Expression Of Growth Factor Research Articles

FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice

Fibronectin type III domain-containing (FNDC) proteins play critical roles in cellular homeostasis and cardiac injury, and our recent findings define FNDC5 as a promising cardioprotectant against doxorubicin- and aging-related cardiac injury. FNDC4 displays a high homology with FNDC5; however, its role and mechanism in cardiac ischemia/reperfusion (I/R) injury remain elusive. Here, we show that cardiac and plasma FNDC4 levels are elevated during I/R injury in a hypoxia-inducible factor 1α (HIF1α)-dependent manner. Cardiac-specific FNDC4 overexpression facilitates, while cardiac-specific FNDC4 knockdown inhibits cardiomyocyte survival and angiogenesis in I/R-stressed hearts of male mice through regulating the proteasomal degradation of HIF1α. Interestingly, FNDC4 does not directly stimulate angiogenesis of endothelial cells, but increases the expression and secretion of fibroblast growth factor 1 from cardiomyocytes to enhance angiogenesis in a paracrine manner. Moreover, therapeutic administration of recombinant FNDC4 protein is sufficient to alleviate cardiac I/R injury in male mice, without resulting in significant side effects. In this work, we reveal that FNDC4 alleviates cardiac I/R injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis, and define FNDC4 as a promising predictive and therapeutic target of cardiac I/R injury.

Investigating the potential effect of Holothuria scabra extract on osteogenic differentiation in preosteoblast MC3T3-E1 cells

The present medical treatments of osteoporosis come with adverse effects. It leads to the exploration of natural products as safer alternative medical prevention and treatment. The sea cucumber, Holothuria scabra, has commercial significance in Asian countries with rising awareness of its properties as a functional food. This study aims to investigate the effects of the inner wall (IW) extract isolated from H. scabra on extracellular matrix maturation, mineralization, and osteogenic signaling pathways on MC3T3-E1 preosteoblasts. The IW showed the expression of several growth factors. Molecular docking revealed that H. scabra BMP2/4 binds specifically to mammal BMP2 type I receptor (BMPR-IA). After osteogenic induction, the viability of cells treated with IW extract was assessed and designated with treatment of 0.1, 0.5, 1, and 5 µg/ml of IW extract for 21 consecutive days. On days 14 and 21, treatments with IW extract at 1 and 5 µg/ml showed increased alkaline phosphatase (ALP) activity and calcium deposit levels in a dose-dependent manner compared to the control group. Moreover, the transcriptomic analysis of total RNA of cells treated with 5 µg/ml of IW extract exhibited upregulation of TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways at days 14. This study suggests that IW extract from H. scabra exhibits the potential to enhance osteogenic differentiation and mineralization of MC3T3-E1 preosteoblasts through TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways. Further investigation into the molecular mechanisms underlying the effect of IW extract on osteogenesis is crucial to support its application as a naturally derived supplement for prevention or treatment of osteoporosis.

Sinensetin inhibits the movement ability and tumor immune microenvironment of non-small cell lung cancer through the inactivation of AKT/β-catenin axis.

Although current treatment strategies have improved clinical outcomes of non-small cell lung cancer (NSCLC) patients, side effect and prognosis remain a hindrance. Thus, safer and more effective therapeutical drugs are needed for NSCLC. Sinensetin (Sin) is a flavonoid from citrus fruits, which exhibits antitumor effect on diverse cancers. However, the effect and mechanism of Sin on NSCLC remain unknown. In this study, NSCLC cell lines, and tumor-bearing mice were treated with Sin. The effect and mechanism of Sin were addressed using cell counting kit-8, transwell, enzyme-linked immunosorbent assay, hematoxylin and eosin, immunohistochemistry, and western blot analysis assays in both cell and animal models. Sin reduced the cell viability of A549 and H1299, with the IC50 of 81.46 µM and 93.15 µM, respectively. Sin decreased invaded cell numbers, the expression of N-cadherin and vascular endothelial growth factor A (VEGFA), while increased the E-cadherin level, the cytotoxicity of CD8+ T cells, and the concentration of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) in NSCLC cells. Mechanistically, Sin declined the expression of protein kinase B (AKT)/β-catenin pathway, which was restored with the application of SC79, an activator of AKT. The inhibitory role of Sin in NSCLC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and immune escape was reversed by the management of SC79. In vivo, Sin reduced tumor size and weight, and the expression of N-cadherin, VEGFA, and AKT/β-catenin pathway, but enhanced the level of E-cadherin and IFN-γ. Taken together, Sin suppressed cell growth, invasion, EMT and immune escape via AKT/β-catenin pathway in NSCLC.

