Epidermal Growth Factor Levels Research Articles

Research on the mechanism of Guanyu Zhixie Granule in intervening gastric ulcers in rats based on network pharmacology and multi-omics

ObjectiveGuanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies.MethodsThe comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT–qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method.ResultsFor the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG’s intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result.ConclusionGYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells.

Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation.So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. The cytotoxic effects of DTX, SNP and2Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24h after various single and combined treatments. The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.

Comparison of epidermal growth factor expression and secretion in human salivary glands

ObjectiveTo investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion. DesignSaliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC). ResultsThe EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands. ConclusionAll salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF.

Urinary Epidermal Growth Factor Level as a Noninvasive Indicator of Tubular Repair in Patients with Acute Kidney Injury.

Epidermal growth factor (EGF), an essential factor for the proliferation and survival of renal tubular cells, is expressed by distal tubules and normally excreted via urine. Previous studies in rats demonstrated that acute tubular injury reduces urinary EGF levels. However, it is unclear whether urinary EGF is a suitable monitoring marker of tubular repair status after acute kidney injury (AKI) in humans. To address this question, we measured serum and urinary EGF in patients with AKI (n = 99) using ELISA and investigated whether urinary EGF levels were associated with the severity of tubular injury and renal prognosis. Urinary EGF was abundant in healthy controls but showed a significant decrease in AKI patients (14,522 ± 2190 pg/mL vs. 3201 ± 459.7 pg/mL, p < 0.05). The urinary EGF level in patients with renal AKI was notably lower than that in patients with pre-renal AKI. Furthermore, the urinary EGF level in patients with AKI stage 3 was significantly lower than that in patients with AKI stage 1. Urinary EGF levels were negatively correlated with urinary β-2MG and serum creatinine levels but positively correlated with hemoglobin levels and eGFR. Urinary EGF was not significantly correlated with urinary NAG, α-1MG, L-FABP, NGAL, KIM-1, or urinary protein concentrations. No significant correlation was observed between serum and urinary EGF levels, suggesting that urinary EGF is derived from the renal tubules rather than the blood. In living renal transplantation donors, the urinary EGF/Cr ratio was approximately half the preoperative urinary EGF/Cr ratio after unilateral nephrectomy. Collectively, these data suggest that urinary EGF is a suitable noninvasive indicator of not only the volume of functional normal renal tubules but also the status of tubular repair after AKI.

The relationship between serum levels of epidermal growth factor and β-human chorionic gonadotropin and the type and prognosis of ectopic pregnancy.

This work aimed to explore the relationship between epidermal growth factor (EGF) and β-human chorionic gonadotropin (β-HCG) and ectopic pregnancy types and impact on prognosis. Twenty women with normal pregnancies (NPs) were recruited as control group, and twenty women each with tubal pregnancy (TP) and cervical pregnancy (CP) were recruited. Blood samples were collected to detect EGF and β-HCG. Data on length of hospital stay and incidence of complications were collected. The differences in serum EGF and β-HCG levels were compared among groups and within various types of ectopic pregnancy using analysis of variance and Pearson correlation analysis. Serum EGF and β-HCG were notably lower in TP and CP group vs. controls (P < 0.05). In subgroup analysis within the types of ectopic pregnancy, serum EGF levels were drastically higher in TP group vs. CP group (P < 0.05). Serum EGF levels were negatively correlated with pregnancy outcomes and incidence of complications (P < 0.05). In patients with TP and CP, serum EGF and β-HCG recovery time and hospital stay differed drastically (P < 0.05). Serum EGF and β-HCG levels showed optimal cutoff values identified at 2.65μg/L and 11,745.35IU/L, respectively. The corresponding area under the curve (AUC) values were 0.885 and 0.841. Elevated levels of EGF may be associated with the occurrence of ectopic pregnancy and may impact the type of ectopic pregnancy, pregnancy outcomes, and the incidence of complications. Further clinical research is warranted to investigate these findings.

