IGF-I Expression Research Articles

Effects of dietary supplementation of different ratios of koumine and gelsemin on the liver immunity of common carp (Cyprinus carpio, FFRC)

Gelsemium elegans Benth. (GEB) exhibits immunoregulatory and growth-promoting effects in animals. However, owing to its complex composition, the specific mechanism remains to be explored. Koumine (KM) and gelsemine (GS) are the two alkaloids with the highest content and strongest biological activity in GEB. In this experiment, four ratios (0,0 mg/kg, 2,2 mg/kg, 2,1 mg/kg, and 2:0.67 mg/kg) of KM: GS from natural GEB were incorporated into the diet of common carp (Cyprinus carpio, FFRC). A 10-week breeding experiment was conducted to explore the immune and metabolic effects of these different KM and GS ratios on the liver of C. carpio, analyzing histology, antioxidant enzyme activity, immune gene expression, and transcriptomics. Hepatocyte edema and apoptosis were observed in the treatment groups. Acid phosphatase activity in the treatment group was significantly higher than that in the control group (P < 0.05), and malondialdehyde activity was lower (P < 0.05) in the treatment group, demonstrating a dose effect of GS. Superoxide dismutase and total antioxidant capacity activities increased gradually with a decreasing GS ratio (P < 0.05). Compared to the control group, changes in the GS ratio regulated the expression of immune genes. The relative expression of CYP1B1, TNF-β, and Myd-88 increased with decreasing GS ratio in the combination. Conversely, the relative expression of CYP1A1, TNF-α, GPX, IGF1, GST, and TLR-2 decreased with decreasing GS ratio in the combination. A total of 81.33 GB of clean data, 1370 DEGs, and 9258 co-expressed genes were obtained from the transcriptome data. These coexpressed genes were grouped into 244 KEGG pathways. Non-alcoholic fatty liver disease, Fatty acid degradation, Oxidative phosphorylation, and the PPAR signaling pathway were among the most abundant signaling pathways identified. This information contributes to a better understanding of the underlying mechanisms of KM and GS on liver immunity and lays a theoretical foundation for their application.

Molecular Mechanisms of Growth Differences in Gymnocypris przewalskii and Gymnocypris eckloni through a Comparative Transcriptome Perspective

Genetic composition plays a crucial role in the growth rate of species, and transcriptomics provides a potent tool for studying genetic aspects of growth. We explored the growth rates and transcriptomes of the Cyprinids G. przewalskii (GP) and G. eckloni (GE). A total of 500 individuals of G. przewalskii and G. eckloni, matched in size, were separately cultured for 9 months in six cement tanks (each group with three replicates). Growth indices were measured, revealing that the growth rate of GE was greater than that of GP (p &lt; 0.05), while there was no significant difference in survival rates (p &gt; 0.05). Simultaneously, we conducted RNA-Seq on the muscles of both GP and GE. The results indicated a significant difference of gene expression between GP and GE, identifying 5574 differentially expressed genes (DEGs). Quantitative real-time reverse transcription–polymerase chain reaction of 10 DEGs demonstrated consistency in expression profiles with the results from the RNA-Seq analysis. The DEGs were significantly enriched in glycolysis/gluconeogenesis (ko00010), arachidonic acid formation (ko00061), arginine biosynthesis (ko00220), and the MAPK (ko04013), PI3K-Akt (ko04151), mTOR (ko04150), and TGF-β (ko04350) signal pathways, as revealed by Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. This study also identified some growth-related DEGs, such as IGF2, Noggin, Decorin and others. Notably, the low expression of IGF2 may be a factor contributing to the slower growth of GP than GE.

Cardamonin-loaded liposomal formulation for improving percutaneous penetration and follicular delivery for androgenetic alopecia.

