Protein Expression In Tissues Research Articles

GPD1L may inhibit the development of esophageal squamous cell carcinoma through the PI3K/AKT signaling pathway: bioinformatics analysis and experimental exploration.

Esophageal squamous carcinoma (ESCC) is the most prevalent pathological subtype of esophageal cancer (EC). It has the characteristics of significant local invasion, quick disease progression, high recurrence rates, and a dismal prognosis for survival. Phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) is a signaling system whose aberrant activation regulates downstream factors, leading to the promotion of cancer development. This study looks at a protein called Glycerol-3-phosphate dehydrogenase 1-like (GPD1L), which strongly affects the development of several cancers. However, its association with ESCC development and its underlying mechanisms are not clear. In this paper, we analyzed six ESCC transcriptome data obtained from the GEO database. We utilized bioinformatics technology and immunohistochemistry to differentially analyze GPD1L levels of mRNA and protein expression in ESCC and normal adjacent tissues. Furthermore, we conducted survival, co-expression, enrichment, immune infiltration and drug sensitivity analysis. Moreover, we further investigated the role and mechanism of GPD1L by Western Blot (WB), Cell Counting Kit-8 (CCK8), wound healing assay, Transwell assay, and flow cytometry. Finally, the addition of IGF-1, the activator of PI3K/AKT, could rescue the inhibitory effect of GPD1L on ESCC. The findings manifest that the expression of GPD1L was low in ESCC, and functional experiments showed that GPD1L promoted apoptosis in vitro while blocking cell migration, invasion, and proliferation. Based on mechanism research, GPD1L's impact on ESCC could be explained by its suppression of the PI3K/AKT signaling pathway's activation. To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.

Abstract 4136316: BMP10 as novel marker for right atrial dilatation and pressure in precapillary pulmonary hypertension

Introduction: Precapillary pulmonary hypertension (precPH) leads to increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein 10 (BMP10) in adults. Aim: This study aims to investigate BMP10 in relation to RA dilatation and pressure overload. Methods: We studied BMP10 mRNA in fresh RA tissue of N=5 Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients and N=9 controls and protein expression in paraffin-embedded RA tissue of N=4 Pulmonary Arterial Hypertension (PAH) patients and N=6 controls. We prospectively included 48 precPH patients (N=22 idiopathic PAH, N=14 hereditary PAH and N=12 CTEPH, and N=16 controls. To study BMP10-induced transcriptional activity, we assayed serum samples in human microvascular endothelial cells (HMEC) with a BMP-responsive transcriptional luciferase assay. BMP10 activity was calculated by subtracting BMP activity after incubation with antibodies for Alk1Fc and bone morphogenetic protein 9 (BMP9). We assessed correlations between BMP10 activity and RA dilatation (RA max volume>79 ml/m 2 for male or >69 ml/m 2 for female) and right ventricular (RV) dilatation (RV end-diastolic volume>108 ml/m 2 for male and >96 ml/m 2 for female). In a cohort of CTEPH patients that underwent pulmonary endarterectomy (PEA) we assessed the effect of pressure unloading on BMP10 activity. Normality of data was checked and statistical differences between groups were tested using an independent sample t-test or Wilcoxon rank-sum test. Results: BMP10 mRNA, protein and downstream activity were higher in the precPH RA tissue (Figure 1A-F). High systemic BMP10 activity was associated with RA dilatation and high RA pressure, but not RV dilatation in precPH (Figure 2A-C). Finally, pressure unloading after PEA in CTEPH patients results in a reduction in BMP10 activity (figure 2D). Conclusions: Local RA BMP10 expression and activity is increased in precPH. Increased systemic BMP10 activity was related to RA dilatation and pressure. Pressure unloading of the right heart leads to a reduction of systemic BMP10 activity. Future studies are needed to determine whether increased BMP10 release is an adaptative mechanism or can be used as therapeutic target.

Analysis of METTL14 expression in pancreatic cancer and adjacent tissues and its prognostic value for patient outcomes.

