Search results for: endothelial cell growth supplement (ECGS)

Authors: Gorbunova Tatiana L.

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The research is dedicated to the study of the polluted river inflow impact on the Black Sea coastal marine environment within the watercourse’s plumes in the Greater Sochi area applying bioassay methods using freshwater and marine microalgae. River waters were analyzed using microalgae Chlorella vulgaris Beijer and sea waters were tested with marine diatoms Phaeodactylum tricornutum Bohlin. Experiments included algae cell abundancy growth assessments in acute (24 hours), sub-acute (72 hours) and chronic (168 hours / 7 days) tests. The increase in algal cell growth rates compared to the control in the summer period was detected as a consequence of the recreational activities intensification during the tourism seasonal peak. Most of the analyzed samples demonstrated a significant effect of algae cell growth stimulation compared to the control. It is established that under the impact of contaminants carried by river drain to the sea, the capacity of the coastal marine ecosystem is partially capable of compensating for its effect on the coastal biocenosis, but the general trends of the impact processes remain constant.

Keywords: algae abundance growth, bioassay, microalgae, modeling

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Authors: Ivan Zupan, Tomislav Saric, Suzana Tkalcic

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IMUNO-2865® is a commercially available, β–glucan based, natural hemicellulose compound with proven immunostimulative properties in people, domestic and some aquatic animals. During the experimental feeding trial with IMUNO-2865® in juvenile wild-caught chub under laboratory conditions, supplementation resulted in overall higher growth performance for all experimental groups regardless of the concentration of the added compound. The maximum, 5% concentration of the supplement, resulted in highest weight gain and calculated specific growth rate. In sea bream, as economically most important species in the Mediterranean aquaculture, significant increases in numbers of monocytes and heterophils were observed in the group supplemented with 2.5 % of IMUNO-2865® in the feed. An overall increase of erythrocytes was noted by the end of the experiment, although with variable distribution among groups. Blood Ca++ levels, total proteins, and total NH₃ were significantly higher after 60 days of feeding in all treatment groups compared to the control and remained elevated in the treated group following the secession of supplementation. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and serum paraoxonase PON1 (U/L) showed similar trends. All these parameters are playing a significant role in either oxygen supplementation of tissues, or anabolic and catabolic processes that on molecular levels contribute to the overall health and immune-building capacity of cells and tissues. The complete lack of mortality in sea bream and presented increases in cellular, biochemical and oxidative stress parameters in the blood suggest that the IMUNO-2865® represents a safe dietary supplement for in aquaculture, with an overall positive and potentially immunostimulative effect on farmed fish.

Keywords: IMUNO-2865®, β–glucans, Mediterranean aquaculture, fish imunnostimulans

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Urasri Imsomboon, Sopita Areerob, Kanchaporn Kongchauy, Tuchapong Ngarmukos

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Objective: The Trans-telephonic Electrocardiography (ECG) monitoring is used to diagnose of infrequent cardiac arrhythmias and improve outcome of early detection and treatment on suspected cardiac patients. The objectives of this study were to explore incidence of cardiac arrhythmia using Trans-Telephonic and to explore time to first symptomatic episode and documented cardiac arrhythmia in outpatients. Methods: Descriptive research study was conducted between February 1, 2016, and December 31, 2016. A total of 117 patients who visited outpatient clinic were purposively selected. Research instruments in this study were the personal data questionnaire and the record form of incidence of cardiac arrhythmias using Trans-Telephonic ECG recorder. Results: A total of 117 patients aged between 15-92 years old (mean age 52.7 ±17.1 years), majority of studied sample was women (64.1%). The results revealed that 387 ECGs (Average 2.88 ECGs/person, SD = 3.55, Range 0 – 21) were sent to Cardiac Monitoring Center at Coronary Care Unit. Of these, normal sinus rhythm was found mostly 46%. Top 5 of cardiac arrhythmias were documented at the time of symptoms: sinus tachycardia 43.5%, premature atrial contraction 17.7%, premature ventricular contraction 14.3%, sinus bradycardia 11.5% and atrial fibrillation 8.6%. Presenting symptom were tachycardia 94%, palpitation 83.8%, dyspnea 51.3%, chest pain 19.6%, and syncope 14.5%. Mostly activities during symptom were no activity 64.8%, sleep 55.6% and work 25.6%.The mean time until the first symptomatic episode occurred on average after 6.88 ± 7.72 days (median 3 days). The first documented cardiac arrhythmia occurred on average after 9 ± 7.92 days (median 7 day). The treatments after patients known actual cardiac arrhythmias were observe themselves 68%, continue same medications 15%, got further investigations (7 patients), and corrected causes of cardiac arrhythmias via invasive cardiac procedures (5 patients). Conclusion: Trans-telephonic: portable ECGs recorder is effective in the diagnosis of suspected symptomatic cardiac arrhythmias in outpatient clinic.

