Expression Of Β-catenin Research Articles

Decoding β-catenin expression patterns in ovarian serous carcinoma with clinicopathological implications: insights from National Cancer Institute

Decoding β-catenin expression patterns in ovarian serous carcinoma with clinicopathological implications: insights from National Cancer Institute

The effects of acetylated cordycepin derivatives on promoting vascular angiogenesis and attenuating myocardial ischemic injury

BackgroundEnhanced angiogenesis following myocardial infarction (MI) is beneficial to preserve cardiac function. The present study aimed to investigate whether acetylated derivatives of cordycepin altered its original antitumor properties and exerted cardioprotective effects by promoting angiogenesis in vitro and in vivo. MethodsCordycepin and its derivatives with single (DA), double (DAA), and triple acetyl groups (DAAA) were assessed. The cell viability of leukemia U937 cells, malignant hepatoma Huh-7 cells, and human umbilical vascular endothelial cells (HUVECs) treated with cordycepin, DA, DAA, and DAAA were determined. The expression of β-catenin in U937 cells, as well as the expression of p65, p38 and other related signal regulators in HUVECs elicited by lipopolysaccharides (LPS) were also observed. Angiogenesis was determined by tube formation in HUVECs and Matrigel plug assay in mice. Cardiac function following administration of DAAA was evaluated in mice MI model simulated by coronary artery ligation. ResultsThe inhibitory effects of cordycepin and its acetylated derivatives on U937 cells, Huh-7 cells, HUVECs, and the expression of β-catenin in U937 cells were mitigated with increasing acetylation. Intriguingly, DAAA preserved the cell viability of HUVECs compared to other acetylated derivatives. Although DAAA had a significantly diminished antitumor effect compared to cordycepin, it promoted angiogenesis in mice and tube formation in HUVECs and attenuated LPS-induced phosphorylation of p65 and p38. Additionally, administration of DAAA improved cardiac function following coronary artery ligation in mice. ConclusionDAAA could be considered a promising adjunctive therapy to prevent post-MI heart failure through promoting angiogenesis.

Compound #41 Targets Acute Myelogenous Leukemia by Inhibiting the Wnt/β-catenin Signaling Pathway.

Aberrant activation of the Wnt/β-catenin signaling pathway contributes to the pathogenesis of acute myelogenous leukemia (AML). Thus, targeting this pathway offers a promising therapeutic strategy against AML. Here, we synthesized a novel dipeptide-type inhibitor of the Wnt/β-catenin signaling pathway, compound #41, and explored its anti-tumor effects on AML cells. We evaluated the inhibitory effect of compound #41 on T cell factor (TCF)/β-catenin transcriptional activity using a luciferase (Luc) reporter assay. The anti-tumor effects were assessed on KG1a and MV4;11 human AML cells using RT-qPCR, western blotting, and WST-8, cell cycle, and apoptosis assays. Differentially expressed genes were analyzed by RNA-sequencing (RNA-seq). Additionally, we investigated the in vivo effects of compound #41 using KG1a-Luc/GFP cells in an orthotopic mouse model. The Luc reporter assay showed that compound #41 decreased the TCF/β-catenin transcriptional activity. Compound #41 blocked the cell cycle progression, inhibited cell proliferation, and induced apoptosis in AML cells. Treatment with compound #41 down-regulated the expression of β-catenin, Survivin, and β-catenin-specific target genes, as demonstrated by RNA-seq. In vivo analysis showed that compound #41 blocked the expansion of KG1a-Luc/GFP cells in the bone marrow and prolonged the overall survival of KG1a-Luc/GFP-transplanted mice. Compound #41 suppressed the Wnt/β-catenin signaling pathway by reducing CTNNB1 levels and induced apoptosis in AML cells. Furthermore, compound #41 inhibited the proliferation of KG1a-Luc/GFP cells in the bone marrow and extended the overall survival of mice. Thus, compound #41 is an attractive Wnt/β-catenin signaling pathway inhibitor of AML.