IGF2BP3/CTCF Axis-Dependent NT5DC2 Promotes M2 Macrophage Polarization to Enhance the Malignant Progression of Lung Squamous Cell Carcinomas.

Lung squamous cell carcinoma (LUSC) is a type of lung cancer that develops in the squamous cells. It is known to be promoted by the activation of various signaling pathways and the dysregulation of key regulatory molecules. One such molecule, 5'-nucleotidase domain containing 2 (NT5DC2), has been identified as a critical regulator in various cancers including lung cancer. However, there are no data regarding its role in LUSC. The mRNA expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), CCCTC-binding factor (CTCF), and NT5DC2 was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR), whereas their protein expression was assessed using a western blotting assay. Cell proliferation was determined using a cell counting kit-8 (CCK-8) assay. Cell apoptosis, CD11b expression, and CD206 expression were analyzed using flow cytometry. Tube formation was assessed through a tube formation assay. Glucose consumption, lactate production, and ATP levels were measured using colorimetric methods. The effect of NT5DC2 on the malignant progression of LUSC cells was analyzed using a xenograft mouse model assay. The levels of transforming growth factor-beta 1 (TGF-β1) and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assays. The associations among IGF2BP3, CTCF and NT5DC2 were identified using dual-luciferase reporter assay, RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay. The expression of NT5DC2 was found to be upregulated in LUSC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Silencing of NT5DC2 inhibited LUSC cell proliferation, tube formation, glycolysis, M2 macrophage polarization, and tumor formation while inducing cell apoptosis. In addition, CTCF was found to transcriptionally activate NT5DC2 in LUSC cells. IGF2BP3 stabilized the mRNA expression of CTCF through m6A methylation. Further, overexpression of CTCF or NT5DC2 attenuated the effects of IGF2BP3 silencing in both NCI-520 and SK-MES-1 cells. The IGF2BP3/CTCF axis-dependent NT5DC2 promotes M2 macrophage polarization, thereby enhancing the malignant progression of LUSC. This study was the first to reveal the role of NT5DC2 in LUSC and the underlying mechanism. The result suggests that targeting the IGF2BP3/CTCF/NT5DC2 axis may have clinical significance in the treatment of LUSC.

Uniaxial static strain enhances osteogenic and angiogenic potential under hypoxic conditions in distraction osteogenesis

ObjectiveBone incision leads to interrupted and sluggish blood flow in the process of distraction osteogenesis (DO), creating a hypoxia (0–2% oxygen tension) at the center of the bone callus. This hypoxia is critical in the coupling of osteogenesis and angiogenesis during DO. This study aimed to investigate the effect of Uniaxial Static Strain (USS) on osteogenesis in osteoblasts under hypoxic conditions, with a focus on the expression of osteogenic markers and angiogenic factors.MethodsThe USS was made by a multi-unit tension compression device.Osteoblasts were subjected to 10% USS made under hypoxic conditions to mimic the process of DO in vitro. The cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of osteogenic and angiogenic markers were evaluated by using a CCK-8 assay, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qRT-PCR, Western blotting and ELISA.ResultsHypoxia inhibited osteoblast cell proliferation, ALP activity, mineralized nodule formation, and the expression of runt-related transcription factor 2 (Runx- 2), osteopontin(OPN), osteocalcin (OCN), collagen type I (Col1a1). Conversely, hypoxia upregulated the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which are associated with angiogenesis. However, the application of USS enhanced osteoblasts’ osteogenic capacity and upregulated angiogenic factors under hypoxic conditions.ConclusionUSS can enhance osteogenesis in osteoblasts under hypoxic conditions. Moreover, it may stimulate angiogenesis by promoting the expression of VEGF, which further contributes to bone formation. This finding provides important implications for understanding the mechanisms involved in bone regeneration and may have clinical applications in optimizing the effectiveness of DO techniques.

