bFGF Levels Research Articles

Investigating the impact of Platelet-Rich Plasma Infusion

Objective: To investigate the impact of Platelet-rich plasma infusion on performance enhancing growth factors and find molecular markers to distinguish athletes treated with such infusions. Study Design: Prospective, Double-blind, Randomized controlled study. Place and Duration: Department of Dental Education and Research, Altamash Institute of Dental Medicine, Karachi from 15th January 2022 to 20th June, 2022. Methodology: The ergogenic growth factors FGF-2 that are basal fibroblast growth factor, vascular endothelial growth factor, IGF-1 (insulin-like growth factor), IGFBP-3 (insulin-like growth factor binding protein-3), and platelet-derived growth factor-BB (PDGF-BB) WADA are tracked that were measured in 25 patients before (baseline) and 0.25, 3, 24, 48, 72, and 97 hours after the test. Patients under observation were prohibited from any movement or any food intake three hours prior to the exam. The change from each participant's baseline was calculated using an enzyme-linked immunosorbent assay to assess growth factors. Results: Total sample size was 23. Platelet-Rich Plasma had considerably higher levels of PDGF-BB (67% higher than standard 392 pg/ml), vascular endothelial growth factor (6.04% higher than standard 236 pg/ml), and bFGF (45% higher than standard 5 pg/ml), than serum, while IGF-1 and hGH levels were unchanged. IGF-1, bFGF, and vascular endothelial growth factor serum levels all significantly rose 24 and 48 hours after Platelet-Rich Plasma injection, as well as 3, 24, 48, 72, and 96 hours afterwards. Additionally, all 23 patients who had Platelet-Rich Plasma therapy had higher levels of vascular endothelial growth factor and success rate is 100% luckily. Conclusion: Serum levels of PDGF-BB, vascular endothelial growth factor, and bFGF significantly increase after Platelet-Rich Plasma injection, suggesting that Platelet-Rich Plasma have ergogenic effects. Following Platelet-Rich Plasma, the IGFBP-3 3 IGF-1 product, an indirect biomarker of hGH doping, significantly rose. All Platelet-Rich Plasma patients exhibited elevated vascular endothelial growth factor. Keywords: PRP Injection, Platelet-Rich Plasma, Human Growth Hormone, Growth Factors, Ergogenic Growth Factors, Insulin Growth Factor, Vascular Endothelial Growth Factor How to Cite This: Rizvi SH, Asphandiar DC, Arshad T, Hashmi FA. Investigating the impact of Platelet-Rich Plasma Infusion. Isra Med J. 2022; 14(3): 121-126. DOI: https://doi.org/10.55282/imj.oa1330

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264-0.892, p = 0.020; OR = 0.323, 95% CI = 0.107-0.972, p = 0.044; OR = 1.492, 95% CI = 1.111-2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.

Effects of acupuncture on angiogenesis-associated factor expression in ischemic brain tissue following cerebral infarction in rats

Background: We aimed to investigate changes into the levels of angiogenesis-associated factors following cerebral infarction and acupuncture intervention and reveal the underlying molecular mechanisms involved in promoting angiogenesis. Methods: Model rats with middle cerebral artery occlusion (MCAO) were randomized into electroacupuncture (EA), model control (MC), and blank control (control) groups. Changes in the degree of neurological impairment following cerebral infarction and angiogenesis in the ischemic center and peripheral area were observed using immunofluorescence double-labeling. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect changes in the Ang-1, Ang-2, PDGF-B, and bFGF levels. Moreover, the effects of EA intervention were evaluated. Results: The neurological severity score of each phase in the EA group was lower than that into the simultaneous phase in the MC group. The proliferation of vascular endothelial cells in the EA group was higher than that in the MC group at 12 hours to 7 days. The Ang-1 and Ang-2 mRNA and protein levels in the EA group were significantly higher than those in the MC group. PDGF-B levels in the EA group were significantly higher than those in the MC group at 3 to 6 hours and 3 to 12 days, and protein levels were high at 6 hours and 3 to 12 days. bFGF mRNA levels at 24 hours to 12 days and bFGF protein at 3 to 12 days were significantly elevated in the EA group than those in the MC group. Conclusions: EA at Shui Gou(DU 26) significantly improved the neurological symptoms of MCAO rats, promoted vascular endothelial cell proliferative activity around the infarct area, significantly advanced the time of proliferation of vascular endothelial cells, and upregulated the expression of angiogenesis-related factors, thereby promoting angiogenesis. Thus, EA may significantly improve the prognosis of cerebral infarction. Graphical abstract: http://links.lww.com/AHM/A43.