SIRT7 stabilizes β-catenin and promotes canonical Wnt activation via upregulating FZD7

AimsThe dysregulated Wnt/β-Catenin signaling pathway leads to occurrence of various diseases, and abnormal activation of β-Catenin is a major characteristic of human HCC. FZD7 is a positive regulator of the Wnt/β-catenin signaling pathway, and its upregulation is related to increase of β-catenin expression and carcinogenesis in human HCC. However, mechanisms underlying FZD7 upregulation in HCC remain elusive. Main methodsNuclear cytosol fractionation, immunofluorescence and Top-Flash were used to detect the activation of β-Catenin. Protein half-life and ubiquitination assays were applied to evaluate protein stability. RNA-seq combined with qRT-PCR was used to evaluate differential gene expressions after SIRT7 knockdown. Wound healing and transwell assays were used to measure cancer cell migration. Key findingsSIRT7-mediated FZD7 expression is essential for stability and activation of β-catenin. Knockdown SIRT7 in HCC cells resulted in enhanced binding of β-catenin to the DC, decreased its stability, nuclear localization and activation. Knockdown FZD7 reversed SIRT7 overexpression mediated β-catenin stabilization and impairment of binding of β-catenin to the DC. At molecular level, SIRT7 promotes FZD7 expression via upregulating transcription factor PU.1, knockdown PU.1 abolished SIRT7-mediated upregulation of FZD7. Finally, we confirmed that FZD7 was responsible for SIRT7-mediated β-catenin stabilization and HCC cells migration. By using clinical samples, we observed strong positive correlations between SIRT7 and PU.1, FZD7, p-GSK3β and β-Catenin in human HCC. SignificanceOur results thus revealed a previously undisclosed role of SIRT7 in regulating the canonical Wnt/β-catenin signaling pathway, thereby offering additional evidence that SIRT7 holds promise as a novel therapeutic target for human HCC.

Wnt3a-induced LRP6 phosphorylation enhances osteoblast differentiation to alleviate osteoporosis through activation of mTORC1/β-catenin signaling

ObjectiveOsteoporosis (OP) is a common cause of morbidity and mortality in older individuals. The importance of Wnt3a in osteogenic activity and bone tissue homeostasis is well known. Here, we explored the possible molecular mechanism by which Wnt3a mediates the LRP6/mTORC1/β-catenin axis to regulate osteoblast differentiation in OP. MethodsOP-related key genes were identified through a bioinformatics analysis. A ROS17/2.8 cell differentiation system for rat osteogenic progenitors and a rat model of senile OP were constructed for in vitro and in vivo mechanism verification. ResultsBioinformatics analysis revealed that LRP6 was poorly expressed in OP and may play a key role in the occurrence of OP by affecting osteoblast differentiation. LRP6 knockdown inhibited osteoblast differentiation in an in vitro model. In addition, Wnt3a promoted osteoblast differentiation by inducing LRP6 phosphorylation. Moreover, LRP6 promoted mTORC1 expression, which indirectly promoted β-catenin expression, thus promoting osteoblast differentiation. Finally, an in vivo assay revealed that LRP6 inhibition improved OP. ConclusionOur study provides evidence that Wnt3a induces phosphorylation of LRP6 to activate the mTORC1/β-catenin axis, thus promoting osteoblast differentiation and ultimately improving OP in aged rats.

High expression of LncRNA HOTAIR is a risk factor for temozolomide resistance in glioblastoma via activation of the miR-214/β-catenin/MGMT pathway

HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell cycle and apoptosis. In this study, we found that HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

Electric Stimulation at 448 kHz Modulates Proliferation and Differentiation of Follicle Dermal Papilla Cells

Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Alopecia is a pathology caused by a deregulation in the hair cycle phases. Currently, the use of physical therapies such as radiofrequency (RF) as an alternative to pharmacological treatment is increasing. Electrical stimulation by capacitive resistive electrical transfer (CRET) is one of these therapies. The objective of the present study was to analyze the effect of RF-CRET currents on DPCs. Cells were treated with subthermal 448 kHz CRET currents with two different types of signals: standard (CRET-STD) or modulated (CRET-MOD). Viability (XTT Assay), proliferation (Ki67 and ERK1/2), apoptosis (p53 and caspase 3), differentiation (β-catenin and α-SMA), and anagen markers (versican and PPARγ) were analyzed by immunofluorescence and immunoblot. CRET caused effects on the proliferation and survival of DPCs associated with increases in the expression of p-MAPK-ERK1/2, cyclin D1, and decreases in the expression of p53 and caspase 3. Also, CRET caused significant transient increases in the expression of β-catenin, involved in hair growth, and in the expression of anagen phase markers such as versican and PPARγ related to hair follicle maintenance. The present study highlights the ability of treatment with CRET therapy to cause molecular alterations in DPC involved in hair regeneration.

The Functional Role of the Long Non-Coding RNA LINCMD1 in Leiomyoma Pathogenesis

Existing evidence indicates that LINCMD1 regulates muscle differentiation-related gene expression in skeletal muscle by acting as a miRNA sponge, though its role in leiomyoma development is still unknown. This study investigated LINCMD1′s involvement in leiomyoma by analyzing paired myometrium and leiomyoma tissue samples (n = 34) from patients who had not received hormonal treatments for at least three months prior to surgery. Myometrium smooth muscle cells (MSMCs) were isolated, and gene expression of LINCMD1 and miR-135b was assessed via qRT-PCR, while luciferase assays determined the interaction between LINCMD1 and miR-135b. To examine the effects of LINCMD1 knockdown, siRNA transfection was applied to a 3D MSMC spheroid culture, followed by qRT-PCR and Western blot analyses of miR-135b, APC, β-Catenin and COL1A1 expression. The results showed that leiomyoma tissues had significantly reduced LINCMD1 mRNA levels, regardless of patient race or MED12 mutation status, while miR-135b levels were elevated compared to matched myometrium samples. Luciferase assays confirmed LINCMD1′s role as a sponge for miR-135b. LINCMD1 knockdown in MSMC spheroids increased miR-135b levels, reduced APC expression, and led to β-Catenin accumulation and higher COL1A1 expression. These findings highlight LINCMD1 as a potential therapeutic target to modulate aberrant Wnt/β-Catenin signaling in leiomyoma.

Blautia coccoides and its metabolic products enhance the efficacy of bladder cancer immunotherapy by promoting CD8+ T cell infiltration

BackgroundImmune checkpoint inhibitors (ICIs) have emerged as a novel and effective treatment strategy, yet their effectiveness is limited to a subset of patients. The gut microbiota, recognized as a promising anticancer adjuvant, is being increasingly suggested to augment the efficacy of ICIs. Despite this, the causal link between the gut microbiota and the success of immunotherapy is not well understood. This gap in knowledge has driven us to identify beneficial microbiota and explore the underlying molecular mechanisms.MethodsThrough 16S rDNA sequencing, we identified distinct gut microbiota in patients undergoing treatment with ICIs. Following this, we assessed the impact of probiotics on anti-PD-1 therapy in bladder cancer using mouse models, employing a multi-omics strategy. Subsequently, we uncovered the mechanisms through which Blautia-produced metabolites enhance antitumor immunity, utilizing untargeted metabolomics and a range of molecular biology techniques.ResultsIn our research, the LEfSe analysis revealed a significant enrichment of the Blautia genus in the gut microbiota of patients who responded to immunotherapy. We discovered that the external addition of Blautia coccoides hampers tumor growth in a bladder cancer mouse model by enhancing the infiltration of CD8+ T cells within the tumor microenvironment (TME). Further investigations through untargeted metabolomics and molecular biology experiments showed that oral administration of Blautia coccoides elevated trigonelline levels. This, in turn, suppresses the β-catenin expression both in vitro and in vivo, thereby augmenting the cancer-killing activity of CD8+ T cells.ConclusionsThis research provided valuable insights into enhancing the efficacy of PD-1 inhibitors in clinical settings. It was suggested that applying Blautia coccoides and its metabolic product, trigonelline, could serve as a synergistic treatment method with PD-1 inhibitors in clinical applications.Graphical

Assessment of the Role of miR-30a-5p on the Proliferation and Apoptosis of Hair Follicle Stem Cells.

