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Apr 2019 DOI 10.14302/issn.2328-0182.japst-19-2759
Sterner OlovCorresponding author
Centre for Analysis and Synthesis, Lund University, P.O.Box 124, 22100 Lund, Sweden
Cancer is the leading cause of death worldwide, and there is a constant need for new treatment strategies. Sesquiterpene lactones containing a 3-methylenedihydrofuran-2(3H)-one (or α-methylene-γ-lactone) moiety, for example damsin (1), are Michael acceptors that affect biological processes such as cell proliferation, death/apoptosis, and cell migration, by interfering with cell signalling pathways. Although the reactivity of the α-methylene-γ-lactone moiety is important for these effects, the Michael addition is reversible and it can be assumed that also other parts of the molecules will moderate any given biological activity. In this investigation, the cytotoxicity of 23 -methylene--lactones towards normal breast epithelial MCF-10A cells as well as breast cancer JIMT-1 cells is compared. Most of the investigated compounds are semisynthetic derivatives prepared by the condensation of the natural product damsin (1) with aldehydes. The two cell lines were treated with various concentrations of the compounds in dose response assays, and the 50 % inhibitory concentration (IC50) was determined from dose response curves. The IC50 values were found to depend strongly on the overall structure. The ratio between the IC50 values for MCF-10A and JIMT-1 cells, as a measure for the selectivity of a compound to kill cancer cells, was calculated, and found to vary between just over 1 to more than 10. The most potent derivatives formed from the condensation of 1 with aromatic aldehydes towards JIMT-1 cells are 3a and 3i, both with ratios between the IC50 values for MCF-10A and JIMT-1 cells close to 5. Also some aldol condensation products with acyclic aldehydes, i.e. 3r and 3u, were equally potent, and the latter showed the highest selectivity (ratio > 10). Structure-activity relationships that may explain the observed differences in potency and selectivity are discussed.
Apr 2019 DOI 10.14302/issn.2379-7835.ijn-19-2690
Taechowisan ThongchaiCorresponding author
Department of Biology, Faculty of Science, Silpakorn University, Nakorn Pathom 73000, Thailand.
Objective To investigate the major constituents of Tinosporacordifolia Willd. growing on Mangiferaindica, and to evaluate the efficacy of their antibacterial and cytotoxicity activities. Methods The ethanolic stem extract of T. cordifolia was subjected to silica gel 60 column chromatography, thin layer chromatography and medium pressure liquid chromatography for isolation of the major compounds. Identification of purified compounds was achieved by spectroscopic methods.. The crude extract and purified compounds were screened for their antibacterial and cytotoxicity properties using standard procedures. Results Two alkaloids were purified and identified as Magnoflorin (1) and Tembetarine (2). These compounds showed high antibacterial activity against Bacillus cereus and Staphylococcus aureus with both MIC (32-64 µg/ml) and MBC (128-256 µg/ml). The cytotoxicity activity of the purified compounds and crude extract was determined using MTT colorimetric assay against L929 and HEK293 cell lines. This showed weak cytotoxicity activity with IC50 values of 1162.24 to 2290.00 µg/ml and 1376.67 to 2585.06 µg/ml towards L929 and HEK293 cell lines, respectively. Conclusion The major compounds present in ethanolic stem extract of T. cordifolia growing on M. indica were extracted, purified and identified. This study suggests that these compounds exhibit great potential for antibacterial activity with weak cytotoxicity activity. They may be useful for their medicinal functions.
Aug 2018 DOI 10.14302/issn.2377-2549.jndc-18-2116
Sarani MinaCorresponding author
Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences.
Silver nanoparticles (Ag-NPs) are versatile materials with a broad range of applications in various fields such as cancer therapy, drug delivery. In this work, cytotoxic and apoptotic activities of silver nanoparticles was evaluation against lung (A549) and colon (HT-29) cell lines. The cytotoxic activity of nanoparticles was performed by MTT assay, while their apoptotic activity was tested through TUNEL method. The results of MTT of A549 have illustrate that fifty percent of cells destruction in concentrations more than 250 µg/ml of Ag-NPs. Apoptotic results of nanoparticles have shown more than fifty percent of apoptosis on A549 cell line. HT-29 display full apoptosis at concentrations more than 500 µg/ml. It seems that synthesized Ag-NPs by using P. farcta extract can be candidate as anti-cancer agent in treatment many cancers through creating or discovering new drug forms
May 2023
Bouguerra FadouaCorresponding author
Background and Aim Breast cancer is the second most common cause of brain metastases after lung cancer. However, the incidence of cerebral metastases from breast cancer has increased during the last years. The purpose of this study is to determine the prognostic value of chemotherapy after whole-brain radiotherapy for patients with brain metastases from breast cancer. Methods We analyzed retrospectively 63 records of patients diagnosed with brain metastases from breast cancer and treated in the radiotherapy department at the Salah Azaiz Institute of oncology over a 5-year period between 2007 and 2011. All patients received whole-brain radiotherapy. Only 4 patients had surgical resection of the metastases before radiotherapy and 36.5% of patients received systemic treatment after irradiation. Results Overall survival was 19% at 1-year and median survival was 4,5 months. Univariate analysis indicated that systemic treatment after irradiation was correlated significantly with longer survival. (p=0,046). Conclusion Determining prognostic factors might help optimize individual treatment for metastatic breast cancer. The results of our study suggest that chemotherapy is more effective on brain metastases after irradiation. This can be explained by the fragilization of the blood-brain barrier by radiation and subsequently a better passage of cytotoxic agents.