Keywords: cardiac arrhythmias, diagnosis, outpatient clinic, trans-telephonic: portable ECG recorder

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Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

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Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

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Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

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Authors: Edite Kulmane, Mara Pilmane, Romans Lacis

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Introduction: Acquired heart diseases remain one of the leading health care problems in the world. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. The aim of this study was to identify appearance and distribution of apoptosis, homeostasis regulating factors, and innervation and ischemia markers in right atrial tissue in different acquired heart diseases. Methods: During elective open heart surgery were taken right atrial tissue fragments from 12 patients. All patients were operated because of acquired heart diseases- aortic valve stenosis (5 patients), coronary heart disease (5 patients), coronary heart disease and secondary mitral insufficiency (1 patient) and mitral disease (1 patient). The mean age was (mean±SD) 70,2±7,0 years (range 58-83 years). The tissues were stained with haematoxylin and eosin methods for routine light-microscopical examination and for immunohistochemical detection of protein gene peptide 9.5 (PGP 9.5), human atrial natriuretic peptide (hANUP), vascular endothelial growth factor (VEGF), chromogranin A and endothelin. Apoptosis was detected by TUNEL method. Results: All specimens showed degeneration of cardiomyocytes with lysis of myofibrils, diffuse vacuolization especially in perinuclear region, different size of cells and their nuclei. The severe invasion of connective tissue was observed in main part of all fragments. The apoptotic index ranged from 24 to 91%. One specimen showed region of newly performed microvessels with cube shaped endotheliocytes that were positive for PGP 9.5, endothelin, chromogranin A and VEGF. From all fragments, taken from patients with coronary heart disease, there were observed numerous PGP 9.5-containing nerve fibres, except in patient with secondary mitral insufficiency, who showed just few PGP 9.5 positive nerves. In majority of specimens there were regions observed with cube shaped mixed -VEGF immunoreactive endocardial and epicardial cells. Only VEGF positive endothelial cells were observed just in few specimens. There was no significant difference of hANUP secreting cells among all specimens. All patients operated due to the coronary heart disease moderate to numerous number of chromogranin A positive cells were seen while in patients with aortic valve stenosis tissue demonstrated just few factor positive cells. Conclusions: Complex detection of different factors may indicate selectively disordered morphopathogenetical event of heart disease: decrease of PGP 9.5 nerves suggests the decreased innervation of organ; increased apoptosis indicates the cell death without ingrowth of connective tissue; persistent presence of hANUP proves the unchanged homeostasis of cardiomyocytes probably supported by expression of chromogranins. Finally, decrease of VEGF detects the regions of affected blood vessels in heart affected by acquired heart disease.

Keywords: heart, apoptosis, protein-gene peptide 9.5, atrial natriuretic peptide, vascular endothelial growth factor, chromogranin A, endothelin

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Mohammad Soltani, Ayoub Saeidi, Nikoo Khosravi, Hanieh Nohbaradar, Seyedeh Parya Barzanjeh, Hassane Zouhal