To investigate the role of miR-30a-5p on the proliferation and apoptosis of hair follicle stem cells (HFSCs) and whether the Wnt/β-catenin signaling pathway is involved. HFSCs derived from the vibrissa of mammary rats were obtained by enzymatic digestion, and subsequently the obtained HFSCs were treated with Lipofectamine 2000 cell transfection and divided into normal cell culture group (control), miR-30a-5p overexpression group (miR-30a-5p mimic), miR-30a-5p empty vector group (miR-NC), miR-30a-5p inhibitor group (in-miR-30a-5p), and in-miR-30a-5p empty vector group (in-miR-NC). After transfection, the cell proliferation and apoptosis rates were examined separately. In addition, the mRNA expression of β-catenin, proliferating cell nuclear antigen (PCNA) and apoptosis-related genes (Bax and Bcl-2) were examined. The results of cell proliferation ability showed that in-miR-30a-5p group promoted cell proliferation of HFSCs relative to other groups, along with significant upregulation of gene levels of PCNA. Apoptosis analysis indicated that apoptosis rate was reduced in the in-miR-30a-5p group, and the expression of Bax was suppressed, while that of Bcl-2 was promoted. Wnt/β-catenin signaling pathway investigation revealed a significant increase in the levels of β-catenin in HFSCs in the in-miR-30a-5p group. Downregulation of miR-30a-5p levels inhibited HFSCs apoptosis and simultaneously promoted proliferation, furthermore, the increased expression of β-catenin indirectly confirmed the activation of the Wnt/β-catenin signaling pathway.

Involvement of β-catenin expression in hepatocellular carcinoma prognosis in a cohort of patients undergoing curative treatment

BackgroundHepatocellular carcinoma is a tumor of epithelial origin that arises from the action of different carcinogens on the hepatocytes and has a high worldwide incidence. The prognostic markers of this disease have not been completely established. Mutations in the gene encoding β-catenin are overexpressed in hepatocellular carcinoma. The objective of our study was to correlate the molecular expression of β-catenin in hepatocellular carcinoma with the already known prognostic markers. MethodsWe conducted an observational and prospective cohort study on adult patients diagnosed with hepatocellular carcinoma from whom samples of nontumor and tumor liver parenchyma were taken intraoperatively to correlate the molecular expression of β-catenin in hepatocellular carcinoma with the known prognostic markers. ResultsA total of 81 samples were collected, of which 48 met the inclusion criteria. The final sample was divided into patients with a diagnosis of hepatocellular carcinoma on a cirrhotic liver, corresponding to 31 patients (64.6%), and patients with a diagnosis of hepatocellular carcinoma on a noncirrhotic liver, corresponding to 17 patients (35.4%). We found that overexpression of β-catenin and the neutrophil/lymphocyte ratio are independently related to disease-free survival, and both overexpression and molecular repression of β-catenin are independently related. ConclusionMolecular overexpression of β-catenin in hepatocellular carcinoma compared with nontumor tissue is associated with worse disease-free survival, and its combination with a high neutrophil-lymphocyte ratio worsens this prognosis.