Feb 2022
K Al Miraj ACorresponding author
Research Assistant, Department of Vascular Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU)Dhaka, Bangladesh.
Introduction Calcium (Ca2+) plays an important role in the pathogenesis of ischemic cell damage. Intracellular Ca2+ accumulation leads to neuronal damage by triggering the cycle of cytotoxic events, however the relationship of serum Ca levels and the pathways involved in ischemic injury is unclear. Aim of Study To investigate the relationship of serum Ca2+ levels with severity of acute ischaemic stroke, serum calcium (Ca2+) levels were measured within the first 48 hours and were compared with the clinical severity of acute ischaemic stroke. Material and Methods A hospital based cross sectional study was performed among 100 patients of acute ischaemic stroke who fulfilled the inclusion criteria. The Study was done from July 2020 to August 2021 in SPRC & Neurology Hospital Dhaka, Bangladesh And BSMMU Hospital Dhaka, Bangladesh. After hospitalization presenting complaints, physical findings of the patients were recorded. Severity of stroke was measured by NIHSS scale. Serum calcium level of every patient was measured. Calcium level was divided into 3 groups by weighted average. Statistical analysis was carried out by a non-parametric Ruska Wallis test. Results Among the 100 patients 59% were male. Among all patients 57% of patients were found to be smokers (98% male, 2% female). Among all patients 63% patients were found hypertensive and 21% of all patients (24% male, 17% female) were diabetic. Mean cholesterol level was 257.98mg/dl with standard deviation 55.49 which is above the reference range suggesting hypercholesterolemia, Triglyceride was borderline and LDL cholesterol was slightly higher and HDL cholesterol was slightly lower. Calcium level was divided into 3 groups and NIHSS score was calculated for every patient in each group. The median NIHSS score for group1 (calcium level ≤8.8 mg/dl) was 9(2-20), for group 2 (calcium level 8.9-9.6 mg/dl) was 6 (1-17) and for group 3 (calcium level ≥9.7mg/dl) was 4 (1-16). Conclusion Commonest risk factor of ischaemic stroke is hypertension. Other risk factors are smoking, diabetes mellitus and hyperlipidemia, cardiac disease. Higher serum calcium level is associated with less severity of ischaemic stroke.
Jan 2020 DOI 10.14302/issn.2690-4829.jen-19-3127
P.A.GhazaryanCorresponding author
Hematology center after prof. R.H.Yeolyan MH RA
The antioxidant and membrane resistant peculiarities of a new derivative (2-cyan-3,4,4-trymethil-2-buten-4-olyd - CTBO) of cyan containing unsaturated lactones have been studied in membranes of hepatocytes with Sarcoma-45 1. The results of our previous research 123 showed significant changes of phospholipid (PL) exchange in hepatocytes of microsomal membranes at experimental animals vaccinated with Sarcoma-45 tumor strain. It is manifested in significant changes of quantitative and qualitative contents of membrane phospholipids separate fractions, increase of cytotoxic lysophospholipids (LPCs), phosphatidylinositol (PI) and phosphatidic acid (PA) levels, significant decrease of phosphatitylcholines (PC) and sphingomyeline (SP) contents, statistically significant changes of PL/PL ratio, peroxidation ratio intensity, dramatic increase of phospholipase A2 (PLA2)activity, quantitative and qualitative changes of adenyl nucleotides, as well as disorders of adenosine triphosphatase (ATPase) system activity 34567.
Feb 2019 DOI 10.14302/issn.2374-9431.jbd-19-2613
H. Radwan EmanCorresponding author
Faculty of Science, Damanhour University, Egypt.
Diabetes mellitus (DM) is a chronic metabolic disorder. Streptozotocin is a naturally occurring cytotoxic chemical, particularly toxic to the pancreas and insulin producing beta cells in mammals and induces diabetes. Glimepiride is a second generation sulfonylurea, used as second-line or add-on treatment options for type 2 diabetes. Fenugreek (Trigonella foenum graecum) seeds have been documented as a traditional plant treatment for diabetes. Soluble dietary fiber of Fenugreek significantly improved oral glucose tolerance in diabetic rats. It also exerts anti-diabetic effects mediated through the inhibition of carbohydrate digestion and absorption and the enhancement of peripheral insulin action. Most herbal remedies can interact with allopathic drugs resulting in altered activity and toxicity. At the same time, herbal remedies might produce the same kind of effects as the drug produce. Current published research information on herb-drug interactions is scanty. So, the aim of this study was to investigate the possible interaction between conventional drug used for the management of diabetes; (Glimepiride) and a traditional herbal remedy; Fenugreek aqueous extract in Streptozotocin induced diabetic male albino rats. In conclusion, combination therapy induces better hematological, biochemical effects and improves the oxidative stress biomarkers and antioxidant enzymes. Histological studies showed better results on some organ functions. The results emphasize the benefit of using the combination of Fenugreek seeds aqueous extracts as supportive complementary anti-diabetic therapy.