Gender effect of glucose, insulin/glucagon ratio, lipids, and nitrogen-metabolites on serum HGF and EGF levels in patients with diabetes type 2.

Hepatocyte growth factor (HGF) exhibits potent growth-inducing properties across various tissues, while epidermal growth factor (EGF) acts as a molecular integration point for diverse stimuli. HGF plays a crucial role in hepatic metabolism, tissue repair, and offers protective effects on epithelial and non-epithelial organs, in addition to its involvement in reducing apoptosis and inflammation, underscoring its anti-inflammatory capabilities. The HGF-Met system is instrumental in hepatic metabolism and enhancing insulin sensitivity in animal diabetes models. Similarly, the EGF and its receptor tyrosine kinase family (EGFR) are critical in regulating cell growth, proliferation, migration, and differentiation in both healthy and diseased states, with EGF also contributing to insulin sensitivity. In this observational study, we aimed to identify correlations between serum levels of HGF and EGF, insulin, glucagon, glucose, and primary serum lipids in patients with type 2 diabetes mellitus (DM), taking into account the impact of gender. We noted differences in the management of glucose, insulin, and glucagon between healthy men and women, potentially due to the distinct influences of sexual hormones on the development of type 2 DM. Additionally, metabolites such as glucose, albumin, direct bilirubin, nitrites, and ammonia might influence serum levels of growth factors and hormones. In summary, our results highlight the regulatory role of insulin and glucagon in serum glucose and lipids, along with variations in HGF and EGF levels, which are affected by gender. This link is especially significant in DM, where impaired cell proliferation or repair mechanisms lead to metabolic changes. The gender-based differences in growth factors point to their involvement in the pathophysiology of the disease.

The Association Between Epidermal Growth Factor rs3756261 A/G Gene Polymorphism and the Risk of Ankylosing Spondylitis in a Chinese Han Population.

Epidermal growth factor (EGF) is a potent pro-angiogenic molecule promoting the angiogenic phenotype of ankylosing spondylitis (AS). Studies demonstrated that EGF rs3756261 polymorphism was associated with the risk of inflammatory diseases, but not including AS. To investigate the association between EGF rs3756261 polymorphism and the risk of AS, we genotyped the EGF rs3756261 polymorphism in 208 patients with AS and 412 controls in a Chinese Han population using a custom-by-design 48-Plex SNP scanTM Kit. The serum EGF levels were measured using an enzyme-linked immunosorbent assay in 208 AS patients and 412 controls. Our data indicated that EGF rs3756261 polymorphism was associated with an increased risk of AS in the Chinese Han population. Stratified analyses indicated that the EGF rs3756261 polymorphism elevated the risk of AS among the males, smokers, drinkers and those aged <30 years. In addition, the EGF rs3756261 polymorphism was related to increased CRP and HLA-B27 levels in AS patients. Next, we found that the average serum levels of EGF were significantly higher in AS patients compared with controls. Meanwhile, EGF serum levels were significantly higher in AG genotype carriers when compared with AA genotype carriers in AS patients. In conclusion, this study indicated that EGF rs3756261 polymorphism was associated with the risk of AS and EGF serum levels in a Chinese Han population.

The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects

PurposeFentanyl, a fully synthetic opioid, is widely used for severe pain management and has a huge abuse potential for its psychostimulant effects. Unlike other opioids, the neurotoxic effects of chronic fentanyl administration are still unclear. In particular, little is known about its effect on the cerebral cortex. The current study aims to test the chronic toxicity of fentanyl in the mice model. MethodsAdult male Balb/c mice were chronically treated with low (0.05 mg/kg, i.p) and high (0.1 mg/kg, i.p) doses of fentanyl for 5 consecutive weeks, and various neurotoxic parameters, including apoptosis, oxidative stress, and neuroinflammatory response were assessed in the cortex. Potential histological as well as neurochemical changes were also evaluated. ResultsThe results of this study show that chronic fentanyl administration induced intense levels of apoptosis, oxidative stress, and neuroinflammation in the cerebral cortex. These findings were found to be correlated with histopathological characteristics of neural degeneration and white matter injury. Moreover, fentanyl administration was found to reduce the expression of both NMDA receptor subunits and dopamine receptors and elevate the level of epidermal growth factor (EGF). ConclusionFentanyl administration induced neurotoxic effects in the mouse cerebral cortex that could be primarily mediated by the evoked oxidative-inflammatory response. The altered expression of NMDA receptors, dopamine receptors, and EGF suggests the pernicious effects of fentanyl addiction that may end in the development of toxic psychosis.