7-Ketocholesterol Effects on Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells

Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in osteogenic or adipogenic media. Osteogenic and adipogenic differentiation was evaluated by Alizarin red and Oil Red O staining, respectively. Osteogenic (ALPL, RUNX2, BGLAP) and adipogenic markers (PPARƔ, C/EBPα) were determined by RT-PCR. Differentiation signaling pathways (SHh, Smo, Gli-3, β-catenin) were determined by indirect immunofluorescence. ATMSCs treated with 7-KC in osteogenic media stained positively for Alizarin Red. 7-KC in adipogenic media decreased the number of adipocytes. 7-KC increased ALPL and RUNX2 but not BGLAP expressions. 7-KC decreased expression of PPARƔ and C/EBPα, did not change SHh, Smo, and Gli-3 expression, and increased the expression of β-catenin. In conclusion, 7-KC favors osteogenic differentiation of ATMSCs through the expression of early osteogenic genes (matrix maturation phase) by activating the Wnt/β-catenin signaling pathway, while inhibiting adipogenic differentiation. This knowledge can be potentially useful in regenerative medicine, in treatments for bone diseases.

Polygenic anti-cancer activity of Indigofera macrophylla in prostate cancer induced animal model

BackgroundProstate cancer (Pca) is a deadly disease prevalent among men, and it accounts for about 7–8 % of mortality globally. Synthetic drugs have proved effective but have limitations and severe side effects. There is, therefore, a need to discover a less expensive, natural therapeutic agent with no side effects in treating the ailment. AimThe study aims to investigate the anti-prostate cancer activity of extracts of Indigofera macrophylla (I. macrophylla) at the physiological and molecular levels in experimental animals. MethodPolyphenol-rich extract of I. macrophylla was subjected to HPLC analysis to identify the plant's phytochemical constituent. Adult Wistar rats were orally administered 2mls of 50, 100 and 200 PPM of the cacodylic acid solution for 28 days to induce prostate cancer, while treatment was carried out by orally administering extract of I. macrophylla at doses of 50, 100 and 200 mg/kg for up to 28 days. The anti-inflammatory and apoptotic properties of the extract in experimental animals were investigated by the expression levels of various genetic biomarkers such as Bax-2, TNF-α, IL-6, COX2, IL-1β, β-Catenin, APC, Bcl2, CEA, Caspase 3 and β-Catenin using reverse transcriptase polymerase chain reaction (RT-PCR). ResultHPLC analysis shows that I. macrophylla has 21 bioactive components which are categorized into seven groups: flavonoid, terpenes, phenols, isoflavonoid, phytosterols, quinone and glycosides. Administration of the drug shows inconsistencies in the mean body weights of the experimental animals. Further investigation revealed that I. macrophylla increased TNF-α upregulation and expression, significantly downregulated IL-1β, significantly decreased IL-6 expression, ameliorated COX2 expression, downregulated β-catenin expression and significantly reduced the expression of the APC gene. These results show that the drug activity modulates the investigated inflammatory and apoptotic genes in the prostate gland of PCa-induced rats, thus demonstrating its anti-PCa potential. ConclusionThe results of this study suggest the potential of a novel treatment protocol of I. macrophylla plant extract to improve therapeutic outcomes for patients with aggressive PCa, which reportedly claims hundreds of thousands of lives yearly.

Upregulation of TREM2 expression in M2 macrophages promotes Brucella abortus chronic infection.

Brucella abortus (B.abortus) is a zoonotic bacterial pathogen that causes chronic host infections. The eradication of brucellosis using antibiotic therapy is often incomplete or slow. In a mouse model, the predominance of alternatively activated macrophages (also known as M2) plays an essential role in sustaining chronic infection. The underlying functional mechanism by which M2 sustains chronic infection remains unclear. Here, we show that B. abortus can enter M2 via triggering receptor expressed on myeloid cells 2 (TREM2) and promotes the upregulation of TREM2 expression of M2 in a type IV secretion system (T4SS)-dependent manner. Increased TREM2 enhances B. abortus growth within M2 by suppressing intracellular ROS production, preventing M2 pyroptosis via suppression of mitochondrial ROS (mROS), and promoting M2 proliferation by increasing β-catenin expression. In line with these results, downregulation of TREM2 expression suppressed B. abortus intracellular growth and M2 proliferation and induced M2 pyroptosis. In our mouse model, upregulation of TREM2 expression sustained the accumulation of M2 and B. abortus chronic infection, whereas downregulation of TREM2 expression restricted M2 proliferation and chronic infection. Collectively, our results suggest that targeting TREM2 may be a potential adjunct to antibiotic therapy for the prevention of chronic Brucella infection.