Fibrosis signaling in endometrial cells and endometriosis development

In endometriosis, the tissues similar to the endometrial tissue attaches outside the uterine cavity, causing inflammation and fibrosis. The retrograde menstruation theory is the most plausible mechanism, though the detailed pathogenesis remains unclear. Our observations suggest that endometriosis-like lesions occur more often at sites of ovarian excision causing bleeding in mouse models. Additionally, prostaglandin E2 (PGE2) and thrombin, a protease-activated receptor (PAR) agonist in menstrual blood exacerbate inflammation in these lesions. Focusing on the hypoxic conditions of menstrual blood, we investigated the effects of PGE2/thrombin on inflammation and fibrosis using primary cultured endometrial stromal cells (ESCs) and glandular epithelial cells (EECs) under low oxygen conditions. Chemokine CXCL12 secreted by endometrial stromal cells under hypoxia acts on CXCR4 receptors on glandular epithelial cells, inducing epithelial-mesenchymal transition (EMT), suggesting a possible role in endometriosis progression. RNA-seq analysis of PGE2/thrombin effects on endometrial stromal cells revealed activation of the transforming growth factor (TGF)-β pathway, particularly increased production and secretion of activin A, a member of the TGFβ family. Activin A, via increased connective tissue growth factor (CTGF) expression, promotes differentiation of endometrial stromal cells from fibroblast-like to myofibroblast transdifferentiation (FMT) of ESCs. In conclusion, targeting the CXCL12/CXCR4 and activin A/CTGF signaling pathways holds promise for improving fibrosis in endometriosis lesions.

LINC00342 regulates the PI3K-AKT signaling pathway via the miR-149-5p/FGF11 axis and affects the progression of oral cancer

BackgroundA large number of long non-coding RNAs (lncRNAs) have been implicated in the progression of oral cancer (OC). This study aimed to investigate the role of a novel lncRNA, LINC00342, in OC and elucidate its molecular mechanism.MethodsDifferential expression of lncRNA/miRNA/mRNA was analyzed using the Gene Expression Omnibus database and validated with RT-qPCR. Additionally, the expression levels of these molecules in OC cells and their effects on cell viability and cell cycle were assessed using the Cell Counting Kit-8 and flow cytometry. RNA bindings was analyzed by dual luciferase, and Western blot was used to detect the activation of relevant pathways.ResultsThis study showed that, in contrast to miR-149-5p, the expression of LINC00342 and fibroblast growth factor 11 (FGF11) were upregulated in OC cells (LINC00342: 10.00 ± 1.06 (FaDu) and 3.55 ± 0.25 (CAL-27) vs 1.00 ± 0.07 (HOECs), P < 0.05; FGF11: 7.31 ± 0.33 (FaDu) and 3.43 ± 0.08 (CAL-27) vs 1.00 ± 0.10 (HOECs), P < 0.05). Dual-luciferase assays confirmed that LINC00342 bind to miR-149-5p in a direct targeting manner. Furthermore, inhibition of LINC00342 expression resulted in decreased proliferation rate (FaDu: 136.22 ± 22.10% vs 59.36 ± 8.98% (control), P < 0.05; CAL-27: 131.40 ± 11.58% vs 49.83 ± 11.19 (control), P < 0.05) and migration ability of OC cells, cell cycle arrest in G1 phase, and inhibition of PI3K-AKT signaling. Inhibition of miR-149-5p or overexpression of FGF11 reversed the effects of si-LINC00342.ConclusionsLINC00342 promotes PI3K-AKT signaling by activating FGF11 through adsorption of miR-149-5p, thereby regulating the progression of OC.