Androgenic alopecia (AGA) has a considerable impact on the physical and mental health of patients. Nano preparations have apparent advantages and high feasibility in the treatment of AGA. Cardamonin (CAR) has a wide range of pharmacological activities, but it has the problems of poor solubility in water and low bioavailability. There are few, if any, researches on the use of nano-loaded CAR to improve topical skin delivery of AGA. In this study, a CAR-loaded liposomal formulation (CAR@Lip and CAR@Lip Gel) was developed and characterized. The prepared CAR@Lip exhibited a uniform and rounded vesicle in size. CAR@Lip and CAR@Lip Gel can significantly improve the cumulative release of CAR. Additionally, CAR@Lip can obviously promote the proliferation and migration of human dermal papilla cells (hDPCs). Cell uptake revealed that the uptake of CAR@Lip significantly increased compared with the free drug. Furthermore, both CAR@Lip and CAR@Lip Gel groups could markedly improve the transdermal performance of CAR, and increase the topical content of the drug in the hair follicle compared with CAR. The ratchet effect of hair follicles could improve the skin penetration depth of nanoformulations. Notably, Anti-AGA tests in the mice showed that CAR@Lip and CAR@Lip Gel groups could promote hair growth, and accelerate the transition of hair follicles to the growth stage. The anti-androgen effect was revealed by regulating the expression of IGF-1, VEGF, KGF, and TGF-β, participating in SHH/Gli and Wnt/β-catenin pathways. Importantly, the nanoformulations had no obvious skin irritation. Thus, our study showed that CAR-loaded liposomal formulation has potential application in the treatment of AGA.

ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression

Helicobacter pylori (H. pylori) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan–Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori. Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori-induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori-induced GC.

Epigenetic modification of histone acetylation in the sensorimotor cortex after intracerebral hemorrhage.

Epigenetic regulation is involved in post-stroke neuroplasticity. We investigated the effects of intracerebral hemorrhage (ICH) on histone acetylation and gene expression related to neuronal plasticity in the bilateral sensorimotor cortices, which may affect post-stroke sensorimotor function. Wistar rats were randomly divided into the SHAM and ICH groups. We performed ICH surgery stereotaxically based on the microinjection of a collagenase solution in the ICH group. Foot fault and cylinder tests were performed to evaluate motor functions at 4-time points, including pre-ICH surgery. The amount of acetyl histones and the mRNA expression of neurotrophic factors crucial to neuroplasticity in the bilateral sensorimotor cortices were analyzed approximately 2 weeks after ICH surgery. Sensorimotor functions of the ICH group were inferior to those of the SHAM group during 2 weeks post-ICH. ICH increased the acetylation of histone H3 and H4 over the sham level in the ipsilateral and contralateral cortices. ICH increased the mRNA expression of IGF-1, but decreased the expression of BDNF compared with the sham level in the ipsilateral cortex. The present study suggests that histone acetylation levels are enhanced in bilateral sensorimotor cortices after ICH, presenting an altered epigenetic platform for gene expressions related to neuronal plasticity.

The Effects of IGF1 and MGF on Neural Stem Cells in Hypoxic Conditions.

Ischemic stroke has high morbidity and mortality rates worldwide. Low oxygen (O2) levels detected in such conditions create a vulnerable environment for neural stem cells (NSC), altering neuronal function, and leading to neuronal injury or death. There are still no effective treatments for such consequences. This study investigates the molecular and functional effects of growth factors, namely, insulin-like growth factor 1 (IGF-I) and mechano growth factor (MGF), in NSC exposed to low O2 levels. An in vitro ischemia model was created by rat hippocampal NSC grown in culture that was exposed to varying oxygen levels, including 0%, 3%, and 20 % for the representation of anoxic, hypoxic, and normoxic conditions, respectively, during 24 h. NSC has investigated IGF-I, MGF, and HIF1-Alpha (HIF-1α) gene expressions by real-time reverse transcription polymerase chain reaction. The effects of external administration of growth factors (IGF-I and MGF) on NSC proliferation in such conditions were explored. Increased IGF-I and MGF gene expressions were detected in the samples exposed to low O2. Anoxia was the highest stimulant for IGF-I and MGF gene expressions. Meanwhile, HIF1-α that encodes hypoxia-inducible factor-1α revealed downregulation in relative gene expression fold change with IGF-I application in all conditions, whereas MGF application upregulated its change in an anoxic environment. Furthermore, MGF-induced NSC had more proliferationmigration rate in all oxygen conditions. IGF-I induced significant NSC proliferation in 0% and 20% O2. These findings suggest that IGF-I and MGF expressions were increased to reduce the damage in NSC exposed to low oxygen, and exogenous MGF and IGF-I application increased NSC proliferation at the time of injury. The results might imply the role of exogenous MGF and IGF-I in the treatment of ischemia for relieving the effect of neuronal damage due to their neuroprotective and proliferative effects.