Effects of Toll-Like Receptor4 Gene Modified Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation on Expression of Basic Fibroblast Growth Factor (bFGF) and Follistatin-Like-1 (FSTL1) in Myocardial Ischemia-Reperfusion Rats

This study assesses the effects of TLR4 gene modified BMSCs transplantation on the expression of bFGF and FSTL1 in myocardial ischemia-reperfusion rats. 30 male SD rats were assigned into control group (myocardial ischemia model), BMSCs group (model + BMSCs transplantation) and transfection group (model + TLR4 gene modified BMSCs transplantation) followed by analysis of TLR4 expression, EGFP, apoptosis and expression of bFGF and FSTL1. Compared with control group (TLR4 concentration 2.86 pg/5×105 cells/mL). The expression of TLR4 in BMSCs group (25.24 pg/5×105 cells/mL) and transfection group (31.55 pg/5×105 cells/mL) was significantly increased (P <0.05), and it was more significant in transfection group. The myocardial tissue of rats in control group produced a large number of scars, hypertrophy and hyperplasia of myocardial cells accompanied by a large number of necrosis; The scar tissue of the myocardium in BMSCs group and transfection group decreased, and viable myocardium increased, with more significant effect in transfection group. Control group showed a large number of blue collagen fibers in the infarction area of left ventricle, which were in the shape of cords, and part of the collagen fibers were fused. The blue collagen fibers in the control group and the transfection group were significantly reduced. Compared with control group, BMSCs group had lower apoptosis, and increased bFGF and FSTL1 levels (P <0.05). Compared with BMSCs group, the apoptosis rate of myocardial cells was decreased, and the levels of bFGF and FSTL1 were increased (P < 0.05). In conclusion, transplantation of BMSCs modified with TLR4 can increase bFGF and FSTL1 levels, reduce the rate of myocardial apoptosis and improve the myocardial pathological tissue, thus playing a therapeutic role.

The Effect Of Fresh Human Amniotic Membrane Storage Time On Growth Factor Levels (EGF, TGF-B, bFGF) in Freeze-Dried Human Amniotic Membranes

Background: Each preservation method can cause different levels of damage to tissue components and can affect the regenerative performance of the amniotic membrane. The concentrations of most of the cytokines were found to decrease during the preservation period. There are still no studies regarding the effect of fresh human amnion storage time on growth factor levels in freeze dried human amnion products. Method: This study used an experimental post test group design. Result: There was no significant difference in EGF levels of freeze-dried human amniotic membrane products resulting from 3 types of fresh human amniotic membrane storage (1 week storage with 8.49 ± 5.16 pg/mL, 3 months with 4.55 ± 1.98 pg/mL, and 9 months with levels of 4.04 ± 2.12 pg/mL). There was no significant difference in bFGF values between freeze-dried human amniotic membrane products resulting from 3 types of storage duration of fresh human amniotic membrane (1 week storage with levels of 97.86 ± 113.98 pg/mL, 3 months with levels of 109.69 ± 113.39 pg/mL, and 9 months with levels of 117.53 ± 73.46 pg/mL). There was a significant difference in the levels of TGF-b, namely in the product from storage for 1 week (97.93 ± 18.27 pg/mL) and 3 months (55.94 ± 28.67 pg/mL). Whereas TGF-b levels in freeze dried human amniotic membrane from the results of fresh human amniotic membrane storage at 1 week and 9 months, and 3 months and 9 months were found to have no significant difference. Conclusion: There was no significant difference in EGF and bFGF levels in this study. There was a significant difference in the levels of TGF-b freeze-dried human amniotic membrane produced from fresh human amniotic membrane with higher growth factor levels at 1 week of storage compared to 3 months.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease.

Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFβ. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

Growth Factors Upregulated by Uric Acid Affect Guanine Deaminase-Induced Melanogenesis.

Uric acid produced by guanine deaminase (GDA) is involved in photoaging and hyperpigmentation. Reactive oxygen species (ROS) generated by uric acid plays a role in photoaging. However, the mechanism by which uric acid stimulates melanogenesis in GDA-overexpressing keratinocytes is unclear. Keratinocyte-derived paracrine factors have been identified as important mechanisms of ultraviolet-induced melanogenesis. Therefore, the role of paracrine melanogenic growth factors in GDA-induced hypermelanosis mediated by uric acid was examined. The relationships between ROS and these growth factors were examined. Primary cultured normal keratinocytes overexpressed with wild type or mutant GDA and those treated with xanthine or uric acid in the presence or absence of allopurinol, H2O2, or N-acetylcysteine (NAC) were used in this study. Intracellular and extracellular bFGF and SCF levels were increased in keratinocytes by wild type, but not by loss-of-function mutants of GDA overexpression. Culture supernatants from GDA-overexpressing keratinocytes stimulated melanogenesis, which was restored by anti-bFGF and anti-SCF antibodies. Allopurinol treatment reduced the expression levels of bFGF and SCF in both GDA-overexpressing and normal keratinocytes exposed to exogenous xanthine; the exogenous uric acid increased their expression levels. H2O2-stimulated tyrosinase expression and melanogenesis were restored by NAC pretreatment. However, H2O2 or NAC did not upregulate or downregulate bFGF or SCF, respectively. Overall, uric acid could be involved in melanogenesis induced by GDA overexpression in keratinocytes via bFGF and SCF upregulation not via ROS generation.

Application of Comfort Therapy under eCASH Concept in Acute and Chronic Wound Treatment.

Given the new ideas on wound care offered by the eCASH (early Comfort using Analgesia, minimal Sedatives, and maximal Humane care) and the substantial differences in clinical treatment between acute and chronic wounds, we aimed to investigate the effect of comfort therapy under the eCASH concept on analgesic sedation and accelerated wound healing in patients with acute or chronic wounds. This randomized clinical study was conducted in two parts: acute wounds and chronic wounds. Patients with acute wounds were allocated into the acute wound control group (AWCG) and the acute wound experimental group (AWEG). Patients with chronic wounds were allocated into the chronic wound control group (CWCG) and two experimental groups, in which they received intermittent negative pressure therapy (IPTEG) and continuous negative pressure therapy (CPTEG). On the basis of the standard treatment for patients in the control group, eCASH therapy was used in the experimental groups. In addition, pain intensity and procedural anxiety were evaluated using the visual analogue score (VAS) and the Hamilton Anxiety Scale (HAM-A). In addition, clinical effects were assessed on the basis of the size of the surface area, rate of healing, and concentration of pro-inflammatory factors (IL-1, IL-6, TNF-α) and growth factors (VEGF, bFGF, TGF-β1). Compared with the control group, the VAS score and HAM-A score in the experimental groups were significantly decreased after intervention (P < 0.05). After intervention, the levels of IL-1β, IL-6, and TNF-α in AWEG, IPTEG, and CPTEG were significantly lower than those in AWCG. In addition, the levels of VEGF, bFGF, and TGF-β1 in IPTEG and CPTEG were significantly higher than those in CWCG (P < 0.05). These results indicated that comfort therapy under the eCASH concept has a significant effect on ameliorating the pain and anxiety of patients, reducing the inflammatory reaction during the period of wound healing in the treatment of acute and chronic wounds. The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200057981).

Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Method: A total of 104 patients with primary HCC, admitted to People's Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients. Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival. Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders

Bipolar disorder (BD) and major depressive disorder (MDD) are severe psychiatric illnesses that share among their environmental risk factors the exposure to adverse childhood experiences (ACE). Exposure to ACE has been associated with long-term changes in brain structure and the immune response. In the lasts decades, brain abnormalities including alterations of white matter (WM) microstructure and higher levels of peripheral immune/inflammatory markers have been reported in BD and MDD and an association between inflammation and WM microstructure has been shown. However, differences in these measures have been reported by comparing the two diagnostic groups. The aim of the present study was to investigate the interplay between ACE, inflammation, and WM in BD and MDD. We hypothesize that inflammation will mediate the association between ACE and WM and that this will be different in the two groups. A sample of 200 patients (100 BD, 100 MDD) underwent 3T MRI scan and ACE assessment through Childhood Trauma Questionnaire. A subgroup of 130 patients (75 MDD and 55 BD) underwent blood sampling for the assessment of immune/inflammatory markers. We observed that ACE associated with higher peripheral levels of IL-2, IL-17, bFGF, IFN-γ, TNF-α, CCL3, CCL4, CCL5, and PDGF-BB only in the BD group. Further, higher levels of CCL3 and IL-2 associated with lower FA in BD. ACE were found to differently affect WM microstructure in the two diagnostic groups and to be negatively associated with FA and AD in BD patients. Mediation analyses showed a significant indirect effect of ACE on WM microstructure mediated by IL-2. Our findings suggest that inflammation may mediate the detrimental effect of early experiences on brain structure and different mechanisms underlying brain alterations in BD and MDD.

Gene expression analysis and the risk of relapse in favorable histology Wilms’ tumor

ABSTRACT Introduction and Objectives Wilms’ tumor (WT) relapse occurs in 15% of patients. We aim to investigate the association between the expression of several genetic markers and WT relapse risk. Materials and methods The study included 51 children treated for WT at a tertiary center between 2001 and 2019: 23 patients had disease relapse (group A) and 28 remained relapse-free after at least 2 years of follow-up (group B). Patients with syndromic, bilateral synchronous or anaplastic WT were excluded. Autologous renal tissue from 20 patients served as control. Total RNA was isolated from tumor tissue and control. Gene expression levels of WT1, HIF1α, b-FGF, c-MYC and SLC22A18 were assessed using quantitative RT-PCR and normalized to GAPDH. Immunohistochemical staining for WT1 and gene expression levels were compared between the study groups. Results Median patient age was 3 (IQR = 2–5) years and 36 (70.6%) had stage I disease. Baseline characteristics were similar between study groups. Relapse occurred at a median of 6.8 (2.8–24.7) months, predominantly in the lungs (11/23, 47.8%). Tumors that relapsed expressed significantly higher levels of WT1, HIF1α, b-FGF and c-MYC and lower levels of SLC22A18 (p < 0.001). Strong immunohistochemical staining for WT1 was seen in 73.9% of group A and 14.29% of group B (p < 0.001). These associations retained statistical significance irrespective of patient and tumor characteristics. Conclusions Higher expression levels of WT1, HIF1 α, b-FGF and c-MYC and lower level of SLC22A18 are associated with increased risk of WT relapse. These genetic markers can serve as future prognostic predictors and help stratify patients for treatment.

SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.

Basic fibroblast growth factor protects against liver ischemia-reperfusion injury via the Nrf2/Hippo signaling pathway

Liver ischemia-reperfusion injury (IRI) continues to play a major role in liver dysfunction and failure, which is involved in the process of liver transplantation, partial hepatectomy, and hemorrhagic shock. Basic fibroblast growth factor (bFGF) is involved in a variety of biological processes. However, bFGF's role in hepatic IRI remains unclear. In our study, we constructed hepatic I/R surgery in WT and nuclear factor-erythroid 2-related factor 2 (Nrf2) KO mice and hypoxia-reoxygenation (H/R) model in AML12 cells to research bFGF's possible role. We found that the expression level of bFGF was highly upregulated in livers after hepatic IRI. In vivo, bFGF treatment led to a significant reduction in the necrotic area, accompanied by alleviation of oxidative stress, cell apoptosis, and inflammation in WT mice. bFGF-induced Nrf2 nuclear translocation and its downstream anti-oxidative proteins production in AML12 cells provide a mechanistic explanation for this phenomenon. In addition, bFGF-induced Nrf2 activation via the protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) pathway. bFGF activated Nrf2 to restrain the phosphorylation of promote Yes-associated protein (YAP) and YAP stabilization, thus reducing cell apoptosis and inflammation in ROS-dependent manner, revealed that Hippo signaling was the downstream of Nrf2 mediating protective effects of bFGF during hepatic IRI. In conclusion, our findings suggest that bFGF could reduce hepatic IRI and hepatocyte injury via the Nrf2/Hippo signaling pathway.

