Process Of Angiogenesis Research Articles

Клінічні особливості персистування бронхіальної астми в дітей за альтернативного вмісту маркерів ремоделінгу в дихальних шляхах

The research of bronchial remodeling and the role of angiogenesis processes in it are currently relevant for the study of the phenotypic features of the course of bronchial asthma in children and require further study in order to develop preventive and therapeutic measures. Purpose - to optimize treatment and prevention measures for persistent bronchial asthma (pBA) in children, to determine the clinical and anamnestic features of its phenotype, taking into account the accumulation of mediators of neoangiogenesis (фактора росту ендотелію судин - VEGF, матрична металопротеїназа-9 - MMP-9) in the respiratory tract as markers of bronchial remodeling. Materials and methods. A comprehensive examination of 116 children with pBA aged from 6 to 17 years (average age 11.6±0.29 years) and disease duration of 4.9±0.38 years was conducted. Three clinical groups were formed: the Group 1 was formed by 37 children with pBA with VEGF >80.0 ng/ml and MMP-9 >5.2 ng/ml in the sputum supernatant; the Group 2 included 41 children with an excess of one of these markers; and the control group consisted of 38 patients with values of these biomarkers below the median (VEGF<80.0 ng/ml and MMP-9 <5.2 ng/ml). The main clinical characteristics of the observation groups were comparable. Results. The article shows that uncontrolled pBA (sum of points >20) during the 4-year follow-up occurred most often in children of еру Group 1 and the Group 2, and indications of insufficient control of asthma indicated a probable risk of developing structural changes in the bronchi: OR - 2.23 (95% CI: 1.2-4.1), RR - 1.5 (95% CI: 1.0-2.2) and RR - 22%. The severe course of pBA was also associated with the risk of bronchial remodeling with the accumulation of angiogenesis mediators in their lumen as follows: OR - 2.2 (95% CI: 1.1-4.52), RR - 1.42 (95% CI: 1.0-2.5) and AR - 19%. Accumulation of remodeling markers in airways in patients with asthma in the Group 1 and the Group 2 is associated with a predominantly eosinophilic phenotype of the disease. At the same time, patients with a low content of markers of bronchial remodeling in sputum (control group) have better chances of achieving complete control over the symptoms of pBA compared to children with a high content (total absolute risk - 19.0%, total relative risk - 45.1%, the minimum number of patients who need to be treated to obtain a positive result - 2.2) and average (total absolute risk - 10.2%, total relative risk - 30.6%, the minimum number of patients who need to be treated to obtain a positive result - 3.2) content of angiogenesis factors in sputum. Conclusions. In patients with pBA, the accumulation of markers of bronchial remodeling in the lumen of the airways was associated with a severe uncontrolled course of asthma and worse chances of achieving disease control. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Targeting OPA1-Mediated Mitochondrial Fusion Contributed to Celastrol's Anti-Tumor Angiogenesis Effect.

Celastrol, an active triterpenoid extracted from one of the most famous traditional Chinese medicines (TCMs), Tripterygium wilfordii Hook.f., is a novel anti-cancer drug with significant anti-angiogenesis activity. However, the exact molecular mechanisms underlying its anti-tumor angiogenesis effect remain unclear. The process of angiogenesis needs lots of energy supply, which mostly derives from mitochondria, the "energy factory" in our body. This study shows that celastrol exerts visible suppression on tumor growth and angiogenesis in a cell-derived xenograft (CDX). Likewise, it reduced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), suppressed the energy metabolism of mitochondria in the Seahorse XF Mito Stress Test, and triggered mitochondrial fragmentation and NF-κB activation. Mechanically, celastrol downregulated the expression of mitochondrial-sharping protein optic atrophy protein 1 (OPA1), which was further estimated by the OPA1 knockdown model of HUVECs. Specifically, celastrol directly suppressed OPA1 at the mRNA level by inhibiting the phosphorylation of STAT3, and stattic (STAT3 inhibitor) showed the same effects on OPA1 suppression and anti-angiogenesis activity. Overall, this study indicates that celastrol inhibits tumor angiogenesis by suppressing mitochondrial function and morphology via the STAT3/OPA1/P65 pathway and provides new insight for mitochondrion-targeted cancer therapy.