Impact of neonatal hyperoxia on the development of the coronary vascular bed: an experimental model for the study of cardiomyopathy associated with premature birth

Abstract Introduction Very preterm birth (PT; &amp;lt;32 weeks of gestation), nearly 2% of all births, leads to short-term complications such as bronchopulmonary dysplasia and retinopathy of prematurity that are driven by compromised organ vascular development. Adults born preterm display an increased risk of ischaemic cardiomyopathy and heart failure. Our group has shown that neonatal rats exposed to hyperoxia, simulating the PT neonatal conditions, develop cardiomyocytes hypertrophy, fibrosis and cardiac dysfunction, or Oxygen-Induced Cardiomyopathy (OIC). Whether cardiac changes also associate with alterations in vascular development in the left ventricle (LV) remains unknown. Purpose We hypothesized that neonatal exposure to hyperoxia impact the development of the LV vascular network. Methods Male pups were exposed to 80% O2 (OIC) or room air (CTRL) from day 3 (P3) to P10 of life. Hearts were collected at P10, 4- and 16 weeks. Arteriolar length and capillary density per cardiomyocyte were measured using stereology (elastin) and immunofluorescence (WGA, α-SMA, CD31). High-resolution 3D reconstruction of the vascular network was achieved by combining fluorescent labelling of coronaries (anti-α-SMA) and capillaries (anti-CD31) with a tissue-cleaning protocol (iDisco+), allowing detailed morphometric characterization of the vascular network. The expression of vascular endothelial growth factors and receptors (VEGFA, VEGFB, VEGFR 1 and 2, NRP1, and PIGF) were quantified by RT-qPCR and Western blots. Differences between groups were analyzed with Student's t-test (P &amp;lt; 0.05) (N = 6 per group). Results At P10, we observed a notable rise in the number of capillaries per cardiomyocyte (0.88 ± 0.05 vs. 0.62 ± 0.02 mm2) and a significant increase in VEGFA (+76%) and NRP1 (+38%) expression in the LV from OIC vs. CTRL rats. By 4 weeks, the OIC group showed a significant reduction in arteriolar length vs. CTRL (6.51 ± 0.76 vs. 9.77 ± 1.12 m/cm3), coupled with an increase in the number of capillaries per cardiomyocyte (1.11 ± 0.05 vs. 0.85 ± 0.03 mm2). VEGFA was decreased (-14%) and PLGF increased (+24%) in the LV of OIC rats. At 16 weeks, the OIC condition displayed a significant increase in the number of capillaries per cardiomyocyte (1.37 ± 0.03 vs. 0.98 ± 0.07 mm2) and a decrease in VEGFA (-23%), along with reduction in its receptors VEGFR1 (-27%), VEGFR2 (-20%) and NRP1 (-17%). Conclusion OIC resulting from neonatal hyperoxia exposure associates with vascular changes in the LV that persist to adulthood. These changes are characterized by a reduction in arteriolar length and an increase in the number of capillaries, accompanied by modulation of the expression of pro-angiogenic VEGFA and receptors. The impact of these vascular alterations on the susceptibility of the LV to ischemic or hypertension-related damage is to be explored. These findings suggest a crucial mechanistic pathway for understanding the risk of cardiac pathologies associated with preterm birth.