This study aims to analyze the differential expression of METTL14 in pancreatic cancer (PC) tissues and adjacent normal tissues, and its correlation with clinical outcomes. According to the inclusion and exclusion criteria, a total of 80 patients diagnosed in our hospital from January 2021 to January 2023 were chosen as research subjects. RTQ-PCR has detected the mRNA level expression of METTL14 in cancer and para-cancerous tissues. Immunohistochemistry was used to detect the protein expression of METTL14 in cancer and para-cancerous tissues. To compare the relationship between METTL14 expression and clinicopathological parameters in different PC patients. Kaplan-Meier survival analysis of the relationship between METTL14 expression in PC tissues and patient survival prognosis. The Multifactor COX model evaluates factors affecting the prognosis of PC. The expression level of METTL14 mRNA in PC tissues was 5.51 ± 0.35 (kDa), and the positive rate of METTL14 protein expression in PC tissues of all patients was 73.75 (59/80). Tumor location (P = 0.012), tumor differentiation degree (P = 0.028), tumor AJCC stage (P = 0.000), and lymph node metastasis (P = 0.000) were significantly related to the positive rate of METTL14 protein expression in PC tissue. Follow-up results showed that among 80 patients, 63 died. The three-year survival rate of the METTL14 positive group was 13.56% (8/59), and the three-year survival rate of the negative group was 42.86% (9/21). The difference in the three-year survival rate between METTL14 positive and negative expression groups was statistically significant (P = 0.031). Multivariate COX regression analysis results showed that METTL14 was positive (OR 2.797, 95% CI 1.233-5.877), tumor AJCC stage II-III (OR 1.628, 95% CI 1.435-3.859) and lymph node metastasis (OR 1.733, 95% CI 1.122-2.372) were substantive risk factors for poor prognosis in patients with PC. METTL14 expression increases in PC tissue, which is related to tumor AJCC stage, tumor differentiation, and lymph node metastasis, and can be evaluated in the survival prognosis of patients with PC.

Berberine ameliorates septic cardiomyopathy through protecting mitochondria and upregulating Notch1 signaling in cardiomyocytes

IntroductionSeptic cardiomyopathy (SCM) arises as a consequence of sepsis-associated cardiovascular dysfunction, for which there is currently no specific targeted therapy available. Previous studies have demonstrated the beneficial therapeutic effect of berberine (BBR) on SCM; however, the underlying mechanisms of action remain unclear. The objective of this is to elucidate how BBR alleviates SCM.MethodsSeptic cardiomyopathy rat model was established by performing cecal ligation and puncture (CLP), while a cardiomyocyte injury model was provoked in H9C2 cells using lipopolysaccharide (LPS). Cardiac function was assessed through echocardiography, and myocardial histopathology was examined with hematoxylin-eosin (HE) staining. Cardiomyocyte viability was determined through Cell Counting Kit-8 (CCK8) assay, and measurement of ATP levels was done with an ATP assay kit. Mitochondrial ultrastructure was observed using transmission electron microscopy. Real-time polymerase chain reaction (RT-PCR) and Western blotting were employed to analyze the expression of Notch1 signaling pathway components and downstream molecules in myocardial tissues and cells.ResultIn vivo, BBR markedly improved symptoms and cardiac function in SCM rats, leading to enhanced ATP content, and ameliorated mitochondrial structure. Additionally, BBR increased Notch1 protein expression in myocardial tissue of the rats. In vitro, BBR elevated the survival rates of H9C2 cell, improved mitochondrial morphology, and raised ATP levels. The mRNA expression of Notch1, Hes1, and Hes2, and Notch1 protein expression was upregulated by BBR. While these effects were reversed upon inhibiting the Notch1 signaling pathway.ConclusionBBR improves septic cardiomyopathy by modulating Notch1 signaling to protect myocardial mitochondria.

Exosomes derived from Umbilical cord mesenchymal stem cell promote hair regrowth in C57BL6 mice through upregulation of the RAS/ERK signaling pathway.