WOUND HEALING CLTI WITHOUT AMPUTATION USING TIME ORIGINAL: A CASE STUDY

Chronic limb-threatening ischemia (CLTI) is clinical syndrome defined by presence PAD in the combination rest pain, gangrene, or lower limb ulceration more than 2 weeks. Arterial ulcers as complication ischemia ulcers risk limb loss, the lesion are generally refractory to healing unless tissue perfusion can be improved prone to progress infection or gangrene. With or without surgery arterial ulcer cause of chronic limb ischemia need wound care treatment. The method is using case study, there are present female 61 years old complain necrotic right & left leg after CABG surgery 1 month ago. Glucose uncontrolled, angiography hard occlusion artery popliteal sinistra and tibialis anterior. Wound management using moist concept with TIME original Framework; tissue management with sharp and safe debridement continue using autolytic debridement using hydrogel base, infection control with iodosorb powder & nano colloidal silver spray alternate every 2 weeks, moisture imbalance using calcium alginate and hydro foam, Migration cell epithelial need the support with collagen lotion to prevent break down periwound skin. This case in wound care management necrotic tissue causes of CLTI failed healing after surgery CABG, using TIME original framework have significant result and wound healing at four months without amputation. Case of wound in critical limb-threatening ischemia need appropriate wound care management to heal the wound. Occlusion artery as problem because cannot heal the wound, but the moist condition granulate tissue will grow with helping vascular endothelium growth factor as angiogenesis process. Using moist concept TIME original framework to create and promote healing without amputation and saving feet to saving lives.
 

Andrographolide Relieves Post-Operative Wound Pain but Affects Local Angiogenesis.

Andrographolide (Andro), the major constituent of Andrographis paniculata Nees (Acanthaceae), is was known to reduces inflammatory reaction. In the current study, the ability of Andro to reduce pain sensation in a rat post-operative wound model was explored. The hind paws of 18 Sprague-Dawley rats (SD) bearing post-operative wounds received the following three treatments: Saline, Andro via direct injection into the paw (Andro-injected) and Tablet containing Andro + poly (lactic-co-glycolic acid) (PLGA) (Andro-tablet). Von Frey tests assessed mechanical allodynia at 1, 3, 5 h and 1-, 2-, 3-, 4-, and 5-days post-operation. Behavioral analyses were performed to measure reaction threshold and reaction frequencies. Immunoreactivity of p-ERK and GluR1 was examined in the dorsal horn of the spinal cord. Histopathological and immunostaining studies were conducted on paw epidermis to observe the gross morphology and angiogenesis. The threshold for inducing allodynia increased and the reaction frequency reduced in the Andro-injected group compared to the saline-group, at 3 h post-surgery and the effect lasted between 3-4 days. The threshold for inducing pain and reaction frequency for the Andro-tablet group did not differ from the saline-treated group. The levels of p-ERK and GluR1 in the dorsal horn were reduced after Andro treatment. No significant difference in wound healing index was observed between saline and Andro-injected groups, but CD-31 staining showed less angiogenesis in the Andro-injected group. Andro significantly reduced mechanical allodynia compared to saline treatment, both in shorter and longer time frames. Furthermore, Andro influenced the expression of p-ERK and GluR1 in the dorsal horn, and the angiogenesis process in the wound healing area.

Therapeutic Role of Curcumin, a Traditional Indian Remedy in Various Ocular Disorders

Curcumin (diferuloylmethane) derived from the rhizome of Curcuma longa L. has been an active ingredient of traditional Chinese medicine and Ayurvedic medicine for thousands of years to treat liver diseases, rheumatoid diseases, diabetes, atherosclerosis, infectious diseases and cancer. Curcumin has multiple essential pharmacological properties namely, antioxidant, anti-inflammatory, antimutagenic, antimicrobial and anticancer activity. Curcumin inhibits oxidative stress, angiogenesis and inflammatory processes and restore body homeostasis. Its effectiveness was also proved for major eye diseases. In this article, the influence of curcumin on various eye diseases such as dry eye disease, conjunctivitis, pterygium, anterior uveitis, glaucoma, cataract, age-related macular degeneration, diabetic retinopathy, corneal neovascularization, corneal wound healing are reported. Data analysis from several clinical and preclinical investigations indicate that curcumin is highly effective as a therapeutic agent in the treatment of various eye disorders.

