EGF Levels Research Articles

Level of circulating cytokines in children with chronic liver diseases at different stages of fibrosis

Liver diseases cause about 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of this number. The cytokine and chemokine balance determines outcomes of immune response. Many cytokines are involved in progression and control of various liver diseases via regulation of cellular activity. Our aim was to assess the level of circulating cytokines and chemokines depending on the stage of fibrosis in children with chronic liver diseases. 51 children with chronic liver diseases were examined (32 children with autoimmune hepatitis, 12 children with Wilson’s disease, 5 children with Gaucher disease and 2 children with glycogen storage disease). All children were assessed for the stage of liver fibrosis (AF) using METAVIR scale (FibroScan F502). The contents of circulating serum cytokines, chemokines, growth factors and angiogenesis was determined by the MILLIPLEX® Human Cytokine/Chemokine/Growth Factor Panel A Magnetic Bead Panel, an immunoassay based on Luminex® technology. Statistical evaluation was carried out using the program “Statistica 10.0”. The levels of EGF, Fractalkine, IFNá, IL-10 and MIG increased significantly from F0 stage to F4 stage. A significant decrease from stage F0 to stage F4 was revealed for eotaxin, IL-5, IL-8, IL-17A. Some cytokines were characterized by nonlinear dynamics: the concentrations of IL-4 and MDC increased significantly from the F0 stage to the F2-3 stage, and then decreased to the F4 stage; the level of IL-18 showed a significant decrease by stage F2-3 relative to F0, then being significantly increased by stage F4. The level of TNFáwas increased at all stages of liver fibrosis and reached its maximum values at stage F2-3 of AF. Our data confirm the significant role of cytokines and chemokines in the pathogenesis of chronic liver diseases. The identified changes in circulating cytokines in the blood serum in children with CKD, depending on the stage of fibrosis, are characterized by differently directed disturbances thus presuming involvement of both pro- and anti-inflammatory mechanisms in the immunopathological process in the course of liver fibrosis formation. Further research is required in order to study the participation of cytokines and chemokines in formation of liver fibrosis for development of targeted therapy for liver diseases.

Determination of Epidermal Growth Factor and Interleukin 6 in Patients with Atopic Dermatitis in karbala Province

The most prevalent chronic skin inflammatory illness, Atopic Dermatitis (AD), significantly lowers the quality of life for those who suffer from it. The clinical course, age at onset, and degree of allergy and non-allergic comorbidities associated with AD vary widely. Epidermal growth factor receptor controls a number from keratinocyte processes, including as migration, adhesion, survival, and differentiation. The contrast between differentiation and cell cycle progression is one of these pleiotropic effects that stand out. Also, Interleukin 6 promotes the healing of corneal epithelial wounds. These cytokines may cause corneal neovascularization because they affect different kinds of cells. measurement the concentrations of EGF and interleukin 6 in the serum of men with Atopic Dermatitis and its correlated with severity of the disease. Serum Samples for the current study were collected from 60 serum samples from men with Atopic dermatitis and 60 samples from the control group. All samples were collected from outpatient dermatology clinics in karbala province. The ages of all men ranged between 28 years and 40 years. By ELISA kits, the epidermal growth factor concentrations and interleukin 6 were measured in serum). Results showed significantly increased in levels of EGF and interleukin 6 (p< 0.05) in patient with Atopic Dermatitis compared with control group. These findings imply that EGF might, in an inflammatory setting, collaborate with other cytokines to strengthen the immunological barrier, The pathophysiology of dermatitis is significantly influenced by IL6, and the clinical severity of AD disease development is correlated with elevated levels of this protein.

May dental implant macro and microgeometry modifications influence peri-implant bone repair in smokers? A randomized clinical trial

BackgroundThis split-mouth, double-masked, randomized clinical trial aimed at evaluating the impact of different macro geometries and nano topographical modifications on peri-implant bone repair in smokers.MethodsThirty-two patients who smoked at least ten cigarettes/day, with the need of a single maxillary or mandibular implant bilaterally, received two implants randomly assigned to DA - Dual Acid-Etched implants (n = 32); HCAN – healing chambers and activated nano surface (n = 32). Implant stability quotient (ISQ) was evaluated 07, 30, 60, 90, and 120 days after implant placement. Levels of bone and angiogenic markers were quantified in the peri-implant fluid after 07, 15, 30, 90, and 120 days of implant insertion. HCAN implants have a higher ISQ than DA implants at 60 days (p < 0.05).ResultsPLGF levels were lower for HCAN implants than for DA implants at 07-day period (p < 0.05). Besides, HCAN implants presented higher levels of OPG at 30 days and OPN, BMP-9, FGF-1, PLGF, and VEGF at 90 days, compared to DA implants (p < 0.05). The levels of EGF were higher for HCAN implants at 15, 90, and 120 days compared with DA implants (p < 0.05). HCAN implants also showed lower levels of TNF-α at 07 days in comparison to DA implants (p < 0.05) but had higher levels of DKK1 at 30 days, while DA implants presented higher levels of this marker at 90 days (p < 0.05).ConclusionMacro geometry and nano topographical modifications positively modulated the bone and angiogenic factors, resulting in higher production of these markers during early peri-implant bone healing and having a positive effect on implant stabilization in smokers.Trial RegistrationRBR-10gjvcyt; date of registration: 06/12/2023 (Retrospectively registered).

Increase in Blood Eosinophil Count Over Time and Sputum IL8 are Associated with FEV1 Decline in Asthma

BackgroundAsthma is associated with accelerated rate of FEV1 decline.ObjectiveTo determine predictive factors associated with accelerated FEV1 decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline.MethodsWe recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV1 decline > 0.85% pred.y−1) and others. Predictive factors were highlighted with linear regression analysis. Sputum EGF, VEGF, FGF, IL5, IL8, TGF-β, and IgE levels were measured in 58 of these patients at both visits by Human XL cytokine Luminex Performance assay and Elisa.ResultsPost-BD FEV1 decline was 0.06 ± 2.44% pred.y−1 in the overall population. Median (IQR) time between visits was 66 (62 – 86) months. The multivariable analysis showed that an increase in blood eosinophils over time (Δ BEC) (Reg. Coef. (95%CI): 0.002 (0.001 to 0.004), p = 0.005)) and onset of asthma (0.04 (0.003 to 0.07), p = 0.036) were independently associated with FEV1 decline. IL8 levels measured at baseline were higher (499 (408—603) pg/ml, p = 0.0040) in patients with accelerated decline compared to others (143 (88—308) pg/ml).ConclusionIn this study, we have confirmed that an increase in blood eosinophil counts over a follow-up of at least 5 years and later onset of asthma are associated with accelerated annual FEV1 decline. Moreover, high sputum IL8 levels could be a risk factor for accelerated decline in asthma patients.

Comparison of the efficacy of tibial transverse transfer and periosteal distraction techniques in the treatment of diabetic foot refractory ulcers.

To investigate the efficacy of comparing tibia transverse transport (TTT) and periosteal distraction in treating diabetic foot ulcers. A retrospective analysis of 19 patients with diabetic foot ulcers treated with both procedures between February 2020 and November 2022, 8 of whom were treated with the tibial transverse transfer technique (transfer group) and 11 with the osteochondral distraction technique (distraction group), was performed to compare and analyze the clinical efficacy of the two methods. All wounds were healed in both groups, and the healing time ranged from 15 to 41days with a mean of 28d. The limb preservation rate was 100%. The operative time, intraoperative bleeding, and pain score in the operative area were significantly less in the distraction group than in the removal group, with statistically significant differences (P < 0.05). Intra-group comparison between the two groups of patients after surgery revealed that the skin temperature, ABI, TcPO2, SWM and VAS of the affected limb were significantly improved compared with those before surgery, and the difference was statistically significant (P < 0.05). The expression levels of VEGF, bFGF, EGF and PDGF were significantly higher than before surgery in both groups, and the difference was statistically significant (P < 0.05). No statistically significant differences were found in skin temperature, ABI, TcPO2, SWM, VAS, VEGF, bFGF, EGF and PDGF between the two groups at the corresponding time points preoperatively and postoperatively (P > 0.05). The Periosteal distraction technique can significantly promote the healing of diabetic foot ulcers. It has the same efficacy as TTT in promoting the healing of diabetic foot ulcer wounds and improving the peripheral circulation of affected limbs. In addition, the periosteal distraction technique has the advantages of small trauma, simple operation, few complications, and convenient nursing care.

Exploring the Wound Healing Potential of Hispidin.

Hispidin, a polyphenol component mainly derived from the medicinal mushroom species Phellinus and Inonotus, shows promise for biomedical applications, yet its potential in wound healing remains largely unexplored. This research investigates the wound healing effects of hispidin through in vitro and in vivo experiments, while also evaluating its antimicrobial properties and safety profile. In vitro scratch assays were conducted to evaluate the impact of hispidin on the migration of NIH-3T3 cells. The wound healing potential of hispidin was assessed in rats using excision wounds, dead space wounds, and linear incisions, treated with various topical ointments including a simple ointment, 2.5% (w/w) and a 5% (w/w) hispidin ointment, and a 0.2% (w/w) nitrofurazone ointment, administered at 0.2 g daily for 14 days. Hispidin demonstrated antimicrobial properties and was particularly effective against Staphylococcus epidermidis. Hispidin enhanced NIH-3T3 cell viability, and promoted wound closure in scratch assays, correlating with increased levels of FGF21, TGF-β1, EGF, and VEGF. In excision wound models, the 5% (w/w) hispidin ointment improved wound contraction, epithelialization, tissue regeneration, fibroblast activity, and angiogenesis. In the granulation tissue from dead space wound models, hispidin reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and lipid peroxidation, while increasing anti-inflammatory cytokines (IL-10) and antioxidant activities (SOD, GPx, CAT), along with connective tissue markers like hydroxyproline, hexosamine, and hexuronic acid. Hispidin also enhanced wound breaking strength in incision models. Acute dermal toxicity studies indicated no adverse effects at 2000 mg/kg. These findings highlight hispidin's potential in wound care, demonstrating its antimicrobial, regenerative, and safety properties.

Transcriptome meta-analysis and validation to discovery of hub genes and pathways in focal and segmental glomerulosclerosis

BackgroundFocal segmental glomerulosclerosis (FSGS), a histologic pattern of injury in the glomerulus, is one of the leading glomerular causes of end-stage renal disease (ESRD) worldwide. Despite extensive research, the underlying biological alterations causing FSGS remain poorly understood. Studying variations in gene expression profiles offers a promising approach to gaining a comprehensive understanding of FSGS molecular pathogenicity and identifying key elements as potential therapeutic targets. This work is a meta-analysis of gene expression profiles from glomerular samples of FSGS patients. The main aims of this study are to establish a consensus list of differentially expressed genes in FSGS, validate these findings, understand the disease’s pathogenicity, and identify novel therapeutic targets.MethodsAfter a thorough search in the GEO database and subsequent quality control assessments, seven gene expression datasets were selected for the meta-analysis: GSE47183 (GPL14663), GSE47183 (GPL11670), GSE99340, GSE108109, GSE121233, GSE129973, and GSE104948. The random effect size method was applied to identify differentially expressed genes (meta-DEGs), which were then used to construct a regulatory network (STRING, MiRTarBase, and TRRUST) and perform various pathway enrichment analyses. The expression levels of several meta-DEGs, specifically ADAMTS1, PF4, EGR1, and EGF, known as angiogenesis regulators, were analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR).ResultsThe identified 2,898 meta-DEGs, including 665 downregulated and 669 upregulated genes, were subjected to various analyses. A co-regulatory network comprising 2,859 DEGs, 2,688 microRNAs (miRNAs), and 374 transcription factors (TFs) was constructed, and the top molecules in the network were identified based on degree centrality. Part of the pathway enrichment analysis revealed significant disruption in the angiogenesis regulatory pathways in the FSGS kidney. The RT-qPCR results confirmed an imbalance in angiogenesis pathways by demonstrating the differential expression levels of ADAMTS1 and EGR1, two key angiogenesis regulators, in the FSGS condition.ConclusionIn addition to presenting a consensus list of differentially expressed genes in FSGS, this meta-analysis identified significant distortions in angiogenesis-related pathways and factors in the FSGS kidney. Targeting these factors may offer a viable strategy to impede the progression of FSGS.

Microbiological and molecular profile of furcation defects in a population with untreated periodontitis.

To describe the microbiological composition of subgingival dental plaque and molecular profile of gingival crevicular fluid (GCF) of periodontal furcation-involved defects. Fifty-seven participants with periodontitis contributed with a degree II-III furcation involvement (FI), a non-furcation (NF) periodontal defect and a periodontally healthy site (HS). Subgingival plaque was analysed by sequencing the V3-V4 region of the 16S rRNA gene, and a multiplex bead immunoassay was carried out to estimate the GCF levels of 18 GCF biomarkers. Aiming to explore inherent patterns and the intrinsic structure of data, an AI-clustering method was also applied. In total, 171 subgingival plaque and 84 GCF samples were analysed. Four microbiome clusters were identified and associated with FI, NF and HS. A reduced aerobic microbiota (p = .01) was detected in FI compared with NF; IL-6, MMP-3, MMP-8, BMP-2, SOST, EGF and TIMP-1 levels were increased in the GCF of FI compared with NF. This is the first study to profile periodontal furcation defects from a microbiological and inflammatory standpoint using conventional and AI-based analyses. A reduced aerobic microbial biofilm and an increase of several inflammatory, connective tissue degradation and repair markers were detected compared with other periodontal defects.

Therapeutic potential of cannabis for surgical wound healing in rats.

This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds. An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis. The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05). To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.

Quantitative SERS detection of serum protein biomarkers for assessment of tumor microwave ablation outcomes

Microwave ablation (MWA) is widely applied in the treatment of cancer, especially hepatocellular carcinoma (HCC). However, the lack of indicators for evaluating ablation completeness limits the success rate and wider application of MWA. This study therefore aims to identify novel serum biomarkers for evaluating the completeness of ablation. Multiple cytokines are preliminarily identified through cell experiments, and the potential as biomarkers is evaluated using clinical serum samples from patients with HCC before and after MWA. CCL20 and EGF are identified as promising biomarkers of the completeness of MWA. Additionally, we develop a highly sensitive and specific quantitative detection method for detecting CCL20 and EGF levels by fabricating a sandwich surface-enhanced Raman spectroscopy (SERS) nano-architecture amplification-based immunosensor. The linear detection range of this SERS platform is 0.1 pg/mL–1 ng/mL with the limit of detections (LoDs) decreasing to 0.082 pg/mL for CCL20 and 0.096 pg/mL for EGF. The remarkable consistency of the SERS immunosensor and ELISA in detecting CCL20 and EGF serum levels highlights the promising clinical utility of SERS in biomarker detection. The exceptional sensitivity of SERS in detecting CCL20 and EGF offers a potential avenue for enhancing the assessment of clinical MWA completeness, consequently leading to improved patient survival rates.

Therapeutic effect and mechanism of Ento-PB on ulcerative colitis in BALB/c mice induced by sodium dextran sulfate

The traditional Chinese medicine (TCM) formula Ento-PB containing Periplaneta americana (Linnaeus) (Blattidae) and Taraxacum mongolicum Hand.-Mazz. (Compositae) has great potential for treating inflammation. Thus, this study aimed to explore the pharmacodynamic effect of Ento-PB on DSS-induced ulcerative colitis in BALB/c mice, and its effects on immune function, JAK2/STAT3-related signaling pathways and intestinal flora in UC mice. It was identified that the extract Ento-PB mainly contained 20 compounds, accounting for 78.50 % of the total peak area. Compared with the model group, each dose group of Ento-PB could reduce the DAI score, colon index, CMDI score and colon HS score of mice to varying degrees (P < 0.05 or P < 0.01). Ento-PB can reduce the content of IL-1β, TNF-α, IFN-γ in serum and IL-7 and IL-17 in colonic tissue, and increase IL-2, IL-10 in serum and EGF in colonic mucosa, TGF-β1 expression level (P < 0.05 or P < 0.01). In conclusion, Ento-PB has a good therapeutic effect on DSS-induced UC mice. Its mechanism of action may be to up-regulate the levels of IL-2, IL-10, EGF, IL-22 and TGF-β1, and down-regulate the levels of TNF-α,IFN-γ, IL-7 and IL-17 in UC mice. This provides sufficient experimental basis for the clinical treatment of UC with Ento-PB.

Distinct biological characteristics of mesenchymal stem cells separated from different components of human placenta

Mesenchymal stem cells (MSCs) have tremendous potential in cell therapy and regenerative medicine. The placenta-derived MSCs (PMSCs) are becoming favorable sources as they are ethically preferable and rich in MSCs. Although several subgroups of PMSCs have been identified from human term placenta, optimal sources for specific clinical applications remain to be elucidated. This study aimed to isolate MSCs from various components of the placenta, and compare their biological characteristics, including morphology, proliferation, immunophenotype, differentiation potential, growth factor and cytokine secretion, and immunomodulatory properties. Finally, four distinct groups of PMSCs were isolated from the placenta: amniotic membrane-derived MSCs (AM-MSCs), chorionic membrane-derived MSCs (CM-MSCs), chorionic plate-derived MSCs (CP-MSCs), and chorionic villi-derived MSCs (CV-MSCs). The results showed that CV-MSCs had good proliferation ability, and were easier to induce osteogenic and chondrogenic differentiation; CP-MSCs exhibited the strongest inhibitory effect on the proliferation of activated T cells, secreted high levels of EGF and IL-6, and could well differentiate into osteoblasts, adipocytes, and chondroblasts; AM-MSCs showed good growth dynamics in the early generations, were able to grow at high density, and tended to induce differentiation into osteogenic and neural lineages. These findings may provide novel evidence for the selection of seed cells in clinical application.

Alpha terpineol preconditioning enhances regenerative potential of mesenchymal stem cells in full thickness acid burn wounds

Regeneration of full thickness burn wounds is a significant clinical challenge. Direct stem cell transplantation at the wound site has a promising effect on wound regeneration. However, stem cell survival within the harsh wound environment is critically compromised. In this regard, preconditioning of stem cells with cytoprotective compounds can improve the efficiency of transplanted cells. This study evaluated the possible effect of alpha terpineol (αT) preconditioned mesenchymal stem cells (αT-MSCs) in full thickness acid burn wound. An optimized concentration of 10 μM αT was used for MSC preconditioning, followed by scratch assay analysis. A novel rat model of full thickness acid burn wound was developed and characterized via macroscopic and histological examinations. Treatment (normal and αT-MSCs) was given after 48 h of burn wound induction, and the healing pattern was examined till day 40. Skin tissues were harvested at the early (day 10) and late (day 40) wound healing phases and examined by histological grading, neovascularization, and gene expression profiling of healing mediators. In scratch assay, αT-MSCs exhibited enhanced cell migration and wound closure (scratch gap) compared to normal MSCs. In vivo findings revealed enhanced regeneration in the wound treated with αT-MSCs compared to normal MSCs and untreated control. Histology revealed enhanced collagen deposition with regenerated skin layers in normal MSC- and αT-MSC treated groups compared to the untreated control. These findings were correlated with enhanced expression of α-SMA as shown by immunohistochemistry. Additionally, αT-MSC group showed reduced inflammation and oxidative stress, and enhanced regeneration, as witnessed by a decrease in IL-1β, IL-6, TNF-α, and Bax and an increase in BCL-2, PRDX-4, GPX-7,SOD-1, VEGF, EGF, FGF, MMP-9, PDGF, and TGF-β gene expression levels at early and late phases, respectively. Overall findings demonstrated that αT exerts its therapeutic effect by mitigating excessive inflammation and oxidative stress while concurrently enhancing neovascularization. Thus, this study offers new perspectives on managing full thickness acid burn wounds in future clinical settings.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation

BackgroundThe aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. MethodsAqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. ResultsCompared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. ConclusionFollowing sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

Therapeutic effect of ZnO NPs–polyhexanide-hydrogel on Staphylococcus aureus-induced skin wound infection in mice

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs–PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-β1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs–PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-β1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs–PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing.

CT-guided high dose rate brachytherapy can induce multiple systemic proteins of proliferation and angiogenesis predicting outcome in HCC

Background and purposeTo determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC). Materials and methodsFor this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years. ResultsProliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively). ConclusionIncreased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome.

Identification of key genes and signalling pathways in clear cell renal cell carcinoma: An integrated bioinformatics approach.

Clear cell Renal Cell Carcinoma (ccRCC) is one of the most prevalent types of kidney cancer. Unravelling the genes responsible for driving cellular changes and the transformation of cells in ccRCC pathogenesis is a complex process. In this study, twelve microarray ccRCC datasets were chosen from the gene expression omnibus (GEO) database and subjected to integrated analysis. Through GEO2R analysis, 179 common differentially expressed genes (DEGs) were identified among the datasets. The common DEGs were subjected to functional enrichment analysis using ToppFun followed by construction of protein-protein interaction network (PPIN) using Cytoscape. Clusters within the DEGs PPIN were identified using the Molecular Complex Detection (MCODE) Cytoscape plugin. To identify the hub genes, the centrality parameters degree, betweenness, and closeness scores were calculated for each DEGs in the PPIN. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) was utilized to validate the relative expression levels of hub genes in the normal and ccRCC tissues. The common DEGs were highly enriched in Hypoxia-inducible factor (HIF) signalling and metabolic reprogramming pathways. VEGFA, CAV1, LOX, CCND1, PLG, EGF, SLC2A1, and ENO2 were identified as hub genes. Among 8 hub genes, only the expression levels of VEGFA, LOX, CCND1, and EGF showed a unique expression pattern exclusively in ccRCC on compared to other type of cancers.

Unveiling the wound healing potential of umbilical cord derived conditioned medium: an in vitro study

Chronic wounds pose a serious threat to an individual’s health and quality of life. As such, therapeutic intervention is often needed to mitigate the improper closure of wounds. Large amounts of research and funding have been directed towards finding a suitable treatment. However, due to the severity and morbidity of such wounds, many pre-existing treatments are inefficient or costly. While the use of skin grafts and other such biological constructs in chronic wound healing has already been characterized, the use of umbilical cord tissue has only recently garnered interest, despite the cytokine-rich composition of Wharton’s jelly (cord component). Our current study aimed to characterize the use of an umbilical cord derived conditioned medium (UC-CM) to treat chronic wounds. We hypothesized that UC-CM contains higher amounts of wound healing cytokines, supporting cell proliferation, migration, and better wound healing properties compared to fetal bovine serum (FBS). Cytokine analysis demonstrated that UC-CM consistently contained desirable levels of HGF, EGF, VEGF, and TGF-β, all of which are vital to the normal wound healing process, whereas there were negligible amounts of growth factors in FBS except for TGF-β. MTT assay confirmed that UC-CM is not cytotoxic and promotes cell proliferation, while the scratch assay demonstrated that UC-CM supports migration of MSCs into the wound site. Taken altogether, our study showed that UC-CM was equally as effective as FBS-containing medium at promoting cell proliferation and wound healing.

FOXO3a deregulation in uterine smooth muscle tumors

ObjectiveThe present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. MethodsThe authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. ResultsThis investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. ConclusionsIn summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.

Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1β, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.