Androgenetic alopecia is one of the common types of hair loss and has become a medical and social problem due to its increasingly young onset. Existing therapies, although effective, have serious side effects and therefore better treatments need to be sought. The aim of this study was to evaluate the efficacy of umbilical cord mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia and to investigate the mechanism of exosome regulation of hair growth. First, we randomly divided 20 C57BL/6J mice into blank group, model group, positive control group and exosomal hydrogel group, and mice were treated with hair removal on the back. The mice were injected intraperitoneally with dihydrotestosterone solution except for the blank group. At the end of the experiment, new hairs were collected and the differences in length, diameter and number of hair follicles were compared among the groups; the histopathological changes of hair follicles were observed by HE staining; the expression of androgen receptor mRNA and protein in skin tissues were compared; and the skin tissues were analyzed by real-time PCR, western blotting, immunofluorescence staining and transcriptome sequencing. Finally, the results of transcriptome sequencing experiments were verified by real-time PCR, western blotting and other techniques for the corresponding genes and proteins. Compared with the blank group, mice in the model group had shorter hair length and reduced hair diameter, and pathological observation showed that the total number of hair follicles was significantly reduced and the hair follicles were miniaturized; compared with the model group, mice in the positive control and exosome groups had longer hair length, larger hair diameter and more hair follicles; the androgen receptor mRNA content and protein expression in the skin tissue of mice in the model group were significantly higher than those in the blank group, and the protein expression in the exosome gel group was lower than that in the model group. Similarly, compared with the model group, the expression of stemness-related proteins K15 and CD200 in the skin tissues of mice in the exosome group increased, and the expression of PCNA, a protein related to cell proliferation, increased. The KEGG data showed that the differential genes were mainly enriched in the RAS/ERK pathway. In this study, we demonstrated the therapeutic effect of umbilical cord MSC-derived exosomes on androgenetic alopecia and verified that exosomes regulate hair follicle stem cell stemness through the RAS/ERK pathway to promote hair proliferation and thus hair growth in mice with androgenetic alopecia, providing a potential therapeutic strategy for androgenetic alopecia.

Taurine and enzymatically modified isoquercitrin synergistically protect against the methotrexate-induced cardiotoxicity in rats: antioxidant and antiapoptotic effects

This study aimed to evaluate the protective potential of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ), both individually and in combination, against MTX-induced cardiotoxicity in male rats. A total of 36 rats were randomly divided into six groups (six animals each): control (vehicle), MTX alone (20 mg/kg, single dose), EMIQ+MTX (EMIQ at 26 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), Tau + MTX (Tau at 500 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), (EMIQ+Tau)+MTX, and (EMIQ+Tau)½+MTX. MTX treatment resulted in elevated levels of cardiac creatine phosphokinase-myocardial band, troponin I, nitric oxide, malondialdehyde, and serum IL-6, while decreasing levels of cardiac myeloperoxidase, catalase, and superoxide dismutase. MTX also reduced expression of BMI-1, induced DNA laddering and fragmentation, and increased cleaved caspase-3 protein expression in cardiac tissue. Both Tau and EMIQ showed equivalent effectiveness in protecting the heart against MTX-induced damage due to their antioxidant, anti-inflammatory, and antiapoptotic properties. Notably, combined treatment with half-doses of Tau and EMIQ offered superior protection compared to full doses of each agent alone. The full-dose combination showed similar efficacy to the half-dose combination, with a few exceptions. Overall, these results suggest a synergistic effect of Tau and EMIQ in mitigating MTX-induced cardiotoxicity, warranting further investigation into the underlying mechanisms.

Inhibition of cytokine-like protein 1 transcription hinders wound-healing process in diabetic rats.

This study explored the function and mechanism of cytokine-like protein 1 (CYTL1) in regulating the wound-healing process of rats with diabetes mellitus (DM). A wound was made in diabetic rats, in which CYTL1 overexpression or HDAC1 expression-interfering adenovirus was injected. The wound area on day 0, 7, 14 and 21 was observed and photographed to calculate the wound-healing rate. The wound tissues were collected for H&E, Masson staining and CD31 immunohistochemistry. The HDAC1 and CYTL1 mRNA and protein expressions in wound tissues were detected by RT-qPCR and western blot. The regulation of HDAC1 on CYTL1 was predicted by hTFtarget and AnimalTFDB database. The H3K27Ac level in the CYTL1 promoter was detected by chromatin immunoprecipitation (ChIP). Diabetic rats with CYTL1 overexpression or interfered HDAC1 expression had accelerated the wound-healing rate, in which massive fibroblasts, attenuated inflammatory infiltration and increased collagen and microvessel density were observed. Further experiments found that HDAC1 can inhibit CYTL1 transcription and expression by inhibiting H3K27Ac expression in CYTL1 promoter. Collected evidence showed HDAC1 can inhibit CYTL1 transcription by down-regulating the H3K27Ac level in CYTL1 promoter to slow down the wound-healing process in diabetic ulcer rats.

Identification of Potential Biomarkers in Papillary Thyroid Carcinoma Based on Proteomics.

