. vannamei, while the incorporation level of 3 g kg–1 reduces the abundance of pathogenic microbes and enhances the growth-, immunity- and stress-related gene expressions of L. vannamei. Full article
(This article belongs to the Special Issue Blue Revolution and Aquatic Life)
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