Clinical Study of Rh-bFGF Combined With Collagen Sponge in the Treatment of Maxillofacial Deep Ⅱ Degree Burn.

To observe the clinical effect of recombinant human alkaline fibroblast growth factor (rh-bFGF) combined with collagen sponge in the treatment of maxillofacial deepⅡ degree burn. From January 2019 to January 2022, 96 patients with maxillofacial deep Ⅱ degree burns were randomly divided into a control group (N=48) and an observation group (N=48). The observation group was treated with rh-bFGF and collagen sponge after debridement, whereas the control group was treated with silver sulfadiazine ointment after debridement. The healing rate and healing time of the wounds were observed, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, epidermal growth factor (EGF), endothelial growth factor growth factor (VEGF), and metalloproteinase tissue inhibitor 1 (TIMP-1) were measured. Vancouver Scar Scale (VSS) was used to evaluate the local scar at 6 months after wound healing in both groups. On the 10th, 14th, and 21st day of treatment, the wound healing rate in the observation group was higher than that in the control group (P<0.05), the wound healing time in the observation group was lower than that in the control group (P<0.05), and on the 14th day of treatment, the levels of TNF-α and IL-6 in the observation group were lower than those in the control group (P<0.05). The levels of IL-10 in the observation group were higher than those in the control group (P<0.05). The levels of EGF, VEGF, and TIMP-1 in the observation group were higher than those in the control group (P<0.05), and the scores of VSS in the observation group were lower than those in the control group (P<0.05). Rh-bFGF combined with collagen sponge can decrease the levels of TNF-α and IL-6 and increase the levels of IL-10, which can control the inflammation effectively, at the same time, it can increase the level of EGF, VEGF, and TIMP-1, promote wound healing, and reduce scar hyperplasia. The treatment protocol is simple, safe, effective, and suitable for clinical application.

Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications

BackgroundPichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities.ResultsTwo novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage.ConclusionsTwo novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

Increased Elastase and Matrix Metalloproteinase Levels in the Pulmonary Arteries of Infants With Congenital Diaphragmatic Hernia

BackgroundPulmonary vascular disease (PVD) complicated with pulmonary hypertension (PH) is a leading cause of mortality in congenital diaphragmatic hernia (CDH). Unfortunately, CDH patients are often resistant to PH therapy. Using the nitrogen CDH rat model, we previously demonstrated that CDH-associated PVD involves an induction of elastase and matrix metalloproteinase (MMP) activities, increased osteopontin and epidermal growth factor (EGF) levels, and enhanced smooth muscle cell (SMC) proliferation. Here, we aimed to determine whether the levels of the key members of this proteinase-induced pathway are also elevated in the pulmonary arteries (PAs) of CDH patients. MethodsNeutrophil elastase (NE), matrix metalloproteinase-2 (MMP-2), epidermal growth factor (EGF), tenascin-C, and osteopontin levels were assessed by immunohistochemistry in the PAs from the lungs of 11 CDH patients and 5 normal age-matched controls. Markers of proliferation (proliferating cell nuclear antigen (PCNA)) and apoptosis (cleaved (active) caspase-3) were also used. ResultsWhile expressed by both control and CDH lungs, the levels of NE, MMP-2, EGF, as well as tenascin-C and osteopontin were significantly increased in the PAs from CDH patients. The percentage of PCNA-positive PA SMCs were also enhanced, while those positive for caspase-3 were slightly decreased. ConclusionsThese results suggest that increased elastase and MMPs, together with elevated tenascin-C and osteopontin levels in an EGF-rich environment may contribute to the PVD in CDH infants. The next step of this study is to expand our analysis to a larger cohort, and determine the potential of targeting this pathway for the treatment of CDH-associated PVD and PH. Type of StudyTherapeutic. Level of EvidenceLEVEL III.