The effects of therapeutic hypothermia on the expression of DKK3 and myocardial ischemia-reperfusion injury

BackgroundThe impact and mechanisms of therapeutic hypothermia (TH) on myocardial ischemia–reperfusion (I/R) injury are still unknown. MethodsSprague-Dawley (SD) rat model and primary cardiomyocytes were applied in our study. TTC staining evaluated myocardial infarction, while H&E staining assessed myocardial injury. ELISA quantified lactate dehydrogenase (LDH), IL-1β, IL-6, and TNF-α. Blood serum concentrations of CK, CK-MB, and cTnT were detected using a biochemical assay. TUNEL assay, flow cytometry and western blot were used to detect cell apoptosis. EdU assay was applied to examine cell proliferation. The expression of DKK3 and β-catenin protein was analyzed using Realtime PCR and Western blot. ResultsTH alleviated myocardial infarction size and injury in rat models of I/R, and reduced serum levels of myocardial injury markers and inflammatory factors in animal and cell models. In addition, TH inhibited the increased apoptosis and β-catenin expression as well as decreased DKK3 expression caused by I/R in I/R cell models, while si-DKK3 reversed the changes brought by TH, and XAV939 inhibited the effects of si-DKK3. ConclusionTH may reduce myocardial infarction size, myocardial injury, inflammatory response and apoptosis through DKK3/Wnt/β-catenin pathway, thereby alleviating myocardial I/R injury.

Facilitation of diabetic wound healing by far upstream element binding protein 1 through augmentation of dermal fibroblast activity.

Diabetes mellitus (DM) often leads to wound healing complications, partly attributed to the accumulation of advanced glycosylation end products (AGEs) that impair fibroblast function. Far Upstream Element Binding Protein 1 (FUBP1) regulates cell proliferation, migration, and collagen synthesis. However, the impact of FUBP1 on diabetic wound healing remains unknown. This study is designed to explore the function and mechanisms of FUBP1 in diabetic wound healing. Eighteen Sprague-Dawley rats (weighing 220-240g) were randomly assigned to three groups (n = 6): a control group (NC) of healthy rats, a model group (DM) of untreated diabetic rats, and a treatment group (DM + FUBP1) of diabetic rats accepting FUBP1 treatment. A 10mm diameter circular full-thickness skin defect was created on the back of each rat. On days 1 and 7, rats in the treatment group received local injections of 5µg FUBP1 protein at the wound site, whereas the control group and model group were administered saline. Wound healing was documented on days 0, 3, 7, 10, and 14, with tissue samples from the wound areas collected on day 14 for histological analysis, including H&E staining, Masson's trichrome staining, and immunohistochemistry. Western blot analysis was utilized to assess the expression of GSK-3β, Wnt3a, and β-catenin. In vitro, the effects of various concentrations of AGEs on cell viability and FUBP1 expression were examined in human dermal fibroblasts (HDF). Cells were genetically modified to overexpress FUBP1 using lentiviral vectors and were cultured for 48h in media with or without AGEs. The impacts on fibroblast proliferation, migration, and Wnt/β-catenin signaling were evaluated using CCK-8, scratch assays, and Western blot analysis. Animal investigation revealed that from day 7 onwards, the wound healing rate of the treatment group was higher than that of the model group but lower than the control group. On day 14, the wound healing rates were as follows: control group (0.97 ± 0.01), model group (0.84 ± 0.03), and treatment group (0.93 ± 0.01). These differences were statistically significant. Histological analysis indicates that FUBP1 promotes granulation tissue formation, re-epithelialization, and collagen deposition in treatment group. Additionally, FUBP1 protein expression decreased in dermal fibroblasts when exposed to AGEs. Overexpression of FUBP1 significantly enhanced fibroblast proliferation and migration, activating the Wnt/β-catenin pathway and mitigating the inhibitory effects of AGEs. Our results suggest that FUBP1 can be a promising therapeutic target for diabetic wound healing, potentially counteracting the detrimental effects of AGEs on dermal fibroblasts through the Wnt/β-catenin pathway.

The potential role of Circular RNA New biomarkers for the prognosis of hepatocellular carcinoma

Abstract Introduction/Objective Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer with related deaths worldwide. The non-coding RNAs as the functions of circRNAs in tumor progression have attracted great attention to the clinicopathological characteristics of HCC. Methods/Case Report The present study was conducted to investigate and evaluate the expression level of hsa_circ_2124, and hsa_circ_4018 downstream target gene pathways related to clinico-pathological parameters of HCC. Cell proliferation was examined by West-1 assay and protein expression levels by using western blotting analysis. Results (if a Case Study enter NA) The hsa_circ_2124 expression level was up-regulated in HepG2 and Hep3B cells, respectively compared to normal liver cells. Furthermore, hsa_circ_4018 was down-regulated in two HCC cell lines compared to the normal cell line (LO2 cells), demonstrating the heterogeneity characteristics of the circRNA expressions in different HCC cell lines. Our data showed a significant inhibition of hsa_circ_4018 in HCC cell lines which in turn inhibited cell proliferation and migration. Besides, there is an inhibition in cell proliferation after hsa_circ_2124 knockdown in the tested cell lines. In addition, our data reported that the Knockdown of hsa_circ_2124 reduced the expression of ERK, c-Myc, and β-catenin expression in Hep-G2 cells. Furthermore, hsa_circ_4018 showed significant inhibition in β-catenin and c-Myc expression levels in Hep3B cells compared to the control. The knockdown of hsa_circ_2124 induced G1-phase arrest in HepG2 cells compared to control, suggesting the role of hsa_circ_2124 in the inhibition of HCC progression. Conclusion All in all, our data revealed that hsa_circ_2124 or hsa_circ_4018 plays a role in the regulation of MAPK and Wnt/β-catenin signaling pathways, which might be potential therapeutic biomarkers for HCC.

Transforming growth factor-beta and Epithelial-mesenchymal transition is considered an attractive pivotal Genetic-Biomarker for Hepatocellular carcinoma with hepatitis C virus-infection patients

Abstract Introduction/Objective Hepatocellular carcinoma (HCC) is the most common cause of cancer worldwide. HCC is induced by hepatitis C-virus (HCV) which represents a major health problem in Egypt. The transforming growth factor- beta (TGF-β) is a potent cytokine that has a multifunctional pro-fibrotic activity, for enhancing liver-inflammation, fibrosis, tumor-progression, and metastasis. TGF-β has a vital role in the regulation of tumorigenesis, by controlling epithelial-mesenchymal-transition (EMT), apoptosis, proliferation, and differentiation process. The dysregulation of TGF-β, Wnt/β-catenin signaling pathways, by HCV-core protein is implicated in the development of HCC. Methods/Case Report The study aims to determine the effect of the HCV-infection in HCC patients with a set of growth-factors, EMT, and anti-apoptotic protein expression levels by using western blotting and immunohistochemistry staining analysis. Results (if a Case Study enter NA) These results observed an insignificant increase in the expression of TGF-β protein for HCC/HCV-infected cells compared to the HCV-uninfected cells, and the expression of the β-catenin protein level is elevated in the nucleus. Also, it showed that Bcl-2 protein is a significant increase in HCV-infected when compared to HCV-free groups. Positive staining for p53 protein was detected in the HCC/HCV-infected, more than in HCC/HCV-uninfected cells. This data indicated that the core-protein of HCV can switch TGF-β from a tumor suppressor to a tumor promoter by suppressing apoptosis of hepatocytes and increasing EMT expression by activation of Wnt/β-catenin signaling pathway. Therefore, HCV-core protein enhances the nuclear accumulation of β-catenin expression protein to activate downstream target genes, which regulate cell-growth and cell-cycle progression. Conclusion It is speculated that HCV may exert an anti-apoptotic effect, and thus enhance tumorigenesis. Also, the accumulation of nuclear Wnt/β-catenin and p53 correlates with TGF-β expression, typically a late event in hepato- carcinogenesis. Taken together, the expression level of TGF-β, Wnt/β-catenin, Bcl-2, and p53 genotype in HCV is considered an indicator of shortened survival in patients, and may be an attractive clinically pivotal genetic biomarker to mediate liver pathogenesis.