To identify biomarkers of papillary thyroid carcinoma (PTC) and explore the possible pathogenic mechanism. This study included five patients with PTC. Protein expression of cancer tissues and adjacent normal thyroid tissues from each patient were analyzed by TMT proteomics technology. Differentially expressed proteins were identified, and functional annotation of differentially expressed proteins was performed by bioinformatics and pathway enrichment analysis. A total of 639 differentially expressed proteins were identified, including 278 upregulated and 361 downregulated proteins. Six upregulated proteins were identified as potential specific markers of PTC. Differentially expressed proteins may represent new molecular markers of PTC. These differentially expressed proteins and the related pathways may provide new insights into the pathogenic mechanisms of PTC.

Jingfang Granules alleviates OVA-induced allergic rhinitis through regulating endoplasmic reticulum stress signaling pathway

Ethnopharmacological relevanceJingfang Granules (JF) is a modified herbal compound preparation that is empirically used in clinical practice for the treatment of allergic diseases. Nevertheless, the role of JF in allergic rhinitis (AR) has yet to be demonstrated, and its potential mechanisms of action remain to be fully evaluated. Aim of studyThe objective of this research is to examine the underlying mechanisms by which JF can be used to treat AR. This will be achieved through the use of an ovalbumin (OVA) /aluminum hydroxide AR model in mice. Materials and methodsICR mice were administered an intraperitoneal (i.p.) injection of OVA/aluminium hydroxide in order to permit the establishment of an AR model. Following the intragastric administration of JF to the mice, testing nose scratching and sneezing behavior in mice to determine modeling status, and stained transverse sections of the mouse nose using the Hematoxylin and Eosin (H&E) method were in vitro evaluated to assess the histological effects of JF on mice with AR. The regulatory network was subjected to proteomic and metabolomic investigation. The expression of serum cytokines as well as histamine (HIS) was detected using ELISA kits. Protein expression in nasal mucosal tissues was identified through the use of a Western blot. ResultsJF demonstrated a notable reduction in nose-scratching and sneezing in AR mice. Concurrently, JF markedly reduced IgE, IL-4, IL-6, IL-13, TNF-α and HIS levels while elevating IFN-γ levels in the serum of AR mice. This was achieved by inhibiting the endoplasmic reticulum (ER) stress-related protein associated proteins including GADD and ATF4, p-eIF2α, p-IRE1α, XBP1s and p-PERK. Proteomics, metabolomics, Western blotting and Quantitative Real-time polymerase chain reaction (qPCR) results confirmed that JF inhibits the glycolysis/arginine biosynthesis pathway by suppressing the ER stress (ERs) signaling pathway, which in turn inhibits the inflammatory response. ConclusionFindings from the present study indicate that JF is an efficacious treatment for OVA/aluminum hydroxide-induced nasal mucosal injury and inflammation in mice. Furthermore, the study demonstrated that JF exhibited anti-AR clinic pharmacological effects by modulating the ERs signaling pathway and inhibiting glycolysis as well as arginine biosynthesis.

Ticagrelor modestly raises plasma riboflavin concentration in humans and inhibits riboflavin transport by BCRP and MRP4.

Riboflavin (vitamin B2) has been proposed as a biomarker for breast cancer resistance protein (BCRP) activity. In recent studies in mice, cynomolgus monkeys, and humans, BCRP-inhibiting drugs increased the plasma concentration of riboflavin. We showed recently that ticagrelor inhibits BCRP and raises the plasma concentrations of the BCRP substrate rosuvastatin in healthy volunteers. In the same drug-drug interaction study, we now investigated whether ticagrelor affects the plasma concentrations of riboflavin. Intake of 90 mg ticagrelor increased the ratio between the peak plasma riboflavin concentration and the fasting riboflavin concentration before ticagrelor administration by 1.20-fold (90% confidence interval, 1.10-1.32; P = 0.006) compared to placebo. In vitro, riboflavin was transported by BCRP and multidrug-resistance-associated protein 4 (MRP4) but no clear transport was observed by MRP2, MRP3, or the P-glycoprotein. Moreover, ticagrelor inhibited the transport of riboflavin in BCRP- and MRP4-expressing membrane vesicles with unbound 50% inhibitory concentrations of 0.020 and 1.1μM, respectively. Based on vesicle and tissue protein expression data, the small intestinal MRP4-mediated efflux clearance of riboflavin (1.2-1.4 nL/min/mg) was estimated to be similar to that mediated by BCRP (0.23-1.3 nL/min/mg). As MRP4 is expressed in the basolateral membrane of enterocytes, it may facilitate the absorption of riboflavin and impair the utility of riboflavin as a biomarker of intestinal BCRP. To conclude, ticagrelor modestly raises the plasma concentration of riboflavin probably by inhibiting intestinal BCRP. Inhibition of intestinal MRP4 may have reduced the absorption of riboflavin and limited the effect of ticagrelor on riboflavin levels.