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics.

https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.

Assessing angiogenesis factors as prognostic biomarkers in breast cancer patients and their association with clinicopathological factors

Introduction Angiogenesis is fundamental for tumor growth and metastasis across many solid malignancies. Considerable interest has focused on the molecular regulation of tumor angiogenesis as a means to predict disease outcomes and guide therapeutic decisions. Methods In the present study, we investigated the prognostic value of transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), delta-like ligand 4 (DLL4), and vascular endothelial growth factor (VEGF) in the serum of 120 women diagnosed with breast cancer using ELISA as well as examined their associations with clinical parameters and the outcome of the disease. Results Our results demonstrated that the serum concentration of TGF-β and EGF were remarkably higher in patients with higher tumor size, end stages of the disease, and positive lymph node involvement compared to patients with lower tumor size, early stages of the disease, and negative lymph node involvement. In addition, we found a significant correlation between the serum concentration of VEGF and the level of EGF, FGF, and DLL4 in patients with breast cancer. Furthermore, both univariate and multivariate analyses showed that TGF-β and EGF can be used as end-stage predictors. Discussion/Conclusion Based on our findings, increasing the level of angiogenesis factors is significantly associated with higher tumor size and late stages of the disease in patients with breast cancer. Moreover, measuring the level of angiogenesis factors could lead to better prediction of disease outcomes and choosing the best treatments for patients.

The Tumor Necrosis Factor-α Level in Platelet-Rich Plasma Might Be Associated with Treatment Outcome in Patients with Interstitial Cystitis/Bladder Pain Syndrome or Recurrent Urinary Tract Infection.

Using platelet-rich plasma (PRP) injections to treat urological diseases has attracted great attention. This study investigated the impact of cytokine concentrations in PRP on the treatment outcome of patients with recurrent urinary tract infection (rUTI) and interstitial cystitis/bladder pain syndrome (IC/BPS). Forty patients with IC/BPS and twenty-one patients with rUTI were enrolled for four-monthly repeated PRP injections. PRP was collected at the first injection and analyzed with multiplex immunoassays for 12 target cytokines. In patients with IC/BPS, a Global Response Assessment (GRA) score ≥ 2 was defined as a successful outcome. In rUTI patients, ≤2 episodes of UTI recurrence during one year of follow-up was considered a successful outcome. Nineteen (47.5%) patients with IC/BPS and eleven (52.4%) patients with rUTI had successful outcomes. The IC/BPS patients with successful outcomes had significantly lower levels of tumor necrosis factor-α (TNF-α) in their PRP than those with unsuccessful outcomes (p = 0.041). The rUTI patients with successful outcomes also had a lower level of TNF-α (p = 0.025) and a higher level of epidermal growth factor (p = 0.035) and transforming growth factor-β2 (p = 0.024) in PRP than those with unsuccessful outcomes. A lower level of TNF-α in PRP might be a potentially predictive factor of treatment outcome.

Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.

The role of EDIL3 in maintaining cartilage extracellular matrix and inhibiting osteoarthritis development

AimsTherapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.MethodsWe used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators.ResultsEDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1).ConclusionEDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA.Cite this article: Bone Joint Res 2023;12(12):734–746.