Targeting G9a/DNMT1 methyltransferase activity impedes IGF2-mediated survival in hepatoblastoma.

As the variable clinical outcome of patients with hepatoblastoma (HB) cannot be explained by genetics alone, the identification of drugs with the potential to effectively reverse epigenetic alterations is a promising approach to overcome poor therapy response. The gene ubiquitin like with PHD and ring finger domains 1 (UHRF1) represents an encouraging epigenetic target due to its regulatory function in both DNA methylation and histone modifications and its clinical relevance in HB. Patient-derived xenograft in vitro and in vivo models were used to study drug response. The mechanistic basis of CM-272 treatment was elucidated using RNA sequencing and western blot experiments. We validated in comprehensive data sets that UHRF1 is highly expressed in HB and associated with poor outcomes. The simultaneous pharmacological targeting of UHRF1-dependent DNA methylation and histone H3 methylation by the dual inhibitor CM-272 identified a selective impact on HB patient-derived xenograft cell viability while leaving healthy fibroblasts unaffected. RNA sequencing revealed downregulation of the IGF2-activated survival pathway as the main mode of action of CM-272 treatment, subsequently leading to loss of proliferation, hindered colony formation capability, reduced spheroid growth, decreased migration potential, and ultimately, induction of apoptosis in HB cells. Importantly, drug response depended on the level of IGF2 expression, and combination assays showed a strong synergistic effect of CM-272 with cisplatin. Preclinical testing of CM-272 in a transplanted patient-derived xenograft model proved its efficacy but also uncovered side effects presumably caused by its strong antitumor effect in IGF2-driven tumors. The inhibition of UHRF1-associated epigenetic traces, such as IGF2-mediated survival, is an attractive approach to treat high-risk HB, especially when combined with the standard-of-care therapeutic cisplatin.

Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures for Lcn13, Asns, Hamp2, Hao2, and Pgc1a.

Growth hormone (GH) modifies liver gene transcription in a sexually dimorphic manner to meet liver metabolic demands related to sex; thus, GH dysregulation leads to sex-biased hepatic disease. We dissected the steps of the GH regulatory cascade modifying GH-dependent genes involved in metabolism, focusing on the male-predominant genes Lcn13, Asns, and Cyp7b1, and the female-predominant genes Hao2, Pgc1a, Hamp2, Cyp2a4, and Cyp2b9. We explored mRNA expression in 2 settings: (i) intact liver GH receptor (GHR) but altered GH and insulin-like growth factor 1 (IGF1) levels (NeuroDrd2KO, HiGH, aHepIGF1kd, and STAT5bCA mouse lines); and (ii) liver loss of GHR, with or without STAT5b reconstitution (aHepGHRkd, and aHepGHRkd + STAT5bCA). Lcn13 was downregulated in males in most models, while Asns and Cyp7b1 were decreased in males by low GH levels or action, or constant GH levels, but unexpectedly upregulated in both sexes by the loss of liver Igf1 or constitutive Stat5b expression. Hao, Cyp2a4, and Cyp2b9 were generally decreased in female mice with low GH levels or action (NeuroDrd2KO and/or aHepGHRkd mice) and increased in HiGH females, while in contrast, Pgc1a was increased in female NeuroDrd2KO but decreased in STAT5bCA and aHepIGF1kd females. Bioinformatic analysis of RNAseq from aHepGHRkd livers stressed the greater impact of GHR loss on wide gene expression in males and highlighted that GH modifies almost completely different gene signatures in each sex. Concordantly, we show that altering different steps of the GH cascade in the liver modified liver expression of Lcn13, Asns, Cyp7b1, Hao2, Hamp2, Pgc1a, Cyp2a4, and Cyp2b9 in a sex- and gene-specific manner.