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Exercise training and herbs supplement represent have role in the treatment for patients with type 2 diabetes (T2D). However, it is unclear combined effects of exercise training and herbs supplements on diabetic risk markers. This study aimed to determine the effect of 12 weeks of combined exercise and broccoli supplementation on decitin-1 and insulin resistance in men with type 2 diabetes. Forty-four type 2 diabetes men (age, 48.52 ± 4.36) were randomly allocated to training -supplement (TS, n = 11), training- placebo (TP, n = 11), supplement (S, n = 11) and control- placebo (CP, n = 11) groups. The combined exercise program included 12 weeks, three sessions per week, that each session contained 45 minutes of resistance training with intensity 60-70% of one maximal repetition and 30 minutes aerobic training (running) with intensity 60-70% of maximum heart rate. In addition supplement groups consumed 10 grams of Broccoli per day for 12 weeks. Plasma Decitin-1, HOMA-IR, Insulin, glucose and body composition were assessed before and after training. Plasma Dectin-1, HOMA-IR, glucose and BMI significantly decreased in TS, TP and S groups compared with CP group (P < .05). In addition Insulin and skeletal muscles mass showed significant increase in TS and TP groups compared with S and CP groups (P < .05). It is concluded that both combined exercise training (aerobic-resistance) or broccoli supplement can improve plasma Decitin-1 and insulin resistance in two diabetic patients however combine of exercise training and broccoli supplement have more effective on these markers.

Keywords: broccoli supplements, combined training, decitin-1, insulin resistance, type 2 diabetes

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Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Ganesh K. Maurya, Reema Chaudhary, Neha Pandey, Hari S. Misra

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PprA, a pleiotropic protein participating in radioresistance, has been reported for its roles in DNA replication initiation, genome segregation, cell division and DNA repair in polyextremophile Deinococcus radiodurans. Interestingly, expression of deinococcal PprA in E. coli suppresses its growth by reducing the number of colony forming units and provide better resistance against γ-radiation than control. We employed different biochemical and cell biology studies using PprA and its DNA binding/polymerization mutants (K133E & W183R) in E. coli. Cells expressing wild type PprA or its K133E mutant showed reduction in the amount of genomic DNA as well as chromosome copy number in comparison to W183R mutant of PprA and control cells, which suggests the role of PprA protein in regulation of DNA replication initiation in E. coli. Further, E. coli cells expressing PprA or its mutants exhibited different impact on cell morphology than control. Expression of PprA or K133E mutant displayed a significant increase in cell length upto 5 folds while W183R mutant showed cell length similar to uninduced control cells. We checked the interaction of deinococcal PprA and its mutants with E. coli DnaA using Bacterial two-hybrid system and co-immunoprecipitation. We observed a functional interaction of EcDnaA with PprA and K133E mutant but not with W183R mutant of PprA. Further, PprA or K133E mutant has suppressed the ATPase activity of EcDnaA but W183R mutant of PprA failed to do so. These observations suggested that PprA protein regulates DNA replication initiation and cell morphology of surrogate E. coli.

Keywords: DNA replication, radioresistance, protein-protein interaction, cell morphology, ATPase activity

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Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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Authors: Ugwuowo Leonard Chidi, Oparaji Chetachukwu Jecinta., Ogidi Chibuzor Agafenachukwu, Onuoha Rebecca Obianuju

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This experiment was conducted to investigate the growth performance, haematology and serum biochemistry indices of broiler birds fed diets containing Neem leaf meal. A total of 96 unsexed day-old broiler birds were allocated to four treatments of T1, T2, T3 and T4 and replicated three times with eight birds per replicate in a Completely Randomized Design. The treatments were diets containing 2.0, 4.0, 6.0 and 8.0% Neem leaf meal respectively. Growth performances, packed cell volume, red blood cell count, haemoglobin, white blood cell count, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration, platelet count, aspartate amino transaminase, alanine amino transaminase, alkaline phosphate, cholesterol, albumin, globulin, urea, glucose, total protein and creatinine were evaluated. Results showed that there were no significant differences (P>0.05) in all the growth performance parameters among the treatments. The results of the experiment showed that there were significant differences (P<0.05) in all the heamatological and serum biochemistry parameters at finisher phases. Mean corpuscular volume, white blood cell count, lymphocytes, red blood cell count, haemoglobin, platelet count, creatinine and triglyceride increased and were highest in treatment two while treatment four had the least values in mean corpuscular volume, urea, white blood cell, haemoglobin and triglyceride. This implies that the levels of inclusion of Neem leaf meal in this experiment did not affect the growth performance of the broiler chicks but the haematological and serum biochemistry indices were affected. Treatment two with a 4% inclusion level of Neem leaf meal has shown the capacity to replace vaccines and antibiotics in broilers due to the positive effects it had on both the haematological and serum biochemistry.

Keywords: leaf meal, broiler, Aziradicta indica, serum biochemistry, haematology

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Authors: Dalia Atallah, Lamiaa Ahmed, Hala Zaki, Mahmoud Khattab

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Background: Isoprenaline (ISO) administration induces myocardial damage via oxidative stress and endothelial dysfunction. Atorvastatin (ATV) treatment improves both oxidative stress and endothelial dysfunction yet recent studies have reported a pro-oxidant effect upon ATV administration on both clinical and experimental studies. The present study was directed to investigate the effect of ATV pre-treatment and treatment on ISO-induced myocardial damage. Methods: Male rats were divided into five groups (n = 10). Rats were given ISO (5mg/kg/day, i.p.) for one week with or without ATV (10mg/kg/day, p.o.). ATV was given either as pre-treatment for one week before its co-administration with ISO for another week or as a treatment for two weeks at the end of the ISO administration. At the end of the experiment, the electrocardiographic examination was done and blood was isolated for the estimation of plasma creatine kinase MB (CK-MB) activity. Rats were then sacrificed and the whole ventricles were isolated for histological examination and the estimation of lipid peroxides as malondialdehyde (MDA) level, reduced glutathione (GSH) level, catalase activity, total nitrate-nitrite (NOx), as well as the estimation of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) protein expression. Results: ISO-induced myocardial damage showed a significant elevation in ST segment, an increase in CK-MB activity, as well as increased oxidative stress biomarkers. Also, ISO-treated rats showed a significant decrease in myocardial NOx level and eNOS as well as degeneration in the myocardium. ATV pre-treatment didn’t show any protection to ISO-treated rats. On the other hand, ATV treatment showed a significant decrease in both the elevated ST wave and CK-MB activity. Moreover, ATV Treatment succeeded to improve oxidative stress biomarkers, tissue NOx, and eNOS protein expression, as well as amelioration of the histological alterations. Conclusion: Pre-treatment with ATV failed to protect against ISO-induced damage. This might suggest a synergistic pro-oxidant effect upon administration of the pro-oxidant ISO along with ATV as demonstrated by the increased oxidative stress and endothelial dysfunction. On the other side, ATV treatment succeeded to significantly improve oxidative stress biomarkers, endothelial dysfunction and myocardial degeneration.

Keywords: atorvastatin, endothelial dysfunction, isoprenaline, oxidative stress

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Authors: Mengfei Peng, Serajus Salaheen, Debabrata Biswas

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Lactobacillus casei found in the human intestine and mouth is commonly applied for dairy production. Recently, it was found that some byproducts produced by Lactobacillus exhibited antimicrobial activities against multiple bacteria. Meanwhile, introduction of prebiotic-like foods (e.g. cocoa) or probiotics or both of them as food supplements in human diets as well as in farm animal feeds is believed to be an effective ways in control/reduce the colonization of foodborne bacterial pathogens infection in the gut environment. We hypothesized that cocoa may stimulate the production antimicrobial components of Lactobacillus casei and may potentially inhibit/reduce the colonization and infection of foodborne bacterial pathogens in the gut. Mixed culture of L. casei (LC) with enterohemorrhagic E. coli EDL933 (EHEC), Salmonella Typhimurium LT2 (ST), or Listeria monocytogenes LM2 (LM) showed that LC could competitively exclude (100%) them within 72 h. Further, investigation of cell-free culture supernatant (CFCS) revealed that the antimicrobial effects of LC came from CFCS. CFCS of LC eliminated (100%) EHEC, ST, and LM within 72 h, and 2 h CFCS treatment increased the hydrophobicity of EHEC (5.10 folds), ST (8.48 folds), and LM (2.03 folds). In addition, LC cells exhibited more inhibitive effects than CFCS on cell adhesive and invasive activities of EHEC (52.14% & 90.45%), ST (66.89% & 93.83%), and LM (61.10% & 83.40%). Two clusters of poly-peptides in CFCS were identified by SDS-PAGE, the molecular weights of which are ≈5 KD and 40-45 KD. LC CFCS with overnight growth in the presence of 3% strengthened all of the antimicrobial activities (growth inhibition, outer membrane disruption, and cell infective ability reduction). Liquid chromatography/Mass spectrometry analysis detected 5 unique components in class of flavonoids in LC CFCS with overnight 3% cocoa supplement. Furthermore, qPCR results showed that CFCSs up-regulated the expression level of genes responsible for flagellin synthesis and motility, but down-regulated genes for specific binding and invasion-associated proteins synthesis. The stimulatory effects of cocoa in producing bioactive components of probiotics may aid prevention of foodborne illness caused by major foodborne enteric bacterial pathogens.

Keywords: foodborne pathogens, probiotics, prebiotics, pathogen exclusion

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Authors: Mosima M. Mabitsela

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Groundnut is preferably grown on light textured soils. Most of these light textured soils tend to be highly weathered and characterized by high soil acidity and low nutrient status. One major soil factor associated with infertility of acidic soils that can negatively depress groundnut yield is aluminium (Al) toxicity. In plants Al toxicity damages root cells, leading to inhibition of root growth as a result of the suppression of cell division, cell elongation and cell expansion in the apical meristem cells of the root. The end result is that roots become stunted and brittle, root hair development is poor, and the root apices become swollen. This study was conducted to determine the effects of aluminium (Al) toxicity on a range of groundnut varieties. Fifteen cultivars were tested in incremental aluminum (Al) supply in an ebb and flow solution culture laid out in a randomized complete block design. There were six aluminium (Al) treatments viz. 0 µM, 1 µM, 5.7 µM, 14.14 µM, 53.18 µM, and 200 µM. At 1 µM there was no inhibitory effect on the growth of groundnut. The inhibition of groundnut growth was noticeable from 5.7 µM to 200 µM, where the severe effect of aluminium (Al) stress was observed at 200 µM. The cultivars varied in their response to aluminium (Al) supply in solution culture. Groundnuts are one of the most important food crops in the world, and its supply is on a decline due to the light-textured soils that they thrive under as these soils are acidic and can easily solubilize aluminium (Al) to its toxic form. Consequently, there is a need to develop groundnut cultivars with high tolerance to soil acidity.

Keywords: aluminium toxicity, cultivars, reduction, root growth

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Authors: E. A. Amao, O. D. Amao, Z. O. Buzari, T. M. Adelegan, W. A. Tiamiyu, M. O. Yunus

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Signals from in vivo as well as in vitro studies shows that botanicals play notable roles in the treatment, prevention and management of diseases. Use of natural compounds in botanicals has been suggested as potential alternative to conventional therapeutic options. Therefore this study aimed to evaluate the effect of varying levels of turmeric powder (Curcuma longa) on semen characteristics and haematological indices of cocks. Turmeric (C. longa) was obtained from a local market in Saki in Oyo State, Nigeria, in March 2023. The rhizomes were washed, its skin scraped and air-dried for about 10 h, and further oven-dried at 40◦C for 12 h. afterwards, the dried turmeric was ground into powder using a blender. The product was kept in an air-tight container until the period of usage. The experimental material was drenched in cocks (60 cocks assigned into four treatments with three replicates) at 0.0g (T1), 0.05g (T2), 1.00g (T3) and 1.5g (T4) after 2 weeks of acclimatization. Semen volume, sperm cell progressive motility, sperm cell liveability, acrosome integrity, sperm cell concentration and normal sperm cell were evaluated for semen characteristics. Haematological parameters measured were: PCV, RBC, WBC Hb, MCV, MCH and MCHC. Data obtained were subjected to one-way analysis of variance. Semen volume (0.34 – 0.37ml), sperm cell progressive motility (68.33 – 80%), sperm cell liveability (46.66 – 85.00%), acrosome integrity (50.00 – 85%) and normal sperm cell (66.66 – 90%) shows significant difference (p<0.05) in favour cocks on higher level of turmeric powder. While sperm cell concentration (28.33 -40.00 X109/ml) shows no significant difference (p>0.05). PCV (36.00 – 40.33%), RBC (3.55 – 3.74 X106/ml), WBC (19.01 – 19.71 X109/ml), Hb (11.66 – 13.00 dl), MCV (100.53 – 109.53 ⴄ), MCH (32.57 – 35.31pg) and MCHC (32.00 – 32.37%) shows no significant difference (p>0.05). all serum biochemical indices showed significant difference (p<0.05) with animals on the test ingredient showed higher values in respect of the increase in turmeric powder.

Keywords: semen volume, total protein, packed cell volume, turmeric powder, albumin

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Authors: Hossein Pourbashash

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Recent experimental studies have shown that HIV can be transmitted directly from cell to cell when structures called virological synapses form during interactions between T cells. In this article, we describe a new within-host model of HIV infection that incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. We conduct the local and global stability analysis of the model. We show that if the basic reproduction number R0 1, the virus is cleared and the disease dies out; if R0 > 1, the virus persists in the host. We also prove that the unique positive equilibrium attracts all positive solutions under additional assumptions on the parameters.

Keywords: HIV virus model, cell-to-cell transmission, global stability, Lyapunov function, second compound matrices

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Authors: Simone F. Medeiros, Isabela F. Santos, Rodolfo M. Moraes, Jaspreet K. Kular, Marcus A. Johns, Ram Sharma, Amilton M. Santos

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Tissue engineering aims to develop alternatives to treat damaged tissues by promoting their regeneration. Its basic principle is to place cells on a scaffold capable of promoting cell functions, and for this purpose, polymeric nanoparticles have been successfully used due to the ability of some macro chains to mimic the extracellular matrix and influence cell functions. In general, nanoparticles require surface chemical modification to achieve cell adhesion, and recent advances in their synthesis include methods for modifying the ligand density and distribution onto nanoparticles surface. However, this work reports the development of biodegradable polymeric nanoparticles capable of promoting cellular adhesion without any surface chemical modification by ligands. Biocompatible and biodegradable nanoparticles based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) were synthesized by solvent evaporation method. The produced nanoparticles were small in size (85 and 125 nm) and colloidally stable against time in aqueous solution. Morphology evaluation showed their spherical shape with small polydispersity. Human osteoblast-like cells (MG63) were cultured in the presence of PHBHV nanoparticles, and growth kinetics were compared to those grown on tissue culture polystyrene (TCPS). Cell attachment on non-tissue culture polystyrene (non-TCPS) pre-coated with nanoparticles was assessed and compared to attachment on TCPS. These findings reveal the potential of PHBHV nanoparticles for cell adhesion and growth, without requiring a matrix ligand to support cells, to be used as scaffolds, in tissue engineering applications.

Keywords: tissue engineering, PHBHV, stem cells, cellular attachment

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Authors: Hawraa Zbeeb, Hala Khalifeh, Mohamad Khalil, Francesca Storace, Francesca Baldini, Giulio Lupidi, Laura Vergani

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Sarcopoterium spinosum, a widely distributed spiny shrub belonging to the Rosaceae family, is rich in essential and beneficial constituents. In fact, S. spinosum fruits and roots are traditionally used as herbal medicine in the eastern Mediterranean landscape, and this shrub is mentioned as a medicinal plant in a large number of ethnobotanical surveys. Aqueous root extracts from S. spinosum are used by traditional medicinal practitioners for weight loss treatment of diabetes and pain. Moreover, the anti-diabetic activity of S. spinosum root extract has been reported in different studies, but the beneficial effects of aerial parts, especially fruits, have not been elucidated yet. The aim of the present study was to investigate the in vitro antioxidant and lipid-lowering properties of an ethanolic extract from S. spinosum fruits using both hepatic (FaO) and endothelial (HECV) cells in an attempt to evaluate its possible employment as a nutraceutical supplement. First of all, in vitro spectrophotometric assays were employed to characterize the extract. The total phenol content (TPC) was evaluated by Folin–Ciocalteu spectrophotometric method and the radical scavenging activity was tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. After that, the beneficial effects of the extract were tested on cells. FaO cells treated for 3 hours with 0.75 mM oleate/palmitate mix (1:2 molar ratio) mimic in vitro a moderate hepato-steatosis. HECV cells exposed for 1 hour to 100 µM H₂O₂ mimic an oxidative insult leading to oxidative stress conditions. After the metabolic and oxidative insult, both cell lines were treated with increasing concentrations of the S. spinosum extract (1, 10, 25 µg/mL) for 24 hours. The results showed the S. spinosum ethanolic extract is rather rich in phenols (TPC of 18.6 mgGAE/g dry extracts). Moreover, the extract showed a good scavenging ability in vitro (IC₅₀ 15.9 µg/ml and 10.9 µg/ml measured by DPPH and ABTS assays, respectively). When the extract was tested on cells, the results showed that it could ameliorate some markers of cell dysfunction. The three concentrations of the extract led to a significant decrease in the intracellular triglyceride (TG) content in steatotic FaO cells measured by spectrophotometric assay. On the other hand, HECV cells treated with increasing concentrations of the extract did not result in a significant decrease in both lipid peroxidation measured by the Thiobarbituric Acid Reactive Substances (TBARS) assay, and in reactive oxygen species (ROS) production measured by fluorometric analysis after DCF staining. Interestingly, the ethanolic extract was able to accelerate the wound repair of confluent HECV cells with respect to H₂O₂-insulted cells as measured by T-scratch assay. Taken together, these results seem to indicate that the ethanol extract from S. spinosum fruits is rich in phenol compounds and plays considerable lipid-lowering activity in vitro on steatotic hepatocytes and accelerates wound healing repair on endothelial cells. In light of that, the ethanolic extract from S. spinosum fruits could be a potential candidate for nutraceutical applications.

Keywords: antioxidant activity, ethanolic extract, lipid-lowering activity, phenolic compounds, Sarcopoterium spinosum fruits

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Authors: Jui-Chien Hsieh

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Background:12-lead electrocardiography(ECG) is one of frequently-used tools to detect atrial fibrillation (AF), which might degenerate into life-threaten stroke, in clinical Practice. Based on this study, the AF detection by the clinically-used 12-lead ECG device has only 0.73~0.77 positive predictive value (ppv). Objective: It is on great demand to develop a new algorithm to improve the precision of AF detection using 12-lead ECG. Due to the progress on artificial intelligence (AI), we develop an ECG deep model that has the ability to recognize AF patterns and reduce false-positive errors. Methods: In this study, (1) 570-sample 12-lead ECG reports whose computer interpretation by the ECG device was AF were collected as the training dataset. The ECG reports were interpreted by 2 senior cardiologists, and confirmed that the precision of AF detection by the ECG device is 0.73.; (2) 88 12-lead ECG reports whose computer interpretation generated by the ECG device was AF were used as test dataset. Cardiologist confirmed that 68 cases of 88 reports were AF, and others were not AF. The precision of AF detection by ECG device is about 0.77; (3) A parallel 4-layer 1 dimensional convolutional neural network (CNN) was developed to identify AF based on limb-lead ECGs and chest-lead ECGs. Results: The results indicated that this model has better performance on AF detection than traditional computer interpretation of the ECG device in 88 test samples with 0.94 ppv, 0.98 sensitivity, 0.80 specificity. Conclusions: As compared to the clinical ECG device, this AI ECG model promotes the precision of AF detection from 0.77 to 0.94, and can generate impacts on clinical applications.

Keywords: 12-lead ECG, atrial fibrillation, deep learning, convolutional neural network

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Authors: Norimichi Nagano, Yoshio Hirano, Tsutomu Yasukawa

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Mesenchymal stem cells are thought to confer neuroprotection, facilitate tissue regeneration and exert their effects on retinal degenerative diseases, however, adverse events such as proliferative vitreoretinopathy and preretinal membrane disease associated with cell suspension transplantation have also been reported. We have recently developed human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) sheets through our proprietary sheet transformation technique, which could potentially mitigate these adverse events. To clarify the properties of our adMSC sheets named PAL-222, we performed in vitro studies such as viability testing, cytokine secretions by ELISA, immunohistochemical study, and migration assay. The viability of the cells exceeded 70%. Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF), which are quite important cytokines for the retinal area, were observed. PAL-222 expressed type I collagen, a strength marker, type IV collagen, a marker of the basement membrane, and elastin, an elasticity marker. Finally, the migration assay was performed and showed negative, which means that PAL-222 is stably kept in the topical area and does not come to pieces. Next, to evaluate the efficacy in vivo, we transplanted PAL-222 into the subretinal space of the eye of Royal College of Surgeons rats with congenital retinal degeneration and assessed it for three weeks after transplantation. We confirmed that PAL-222 suppressed the decrease in the thickness of the outer nuclear layer, which means that the photoreceptor protective effect treated with PAL-222 was significantly higher than that in the sham group. (p < 0.01). This finding demonstrates that PAL-222 showed their retinoprotective effect in a model of congenital retinal degeneration. As the study suggested the efficacy of PAL-222 in both in vitro and in vivo studies, we are presently engaged in clinical trials of PAL-222 for myopic chorioretinal atrophy, which is one of the retinal degenerative diseases, for the purpose of regenerative medicine.

Keywords: cell sheet, clinical trial, mesenchymal stem cell, myopic chorioretinal atrophy

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Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar

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Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.

Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT

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Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue

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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.

Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation

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Authors: Ehsan Ahmadifar

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In this research, the effects of different levels (control group (T0), (T1)1, (T2)2 and (T3)3 gr Inulin per Kg diet) of prebiotic Inulin as nutritional supplement on Danio rerio were investigated for 4 month. Since the beginning of feeding larvae until adult (average weight: 67.1 g, length: 4.5 cm) were fed with experimental diets. The survival rate of fish had no significant effect on rate survival (P > 0.05). The highest food conversion ratio (FCR) was in control group and the lowest was observed in T3. Treatment of T3 significantly caused the best feed conversion ratio in Zebra fish (P < 0.05). By increasing the inulin diet during the experiment, specific growth rate increased. The highest and the lowest body weight gain and condition factor were observed in T3 and control, respectively (P < 0.05). Adding 3 gr inulin in Zebra fish diet can improve the performance of the growth indices and final biomass, also this prebiotic can be considered as a suitable supplement for Cyprinidae diet. In the first sampling stage for feeding fish, fat and muscle protein was significantly higher than the second sampling stage (P < 0.05). Given that the second stage fish were full sexual maturity, the amount of fat in muscle decreased (P < 0.05). Moisture and ash levels were significantly (P < 0.05) higher in the second stage sampling than the first stage. Overall, different stage of living affected on muscle chemical composition muscle. Reproductive performance in treatment T2 and T3 were significantly higher than other treatments (P < 0.05). According to the results, the prebiotic inulin does not have a significant impact on the sex ratio in zebrafish (P > 0.05). Based on histology of the gonads, the use of dietary inulin accelerates the process of gonad development in zebrafish.

Keywords: inulin, zebrafish, reproduction, histology

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Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4, and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.

Keywords: hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Saman Khan, Imrana Naseem

Abstract:

Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

Procedia PDF Downloads 271

Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Dedy Pratama, Akhmadu Muradi, Hilman Ibrahim, Raden Suhartono, Alexander Jayadi Utama, Patrianef Darwis, S. Dwi Anita, Luluk Yunaini, Kemas Dahlan

Abstract:

Introduction: Vascular endothelial growth factor (VEGF) gene shows association with various angiogenesis conditions including Diabetic Foot Ulcer (DFU) disease. In this study, we performed this study to examine VEGF gene polymorphism associated with DFU. Methods: Case-control study of polymorphism of VEGF gene +405 C>G and -460 T>C, of diabetes mellitus (DM) type 2 with Diabetic Foot Ulcer (DFU) in Cipto Mangunkusumo National Hospital (RSCM) Jakarta from June to December 2016. Results: There were 203 patients, 102 patients with DFU and 101 patients without DFU. Forty-nine point 8 percent of total samples is male and 50,2% female with mean age 56,06 years. Distribution of the wild-type genotype VEGF +405 C>G wild type CC was found in 6,9% of respondents, the number of mutant heterozygote CG was 69,5% and mutant homozygote GG was 19,7%. Cumulatively, there were 6,9% wild-type and 85,2% mutant and 3,9% of total blood samples could not be detected on PCR-RFLP. Distribution of VEGF allele +405 C>G C alleles were 43% and G alleles were 57%. Distribution of genotype from VEGF gene -460 T>C is wild type TT 42,9%, mutant heterozygote TC 37,9% and mutant homozygote CC 13,3%. Cumulatively, there were 42,9% wild-type and 51% mutant type. Distribution of VEGF -460 T>C were 62% T allele and 38% C allele. Conclusion: In this study we found the distribution of alleles from VEGF +405 C>G is C 43% and G 57% and from VEGF -460 T>C; T 62% and C 38%. We propose that G allele in VEGF +405 C>G can act as a protective allele and on the other hands T allele in VEGF -460 T>C could be acted as a risk factor for DFU in diabetic patients.

Keywords: diabetic foot ulcer, diabetes mellitus, polymorphism, VEGF

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