The Anticancer Poperties of Diosgenin on Colorectal Cancer Cells Induced by Wnt/Β Catenin Signaling Pathway

Background: Colorectal cancer (CC) is one of the most prevalent cancers globally. Due to the severe side effects and the development of drug resistance in CC treatments, current therapeutic strategies often prove ineffective. As a result, there is a growing interest in exploring traditional medicinal plants as alternative treatment options for various human diseases. Diosgenin, a bioactive compound derived from plants, has shown potential in inhibiting the growth of human CC cells. The Wnt/β-catenin signaling pathway plays a critical role in colorectal tumorigenesis. Objectives: This study investigates the effects of Diosgenin on the Wnt/β-catenin pathway in CC cells. Methods: Colorectal cancer cells were treated with Diosgenin, and cell viability and plasma membrane integrity were assessed using the MTT assay and lactate dehydrogenase (LDH) activity assay, respectively. Apoptosis was evaluated through Annexin V/PI staining. The expression of Wnt/β-catenin-related genes was analyzed by quantitative PCR (qPCR). Results: Diosgenin significantly inhibited CC cell viability in a time- and concentration-dependent manner after 24, 48, 72, and 96 hours of exposure (P < 0.05). The IC50 values were determined to be 203.55, 122.95, 70.11, and 7.34 µM at 24, 48, 72, and 96 hours, respectively. Diosgenin at its IC50 concentration induced a significant increase in cell apoptosis after 24 hours of treatment (P < 0.05). Additionally, it caused a significant reduction in the expression of β-catenin, cyclin D1, and Pin1 (βCP). Conclusions: Diosgenin exhibits anti-CC effects by inhibiting the expression of βCP genes involved in the Wnt/β-catenin pathway, suggesting its potential as a therapeutic agent for CC.

Pilomatrix-like breast carcinoma: A mammary analog of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC).

To describe what is, to our knowledge, the first recognized case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype.Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a high-grade carcinoma with divergent differentiation resembling cutaneous pilomatrix carcinoma that was recently described in the endometrium and ovary. For reference, pertinent features of PiMHEC include (1)high-grade basaloid to squamoidmorphology withthe presence of ghost cells; (2) only focal p63 and/or p40 expression despite a squamoid appearance; (3) CTNNB1 mutation, accompanied by diffusely aberrant β-catenin expression and LEF1 and/or CDX2 expression; and (4) loss of site-specific markers (ie, PAX8, ER). Here we report the histologic, immunophenotypic and molecular genetic features ofa case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype. The tumor developed immediately adjacent to a HER2+, androgen receptor (AR)+, GATA3+ conventional grade 3 invasive ductal carcinoma (IDC) with only membranous β-catenin expression. The PiMHEC-like component had all of the above-noted morphologic and immunophenotypic features of endometrial PiMHEC but with loss of GATA3 and AR rather than PAX8 and ER.Molecular analysis performed on both tumor components demonstrated a shared TP53 point mutation and an exon 3 CTNNB1 mutation restricted to the PiMHEC-like component, implying a clonal relationship with secondary acquisition of CTNNB1. Following neoadjuvant chemotherapy, the HER2+ conventional component had completely resolved, but the PiMHEC-like component had very little response. This case demonstrates that a PiMHEC-like phenotype may be seen as a form of TNBC that can develop from conventional IDC, with loss of site-specific biomarkers, acquisition of CTNNB1 mutation, and resistance to conventional chemotherapy.