Transcriptome Analysis Reveals the Molecular Mechanisms Underlying Growth Superiority in a Novel Gymnocypris Hybrid, Gymnocypris przewalskii ♀ × Gymnocypris eckloni ♂.

Artificial hybrid breeding can optimize parental traits to cultivate excellent hybrids with enhanced economic value. In this study, we investigated the growth performance and transcriptomes of Gymnocypris przewalskii (♀) and Gymnocypris eckloni (♂) and their F1 hybrid fishes. Hatched individuals of G. przewalskii (GP) and G. eckloni (GE) of the same size and their F1 hybrids (GH) were separately cultured for eight months in three cement tanks (n = 3). The growth indexes were measured, which showed that the growth rate of the groups was GE > GH > GP, while the survival rate was GH > GE > GP. The RNA-Seq data analysis of the muscles from the three Gymnocypris fish strains revealed that gene transcription has a significant impact on F1 hybrid fish and its parents. The differentially expressed genes (DEGs) in GH show less differences with GP, but more with GE. qRT-PCR was used to confirm the expression profiles of the chosen DEGs, and the results showed positive correlations with the RNA-seq data. KEGG enrichment results indicated that the DEGs were related to a variety of molecular functions, such as glycolysis/gluconeogenesis, arachidonic acid formation, citrate cycle, and the MAPK, PI3K-Akt, or mTOR signal pathways. Subsequent analysis indicated that there may be a significant correlation between the differential expression of IGF2 and a difference in the growth of GE and GP.

β2-Adrenoceptors activation regulates muscle trophic-related genes following acute resistance exercise in mice.

Resistance exercise (RE) training and pharmacological stimulation of β2-Adrenoceptors (β2-ARs) alone can promote muscle hypertrophy and prevent muscle atrophy. Although the activation of the sympathetic nervous system (SNS) is a well-established response during RE, the physiological contribution of the endogenous catecholamines and β2-ARs to the RE-induced changes on skeletal muscle protein metabolism remains unclear. This study investigated the effects of the β2-ARs blockade on the acute molecular responses induced by a single bout of RE in rodent skeletal muscles. Male C57BL6/J mice were subjected to a single bout of progressive RE (until exhaustion) on a vertical ladder under β2-AR blockade with ICI 118,551 (ICI; 10mgkg-1, i. p.), or vehicle (sterile saline; 0.9%, i. p.), and the gene expression was analyzed in gastrocnemius (GAS) muscles by qPCR. We demonstrated that a single bout of RE acutely increased the circulating levels of stress-associated hormones norepinephrine (NE) and corticosterone (CORT), as well as the muscle phosphorylation levels of AMPK, p38 MAPK and CREB, immediately after the session. The acute increase in the phosphorylation levels of CREB was followed by the upregulation of CREB-target genes Sik1, Ppargc1a and Nr4a3 (a central regulator of the acute RE response), 3h after the RE session. Conversely, β2-AR blockade reduced significantly the Sik1 and Nr4a3 mRNA levels in muscles of exercised mice. Furthermore, a single bout of RE stimulated the mRNA levels of the atrophic genes Map1lc3b and Gabarapl1 (autophagy-related genes) and Mstn (a well-known negative regulator of muscle growth). Unexpectedly, the gene expression of Igf-1 or Il-6 were not affected by RE, while the atrophic genes Murf1/Trim63 and Atrogin-1/Mafbx32 (ubiquitin-ligases) were increased only in muscles of exercised mice under β2-AR blockade. Interestingly, performing a single bout of RE under β2-AR blockade increased the mRNA levels of Mstn in muscles of exercised mice. These data suggest that β2-ARs stimulation during acute RE stimulates the hypertrophic gene Nr4a3 and prevents the overexpression of atrophic genes such as Mstn, Murf1/Trim63, and Atrogin-1/Mafbx32 in the first hours of postexercise recovery, indicating that he SNS may be physiologically important to muscle adaptations in response to resistance training.

Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration.

Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction. We extracted the Prom1-deficient retina subjected to light exposure for a short time, conducted single-cell expression profiling, and compared the gene expression with and without stimuli. We identified the cells and genes whose expression levels change directly in response to light stimuli. Among the genes altered by light stimulation, Igf1 was decreased in rod photoreceptor cells and astrocytes under the light-stimulated condition. Consistently, the insulin-like growth factor (IGF) signal was weakened in light-stimulated photoreceptor cells. The recovery of Igf1 expression with the adeno-associated virus (AAV) prevented photoreceptor cell death, and its treatment in combination with the endothelin receptor antagonist led to the blockade of abnormal glial activation and the promotion of glycolysis, thereby resulting in the improvement of retinal functions, as assayed by electroretinography. We additionally demonstrated that the attenuation of mammalian/mechanistic target of rapamycin (mTOR), which mediates IGF signalling, leads to complications in maintaining retinal homeostasis. Together, we propose that combinatorial manipulation of distinct mechanisms is useful for the maintenance of the retinal condition.

Dynamic Changes and Effects of H2S, IGF-1, and GH in the Traumatic Brain Injury.

The aim of this study was to examine the expression changes of H2S, IGF-1, and GH in traumatic brain injury (TBI) patients and to detect their neuroprotective functions after TBI. In this study, we first collected cerebrospinal fluid (CSF) and plasma from TBI patients at different times after injury and evaluated the concentrations of H2S, IGF-1, and GH. In vitro studies were using the scratch-induced injury model and cell-cell interaction model (HT22 hippocampal neurons co-cultured with LPS-induced BV2 microglia cells). In vivo studies were using the controlled cortical impact (CCI) model in mice. Cell viability was assessed by CCK-8 assay. Pro-inflammatory cytokines expression was determined by qRT-PCR, ELISA, and nitric oxide production. Western blot was performed to assess the expression of CBS, CSE, IGF-1, and GHRH. Moreover, the recovery of TBI mice was evaluated for behavioral function by applying the modified Neurological Severity Score (mNSS), the Rotarod test, and the Morris water maze. We discovered that serum H2S, CSF H2S, and serum IGF-1 concentrations were all adversely associated with the severity of the TBI, while the concentrations of IGF-1 and GH in CSF and GH in the serum were all positively related to TBI severity. Experiments in vitro and in vivo indicated that treatment with NaHS (H2S donor), IGF-1, and MR-409 (GHRH agonist) showed protective effects after TBI. This study gives novel information on the functions of H2S, IGF-1, and GH in TBI.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-β-d-glucoside, kaempferol-3-O-β-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/β-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/β-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Assessment of serum levels and placental bed tissue expression of IGF-1, bFGF, and PLGF in patients with placenta previa complicated with placenta accreta spectrum disorders.