CSWT improves ventricular function by promoting angiogenesis through Rho/ROCK/ERK1/2 signal pathway in infarcted myocardium in rats

Abstract Objective This study aimed to investigate the effects of extracorporeal cardiac shock wave therapy (CSWT) on myocardial ischemia and cardiac function in rats with myocardial infarction, and to explore its impact on the expression of myocardial vascular endothelial growth factor and the extent of myocardial fibrosis, thereby elucidating the mechanism of angiogenesis. Methods A rat model of myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery, confirmed by echocardiography. Animals were randomly assigned to five groups: sham operation group, myocardial infarction group, myocardial infarction + CSWT group, myocardial infarction + Y-27632 group, and myocardial infarction + CSWT + Y-27632 group. Cardiac function was evaluated by echocardiography on the 16th and 72nd day post-surgery. Myocardial morphology was assessed by HE staining, and the extent of myocardial fibrosis was determined by Masson's trichrome staining. Immunohistochemical staining for factor VIII was conducted to observe angiogenesis in each infarcted area. Western blotting was employed to detect the protein expression of extracellular regulated kinase (ERK1/2) and pro-angiogenic cytokines in the infarct border zone. Results CSWT treatment significantly reduced myocardial fibrosis and improved cardiac function compared to the myocardial infarction group. Additionally, CSWT upregulated ERK expression and angiogenesis-related factors, promoting angiogenesis. The beneficial effects of CSWT were abolished by inhibiting the Rho/ROCK/ERK1/2 pathway. Furthermore, the area of myocardial fibrosis was significantly reduced in the MI+Y-27632 group compared to the myocardial infarction group (p &amp;lt; 0.01), and left ventricular systolic function index was significantly higher in the myocardial infarction group. Conclusions CSWT may promote angiogenesis post-myocardial infarction by activating the Rho/ROCK/ERK1/2 pathway. Additionally, Y-27632 may improve cardiac function in rats with myocardial infarction, potentially through mitigating myocardial fibrosis.echo images of ratsprotein expression by WB

Morphological assessment of angiogenesis factor expression in tumor and microenvironment of breast fibroadenoma and ductal carcinoma: An observational cohort study

Background. Angiogenesis plays a crucial role in the progression of breast cancer. Identifying and investigating the key components of this process, focused on phenotype as well as microenvironment of the tumor, is considered highly relevant for understanding tumor biology. Studies into the expression of angiogenesis-related factors by means of immunohistochemical methods appear valuable for both assessing conventional chemotherapy options and identifying new targets in targeted therapy for breast cancer. Objectives. To investigate angiogenesis in breast ductal carcinoma by assessing the expression of vascular endothelial growth factor, angiopoietin-2, and hypoxia-inducible factor alpha in the context of various therapeutic strategies. Methods. An observational cohort study was conducted using biopsy samples from female patients with confirmed diagnoses of “fibroadenoma” and “ductal carcinoma of the breast,” residents of the Republic of Crimea, who applied to oncological hospitals in Simferopol from January 2021 to January 2023. Examination involved histological sections of breast tumor tissue from 68 patients with verified diagnoses of “ductal carcinoma” and “fibroadenoma” (the mean age of the patients was 65 ± 5). The following cohorts were formed in the study: control group, consisting of patients with breast fibroadenoma (n = 20); two subgroups of patients with ductal carcinoma of the breast (n = 48), including Group I — patients with ductal carcinoma of the breast who had not received chemotherapy (n = 23), Group II — patients with ductal carcinoma of the breast, who underwent surgery following one or more courses of chemotherapy (n = 25). The study involved examining the tumor tissue sections obtained from paraffin blocks, assessing the expression of angiogenesis markers via immunohistochemistry using primary antibodies against vascular endothelial growth factor, angiopoietin 2, and hypoxia-inducible factor alpha. Statistical analysis was carried out using Statistica 10.0 (StatSoft, USA). Differences were considered significant at error probability p ≤ 0.05. The value of p &lt; 0.05 was deemed statistically significant for all types of analysis. Results. The expression of hypoxia-inducible and vascular growth factors differed significantly between both groups with breast ductal carcinoma as well as when compared to the control group. The hypoxia-inducible factor having cytoplasmic localization was detected in the control group with benign processes, whereas the nuclear expression was noted in the breast ductal carcinoma groups. Significant differences in the nuclear expression of hypoxia-inducible factor have been established among groups of patients with confirmed ductal carcinoma of the breast: in Group II, which underwent chemotherapy, expression was notably higher in both the tumor stroma and in the stroma of tumor-free areas. The hypoxia-inducible factor expression was significantly greater at the demarcation zone than that observed in samples from surgically treated women in Group I (p = 0.033; p = 0.034, p &lt; 0.001, respectively). In the tumor epithelium of patients with breast ductal carcinoma, vascular endothelial growth factor was expressed significantly more intensively in the group who did not receive chemotherapy compared to the other group (p &lt; 0.001). Conversely, in the tumor stroma, angiopoietin exhibited significantly higher expression levels among patients who underwent chemotherapy compared to those who received no treatment; this was observed in both the tumor areas due to endothelial cell involvement (p = 0.004) and in conditionally healthy regions of the breast (p &lt; 0.001). In the control group represented by fibroadenoma patients, the expression of the studied factors is more pronounced than in the groups with ductal carcinoma of the breast. Conclusion. The obtained data indicate the activation of angiogenesis processes in the group of patients after chemotherapy, as evidenced by the increased expression of hypoxia-inducible factor, vascular endothelial growth factor, and angiopoietin. This result is associated with the high prevalence of resistant forms of breast ductal carcinoma in Group II. The study of the signaling pathways of angiogenesis and its components provides valuable insights into patterns of occurrence and strategies to overcome chemotherapy resistance in ductal carcinoma of the breast.