TRIM11 Prevents Ferroptosis in model of asthma by UBE2N-TAX1BP1 signaling

Asthma is a complex chronic respiratory inflammatory disease affected by both genetic and environmental factors. Therefore, our study explored the influence of TRIM11 on asthma and its underlying mechanisms. Our research involved patients diagnosed with asthma and healthy volunteers recruited from our hospital. We observed a reduction in serum TRIM11 expression in asthma patients, which positively correlated with the levels of anti-IgE or IgE. Additionally, both TRIM11 mRNA and protein expression in lung tissue were diminished. The introduction of the TRIM11 gene resulted in a reduction in inflammation in an in vitro asthma model and prevented the development of asthma in a mouse model. Moreover, the TRIM11 gene exhibited a suppressive effect on Ferroptosis and mitigated ROS-induced mitochondrial damage in the asthma model. TRIM11 was found to stimulate UBE2N-TAX1BP1 signaling in the asthma model, with UBE2N being identified as the specific target for TRIM11’s effects on Ferroptosis. Furthermore, TRIM11 protein interacted with UBE2N protein and facilitated the dissociation of UBE2N-UBE2N in the asthma model. In conclusion, TRIM11 plays a vital role in preventing Ferroptosis in the asthma model through UBE2N-TAX1BP1 signaling. This indicates that targeting the TRIM11 mechanism could serve as a promising strategy for anti-Ferroptosis immunotherapy in asthma treatment.

Mitochondrial Oxidative Stress and Cardiac Dysfunction in TERT Knockout Mice

Abstract Background Heart failure (HF) is a major cause of hospitalization in the elderly, with its incidence increasing due to aging and associated risk factors like hypertension, diabetes, and myocardial fibrosis. Aging-related myocardial fibrosis, characterized by alterations in the extracellular matrix and myocardial structure, impairs cardiac function. Mitochondrial oxidative stress plays a pivotal role in cardiac electrical and structural remodeling, necessitating a deeper understanding of its involvement in aging-related heart failure. Purpose The purpose of this study is to investigate the mechanisms of aging-related ventricular electrical and structural remodeling by constructing an aging mouse model. This research aims to provide potential therapeutic targets for heart failure associated with aging. Methods We developed a third-generation homozygous telomerase reverse transcriptase (TERT) knockout mouse model. Comparing third-generation homozygous TERT knockout mice (F3 group) with age-matched wild-type males (WT group). The study encompassed blood pressure measurement, electrocardiographic analysis, echocardiography, ELISA for cardiac biomarkers, ventricular tissue electrophysiology, fibrosis assessment through staining, transcriptomic profiling via RNA-seq, and electron microscopy of ventricular mitochondria. Results Compared to the WT group, the F3 group demonstrated increased P53 and P16 protein expression. Decreased LVEF and FS, along with increased interventricular septum thickness, left ventricular diameter, and left ventricular volume. Elevated serum NT-pro-BNP and troponin I (cTnI) levels, with prolonged QRS duration. Decreased left and right ventricular conduction velocity, accompanied by increased conduction dispersion. Notable elevation in COLI, TGFβ, and α-SMA gene transcription and protein expression in ventricular tissue. Significant differences in mitochondrial oxidative stress signal pathways via RNA-seq analysis. Elevated serum MDA levels and decreased SOD levels, with up-regulated Mn-SOD gene transcription and protein expression, and down-regulated MFN2 and Drp1 gene transcription and protein expression in ventricular tissue. Electron microscopy revealed mitochondrial abnormalities such as loose arrangement, decreased number, swelling, vacuolation, and myofilament disintegration or breakage in the F3 group. Conclusion Third-generation TERT-/- senescent mice exhibit notable cardiac impairments, including electrical remodeling, structural changes, and mitochondrial dysfunction. These findings suggest a potential link between mitochondrial oxidative stress and aging-related heart failure, indicating novel therapeutic opportunities targeting mitochondrial dysfunction for managing such conditions.