This study aims to detect the serum levels of IGF-1, bFGF, and PLGF and their expressions in placental bed tissues of patients with placenta previa complicated with PAS disorders. This case and control study included 40 multiparous pregnant women with complete placenta previa between 34 weeks and 38 weeks of gestation and they were divided into two groups: 25 patients with PAS (case group) and 15 patients without PAS (control group). The venous blood samples were collected 2 h before the cesarean section, and the placental bed tissues were taken intraoperatively at the placental implantation site and then were histologically examined to evaluate the gravity of the myometrial invasion of the placenta. According to FIGO PAS increasing grading, the 25 patients were also divided into three groups: PAS grade I group, PAS grade II group, and PAS grade III group. The concentrations of IGF-1, bFGF, and PLGF in serum were measured using ELISA, and the mean ratio of the relative mRNA expression of each biomarker in placental bed tissues was calculated using qRT-PCR. The staining intensity and the positive cells were quantitatively measured and expressed as means by using Image J software for IHC analysis. IGF-1 had low serum levels and high placental bed expression in placenta previa patients with PAS disorders compared to those without PAS (all p < 0.0001). PLGF had high serum levels (p = 0.0200) and high placental bed expression (p < 0.0001) in placenta previa patients with PAS disorders compared to those without PAS. IGF-1 serum levels decreased up to PAS grade II (means were 24.3 ± 4.03, 21.98 ± 3.29, and 22.03 ± 7.31, respectively for PAS grade I, PAS grade II, PAS grade III groups, p = 0.0006). PLGF serum levels increased up to PAS grade II (means were 12.96 ± 2.74, 14.97 ± 2.56, and 14.89 ± 2.14, respectively for the three groups, p = 0.0392). However, IGF-1 and PLGF mRNA placental bed expression increased up to PAS grade III. The relative expression of mRNA means for the three groups was 3.194 ± 1.40, 3.509 ± 0.63, and 3.872 ± 0.70, respectively for IGF-1; and 2.784 ± 1.14, 2.810 ± 0.71, and 2.869 ± 0.48, respectively for PLGF (all p < 0.0001). Their IHC (immunohistochemical) staining also had increasing trends, but p > 0.05. bFGF was not significantly expressed in placenta previa with PAS disorders in most of the analysis sections (p > 0.05). Low serum levels and high expression in placental bed tissues of IGF-1, or high serum levels and high expression in placental bed tissues of PLGF, may differentiate placenta previa patients with FIGO PAS grade I and PAS grade II from those without PAS disorders. However, they could not significantly predict the degree of placental invasiveness in FIGO PAS grades II and III.

Circular RNA circRNA_100349 functions as a miR-218–5p sponge for suppressing the cell proliferation of gastric cancer via regulation of IGF2 expression

BackgroundCircular RNAs (circRNAs) hold critical importance due to their notable function in developing Gastric Cancer (GC), which is a malignancy with the third most frequent occurrence worldwide. The aim of this study was to see if circRNA_0044516 would control GC cell proliferation and establish more effective therapeutic strategies. MethodsIn GC tissues or cells, quantitative Real‑Time Polymerase Chain Reaction (qRT-PCR) was employed for the detection of the expression of circRNA_100349, Insulin-like Growth Factor II (IGF2), and miR-218–5p. CCK-8 assays were employed to gauge the proliferation of cells. A luciferase reporter was employed to establish the relationship of circRNA_100349 or IGF2 with miR-218–5p. ResultsCircRNA_100349 was observed to undergo upregulation in GC cell lines along with tissues. GC cell proliferation was prevented by downregulating circRNA_100349. MiR-149 was targeted by CircRNA_100349, and its downregulation increased the amount of miR-218–5p in GC cells. Simultaneously silencing circRNA_100349 decreased IGF2 expression via miR-218–5p, and thus suppressed GC cell proliferation. Furthermore, in nude mice, circRNA_100349 knockdown prevented the tumor development of GC cells. ConclusionsThe findings furnished evidence of the critical involvement of circRNA_100349 in GC and that its downregulation impedes GC cell proliferation via the miR-218–5p/IGF2 axis.

Urine-derived stem cells genetically modified with IGF1 improve muscle regeneration.

In this study we aimed to determine the impact of human urine derived stem cells (USC) and genetically modified USC that were designed to overexpress myogenic growth factor IGF1 (USCIGF), on the regenerative capacity of cardiotoxin (CTX)-injured murine skeletal muscle. We overexpressed IGF1 in USC and investigated the alterations in myogenic capacity and regenerative function in cardiotoxin-injured muscle tissues. Compared with USC alone, USCIGF1 activated the IGF1-Akt-mTOR signaling pathway, significantly improved myogenic differentiation capacity in vitro, and enhanced the secretion of myogenic growth factors and cytokines. In addition, IGF1 overexpression increased the ability of USC to fuse with skeletal myocytes to form myotubes, regulated the pro-regenerative immune response and inflammatory cytokines, and increased myogenesis in an in vivo model of skeletal muscle injury. Overall, USC genetically modified to overexpress IGF1 significantly enhanced skeletal muscle regeneration by regulating myogenic differentiation, paracrine effects, and cell fusion, as well as by modulating immune responses in injured skeletal muscles in vivo. This study provides a novel perspective for evaluating the myogenic function of USC as a nonmyogenic cell source in skeletal myogenesis. The combination of USC and IGF1 expression has the potential to provide a novel efficient therapy for skeletal muscle injury and associated muscular defects in patients with urinary incontinence.

Productive Performance and Serum Biochemical Parameters of Nile Tilapia Fingerlings Fed on Different Dietary Carbohydrate: Protein Ratios with Biotin Supplementation

The current experiment evaluated the effects of different dietary carbohydrate: protein ratios (CHO: CP ratio) without or with biotin supplementation on the growth performance, body composition, serum biochemical parameters and intestinal morphology in Nile tilapia. Fingerlings were assigned to 6 treatments arranged as following; Group 1 (G1) fed the basal diet (BD) with a medium CHO: CP ratio (47:32); G2 with high CHO: CP ratio (57:21); G3 with low CHO: CP ratio (36:42); while G4, G5 and G6 had the same previous experimental design of the first 3 groups but with biotin supplementation (0.06 mg/kg diet). The growth performance was only assessed for the first 6 weeks, then the experiment continued to 4 months and ended by sampling for other parameters determined. Fish feeding on high CHO: CP ratio (57:21) significantly reduced the fish body weight, gain and feed intake (FI) (P ≤ 0.05), while improved the feed efficiency compared to the medium and low ratios. Biotin addition to the high or the medium ratios containing diets resulted in lower growth, increased FI and deteriorated the feed efficiency when compared to their control groups without biotin addition (P≤ 0.05). Different dietary CHO: CP ratios significantly altered tilapia body composition of nutrients (moisture, EE, and ash), serum parameters (glucose, triglyceride, LDL and VLDL) and the liver function enzymes (GPT and GOT) (P≤ 0.05). The relative mRNA expression of GHR and IGF was significantly upregulated in fish fed on the low and the high ratios containing diets respectively. In conclusion, feeding of the early fingerling of tilapia on the high CHO: CP ratio during the first 6 weeks of life resulted in lower growth, however, it showed a protein sparing effect. Supplementation of biotin (extra over the diet) was not recommended as it showed adverse effects on tilapia growth especially during the first periods of life, however it showed some beneficial effects on alleviating the high-dietary carbohydrate-induced effects. Feeding on medium CHO: CP ratio (47:32) or low ratio (36:42) would be recommended during the fry and early fingerling stage of tilapia while the high ratio (57:21) would be beneficial in the diet of late fingerlings or adult tilapia.

Effect of Dietary Seaweed (Gracilaria pulvinata and Sargassum ilicifolium) on Serum and Mucosal Immunity, Some Growth and Immune‐Related Genes Expression, Antioxidant Status, and Fatty Acid Profile in Asian Seabass (Lates calcarifer)