Fenugreek Extract-Loaded Polycaprolacton/Cellulose Acetate Nanofibrous Wound Dressings for Transplantation of Unrestricted Somatic Stem Cells: An In Vitro and In Vivo Evaluation

Complex pathophysiology of diabetic wounds causes a delayed wound healing response. Advanced wound dressing materials that deliver biochemical cues are of particular interest in wound healing research. Here, we developed a dual-function delivery vehicle for drug and cell delivery applications to treat diabetic wounds. The delivery system was developed via electrospinning of polycaprolacton/cellulose acetate solution containing fenugreek extract. The produced delivery vehicle was characterized using microstructural studies, cell viability assay, cytoprotection assay, cell migration assay, In Vitro anti-inflammatory assay, free radical scavenging assay, tensile strength studies, swelling studies, and protein adsorption test. Scaffolds were then seeded with 30000 unrestricted somatic stem cells and transplanted into the rat model of excisional diabetic wound. Wound healing assay showed that the co-delivery of fenugreek extract and unrestricted somatic stem cells led to a substantial improvement in the healing activity of electrospun dressings, as evidenced by higher wound contraction, epithelial thickness, and collagen deposition in this group compared with other experimental groups. Gene expression analysis showed that dual-function delivery system could increase the expression level of VEGF, b-FGF, and collagen type II genes. Furthermore, the tissue expression level of IL-1β and glutathione peroxidase genes was significantly reduced in this group compared with other groups. This study shows that the developed system may be considered as a potential treatment modality for diabetic wounds in the clinic.

Effects of EGFR Mutations on NSCLC Patients Treated by Ramucirumab plus Docetaxel

The present paper attempted to define the effects of epidermal growth factor receptor (EGFR) mutations on patients with non-small cell lung cancer (NSCLC) treated by ramucirumab plus docetaxel. Of the 82 enrolled patients, 48 underwent EGFR mutations, showing relevance to sex and smoking history (P&lt;0.05). The analysis yielded that EGFR-mutant (EGFR-Mut) group had a higher objective response rate versus EGFR-wild-type (EGFR-Wt) group (P&lt;0.05). Subsequent to treatment, serum VEGF, bFGF, HDGF, CEA, CA153, CYFRA21-1 and CA199 levels dropped more significantly in EGFR-Mut group (P&lt;0.05). Beyond that, EGFR-Mut exhibited a lower ZPS score and a higher KPS score versus EGFR-Wt group (P&lt;0.05). Further, EGFR-Mut patients displayed strikingly longer median survival time versus EGFR-Wt patients (P&lt;0.05). Ramucirumab plus docetaxel can safely inhibit tumour angiogenesis and regulate the levels of serum tumour markers. EGFR-Mut NSCLC patients with brain metastasis have better treatment outcomes and longer survival.

Effects of Infrared Combined with Methylcobalamin on the Vibratory Sensory Threshold and Nerve Conduction Velocity of the Lower Extremity in Patients with Diabetic Foot Treatment.

Objective To investigate the effect of infrared combined with methylcobalamin on the vibratory sensory threshold and lower limb nerve conduction velocity of patients with diabetic foot. Methods One hundred and six patients with diabetic foot in our hospital from February 2018 to December 2020 were enrolled and divided into the study and control groups. The patients in the control group were given methylcobalamin, and the patients in the research group were treated with infrared light on the basis of the control group. The therapeutic effect, vibration sensory threshold, lower limb nerve conduction velocity, and related biochemical index levels before and after treatment in the two groups were counted. Result The total effective rate of the study group (94.34%) was significantly higher than that of the control group (81.13%). The left/right lower limb vibration sensation threshold decreased in both groups after treatment, and the study group was lower than that of the control group (P < 0.05). The conduction velocity of the left/right common peroneal nerve and tibial nerve increased in both groups after treatment, and the study group was larger than that of the control group (P < 0.05). The bFGF, VEGF, and APN increased in both groups after treatment. VEGF and APN increased and IL-6 and TNF-α decreased in both groups after treatment, and the study group was better than the control group (P < 0.05). Conclusion Infrared and methylcobalamin combined treatment of diabetic foot can effectively improve lower extremity nerve conduction velocity and vibration sensory threshold, regulate serum bFGF and VEGF levels, reduce the degree of inflammatory response, and help improve the overall treatment effect.

Biophotonic Effects of Low-Level Laser Therapy at Different Wavelengths for Potential Wound Healing

Our objective was to assess the effect of low-level laser therapy (LLLT) administered using a diode laser on the growth processes of human fibroblast cells involved in wound healing. Initially, studies were conducted using a diode laser at wavelengths of 633, 520, and 450 nm with an irradiance of 3 mW/cm2. The distance between the light source and culture plate was 3 cm. The mechanism(s) of action of the diode laser illumination on human fibroblast cells were studied by examining different wavelengths to determine the relevant light parameters for optimal treatment. In addition, the percentages of fibroblast-mediated procollagen and matrix metallopeptidase (MMP)-1, -2, and -9 production were compared. In the clinical study, the changes in basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and fibroblast collagen production were assessed in 60 patients with complicated wounds who received LLLT (633 nm). No statistically significant difference was observed between red light versus green and blue light in the viability analysis. In addition, the effects of LLLT on the cell cultures of fibroblast cells in vitro demonstrated a decrease in the relative expression of MMP-1, -2, and -9 while using light with a wavelength of 633 nm. In the clinical study, 633 nm diode laser LLLT at 2–8 J/cm2 was administered to 60 patients with complicated wounds; all patients showed increased levels of bFGF and VEGF and the occurrence of collagen synthesis. Our studies demonstrated that LLLT might affect fibroblast cell growth processes involved in wound healing.

Transverse Tibial Bone Transport Enhances Distraction Osteogenesis and Vascularization in the Treatment of Diabetic Foot.

ObjectiveTo investigate the effect of transverse tibial bone transport on the treatment of Wagner Stage 4 diabetic foot.MethodsFrom January 2017 to October 2019, a total of 19 patients with Wagner Stage 4 diabetic foot ulcers were recruited. All patients were treated with transverse tibial bone transport. A detailed follow‐up was carried out at 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. The wound healing rate and the limb salvage rate at 1 year after the surgery were evaluated. Preoperative and 3‐month postoperative digital subtraction angiography (DSA) were obtained. The level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet‐derived growth factor (PDGF) before surgery and on 1st, 4th, 11th, 18th, 28th, and 35th days after surgery were measured. Operation time, intraoperative blood loss, postoperative complications, visual analog scale (VAS) pain score, skin temperature, Semmes‐weinstein monofilament (SWM), and ankle brachial index (ABI) were also assessed.ResultsThe wound healing rate and the limb salvage rate were both 94.74% in the patients at 1 year after the surgery. DSA showed the thickening of the calf and foot arteries, clear visualization, and a rich vascular network. The levels of VEGF, bFGF, and PDGF on the 11th, 18th, 28th, and 35th days after surgery were significantly higher than those before surgery (p < 0.05). The EGF level on the 18th, 28th, and 35th days after surgery was significantly higher than that before surgery (p < 0.05). Superficial wound complications occurred in one patient during the hospitalization. There was no movement area infection, skin flap necrosis, tibial fracture, loosening of the external fixator, or rupture in study.ConclusionTransverse tibial bone transport can improve the blood circulation of the affected limbs, promote the healing of diabetic foot wounds, and reduce the amputation rate of the affected limbs. Transverse tibial bone transport can promote the healing of Wagner Stage 4 diabetic foot.

Study of the Level of Pro- and Antiangiogenic Growth Factors in Vitreous Fluid in Neovascular Age-Related Macular Degeneration on the Background of Treatment

Purpose: to study the level of pro- and antiangiogenic growth factors in the vitreous fluid of the eyes with the neovascular form of agerelated macular degeneration (nAMD) against the background of antiangiogenic therapy.Patients and methods. The concentration of proangiogenic (IL-8, angiogenin, TNF-α, VEGF, bFGF) and antiangiogenic (IFN-α, TGF-β IFN-γ) growth factors in the vitreous fluid of nAMD patients was determined by multiplex flow cytometry. Patients with senile cataracts without signs of AMD and cataract patients burdened with naïve (untreated) nAMD were in the comparison groups.Results. Compared with senile cataracts, proangiogenic cytokines TNF-α were present more frequently and at a higher level in the vitreous fluid of the eyes with treated nVMD (75 % vs. 47.5 %, p &lt; 0.05; Msr ± m: 2.4 ± 0.5 vs. 1.4 ± 0.3 pg/ml, p &lt; 0.05), IL-8 (100 % vs. 75 %, p &lt; 0.01; 492.9 ± 75.7 vs. 8.5 ± 1.5 pg/ml, p &lt; 0.01), angiogenin (3822.4 ± 498.6 vs. 2820.2 ± 319.3, p &lt; 0.01) and FGFb (58.3 % vs. 26.7 %, p &lt; 0.05; 10.1 ± 5.9 vs. 2.7 ± 1.0, p &lt; 0.01). In both groups of patients, antiangiogenic factors IFN-γ and TGF-β were practically not detected, but the concentration of IFN-α was significantly higher (6.4 ± 1.7 versus 4.4 ± 0.4, p &lt; 0.01). VEGF levels in both nosological groups were almost identical: 17.5 ± 14.0 (with nAMD) versus 18.4 ± 3.2 (n/a), while VEGF was found in vitreous fluid in the cataract group significantly more often (68.2 % vs. 17 %, p &lt; 0.01). By way of explanation, the authors suggested that since patients with nAMD had previously been administered the anti-angiogenic drug Ranibizumab, it is possible that the VEGF production was under the control of the drug, that is, suppressed or blocked.Conclusion. Elevated levels of proangiogenic growth factors IL-8, angiogenin, TNF-α and bFGF in vitreous fluid with nAMD against the background of antiangiogenic therapy with ranibizumab suggest the presence of other, independent of VEGF, acting mechanisms for stimulating angiogenesis. The absence of antiangiogenic growth factors IFN-γ and TGF-β in the vitreous fluid allows us to think about the presence of a defect in the control and regulation of angiogenesis in nAMD. The rare detection of VEGF in combination with a significant decrease in its concentration compared to senile cataracts against the background of treatment with ranibizumab of the eyes with nAMD demonstrates targeted inhibition in practice. Against the background of treatment with angiostatic drugs, an inversion of the angiogenic phenotype occurs with the formation of new workarounds of angiogenesis, which apparently dictates the connection of drugs with other mechanisms of action.

Topical and oral applications of Aloe vera improve healing of deep second-degree burns in rats via modulation of growth factors

Introduction Burn injuries are underappreciated injuries that cause significant morbidity and mortality. Burn injuries, especially severe burns, trigger immunological and inflammatory responses, metabolic abnormalities, and distributive shock, all of which can be extended to multiple organ failures. Aloe vera (A. vera) has been exploited for its medicinal properties for centuries. The goal of the present study is to examine the therapeutic effect of topical and oral administration of A. vera against deep second-degree burn in rats. Materials and methods skin burn was created on the back of rats, and wound healing was assessed within the three examined groups; control, topical A. vera and oral A. vera throughout 30 days. Wound tissues were examined histologically, immunohistochemically for the expression of transforming growth factor beta-1 (TGF-β1), peroxiredoxin (Prdx6), and mRNA abundance of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was assessed. Results Our finding showed acceleration of wound contraction with both topical and oral A. vera administration. Maturation of granulation tissues was seen in both A. vera-supplemented groups. The topical application of A. vera revealed marked remodelling of the granulation tissues and higher expression levels of TGF-β1, VEGF, bFGF, and Prdx6 in comparison with control and oral A. vera groups (P < 0.001). Conclusion Both oral and topical applications of A. vera have beneficial effects in deep second-degree burn wound healing by boosting the growth factors and antioxidant status of skin tissue. The topical treatment was more efficient in accelerating wound healing and hence could be used efficiently to treat second-degree burns.