The content of VEGF, COX-2 and PGE-2 in the blood serum of patients with non-small cell lung cancer with different schemes of conformal radiotherapy in the dynamics of treatment

Background. Overcoming radioresistance is an important problem in radiation oncology. Therefore, the development of new approaches to modeling the radiosensitivity of tumors in cancer patients becomes relevant and important. Cyclooxygenase-2 (COX-2) inhibitors are new agents for radiomodification in various radiation therapy schemes, the use of which slows down angiogenesis by suppressing the activity of the COX-2 enzyme.
 Purpose. To determine the content of indicators of radioresistance: vascular endothelial growth factor (VEGF), COX-2, prostaglandin E-2 (PGE-2) in the blood serum of patients with non-small cell lung cancer (NSCLC) and changes in their levels with different schemes of radiation therapy (RT).
 Materials and methods. 36 patients with NSCLC were examined and treated, who were divided into four groups: RT (the first group – 16 patients), RT with the COX-2 inhibitor – ranselex (the second group – 9 patients), RT with ranselex and cisplatin (the third group – 5 patients ) and RT with cisplatin (fourth group – 6 patients). The patients received a course of radiation treatment using a Clinac 600C linear accelerator. The classical fractionation mode was used, the total focal doses were 60–66 Gy. Cisplatin was prescribed at 30 mg/m2 per week up to a total dose (SD) of 200 mg, the COX-2 inhibitor Rancelex® at a dose of 100 mg per day (active substance – celecoxib). The levels of VEGF, COX-2, and PGE-2 in the blood serum of patients with NSCLC were determined by enzyme-linked immunosorbent assay (ELISA) before and after treatment.
 Results. The level of the angiogenesis marker VEGF after treatment in the group with RT decreases by 1.46 times, in the group with the combined action of RT and ranselex – 2.4 times, in the group with the combined action of PT, ranselex and cisplatin – by 3.7 times, and in the group with the combined effect of RT and cisplatin, it decreases by 1.1 times. The greatest decrease in the level of VEGF is observed with RT in combination with ranselex and cisplatin, which indicates a more effective enhancement of the antiangiogenic effect.
 Conclusions. It has been proven that with various schemes of RT using the COX-2 inhibitor – ranselex and cisplatin in patients with NSCLC, there is a decrease in the radioresistance markers PGE-2 and COX-2, the angiogenesis marker – VEGF, which indicates that the effect of radiomodification on the angiogenesis process is most pronounced in the combined actions of RT and both radio modifiers. The use of COX-2 inhibitors as radiosensitizers in combination with RT provides a new opportunity to increase tumor radiosensitivity.

Testosterone replacement relieves ligature-induced periodontitis by mitigating inflammation, increasing pro-resolving markers and promoting angiogenesis in rats: A preclinical study

ObjectivesThis study aimed to evaluate the inflammatory profile as well as the resolution of inflammation in a ligature-induced periodontal inflammation in rats with depletion and/or supraphysiological testosterone replacement. DesignSixty male rats (Holtzman) were used in the present study. Study groups were created as following: (1) Sham (no testicle removal); (2) Orchiectomy (OCX), 3) OCX + Testosterone (OCX + T); (4) Sham + Ligature (SH + L); (5) OCX+L; and 6) OCX + T + L. The surgeries were performed on day 1, and testosterone was administered weekly since day 1. On day 15, a cotton ligature was placed around the lower first molars and maintained for 15 days. Morphological changes in periodontal tissues were determined by histopathological analysis. Immunohistochemistry (factor VIII) and immunoenzymatic assay were performed to evaluate angiogenesis process and (pro- and anti-) inflammatory markers, respectively. ResultsLigature promoted a marked inflammatory gingival infiltrate and bone loss (P < 0.05). Supraphysiological testosterone treatment increased the percentage of blood vessels, extracellular matrix and fibroblasts in the presence and absence of periodontal inflammation (P < 0.05). A high dose of testosterone increased factor VIII+ blood vessels and IL-10 expression in inflamed gingival tissue, while PGE2, LXA4 and MPO were reduced as a result of supraphysiological testosterone administration (P < 0.05). ConclusionsThese results, in our experimental model, suggest that supraphysiological testosterone treatment stimulated gingival tissue repair during ligature-induced periodontitis, and it seems to be related to an anti-inflammatory and pro-resolutive mechanism resulting by the modulatory effect on PGE2 and IL-10 related to an enhanced angiogenesis.

Anti-Inflammatory Effect of Channa micropeltes Extract in Angiogenesis of Diabetes Mellitus Wound Healing

OBJECTIVE: Channa micropeltes extract contains albumin and omega-6 which possess antioxidant and anti-inflammatory agents that can promote macrophages in the wound healing process associated with diabetes mellitus (DM). In this study, we analyzed Nuclear Factor kappa B (NF-κB) and Vascular Endothelial Growth Factor (VEGF) expression as well as neovascular cells in the inflammatory stage of DM wound healing. METHODS: The 24 males Rattus novergicus were divided into 3 groups that were 20% Channa micropeltes ointment (Group I), 10% Channa striata extract ointment (Group II), and placebo ointment as a control (Group III). Ointments were applied 3 times daily. RESULTS: The highest expression of NF-κB was observed in Group III on Day 4 (15.50 ± 2.38), and the lowest was in treatment of Group I and Group II on Day 8 (4.75 ± 0.96). The highest expression of VEGF was observed in Group I on Day 8 (14.75 ± 0.96), and the lowest was Group III on Day 4 (7.00 ± 1.41). The highest count of neovascular cells was observed in Group I on Day 8 (11.00 ± 2.16), and the lowest was in Group III on Day 4 (5.50 ± 0.58). CONCLUSIONS: Channa micropeltes has an anti-inflammatory effect by regulating NF-κB expression and elevating VEGF expression in the angiogenesis process of DM wound healing.

Gastric Cancer Cell-Derived Exosomal GRP78 Enhances Angiogenesis upon Stimulation of Vascular Endothelial Cells.

Exosomes containing glucose-regulated protein 78 (GRP78) are involved in cancer malignancy. GRP78 is thought to promote the tumor microenvironment, leading to angiogenesis. No direct evidence for this role has been reported, however, mainly because of difficulties in accurately measuring the GRP78 concentration in the exosomes. Recently, exosomal GRP78 concentrations were successfully measured using an ultrasensitive ELISA. In the present study, GRP78 concentrations in exosomes collected from gastric cancer AGS cells with overexpression of GRP78 (OE), knockdown of GRP78 (KD), or mock GRP78 (mock) were quantified. These three types of exosomes were then incubated with vascular endothelial cells to examine their effects on endothelial cell angiogenesis. Based on the results of a tube formation assay, GRP78-OE exosomes accelerated angiogenesis compared with GRP78-KD or GRP78-mock exosomes. To investigate the mechanisms underlying this effect, we examined the Ser473 phosphorylation state ratio of AKT, which is involved in the angiogenesis process, and found that AKT phosphorylation was increased by GRP78-OE exosome application to the endothelial cells. An MTT assay showed that GRP78-OE exosome treatment increased the proliferation rate of endothelial cells, and a wound healing assay showed that this treatment increased the migration capacity of the endothelial cells. These findings demonstrated that GRP78-containing exosomes promote the tumor microenvironment and induce angiogenesis.