Low-Energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: An experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

Protein expression of estrogen, progesterone, and human epidermal growth factor receptors in young Iraqi women with breast cancer

Breast cancer is currently evaluated by the presence of hormonal receptors in the tumor tissue, which are among the most important prognostic and predictive markers used at present. The current study was conducted in Thi-Qar Governorate (Iraq) on women aged 20-40 years who have breast cancer (BC), highlighting­ the spread of this disease among young groups. The expression of estrogen (ER), progesterone (PR), and human epidermal growth factor (Her2/neu) receptors in breast tissues using immunohistochemical analysis was estimated. Breast tissue samples were collected from patients undergoing breast surgery and biopsy. Formalin-fixed paraffin-embedded samples were divided into BC (80), and control (20) groups. The study found that protein expression of both ER and PR was positive in 87.5% and negative in 12.5%, Her2/neu positive in 60% and negative in 40% of BC samples. The subtypes identified were luminal A (58.75%), luminal B (31.25%), HER2-positive (6.25%), and triple-negative (3.75%) BC. The high percentage of luminal A molecular subtype of BC is considered a good prognosis and treatable by anti-hormonal therapy. Keywords: breast cancer, estrogen, human epidermal growth factor, immunohistochemistry, progesterone, receptors

Hair Growth Effect and the Mechanisms of Rosa rugosa Extract in DHT-Induced Alopecia Mice Model

Rosa rugosa is a medicinal plant known for its potential anti-inflammatory, antioxidant, anti-cancer, and antimicrobial benefits. The pharmacological effects of Rosa rugosa extract on hair loss have not yet been documented. This research sought to assess the inhibitory effects and mechanisms of action of Rosa rugosa water extract (RWE) in a mouse model of dihydrotestosterone (DHT)-induced alopecia. The study was conducted using C57BL/6 mice, which were assigned to five groups: control, DHT-treated, Rosa rugosa water extract (RWE) at doses of 25 mg/kg and 100 mg/kg body weight, and bicalutamide-treated. To induce hair loss, dihydrotestosterone (1 mg/day per body weight) was administered via intraperitoneal injections, and dorsal hair removal was timed to align with the telogen phase. Each group received oral treatments for a period of 23 days. In this study, we assessed hair growth activity, examined histological changes, and performed immunoblot analysis. We noted improvements in hair length and thickness. Additionally, the protein expression of growth factors associated with hair growth, including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and insulin-like growth factor-1 (IGF-1), showed significant increases in the group treated with RWE. Additionally, treatment with RWE suppressed the protein expression of hair growth inhibitory factors, including dickkopf WNT signaling pathway inhibitor 1 (DKK1) and interleukin (IL)-6. Moreover, hair growth regulatory pathway related factors, including ERK, AKT, and GSK-3β, were activated. These findings indicate that RWE could serve as a promising natural therapy for preventing hair loss by enhancing the production of factors that promote hair growth while inhibiting those that suppress it.