This study was done to appraise the effects of the combination of dietary Gracilaria pulvinata and Sargassum ilicifolium on growth, immunity, and fatty acid profile in Asian seabass (Lates calcarifer). A total of 540 juveniles (36.06 ± 0.05 g) were stocked into eighteen 200 L tanks and divided into six experimental treatments, each in triplicate. Fish were fed diets containing 0 (control), 3% (SW3), 6% (SW6), 9% (SW9), 12% (SW12), and 15% (SW15) mixtures of both seaweeds powder in equal proportions (1 : 1) for 56 days. There was no improvement in weight gain parameters. Serum lysozyme and peroxidase activities in SW9 and SW12 treatments were significantly higher in compare to other treatments. The highest activities of skin mucus lysozyme, alkaline phosphatase, and total protease were observed in the SW12. Liver igf-1, il-1β, il-8, and lysozyme expression showed a rising trend up to SW9 and then decreased. Liver antioxidant enzymes activity and glutathione content showed a similar pattern of changes. Liver total antioxidant capacity was highest in the SW9 treatment, while the lowest value of liver malondialdehyde was observed in the 12% seaweed treatment. The amount of total n‐3 polyunsaturated fatty acids, especially docosahexaenoic acid, was higher in the SW12 and SW15 treatments in compare to others. Our findings suggest that adding 9%–12% of Gracilaria and Sargassum seaweed powder to the diet improves serum and mucosal immunity, antioxidant status, and fatty acid profile in L. calcarifer juveniles.

A comparative study on the expression of myogenic genes, and their effects on performance and meat quality in broiler chicken strains.

The aims of current investigation were to study the growth performance, carcass traits, meat quality and expression profile of Myostatin (MSTN), Insulin-like growth factor-1 (IGF-I), Myogenin (MyoG) and Myogenic regulatory factor 4 (MRF4) genes in three commercial broiler strains including Ross (Ross 308), Cobb (Cobb 500), and Arian in 2023. A total number of 240 one-day-old chicks were reared under an equalized standard management condition for 6 weeks. Performance, organ weights, meat quality and the expression level of the myogenic genes in the pectoral muscle were investigated. The lowest body weight (BW), feed intake, weight gain and highest feed conversion ratio (FCR) was observed for Arian at the end of the study. The meat quality was similar between strains. The IGF-I expression level was significantly higher on 42 days of age in Cobb compared to Ross and Arian. The MRF4 expression level was significantly higher on 28 days of age in Cobb compared to Ross. The MyoG expression level was significantly lower in Arian compared to Cobb on 42 days of age. Furthermore, the MSTN expression level was significantly lower in Cobb compared to Ross and Arian on 42 days of age. The remarkable differences in gene expression levels at the end of the rearing period was supported by higher growth performance and BW of Cobb compared to Ross and Arian strains. In conclusion, the findings of current study could conveniently help assess the performance of these broiler strains under similar rearing condition.

Resveratrol protects mesangial cells under high glucose by regulating the miR-1231/IGF1/ERK pathway.

Diabetic nephropathy (DN) is one of the complications of diabetes mellitus and the main cause of end-stage renal disease (ESRD), which is a serious threat to human health. In DN, mesangial cells (MCs) are a critical target cell that perform a variety of key functions, and abnormal proliferation of MCs is a common and prominent pathological change in DN. In recent years, the investigation of Chinese medicine interventions for DN has increased significantly in recent years due to the many potential adverse effects and controversies associated with the treatment of DN with Western medicines. In this study, we evaluated the protective effect of resveratrol (RES), an active ingredient known as a natural antioxidant, on HMCs under high glucose and explored its possible mechanism of action. We found that RES inhibited the proliferation of human mesangial cell (HMC) under high glucose and blocked cell cycle progression. In the high glucose environment, RES upregulated miR-1231, reduced IGF1 expression, inhibited the activity of the extracellular signal-regulated kinase (ERK) signaling pathway and reduced levels of the inflammatory factors TNF-α and IL-6. In addition, we found that miR-1231 mimics were synergistically inhibited with RES, whereas miR-1231 inhibitor attenuated the protective effect of RES on HMCs. Thus, our results suggest that the protective effect of RES on HMCs under high glucose is achieved, at least in part, through modulation of the miR-1231/IGF1/ERK pathway. The discovery of this potential mechanism may provide a new molecular therapeutic target for the prevention and treatment of DN, and may also bring new ideas for the clinical research in DN.