The values of HER-2 expression in the non-muscle-invasive bladder cancer: a retrospective clinical study

PurposeThe purpose of this research is to evaluate the association between HER-2 expression and clinicopathological features in patients with non-muscle-invasive bladder cancer (NMIBC).MethodsBetween 2019 and 2022, 204 patients treated with Transurethral resection of the bladder tumor (TURBT) were included in this study. Data of pathologic T (pT) stage, grades of the tumor, age, sex, tumor size and number of the tumors were collected and compared according to the expression level of the human epidermal growth factor 2 (HER-2). ROC curve analysis was performed to assess the discriminative ability of HER-2 expression for tumors grades and pT stage. Multivariable logistic regression analysis were used to evaluate the association between HER-2 expression and tumor grades and pT stage.ResultsPatients were divided into low grade (110, 53.9%) and high grade groups (94, 46.1%) according to the tumor grade. Pathologic stage consisted of pTa in 166 (81.4%) and pT1 in 38 (18.6%). HER-2 expression was semi quantitatively scored to 0 in 44 (21.6%), 1 in 58 (28.4%), 2 in 91 (44.6%), and 3 in 11 (5.4%) cases. HER-2 expression was significantly associated with tumor stages and histological grades, but not with sex, tumor size or number of tumors. The AUC for combination of HER-2 expression with tumor stages and histological grades was 0.652 (p &amp;lt; 0.003) and 0.727 (p &amp;lt; 0.001), respectively.ConclusionThis study demonstrated that HER-2 expression is associated with tumor stages and histological grades in NMIBC. It has diagnostic value for cystoscopic biopsy.

Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats

BACKGROUND Atractylodes japonica Koidz. ex Kitam. (A. japonica , Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it’s often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1β, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.

Novel scoring system for early diagnosis of necrotizing enterocolitis: integrating clinical and laboratory data with urinary caveolin-1 levels.

Necrotizing enterocolitis (NEC) poses a significant threat to preterm infants, with nonspecific early manifestations complicating timely diagnosis. Therefore, this study aimed to develop a novel scoring system for early diagnosis of NEC, incorporating clinical and laboratory data with urinary caveolin-1 levels. A single-center prospective cohort study was conducted at a tertiary hospital in East Java, Indonesia. NEC diagnosis was established by Bell's criteria and proven gut dysbiosis. Urinary levels of claudin-2, caveolin-1, and epidermal growth factor (EGF) were assessed as potential indicators of tight junction disruption. The selected urine biomarker cutoff value was determined using symbolic classification analysis and combined with clinical and laboratory parameters from Bell's criteria to create an NEC scoring system, validated with the Aiken index. Sensitivity and specificity analyses were performed. Thirty-four neonates, comprising NEC, preterm non-NEC, and term infants, were included. qPCR analysis highlighted elevated Klebsiella, Lactobacillus, Clostridium, and Bacteroides levels in NEC patients, indicating a gut dysbiosis trend. Among 3 biomarkers, caveolin-1 ≥ 17.81 ng/dl on day 3 demonstrated 72.86% negative predictive value and 87.50% positive predictive value. The combined scoring system which comprised abdominal cellulitis, distension, radiology, advanced resuscitation at birth, prematurity or low birthweight, platelet count, sepsis, orogastric retention, metabolic acidosis and caveolin-1 findings exhibited an AUC of 0.922 (95% CI: 0.81-1.00, p < 0.001), with ≥ 1.81 as the cutoff, offering 93% sensitivity and 94% specificity. Urine caveolin-1 on day 3 signifies enterocyte tight junction damage and the acute phase of NEC in premature infants. The proposed scoring system demonstrates good performance in predicting NEC incidence in preterm infants.

Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis.

Chronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD. We screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed. A total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and in vivo experiments indicated that the expression levels of APOH and EGF in the fibrosis group were significantly lower than those in the control group, while the expression levels of LTF, LYZ, PLTP, and SLPI were higher (all P < 0.05). These IRGs also showed a significant correlation with renal function impairment. Moreover, four upregulated IRGs were positively associated with various T cell populations, which were enriched in RIF tissues, whereas two downregulated IRGs had opposite results. Several signaling pathways, such as the "T cell receptor signaling pathway" and "positive regulation of NF-κB signaling pathway", were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs. In summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-κB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD.