Growth Factor Levels Research Articles

Unique content of breastmilk: neurotrophic growth factors in breastmilk at 2 years and beyond.

The aim of our study was to show the presence of neurotrophic factors in breast milk that have a significant impact on neurocognitive development of children aged two years and beyond. Mothers expressed at least 5mL of breast milk into sterile containers when their children 18, 24, and ≥ 25months of age, and then specimens were transferred to Eppendorf tubes and stored at -20 °C. One day before the analysis, specimens were kept at +4°C and then thawed at room temperature to prepare them for analysis. Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and S100B neurotrophic growth factor levels were analyzed using the sandwich enzyme-linked immunosorbent assay (ELISA) principles. Sixty-two mothers with children aged 18months were included in the study. The mean age of the mothers was 33.4 (± 0.71) years. Due to the detection limits of the commercial kits, BDNF and S100B analyses could not be conducted. Therefore, only GDNF was analyzed. The presence of GDNF was found in the breast milk samples taken at 18, 24, and ≥ 25months, and the median (min max) values were 315,505ng/mL (193,067 750,718), 316,721ng/mL (161,278l-752,252), and 564,577ng/mL (238,528-781,104) respectively. There were no significant differences between GDNF levels of breast milk samples collected from the same mother at the three different time points (18, 24, and ≥ 25months) (p = 0.278). Conclusion: Our study was the first to show the presence of neurotrophic factors in the breast milk of mothers with healthy children over one year of age. Our results provide evidence-based data on the importance of breastfeeding until children are at least two years of age. What is Known: • Presence of Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and S100B neurotrophic growth factor have been shown in the breast milk of mothers whose infants are the first year of life. What is New: • Glial Cell Line-Derived Neurotrophic factors continue to present in breast milk of mothers with children aged 18, 24, and ≥ 25months, without any significant difference in level between months.

Second-line Treatment Strategy in Unresectable Hepatocellular Carcinoma After First-line Atezolizumab Plus Bevacizumab.

Atezolizumab plus beva-cizumab (AteBev) are an integral part of first-line therapy for unresectable hepatocellular carcinoma (uHCC), whereas no second-line regimen has been developed for these patients. This study evaluated the efficacy of second-line therapy for uHCC following AteBev treatment. Sixty uHCC patients who were administered AteBev therapy were included in the study. Dynamic computed tomography was conducted after 6, 9, and 12 weeks, and blood tests were performed at baseline and after three weeks. After six weeks of AteBev therapy, 19 patients experienced partial response (PR), 12 had stable disease (SD), and 29 exhibited progressive disease (PD), with an overall response rate (ORR) of 31.7%. Of the 21 patients treated with lenvatinib as second-line treatment, one dropped out, nine experienced a compete response (CR) or PR, and 11 had SD or PD, resulting in an ORR of 45.0%. Serum levels of fibroblast growth factors (FGF)-19 increased substantially following lenvatinib therapy in the CR+PR group, although the levels decreased significantly in the SD+PD group. Soluble FGF-R4 levels did not differ significantly between the CR+PR group and the SD+PD group when assessed before and after lenvatinib treatment. Lenvatinib is useful as second-line treatment after Ate/Bev for uHCC patients who do not response to Ate/Bev treatment. Changes in serum FGF-19 levels after three weeks of AteBev therapy may serve as a biomarker for selecting lenvatinib as second-line therapy.

Effect of Single Session of Swedish Massage on Circulating Levels of Interleukin-6 and Insulin-like Growth Factor 1.

Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and endocrine fashion. The aim of this intervention study was to investigate if massage therapy affects circulating myokine levels. A total of 46 healthy, normal-weight subjects (15 men) aged 18-35 were recruited. Forty-five minutes of massage Swedish therapy was applied to the back and hamstrings. Blood samples via cannula were taken at the baseline, during the massage (30 min), end of the massage (45 min), and 30 min and 1 h after the massage. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) were measured as surrogate markers by ELISAs. There was a significant increase in IL-6 from 1.09 pg/mL to 1.85 pg/mL over time (Wilks' Lambda Value 0.545, p < 0.000; repeated measures ANOVA). Pair-wise comparisons showed a significant increase after 1 h of massage. No significant increase was observed in IGF-1 levels. The change in myokine levels was not correlated with muscle mass (p = 0.16, 0.74). The increase in IL-6 suggests that there might be anti-inflammatory effects, affecting glucose and lipid metabolism pathways via IL-6 signaling to muscles, fat tissue, and the liver.

Using Dual-Target rTMS, Single-Target rTMS, or Sham rTMS on Post-Stroke Cognitive Impairment.

The clinical application of 10 Hz repetitive transcranil magnetic stimulation (rTMS) remains limited despite its demonstrated effectiveness in enhancing cortical excitability and improving cognitive function. The present study used a novel stimulus target [left dorsolateral prefrontal cortex + primary motor cortex] to facilitate the enhancement of cognitive function through the bidirectional promotion of cognitive and motor functions; Methods: Post-stroke cognitive impairment patients (n = 48) were randomly assigned to receive either dual-target, single-target, or sham rTMS for 4 weeks. Before and after 4 weeks of treatment, participants were asked to complete the Montreal Cognitive Assessment (MoCA) test, the Modified Barthel Index (MBI), the Trail-making Test (TMT), and the Digital Span Test (DST). In addition, the levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in serum were also measured. After adjusting for pre-intervention (baseline) MoCA scores, the post-intervention MoCA scores varied significantly. After post-hoc analysis, differences existed between the post-treatment scores of the dual-target rTMS group and the sham rTMS group (the experimental group scores were significantly higher), and between those of the dual-target rTMS group and the single-target rTMS group (the dual-target rTMS scores were significantly higher). The serum VEGF levels of the dual-target rTMS group were significantly higher those that of the sham rTMS group. The present study presented data showing that a dual-target rTMS therapy is effective for Post-stroke cognitive impairment (PSCI). The stimulation exhibited remarkable efficacy, suggesting that dual-target stimulation (left dorsolateral prefrontal cortex+motor cortex (L-DLPFC+M1)) holds promise as a potential target for TMS therapy in individuals with cognitive impairment after stroke. No: ChiCTR220066184. Registered 26 November, 2022, https://www.chictr.org.cn.

A serum-free culture medium production system by co-culture combining growth factor-secreting cells and l-lactate-assimilating cyanobacteria for sustainable cultured meat production

Large-scale production of cultured meat requires bulk culture medium containing growth-promoting proteins from animal serum. However, animal serum for mammalian cell culture is associated with high costs, ethical concerns, and contamination risks. Owing to its growth factor content, conditioned medium from rat liver epithelial RL34 cells can replace animal serum for myoblast proliferation. More seeded cells and longer culture periods are thought to yield higher growth factor levels, resulting in more effective muscle cell proliferation. However, RL34 cells can deplete nutrients and release harmful metabolites into the culture medium over time, potentially causing growth inhibition and apoptosis. This issue highlights the need for waste clearance during condition medium production. To address this issue, we introduced a lactate permease gene (lldP) and an l-lactate-to-pyruvate conversion enzyme gene (lldD) to generate a recombinant l-lactate-assimilating cyanobacterium Synechococcus sp. KC0110 strain. Transwell co-culture of this strain with RL34 cells exhibited a marked reduction in the levels of harmful metabolites, lactate and ammonium, while maintaining higher concentrations of glucose, pyruvate, and pyruvate-derived amino acids than those seen with RL34 cell monocultures. The co-culture medium supported myoblast proliferation without medium dilution or additional nutrients, which was attributed to the waste clearance and nutrient replenishment effects of the KC0110 strain. This culture system holds potential for the production of low-cost, and animal-free cultured meat.

Alleviating effects of guar gum on high-fat diet-induced liver injury in common carp (Cyprinus carpio)

This research aimed to determine the effect of dietary guar gum inclusion in high-lipid diets on the liver health of common carp (Cyprinus carpio). Four high-fat diets (10 % crude lipid) containing 0 % (HF), 0.3 % (HFG0.3), 1 % (HFG1), and 3 % (HFG3) of guar gum and a normal-lipid diet (5 % crude lipid; Control) were formulated. The tested diets were evenly and randomly distributed to fifteen tanks, with each tank containing thirty fish (4.53 ± 0.05 g). Fish were fed until apparent satiation for eight weeks. Compared to HF, diets HFG0.3, HFG1, and HFG3 significantly improved feed efficiency, with the HFG0.3 diet enhancing weight gain rate and specific growth rate. The results indicated that HF induced gut dysbiosis, hepatic lipid accumulation, oxidative stress, inflammation, and disturbance in hepatic lipid and cholesterol metabolism. Compared to the HF diet, diets HFG0.3, HFG1, and HFG3 substantially decreased hepatic lipid accumulation and malonaldehyde content, increased catalase activity and the expression of AMP-activated protein kinase (AMPKα2), peroxisomal proliferator-activated receptor alpha (PPARα), cholesterol 7alpha-hydroxylase, and decreased the expression of interleukin-1β (IL-1β). Moreover, the HFG0.3 and HFG1 diets dramatically increased nuclear factor erythroid 2-related factor 2 and liver X receptor expression and decreased protein carbonyl contents and expression of IL-8, nuclear factor kappa B (NF-κB p65), and tumor necrosis factor α. Furthermore, the HFG1 diet significantly increased carnitine palmitoyltransferase 1 and peroxisomal proliferator-activated receptor gamma coactivator 1 expression and reduced expression levels of fibroblast growth factor 19, farnesoid X receptor, and sterol regulatory element-binding protein type 1. The linear discriminant analysis effect size (LEfSe) analysis showed that HFG 0.3 and HFG1 substantially increased the enrichment of beneficial microbiota (e.g., lactic acid bacteria, Cetobacterium, and Fusobacterial) and decreased the enrichment of harmful microbiota (e.g., Proteobacteria, Acinetobacter, and Pseudomonas) compared to HF. These results suggested that guar gum can mitigate high-fat diet-induced liver damage in fish.

Multifunctional Chi-Ag@HMPB@CBD nanocomposites for eradicating multidrug-resistant bacteria and promoting diabetic damaged tissue repair

Injured tissues are vulnerable to polymicrobial infection, resulting in insufficient blood supply, excessive oxidative stress, and inflammation, seriously affecting skin regeneration. Therefore, there is an urgent need to develop effective strategies to treat multiple bacterial infections and damaged tissues and tissue repair for clinical treatment. Herein, we designed new nano-complexes of Chi-Ag@HMPB@CBD NPs via hollow mesoporous Prussian blue nanoparticles (HMPB NPs) loaded with cannabidiol (CBD) and chitosan-modified silver nanoparticles (Chi-Ag NPs) to treat multiple bacterial infected damaged tissues. In vitro experiments show that Chi-Ag@HMPB@CBD NPs synergizes with CBD and Chi-Ag NPs to effectively kill the mixture of Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) via disrupting the cell membranes and established biofilms. Meanwhile, Chi-Ag@HMPB@CBD NPs can decompose H2O2 and increase O2 levels, thereby alleviating microenvironmental hypoxia and protecting cells from oxidative stress damage. Moreover, Chi-Ag@HMPB@CBD NPs can promote Human Umbilical Vein Endothelial Cells (HUVECs) proliferation, migration, and neovascularization by inhibiting Matrix Metalloprotein-9 (MMP-9) expression. In vivo experiments show that Chi-Ag@HMPB@CBD NPs exhibit high efficacy against mixed infections of E. coli and MRSA, accelerating damaged tissue repair via upregulating levels of Vascular Endothelial Growth Factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD31). Collectively, this study demonstrates that Chi-Ag@HMPB@CBD NPs are versatile nanomaterials with a great potential in clinical treatment of mixed bacterial-infected damaged tissue repair.

Placental growth factor at 24-28 weeks for aspirin discontinuation in pregnancies at high risk for preterm preeclampsia: Post hoc analysis of StopPRE trial.

This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation. This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups. Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82). Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial.

TWEAK increases angiogenesis to promote diabetic skin wound healing by regulating Fn14/EGFR signaling.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of tumor necrosis factor superfamily, can bind to fibroblast growth factor-inducible 14 (Fn14) receptor and stimulate angiogenesis. The interaction between epidermal growth factor receptor (EGFR) and endothelial growth factor (EGF) leads to EGFR signal transduction and promotes angiogenesis. The objective of this study was to explore whether TWEAK participated in the diabetic skin wound healing by regulating Fn14/EGFR signaling. Human umbilical vein endothelial cells (HUVECs) were treated with 35 mmol/L d-glucose and classified into the Control Group, High Glucose (HG) Group and HG + TWEAK Group. Then, the TWEAK expression and the proliferation, migration and tubule formation of HUVECs were detected, respectively. Invivo experiment, the diabetic model was established by injecting streptozotocin (STZ, 50 mg/kg) into male BALB/c mice. On the back of successfully modeled diabetic mice, a full-thickness skin wound of 6 mm diameter was formed. Then, the mice were randomly assigned into three groups: Blank Group, Phosphate Buffer Saline (PBS) Group, and TWEAK Group. Subsequently, expression levels of TWEAK, Fn14, EGFR and vascular endothelial growth factor (VEGF)-A were measured, and the CD31 expression in the wounded skin tissue of mice was checked by immunohistochemistry staining. The expression level of TWEAK in HUVECs of HG Group decreased significantly, as well as the viability, migration, and tubule formation of cells. After over-expression of TWEAK, the cell viability, migration, and tubule formation abilities of HUVECs recovered remarkably. Invivo, the wound healing rate of diabetic mice was raised, the neovascularization was increased, and the CD31 expression in the wounded tissue was obviously upregulated after injection with recombinant TWEAK antibody. TWEAK stimulates angiogenesis and accelerates the wound healing of diabetic skin by regulating Fn14/EGFR signaling.

Genetic association of serum calcium, phosphate, vitamin D, parathyroid hormone, and FGF23 with the risk of aortic stenosis

Disorders of mineral metabolism, including elevated levels of serum calcium, phosphate, 25-hydroxyvitamin D (25OH-VitD), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), have been reported in patients with calcific aortic valve stenosis (CAVS). However, evidence of the causal role of mineral metabolism in CAVS is still lacking. In this study, we employed a systematic pipeline combining Mendelian randomization (MR), Steiger directionality test, colocalization analysis, protein-protein network, and enrichment analysis to investigate the causal effect of mineral metabolism on CAVS. Genome-wide association study (GWAS) and protein quantitative trait loci data for mineral metabolism markers were extracted from large-scale meta-analyses. Summary statistics for CAVS were obtained from two independent GWAS datasets as discovery and replication cohorts (n = 374,277 and 653,867). In MR analysis, genetic mimicry of serum FGF23 elevation was associated with increased CAVS risk [ORdiscovery = 3.081 (1.649–5.760), Pdiscovery = 4.21 × 10−4; ORreplication = 2.280 (1.461 – 3.558), Preplication = 2.82 × 10−4] without evidence of reverse causation (Psteiger= 7.21 × 10−98). Strong colocalisation association with CAVS was observed for FGF23 expression in the blood (PP.H4 = 0.96). Additionally, we identified some protein-protein interactions between FGF23 and known CAVS-associated genes. Serum calcium, phosphate, 25OH-VitD, and PTH failed to show causal effects on CAVS at Bonferroni-corrected significance (all P > 0.05/5 = 0.01). In conclusion, elevated serum FGF23 level may act as a causal risk factor for CAVS, and its mechanism of action in CAVS development may be independent of its function in regulating mineral metabolism. Hence, FGF23 may serve as a circulating marker and a promising preventive target for CAVS, warranting further investigation.

Effects of no-ozone cold plasma and mouse mesenchymal stem cell treatments on wound healing in a mouse skin model

Skin wounds heal faster during stem cell differentiation. Cold plasma reportedly enhances cell proliferation and differentiation and enhances the efficacy of stem cell therapy. However, the exact mechanism of action involved remains unknown. Therefore, this study aimed to evaluate the effect of a combination therapy involving the transplantation of mouse mesenchymal stem cells (mMSCs) into mice with wounds followed by their activation using no-ozone cold plasma (NCP). Balb/c mMSCs were transplanted into BALB/c mice and treated with NCP for 5 min. The animals were divided into four groups based on treatments received: no treatment (Wound), mMSCs only (mMSC), NCP only (NCP), and both mMSC and NCP (mMSC + NCP). NCP treatment was administered six times over two weeks, and tissue samples were prepared by sacrificing the mice in the 1st and 2nd weeks. The wound healing efficacy was assessed using morphological, histological, and molecular approaches including wound healing length measurements, hematoxylin and eosin staining, Masson trichrome staining, immunofluorescence staining, immunohistochemistry, and real-time polymerase chain reaction. The wound healing effect was better in the mMSC + NCP group than that in the groups treated with either. Tracking the injected mMSCs in mice also revealed that the mMSC + NCP group had a greater survival rate. Furthermore, upon wound healing, the mMSC + NCP group exhibited elevated levels of growth factors, like platelet-derived growth factor, transforming growth factor-beta, and vascular endothelial growth factor. These results suggest that NCP stimulated transplanted mMSCs, resulting in faster wound healing. Therefore, further studies are warranted in preclinical and clinical studies to confirm this effect.

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35-95% of patients with malignant cerebral gliomas of low malignancy and in 29-71% of patients with gliomas of high malignancy. Seizures can be both the first manifestation of malignant cerebral glioma and appear in the postoperative period and during chemoradiotherapy. This requires the use of antiepileptic drugs, which should control the seizure syndrome, provide control and secondary prevention of seizures, without reducing the response of anti-tumour therapy and the the patient QoL. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms in which glutamate plays a key role. Hypersecretion of glutamate is accompanied by increased expression and activation of its receptors, which increases convulsive readiness. This is accompanied by increased level of brain neurotrophic growth factor, the number of synapses between peritumoral neurons and glioma cells, and increased expression of a number of growth factors, which contributes to tumourous proliferation. In this regard, special attention when treating epilepsy in patients with malignant cerebral gliomas is given to perampanel, a glutamate receptor blocker, a 3rd generation antiepileptic drug. The findings show that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas, but also suppresses tumourous proliferation. Perampanel is able to dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. The findings have revealed synergistic effect of perampanel in combination with temozolamide. In conditions of chemoradiation therapy perampanel has a protective effect on healthy peritumoral tissues. Undesirable drug reactions during the use of perampanel are infrequent and insignificant. Additional studies are needed to further research the anticonvulsant and antitumour efficacy of perampanel to treat epilepsy in patients with malignant brain tumours.

Cord blood cytokine profiles in children later diagnosed with autism spectrum disorder: Results from the prospective MARBLES study

In studies investigating the etiology and pathophysiology of autism spectrum disorder (ASD), immune dysregulation is commonly observed, with elevated levels of inflammatory cytokines frequently found in gestational tissues. However, studies investigating the relationship between early immune dysregulation within the umbilical cord blood (CB) compartment and neurodevelopmental outcomes remains limited. In this exploratory study, we utilized data from the prospective Markers for Autism Risk in Babies – Learning Early Signs (MARBLES) study to examine cytokine levels in the plasma fraction of CB in infants later diagnosed with ASD (n = 38) compared to infants typically developing (TD) at age 3 years (n = 103), using multiplex cytokine assays. Our findings reveal altered levels of several inflammatory cytokines in children later diagnosed with ASD, including increased granulocyte colony-stimulating factor (G-CSF) and decreased interleukin-1α (IL-1α), IL-1β, and IL-4 in CB. Furthermore, we identified several associations between behaviors and levels of cytokines, chemokines and growth factors. IL-1α, IL-17A, interferon γ-induced protein 10 (IP-10), and epidermal growth factor (EGF) were associated with worse scores on Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) assessments. In summary, our study demonstrates dysregulated levels of inflammatory cytokine mediators in the CB of children later diagnosed with ASD and that inflammatory mediators were associated with ASD severity, comorbid behaviors, and neurodevelopmental measures. These findings have important implications for the possible predictive value of early cytokine measures in neurodevelopmental outcomes and subsequent behavioral manifestations.

Association between calcium-channel blockers and gingival enlargement: A case-control study

ObjectivesAs reported by the existing literature, calcium-channel blockers (CCB) can lead to gingival enlargement. The aims of this study were to investigate the factors associated with gingival enlargement in patients on CCB and to assess the saliva and gingival crevicular fluid (GCF) profile of patients on CCB with gingival enlargement. MethodsA total of 131 participants were included. Data were collected from 91 patients taking CCB for treatment of systemic hypertension. The presence of drug-induced gingival enlargement (DIGE) was assessed clinically and associated with patient factors. Patients with DIGE were group-matched for gender and ethnicity with an equal number of consecutive CCB non-DIGE patients (control 1), no-CCB no-DIGE (control 2) and periodontally healthy with no DIGE (control 3) for the saliva and GCF analysis. A bead-based multiplex immunoassay was used to assess a panel of biomarkers. ResultsTwenty-two percent of patients on CCB were diagnosed with DIGE. Lack of daily interdental cleaning and self-reported diagnosis of type II diabetes were associated with the diagnosis of DIGE. When analysing patients only on CCB, those with DIGE had higher GCF levels of vascular endolthelial growth factor (VEGF) (p = 0.032), epidermal growth factor (EGF) (p = 0.030) and matrix metalloproteinase-8 (MMP-8) (p = 0.008). Among the salivary markers, only MMP-8 showed a statistically significant difference across groups (p < 0.001). ConclusionsThis is the first study investigating saliva and GCF biomarkers in patients with DIGE and different control groups, suggesting that causes of the overgrowth might involve inflammatory processes, tissue damage pathways, and potentially an impact on growth factors like VEGF. Future research should verify these results in independent populations and explore the underlying pathogenic mechanisms in-depth. Clinical significanceCalcium-channel blockers (CCB) can lead to gingival enlargement. This study confirms lack of interdental cleaning and type II diabetes as risk factors. Elevated levels of VEGF, EGF, and MMP-8 in gingival crevicular fluid and MMP-8 in saliva suggest inflammatory processes and growth factors might play roles in this condition.

Neuroretinal and microvascular retinal features in dementia with Lewy body assessed by optical coherence tomography angiography.

To explore retinal changes in patients with Dementia with Lewy Bodies (DLB) using Spectral Domain-Optical Coherence Tomography (SD-OCT) and Optical Coherence Tomography Angiography (OCTA), aiming to identify potential biomarkers for diagnosis and monitoring. A cross-sectional study analyzed 15 DLB patients and 18 matched controls. Participants underwent physical, neurological, neuropsychological, and ophthalmological evaluations, including SD-OCT and OCTA. Logistic regression, adjusted for age, sex, and inter-eye correlation, was employed to identify retinal alterations in patients affected by DLB. OCTA revealed that DLB is associated with reduced superficial and deep vessel densities (SVD and DVD) in the macula (p < 0.01), as well as decreased peripapillary vessel density (ppVD, p < 0.01). SD-OCT parameters showed correlations with DLB, including reduced central macular thickness (CMT, p < 0.001) and thinning of the ganglion cell layer-inner plexiform layer (GCL-IPL, p < 0.01). Logistic regression (R²=0.26) identified reduced ppVD as a significant predictor of DLB (p = 0.030). Impairments in retinal capillaries, especially lower ppVD, might mirror cerebral hypoperfusion in DLB, potentially due to reduced Vascular Endothelial Growth Factor (VEGF) levels and increased α-synuclein. Further investigations are warranted to confirm the causal relationship between these observations, disease severity, and progression, as well as their potential role as biomarkers for DLB.

A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.Graphical

Effect of bovine hydroxyapatite composite with secretome under normoxia and hypoxia conditions on inflammatory parameters in massive bone defect of rabbit radius bone.

Hydroxyapatite as a scaffold is capable of producing good bone regeneration formation. Incorporating secretome into scaffolds optimizes the bone healing process. The increase in proinflammatory, anti-inflammatory, and growth factors is one of the key factors in bone healing. In this study, we measured the levels of IL-6, IL-10, and FGF-2 to determine the effectiveness of bovine hydroxyapatite with secretome from normoxia and hypoxia on bone healing. This animal study employed a pure experimental research design, utilizing a post-test-only control group design. Bone marrow mesenchymal stem cells from rabbit thigh bones were used to derive secretomes under hypoxic and normoxic conditions. Bovine bone-derived hydroxyapatite (BHA) was treated with secretomes under both conditions. Rabbits' radius bones were implanted with BHA alone, BHA with normoxic secretome, and BHA with hypoxic secretome, then observed for 30 and 60 days. Levels of IL-6, IL-10, and FGF-2 were examined on days 30 and 60. On the 30th day, there was a significant increase in the levels of FGF-2, IL-6, and IL-10, with a dominance of strongly positive levels in BHA alone. However, on the 60th day, the levels of FGF-2, IL-6, and IL-10 started to decrease in all groups, with a dominance of moderately positive levels. Statistical tests showed significant results in all groups on days 30 and 60 (p < .05). Among the three groups, the best levels of growth factors and pro-inflammatory factors, and the lowest levels of anti-inflammatory factors were found in the BHA alone group on evaluation day 30.

Pegylated chitosan nanoparticles of fluoxetine enhance cognitive performance and hippocampal brain derived neurotrophic factor levels in a rat model of local demyelination

Cognitive impairment is a common feature in neurodegenerative diseases such as multiple sclerosis (MS). This study aims to explore the potential of enhancing the beneficial effects of fluoxetine (FLX), a neuroprotective agent known for its ability to increase neural plasticity by utilizing nanoparticles. The study specifically focuses on the synthesis and evaluation of PEGylated chitosan nanoparticles of FLX and its effect on demyelination and the subsequent cognitive impairment (CI) in the hippocampus of rats induced by local injection of lysophosphatidylcholine (LPC). Chitosan/polyethylene glycol nanoparticles were synthesized, and their properties were analyzed. Demyelination was induced in rats via hippocampal injections of lysolecithin. Behavioral assessments included open field maze, elevated plus maze, and novel object recognition memory (NORM) tests. Hippocampal levels of insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) were measured using enzyme-linked immunoassay (ELISA). The extent of remyelination was quantified using Luxol fast blue staining. Nanoparticle size measured 240.2 nm with 53 % encapsulation efficacy. Drug release exhibited a slow pattern, with 76 % released within 4 h. Nanoparticle-treated rats displayed reduced anxiety-like behavior, improved memory, increased BDNF levels, and a reduced extent of demyelination, with no change in IGF- levels. In addition, FLX -loaded chitosan nanoparticles had better effect on cognitive improvement, BDNF levels in the hippocampus that FLX. Altering pharmacokinetics and possibly pharmacodynamics. These findings highlight the potential of innovative drug delivery systems, encouraging further research in this direction.

The growth factor content as an indicator of platelet counts in platelet-rich plasma

BackgroundPlatelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and −AB), and transforming growth factor (TGF)-β. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations. MethodIn this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- β1 (TGF-β1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis. ResultsPearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively) ConclusionsThere was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-β, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.

Targeting OGF/OGFR signal to mitigate doxorubicin-induced cardiotoxicity

Enkephalins are reportedly correlated with heart function. However, their regulation in the heart remains unexplored. This study revealed a substantial increase in circulating levels of opioid growth factor (OGF) (also known as methionine enkephalin) and myocardial expression levels of both OGF and its receptor (OGFR) in subjects treated with doxorubicin (Dox). Silencing OGFR through gene knockout or using adeno-associated virus serotype 9 carrying small hairpin RNA effectively alleviated Dox-induced cardiotoxicity (DIC) in mice. Conversely, OGF supplementation exacerbated DIC manifestations, which could be abolished by administration of the OGFR antagonist naltrexone (NTX). Mechanistically, the previously characterized OGF/OGFR/P21 axis was identified to facilitate DIC-related cardiomyocyte apoptosis. Additionally, OGFR was observed to dissociate STAT1 from the promoters of ferritin genes (FTH and FTL), thereby repressing their transcription and exacerbating DIC-related cardiomyocyte ferroptosis. To circumvent the compromised therapeutic effects of Dox on tumors owing to OGFR blockade, SiO2-based modifiable lipid nanoparticles were developed for heart-targeted delivery of NTX. The pretreatment of tumor-bearing mice with the assembled NTX nanodrug successfully provided cardioprotection against Dox toxicity without affecting Dox therapy in tumors. Taken together, this study provides a novel understanding of Dox cardiotoxicity and sheds light on the development of cardioprotectants for patients with tumors receiving Dox treatment.