Proteomic Signatures of Right Ventricular Outcomes in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH. Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance. A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression. Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets.

Synthetic free fatty acid receptor (FFAR) 2 agonist 4-CMTB and FFAR4 agonist GSK13764 inhibit colon cancer cell growth and migration and regulate FFARs expression in in vitro and in vivo models of colorectal cancer.

Free fatty acid receptors (FFARs) are G protein-coupled receptors that divide into 4 subtypes; FFAR2 and FFAR3 are activated by short-chain fatty acids, while FFAR1 and FFAR4 - by long-chain fatty acids. Recent studies show the potential involvement of FFARs in the pathophysiology of colorectal cancer (CRC). A decrease in FFAR2 and FFAR4 gene expression is observed in patients with CRC. The aim of our study was to evaluate the anti-cancer effect of FFAR2 and FFAR4 stimulation by selective synthetic agonists in in vitro and in vivo models of CRC. FFAR2 agonist, 4-CMTB, and FFAR4 agonist, GSK137647 were used. Cell viability (CCD 841 CoN and SW-480) was determined after 48h incubation with tested compounds using MTT assay. Real-time qPCR and Western Blot were used to identify changes in FFARs expression. Migration and invasion were characterized by commercially available tests. Colitis-associated CRC (CACRC) mouse model was induced by azoxymethane and dextran sodium sulfate. 4-CMTB and GSK137647 significantly reduced cancer cell growth as well as migration and invasion capacities. Both synthetic compounds increased FFAR2 and FFAR4 expression in SW-480 cells. Neither 4-CMTB nor GSK137647 influenced the course of AOM/DSS-induced CACRC in mice, however, 4-CMTB elevated FFAR2 protein expression in mouse tissues. We presented that stimulation of FFAR2 and FFAR4 may inhibit CRC cell viability and migration and that the FFAR2 and FFAR4 expression decreased in CRC can be restored by treatment with respective agonists, indicating new promising pharmacological targets in CRC treatment.

CORO1C Regulates the Malignant Biological Behavior of Ovarian Cancer Cells and Modulates the mRNA Expression Profile through the PI3K/AKT Signaling Pathway.

Ovarian cancer (OC) is a frequently occurring gynecological tumor, and its global incidence has recently increased. Coronin-like actin-binding protein 1C (CORO1C) is known to activate the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) pathway and promote tumor progression. However, its role in OC remains unclear. This study investigated the role of CORO1C in OC malignancy. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine AKT and CORO1C mRNA expression in clinical OC tissues and cells. Immunohistochemical analysis and western blotting were used to examine protein expression in OC tissues and cells, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound-healing, and Transwell assays were performed to examine cell proliferation and migration. RNA-Seq was used to validate the relationship between AKT and CORO1C expression. The results showed that CORO1C was highly expressed in clinical OC tissues and SKOV3 cells, correlating with the International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, CORO1C knockout inhibited the proliferation, migration, and invasion of SKOV3 cells; altered the gene expression patterns in these cells; and was closely associated with the PI3K/AKT pathway. Western blotting confirmed that CORO1C knockout reduced the levels of phosphorylated PI3K and AKT. Additionally, CORO1C knockout increased phosphatase and tensin homologs deleted on chromosome 10 (PTEN) protein expression, whereas CORO1C overexpression decreased it. In conclusion, this study demonstrated that high CORO1C levels in OC are associated with greater metastasis and worse prognosis. CORO1C negatively regulates PTEN expression, activates the PI3K/AKT pathway, and promotes OC cell malignancy In patients with OC, CORO1C may function as an effective therapeutic and predictive biomarker.

Expression of neutrophil extracellular trap-related proteins and its correlation with IL-17 and TNF-α in patients with oral lichen planus.

Neutrophil extracellular traps (NETs) are produced by polymorphonuclear neutrophils (PMNs) stimulated by interleukin-17 (IL-17) and tumor necrosis factor α (TNF-α). However, the level and role of NETs in oral lichen planus (OLP) remain poorly understood. This study aimed to investigate the expression of NETs in OLP and explore the correlation between NETs and the levels of IL-17 and TNF-α. The expression and distribution of NET-related proteins in tissue samples from each group were assessed using hematoxylin-eosin (HE) staining and immunofluorescence (IF). Additionally, the expression of NET-related proteins in peripheral blood samples from each group was evaluated using cell IF technique and fluorescence spectrophotometry. The relative formation level of NETs in each group was determined by fluorescence spectrophotometry via plasma co-culture. Furthermore, the levels of inflammatory cytokines IL-17 and TNF-α in plasma and culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA). NET-related proteins were located in the subepithelial and lamina propria layers of OLP lesions. OLP had significantly higher expression of NET-related proteins in lesion tissues and peripheral blood compared to the healthy control (HC) group (p < 0.05). The rate of NETs formation in the erosive-stage OLP (EOLP) group was significantly higher than that in the HC group (p < 0.05), in contrast, no significant increase was observed in the non-erosive OLP (NEOLP) group (p > 0.05). Furthermore, the levels of IL-17 and TNF-α in the EOLP group were significantly elevated compared to those in the NEOLP group and HC group (p < 0.05), while the levels in the NEOLP group did not significantly differ from those in the HC group (p > 0.05). The rate of NETs formation showed a positive correlation with the levels of IL-17 and TNF-α in plasma. The expression of NET-related proteins was upregulated in OLP lesion tissues and peripheral blood. Elevated levels of IL-17 and TNF-α in peripheral blood plasma positively correlated with the rate of NETs formation, suggesting that IL-17 and TNF-α mediate the formation of NETs in OLP patients, and may thereby contribute to the development of OLP.

Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

BACKGROUND Diabetic nephropathy (DN) is a severe microvascular complication of diabetes characterized by inflammation, oxidative stress, and renal fibrosis. Asiaticoside (AC) exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties, suggesting potential therapeutic benefits for DN. This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant pathway. AIM To investigate the renoprotective effects of AC against DN and elucidate the role of the NRF2/HO-1 pathway. METHODS The effects of AC on high glucose (HG)-induced proliferation, inflammation, oxidative stress, and fibrosis were evaluated in rat glomerular mesangial cells (HBZY-1) in vitro . A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury, inflammation, oxidative stress, and fibrosis. The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model. RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats, including reduced body weight, and elevated blood glucose, serum creatinine, blood urea nitrogen, and 24-h urine protein. Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, reactive oxygen species, and malondialdehyde levels while increasing superoxide dismutase activity. Additionally, AC suppressed the expression of fibrogenic markers such as collagen I, collagen IV, and fibronectin. AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase (Quinone) 1 protein expression in renal tissues and HG-induced HBZY-1 cells. CONCLUSION AC improves DN by reducing inflammation, oxidative stress, and fibrosis through the activation of the NRF2/HO-1 signaling pathway. These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Effects of wheat-grain moxibustion on autophagy and endoplasmic reticulum stress in rats with cervical spondylotic radiculopathy

To observe the effects of wheat-grain moxibustion on autophagy and endoplasmic reticulum stress (ERS) in the spinal cord and nerve root tissues of rats with cervical spondylotic radiculopathy (CSR), and to explore the potential mechanisms by which wheat-grain moxibustion alleviates neuropathic pain in CSR. Forty-eight SPF-grade SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group, and a wheat-grain moxibustion + 3-methyladenine (3MA) group, with 12 rats in each group. The CSR model was established in the model group, the wheat-grain moxibustion group, and the wheat-grain moxibustion + 3MA group using the spinal canal insertion method. From the third day after successful modeling, the wheat-grain moxibustion group received wheat-grain moxibustion at "Dazhui" (GV 14), once daily, six cones each session. The wheat-grain moxibustion + 3MA group received intraperitoneal injection of 3MA (2.5 mg/kg), followed by the same wheat-grain moxibustion intervention as the wheat-grain moxibustion group. Interventions were performed once daily for seven consecutive days. The gait disturbance scores and peripheral nerve mechanical pain thresholds were observed before and after the intervention. Western blot was used to detect the expression of ERS apoptosis factors C/EBP-homologous protein (CHOP) and Caspase-12, as well as autophagy substrate P62 in spinal cord and nerve root tissues. Transmission electron microscopy was used to observe autophagosomes and cellular ultrastructure in spinal cord and nerve root tissues. After modeling, compared with the sham operation group, gait disturbance scores were increased (P<0.05) and peripheral nerve mechanical pain thresholds were decreased (P<0.05) in the model group, the wheat-grain moxibustion group, and the wheat-grain moxibustion + 3MA group. After intervention, compared with the sham operation group, gait disturbance scores were increased (P<0.05) and peripheral nerve mechanical pain thresholds were decreased (P<0.05) in the model group; compared with the model group, gait disturbance score was decreased (P<0.05) and peripheral nerve mechanical pain threshold was increased (P<0.05) in the wheat-grain moxibustion and the wheat-grain moxibustion + 3MA group; compared with the wheat-grain moxibustion + 3MA group, gait disturbance score was decreased (P<0.05) and peripheral nerve mechanical pain threshold was increased (P<0.05) in the wheat-grain moxibustion group. Compared with the sham operation group, the expression of CHOP and Caspase-12 proteins in spinal cord and nerve root tissues was increased in the model group (P<0.05); compared with the model group and the wheat-grain moxibustion + 3MA group, the expression of CHOP, Caspase-12, and P62 proteins in spinal cord and nerve root tissues was decreased in the wheat-grain moxibustion group (P<0.05). Compared with the model group and the wheat-grain moxibustion + 3MA group, the number of autophagosomes in spinal cord and nerve root tissues was increased in the wheat-grain moxibustion group, and the cellular ultrastructure was clear and intact, similar to the sham operation group. Wheat-grain moxibustion at "Dazhui" (GV 14) could effectively alleviate neuropathic pain in CSR model rats. The analgesic mechanism may be related to promoting autophagy, inhibiting ERS, reducing ERS-mediated apoptosis, and repairing damaged nerves.

Effects of Environmental Noise Stress on Mouse Metabolism

Environmental noise is associated with various health outcomes. However, the mechanisms through which these outcomes influence behavior and metabolism remain unclear. This study investigated how environmental noise affects the liver, adipose tissue, and brain metabolic functions, leading to behavioral and body weight changes. Mice were divided into a noise group exposed to construction noise and an unexposed (control) group. Behavior and body weight changes were monitored over 50 days. Early changes in response to noise exposure were assessed by measuring plasma cortisol and glial fibrillary acidic protein expression in brain tissues on days 1, 15, and 30. Chronic responses, including changes in lipoprotein and fat metabolism and neurotransmitters, were investigated by analyzing serum lipoprotein levels and body fat mass and evaluating liver, fat, and brain tissue after 50 days. The noise group showed higher locomotor activity and reduced anxiety in the open-field and Y-maze tests. Noise exposure caused an initial weight loss; however, chronic noise increased fat mass and induced adipocyte hypertrophy. Our findings underscore the role of environmental noise-induced stress in augmenting locomotor activity and reducing anxiety in mice through neurotransmitter modulation while increasing the risk of obesity by decreasing HDL cholesterol levels and promoting adipocyte hypertrophy.

Preventive Effect of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole on Pulmonary Fibrosis through Inhibition of Inflammation and Down-regulation of TGF-b Signaling Pathway.

In the present study effect of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on plmonary fibrosis development was investigated in vitro in primary lung fibroblasts as well as in vivo in mice model. The results demonstrated that STT treatment effectively inhibited the TGF-β1 induced increase in expression of α-SMA and collagen I proteins in PLFs. STT treatment effectively reversed the TGF-β1 induced increase in expression of LOXL2 protein and phosphorylation of Smad2/3 proteins. Treatment of PLFs with STT reversed the TGF-β1-induced increase in expression of NOX4 and suppression of p-AMPK protein. In mice model of pulmonary fibrosis STT treatment significantly inhibited the BLM-mediated decrease in body weight and survival rate. The BLM induced increase in pulmonary index in mice was also effectively inhibited on treatment with STT. Treatment of the mice with STT inhibited the BLM-induced increase in α-SMA and Col I protein expression in pulmonary tissues. The BLM-induced increase in TGF-β1 protein expression in pulmonary tissues of the mice was inhibited on treatment with STT. Treatment with STT effectively promoted the AMPK activation in lung tissues of the BLM administered mice. In summary, the present study demonstrates that STT treatment prevents TGF-β1 induced up-regulation of α-SMA, collagen I, LOXL2 protein expression and targets phosphorylation of Smad2/3 proteins in PLFs. Moreover, it inhibits TGF-β1-induced increase in expression of NOX4 and reverses TGF-β1-mediated suppression in expression of p-AMPK protein. Therefore, STT inhibits fibrosis development in vitro as well as in vivo and therefore can be investigated further as a therapeutic agent for the treatment of lung fibrosis.