Acute and chronic impact of interleukin-33 stimulation on chemokines and growth factors in human cord blood-derived mast cells.

Mast cells (MCs) are multifaceted immune cells that are capable of recognizing and responding to various stimuli by releasing an array of cytokines. We aimed to use human cord blood-derived mast cells (hCBMCs) as a model to evaluate different conditions under which chemokines and growth factors are expressed and secreted as mediators upon stimulation with the alarmin interleukin-33 (IL-33). hCBMCs were stimulated with 10 ng/mL or 20 ng/mL of recombinant human IL-33 (rhIL-33) for 6 h (acute) or 24 h (chronic). The mRNA expression of chemokines and growth factors was analyzed using microarrays, and the mediators released in the supernatant were evaluated using a multiplex assay. The mRNA expression levels of C-C chemokine ligands (CCL) CCL1, CCL5, granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein (MIP)-4/CCL18 were upregulated under all conditions. In contrast, C-X-C motif chemokine ligand (CXCL) CXCL8 and CCL24 levels increased only under acute (6 h) and prolonged (24 h) conditions, respectively. Moreover, high levels of CXCL8, MIP-1α, and MIP-1β were secreted during acute inflammation, whereas the release of GM-CSF and CXCL9 proteins increased under all four conditions. This study highlights the sentinel role of MCs in mounting a specific immune response against a pathogenic-like stimulus in a timely and dose-dependent manner and is relevant for improving inflammatory treatment options.

Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions.

Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

SiLOXL2 inhibits endothelial inflammatory response and EndMT induced by Ox-LDL.

Our research aimed to investigate the potential role and mechanism of lysyl oxidase (LOX)-like-2 (LOXL2) in atherosclerosis (AS) by using the human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). HUVECs were treated with ox-LDL at different concentrations (0, 10, 25, 50, and 100 μg/mL) and incubated for 24 hours. The transfection efficacy of siLOXL2 was investigated by western blot and RT-qPCR. Cell migration, intracellular ROS measurement, oxidative stress, ELISA, and adhesion assays were carried out to examine the ox-LDL-induced HUVECs injury. RT-qPCR and Western blot were used to determine gene and protein expression levels. LOXL2 protein expression increased in ox‑LDL‑induced endothelial cells. Ox-LDL+siLOXL2 significantly inhibited the migration ability of HUVECs and reduced the expression of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase 9 (MMP-9) gene expressions (all, P &lt;0.05). The ox-LDL+siLOXL2 significantly reduced intracellular ROS production and inhibited the expression of Malondialdehyde (MDA), whereas it markedly enhanced superoxide dismutase (SOD) and catalase (CAT) (all, P &lt;0.05). Supernatant levels of Interleukin-1 beta (IL-1β), Interleukin 6 (IL-6), and Tumor necrosis factor alpha (TNF-α) were significantly attenuated by the ox-LDL+siLOXL2 treatment (all, P &lt;0.05). Ox-LDL+siLOXL2 markedly suppressed the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (all, P &lt;0.05). ox-LDL+siLOXL2 treatment remarkably reduced the expression of α-smooth muscle actin (α‑SMA) and Vimentin, while increased CD31 and von Willebrand factor (vWF) gene expression (all, P &lt;0.05). LOXL2 silencing is protected against ox-LDL-induced endothelial cell dysfunction, and the mechanism may be related to the inhibition of the EndMT pathway.

Inhibition of angiogenesis and regenerative lung growth in Lepob/ob mice through adiponectin-VEGF/VEGFR2 signaling.

Obesity is associated with impairment of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in regenerative lung growth after unilateral pneumonectomy (PNX). We have reported that obesity inhibits angiogenesis. The effects of obesity on post-PNX lung vascular and alveolar regeneration remain unclear. Unilateral PNX is performed on Lep o b / o b obese mice to examine vascular and alveolar regeneration. Regenerative lung growth and expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 induced after PNX are inhibited in Lep o b / o b obese mice. The levels of adiponectin that exhibits pro-angiogenic and vascular protective properties increase after unilateral PNX, while the effects are attenuated in Lep o b / o b obese mice. Post-PNX regenerative lung growth and increases in the levels of VEGF and VEGFR2 are inhibited in adiponectin knockout mice. Adiponectin stimulates angiogenic activities in human lung endothelial cells (ECs), which is inhibited by decreasing the levels of transcription factor Twist1. Adiponectin agonist, AdipoRon restores post-PNX lung growth and vascular and alveolar regeneration in Lep o b / o b obese mice. These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin is one of the key factors to improve lung regeneration in obese people.

Rapid cyclic stretching induces a synthetic, proinflammatory phenotype in cultured human intestinal smooth muscle, with the potential to alter signaling to adjacent bowel cells.

Bowel smooth muscle experiences mechanical stress constantly during normal function, and pathologic mechanical stressors in disease states. We tested the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching. Primary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-ε-caprolactone nano-fibrous scaffolds, were subjected to pathologic, high frequency (1 Hz) uniaxial 3% cyclic stretch (loaded) or kept unloaded in culture for 6 hours. Total RNA sequencing, qRT-PCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells. Loading induced differential expression of 4537 genes in HISMCs. Loaded HISMCs had a less contractile phenotype, with increased expression of synthetic SMC genes, proinflammatory cytokines, and altered expression of axon guidance molecules, growth factors and morphogens. Many differentially expressed genes encode secreted ligands that could act cell-autonomously on smooth muscle and on other cells in the bowel wall. HISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMCs into proliferative, fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.

Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes.

Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here, we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. We found that Yap, and not Taz, expression patterns differed in a post-myocardial infarct compared to a peri-infarct region of rat hearts post-myocardial infarction, suggesting cell specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were determined to be more sensitive to nutrient deprivation than other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, predominantly L-isoleucine, and influences the expression of connective tissue growth factor (Ctgf)-a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation.

RGDSP-functionalized peptide hydrogel stimulates growth factor secretion via integrin αv/PI3K/AKT axis for improved wound healing by human amniotic mesenchymal stem cells.

The wound healing process involves communication among growth factors, cytokines, signaling pathways, and cells in the extracellular matrix, with growth factors acting as key regulators. Although stem cells can promote wound healing by secreting diverse growth factors, their therapeutic potential is hindered by poor survival and engraftment. Mimicking the stem cell-matrix interactions can improve stem cell survival, regulate their fate, and even enhance their paracrine effects. This study investigated the use of composite RGDmix hydrogel, which can support the survival and proliferation of human amniotic mesenchymal stem cells (hAMSCs), and effectively increase the expression of various growth factors, thereby promoting wound re-epithelialization, angiogenesis, and epidermal maturation. At last, the specific role of integrin αv and PI3K/AKT signaling pathways in the secretion of growth factors were examined by silencing them in vitro and in vivo. Results suggested that the RGDmix hydrogel improved the secretion of growth factors by hAMSCs through the RGDSP/integrin αv/PI3K/AKT axis, thereby enhancing the therapeutic effect in wound healing.