Clinical efficacy of the combined use of a pulsed dye laser and enzyme preparation phonophoresis in patients with immature hypertrophic skin scars

BACKGROUND: Taking into account the role of angiogenesis processes in the zone of development of immature scar tissue, it seems pathogenetically justified to use a vascular laser for the correction of hypertrophic skin scars that are at the maturation stage. In this regard, we used a pulsed dye laser, the effect of which is perceived by the patient without pronounced pain, and the technology itself is quite safe and leads to a rapid recovery of the skin after the procedure. Fermencol phonophoresis supplementation of laser therapy with pulsed dye laser has the potential to enhance the therapeutic efficacy of a vascular laser, since Fermenkol is a preparation of collagenases of hydrobiont origin that can destroy the components of the extracellular matrix, the formation of which exceeds in intensity its degradation by matrix metalloproteinases at the stage of formation scar. The use of ultrasound in this case not only accelerates the delivery of proteolytic enzymes, but also exhibits independent fibromodulatory activity.&#x0D; AIM: comparative evaluation of the effectiveness of the use of physiotherapeutic factors (Fermenkol phonophoresis, pulsed dye laser therapy and their combination) in patients with immature hypertrophic skin scars, taking into account clinical research methods.&#x0D; MATERIAL AND METHODS: The study was performed on 125 patients aged 19 to 50 years with immature (less than 6 months) hypertrophic skin scars. All patients were divided into 4 groups according to the simple fixed randomization procedure. The first group (control, 32 patients) received course local compression therapy using silicone plates for two months. The second group (31 patients) was treated with phonophoresis of 0.01% Fermencol gel. The third group (31 patients) was treated with pulsed dye laser. The fourth group (31 patients) received complex treatment, including a combination of two pulsed dye laser procedures and two cycles of Fermencol phonophoresis. Patients were examined twice: before the start of treatment and 2 weeks after the end of the course of treatment. The assessment of the clinical condition of patients was carried out according to the modified Vancouver scale for assessing the signs of cicatricial deformity.&#x0D; RESULTS: Conducting a course of treatment of patients with immature hypertrophic skin scars made it possible to establish a good tolerability of the effects of physiotherapeutic factors. At the same time, the positive dynamics of clinical manifestations of cicatricial changes in the skin, assessed by Vancouver scar scale, in the control and main groups was not the same and increased in the following order: Control Fermencol phonophoresis pulsed dye laser pulsed dye laser + Fermencol phonophoresis. The use of the correlation adaptometry technique, which makes it possible to objectify the obtained clinical data, evaluating them using the category of functional reserves of the body, confirmed that the best clinical result was achieved in the group recieved combined use of pulsed dye laser and Fermencol phonophoresis.&#x0D; CONCLUSION: The conclusion was made about the maximum therapeutic effect in the group of complex use of pulsed dye laser and ultrasound administration of an enzyme preparation, which manifested itself due to the synergistic type of interaction between two physiotherapeutic factors that have different modalities, points of application and mechanisms for implementing their therapeutic activity.

Micronome Revealed miR-205-5p as Key Regulator of VEGFA During Cancer Related Angiogenesis in Hepatocellular Carcinoma.

The high ratio of global mortality rate to incidence rate and steep increase in incidence of liver cancer warrants need for advancement of innovative cancer treatment and therapy for hepatocellular carcinoma (HCC). miRNAs are fascinating prospects as treatments in the form of miRNA mimics or therapeutic targets because of their capacity to target various mRNAs that are changed in diseased states. Micronome is a tool to find signature miRNA for any disease and there is hardly any study on micronome in HCC. The aim of the present study was to identify the genes involved in tumor growth and angiogenesis in HCC patients and determine the signature miRNA by constructing a micronome. Herein, we performed a comprehensive analysis on dysregulated genes obtained from liver cancer gene databases. Only experimentally validated miRNA of angiogenesis genes were included in the study. Micronome was constructed using Cytoscape software and search tools for the retrieval of interacting genes (STRING) database. Dysregulated genes of HCC were integrated with miRNAs for identification of signature miRNA involved and identify genes (acting as positive or negative regulator) to elucidate the potential regulatory pathway or signaling. The study clearly reflects that hsa-mir-205-5p is the signature miRNA for positively regulating angiogenesis in HCC through VEGFA. These regulatory genes and signature miRNAs may be useful to understand the unique angiogenesis process of HCC and quick development of novel/better and cost effective molecular-targeted treatment strategies in HCC as the responsible regulatory molecules can be pinpointed with limited resources with use of bioinformatics.

Antiangiogenic Activity of Quinine Alone and in Combination with vitamin C in both ex vivo and in vivo Assays.

Angiogenesis is the process of vascularization from preexisting blood vessels. It is essential for many physiological and pathological processes. Quinine is an anti-malarial agent belongs to the quinoline alkaloid that can inhibit angiogenesis. Vitamin C is also an important antioxidant and has been shown to reduce angiogenesis in tumor. The study was aimed at investigating the effect of quinine alone and in combination with vitamin C on angiogenesis process. 12 to 14 weeks old male albino rats were used for the study. Quinine was prepared by dissolving in DMSO and was serially diluted. The rat aorta ring assay was employed to investigate the antiangiogenic effect of quinine ex vivo. An in vivo chorioallantoic membrane (CAM) assay was used to measure the blood vessels inhibition zone by quinine. The zone of inhibition was calculated as the mean inhibition area of a blood vessel in mm±SD.The obtained data were statistically analyzed. The results revealed that quinine has a significant dose-dependent inhibition effect on the growth of blood vessels by 98% ± 0.07 in concentration 100µg/ml when compared to the negative control. moreover, the inhibition of blood vessels growth as a measure of the antiangiogenic activity of quinine in combination with vitamin C shows a synergistic effect when the concentration that inhibit 50% of blood vessels growth (IC50) which equals to 5.05 µg/ml resulted in 85% of growth inhibition when combined with IC50 of vitamin C which equals to 22..87µg/ml. The findings suggest that the activity of quinine with vitamin C synergism can greatly lower blood vessels growth in rat aorta rings and CAM assays. Quininehas an inhibitory effect on tumor and can be utilized as an antiangiogenic agent alone or in combination with vitamin C.

Thienopyrimidine-based agents bearing diphenylurea: Design, synthesis, and evaluation of antiproliferative and antiangiogenic activity.

An important role has been considered forthe vascular endothelial growth factor receptor 2 (VEGFR-2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC50 values of 4.5-15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR-2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h.

TGF-β1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.

Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-β and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism. Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-β1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-β1 on breast cancer progression. In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-β1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-β1 induced EndMT by activation of TGF-β and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-β and Notch signaling pathways. Our findings elucidated the mechanism of TGF-β1 in the promotion of angiogenesis and progression by EndMT in breast cancer.

Differentially Expressed Genes Enrichment Analysis of Pancreatic Ductal Adenocarcinoma and Pancreatic Intraepithelial Neoplasia; an In Silico Study

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death in the United States. Determining the genetic alterations involved in the formation of PDAC and its precursor, pancreatic intraepithelial neoplasia (PanIN), may lead to earlier detection and new therapeutic options. We performed an analysis of the genetic alterations responsible for the progression of the normal pancreatic tissue to PanIN and ultimately from PanIN to PDAC. Methods/Case Report Initially, we used the continuous bioinformatic analysis in such a way that the RNA-seq datasets were extracted from the Biojupies database. We separately analyzed two datasets that included PDAC and PanIN, where their differentially expressed genes (DEGs) were obtained by comparison with controls. A Venn diagram was drawn to visualize the overlapping and non-overlapping DEGs in both groups. Using the Enrichr and ShinyGO databases, we examined the cell signaling pathways and ontologies of up/down-regulated genes. We mapped the protein network of important genes involved in cancer pathways by the STRING database. Finally, the shared and non-shared candidate proteins in the PDAC and PanIN pathways with the GEPIA database were confirmed in human samples. Results (if a Case Study enter NA) We found six shared genes in PDAC and PanIN including RAC1, RAP1A, ITGA5, RHOA, FZD2, and FN1, which appear to take part in the transition of PanIN to PDAC. Our result showed that the aforementioned genes are critical in the cell cycle, angiogenesis, and cell death processes. In the next step, the DEGs analysis in both PDAC and PanIN revealed the role of candidate genes (COX5B, NME2, MGLL, and PAICS for PanIN and PRKCA, PLCG2, NOS3, and PTK2 for PDAC) in cellular aging, MAPK, and PI3K/Akt signaling pathways. Conclusion Our findings showed that the overexpression of RAC1, RAP1A, ITGA5, RHOA, FZD2, and FN1 may have an important role in PanIN shifting to PDAC.

The mechanisms of Qizhu Tangshen formula in the treatment of diabetic kidney disease: Network pharmacology, machine learning, molecular docking and experimental assessment

BackgroundQizhu Tangshen Formula (QZTS) has been shown therapeutic effects on diabetic kidney disease (DKD). However, to date, the pharmacological mechanisms remain vague. MethodsTo explore the underlying mechanisms of QZTS in treating DKD using network pharmacology, machine learning, molecular docking and experimental assessment. ResultsFirst, we found that QZTS improved glycolipid metabolism disorder, decreased proteinuria and alleviated kidney tissue injury in DKD model KKAy mice. Then, by integrating multiple databases, a total of 96 targets of 74 active compounds in QZTS and 759 DKD-related genes were acquired. Next, we identified 13 hub targets of QZTS in DKD by three rank algorithms, including functional similarity, topological similarity and shortest path. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that the pathways mainly centered on the processes of glycolipid metabolism disorder, inflammation and angiogenesis. Among them, VEGF signaling pathway was significantly enriched. Molecular docking showed that key active compounds of QZTS all had relatively good binding affinity with predicted hub targets. Finally, animal experiments found that QZTS significantly inhibited the secretion of plasma VEGF and downregulated the protein and mRNA expression levels of AKT, p38MAPK and VEGFR2. ConclusionOur results indicated that QZTS treated DKD via multiple targets and pathways and the VEGF signaling pathway may be highly involved in this process.

Netrin-1 Secreted by Human Osteoarthritic Articular Chondrocytes Promotes Angiogenesis in Vitro.

Netrin-1 expression in articular cartilage is correlated with osteoarthritic changes. We aimed to investigate the contribution of Netrin-1 secreted by human osteoarthritic articular chondrocytes to angiogenesis process in vitro. Human articular chondrocytes were extracted from non-osteoarthritic (n = 10) and osteoarthritic (n = 22) joints obtained from surgical specimens and incubated for 24 hours. Medium conditioned by non-osteoarthritic and osteoarthritic articular chondrocytes were collected. Human umbilical vein endothelial cells (HUVEC) were treated with control and conditioned medium and assessed using assays for cell adherence, migration, and tube formation. Netrin-1 expression and secretion was compared between non-osteoarthritic and osteoarthritic chondrocytes by qPCR, Western blot, and ELISA. The role of chondrocyte-secreted Netrin-1 on HUVEC functions was assessed by immunological neutralization using an anti-Netrin-1 monoclonal antibody. As compared with medium conditioned by non-osteoarthritic chondrocytes, medium conditioned by osteoarthritic chondrocytes permitted tube formation by HUVEC. Both non-osteoarthritic and osteoarthritic chondrocytes expressed Netrin-1 at the RNA and protein levels. At the RNA level, Netrin-1 expression did not differ between non-osteoarthritic and osteoarthritic chondrocytes. At the protein level, Netrin-1 appeared as a full protein of 64 kDa in non-osteoarthritic chondrocytes and as two cleaved proteins of 55 kDa and 64 kDa in osteoarthritic chondrocytes. Immunological neutralization of endogenous Netrin-1 reduced the pro-angiogenic and pro-inflammatory transcriptional profile of HUVEC treated with the medium conditioned by osteoarthritic chondrocytes, as well as their capacities to form tubes. Medium conditioned by osteoarthritic chondrocytes permits tube formation by HUVEC in vitro. This permissive effect is mediated by Netrin-1.

Quantitative study of tumor angiogenesis in three-dimensional matrigel barrier using electric impedance measurement technique

Tumor angiogenesis refers to the development of new blood vessels in tumors and is a vital indicator of cancer metastasis which is the major cause of cancer-related deaths. Study of tumor angiogenesis is critical for the development of potential therapeutic strategies of suppressing cancer metastasis. In the current work, a microfluidic device has been developed and was composed of 2 reservoirs connecting with a Matrigel-filled microchannel. The microchannel was mimicked as a biological barrier and embedded with measurement microelectrodes. New blood vessels were successfully induced to extend along the microchannel. Meanwhile, real-time impedance measurement was conducted to quantitatively monitor the tumor angiogenesis process. The results revealed the extension speed of new blood vessels was proportional to chemical induction level, i.e., VEGF165 concentration. Moreover, tumor angiogenesis was shown to be induced by the VEGF released from cancer cells and significantly correlated to the number of cancer cells. In addition, anti-VEGF suppressor was quantitatively evaluated to study the suppression efficacy of tumor angiogenesis. The current microfluidic device provides a promising tool to study tumor angiogenesis in 3D biological barrier. The impedance technique offers reliable and quantitative evidences for evaluating drug efficacy. Development of tumor angiogenesis analytical platform can potentially lead to develop novel therapeutic strategies of suppressing cancer metastasis.

Topical probiotics and steroids can accelerate the process of angiogenesis in wound repair: A comparative study in rats.

Objective: To asses if Topical probiotics and steroids can accelerate the process of angiogenesis in wound repair. Study Design: Longitudinal Experimental study. Setting: Al-Tibri Medical College. Period: Jan 2020 to Dec 2020. Material &amp; Methods: Total 72 male albino rats were acquired from the animal house of the institution, and 18 as a requirement of per day of sampling included 6 animals/gp. An equal size incision of (2x2cm2) was made in all the animals. Group A was given Topical Normal Saline (Control Group), Group B was given the Probiotic (Lactobacillus Acidophilus), and Group C was given Topical Steroid (Dexamethasone). Samples from the wound created surgically was obtained on the 3rd, 7th, 14th, and 21st Day and slides were created to observe the number of blood vessels formed and angiogenesis under a light microscope. Data was analyzed using SPSS version 21.0. To compare the mean between the groups, the ANOVA was applied along with post hoc Tukey's test. The level of significance was considered P≤0.05. Results: The mean number of blood vessels formed in Group A (Control Group) was 2.75, 4, 5.25, and 5.50, in Group B (Probiotics Group) was 10, 13.50, 2.25, and 1, and in Group C (Steroid Group) was 3.75, 5.50, 3, and 2.25 on the 3rd, 7th, 14th, and 21st Day respectively. Significant difference was seen in the mean number of blood vessels formed when the Probiotic group was compared to Group A and C. Conclusion: Topical Probiotic accelerates the process of angiogenesis in wound repair due to their anti-inflammatory response.

Determination of Microvessel Density by CD34 Immunoreactivity in Female Breast Cancer and its Relation with Grading and Staging

Background: Angiogenesis is a basic process that enables neoplasm to thrive. Microvessel density (MVD) evaluation is an accepted parameter for assessing the angiogenesis process within a tumour. The research was focused to evaluate angiogenesis by using CD34 immunomarker in invasive breast cancer and to correlate the microvessel density with grades and stages. Objective: To determine microvessel density by CD34 immunoreactivity in female breast cancer and its relation with grading and staging. Methods: This cross-sectional descriptive type of study was conducted in the Department of Pathology, Rajshahi Medical College. Forty-five untreated cases of breast cancer were included in this study between the period of July 2019 to June 2021 and paraffin embedded sections were obtained from representative mastectomy specimen. The sections were stained with hematoxylin and eosin stain followed by evaluation of angiogenesis by using CD34 antibody. Results: In this study, most of the patients (71.1%) belonged to age &lt; 50 years where the mean age was found 47.5 + 12.4 years. In 45 cases, tumour sizes ranged from 1-8 cm. 86.7% (39 cases) ranges from 0-5 cm, where only (6 cases) 13.3% were more than 5 cm. About 30 cases (66.7%) lymph nodes were positive for metastasis. According to histopathological grade 51.1% belonged to grade III followed by 28.9% grade II and 20% grade I. Histological stage showed most of the cases was stage II (48.9 %) followed by stage I (26.7 %) then stage III (24.4 %). Upon statistical analysis, a significant relation was obtained between MVD with increasing histologic grades and stages. Conclusion: As a new prognostic marker it would be of great value in diagnosis and in identifying patients at high risk of tumor recurrence more accurately. By this way breast cancer patients might be benefited from adjuvant therapies.