Sep 2018
Di Gianfilippo RiccardoCorresponding author
The University of Michigan - School of Dentistry, Department of Periodontics and Oral Medicine, 1011 North University Avenue, 48109-1078, Ann Arbor, MI – USA
MicroRNAs are short sequences of non-coding RNAs crucial in regulation of cell development, proliferation and differentiation. Some of them showed to be related with the expression of osteogenic genes. Aim of the present review was to evaluate the biological effects of titanium implant surfaces activated with miRNAs or antimiRNAs. A bibliographical electronic research was carried out on PubMed/Medline. Articles investigating the influences of miRNA functionalized surfaces on human or animal cells were included. Reports were excluded if investigating surfaces modified with molecules different from miRNAs, if miRNAs were not loaded to titanium surfaces. Five articles met the inclusion criteria. Surfaces functionalized with miRNAs showed to up-regulate the expression of osteogenic genes like RUNX2, OPN, OCN, BMP, OSX, ALP, COL1 and COL3. Investigated surfaces additionally showed more bone-like mineralized tissues, bone lacunae, osteocytes and new blood vessels. MiRNAs loaded to titanium implant surfaces stimulate the expression of genes related to osteoblasts differentiation, osteogenesis, osseointegration and reparation of mineralized tissues. Vectors used to link titanium surfaces and miRNAs did not show cytotoxicity or interference with cells’ viability.
Jan 2018
J Gonzalez MichaelCorresponding author
University of Puerto Rico, Medical Sciences Campus, School of Public Health, San Juan, Puerto Rico
Breast cancer is the most common cancer in women worldwide. In the United States, is the second leading cause of cancer deaths in women. In Puerto Rico between 2008 and 2012, breast cancer was the most diagnosed type of cancer and the leading cause of cancer deaths among women. This is a case of 54 years old female diagnosed with stage IV right breast carcinoma. The patient complaints were weakness and a right breast ulcer. She started a metabolic correction therapy, which consisted of high intravenous vitamin C infusions, a nutritional supplementation plan, and Paleolithic diet. During treatment, both Glycohemoglobin and Carcinoembryonic Antigen levels decreased significantly, the right breast ulcer decreased in size, and the patient’s quality of life improved. Over the years, vitamin C studies have demonstrated a cytotoxic action against malignant cells. Based on the results from this case, we advocate continue studying possible adjuvant treatments for cancer patients, involving IV infusions of vitamin C and metabolic correction plans.
Jul 2017 DOI 10.14302/issn.2471-2140.jaa-17-1630
Aholia Jean- Baptiste AdépoCorresponding author
Laboratoire de Toxicologie et Hygiène Agro-industrielle, UFR Sciences Pharmaceutiques et Biologiques, Université Félix Houphouët-Boigny, BP V 34, Abidjan, Côte d’Ivoire
Introduction: Aflatoxins are cytotoxic andserve as one of the key risk factors of hepatocellular carcinoma. Currently, plants and extract are widely used as potential scavenging substances for the detoxification of mycotoxins. Thus, this study aims to investigate the activity of the crude ethanolic leaves extract from Alchorneacordifolia in aflatoxicosis prevention. Material and Methods: The phytochemical screening was performed through qualitative analysis based on coloring and/or precipitation reactions. Groups of rats were treated daily with a mixture dose of aflatoxin B1 (AFB1) at 150 µg/kg and the crude extract of Alchorneacordifolia at doses of 50, 100, and 300 mg/kg for 21 days. The body weight, biochemical, and histological assessments were determined. Results: The phytochemical screening revealed the presence of polyphenols, flavonoids, sterols and terpenoids, quinoid compounds, tannins catechic and alkaloids. AFB1 treatmentcaused a significant increase of transaminases, urea, and creatinine abundances but reduced the rates of albumin and total proteins. Alchorneacordifolia administration alleviated biochemical parameters and body weight gain compared with the AFB1 group (p<0.05). The histological lesions of organs (liver and kidney) caused by AFB1 were significantly improved after administration of the extract at a dose of 300 mg/kg. Conclusion: This plant plays a beneficial role in AFB1-induced injury and may be used in the treatment of aflatoxicosis.
Aug 2016 DOI 10.14302/issn.2474-9273.jbtm-16-1151
Xing GuoqiangCorresponding author
Departments of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Oxidative stress mediated neural cell death is thought to be involved in the progression of secondary cell injury following brain trauma. Agents that can block oxidative stress-related injury could be potential therapies for TBI. Resveratrol, a polyphenol found in plants and red wine, is cytoprotective due to its potent antioxidant activities. To further understand how resveratrol could affect oxidative stress-induced injury, we hypothesized that the cytoprotective activities of resveratrol could be dose-dependent. In this study, resveratrol-induced cytoprotection was evaluated in cultured astrocytes. Primary rat astrocytes were cultured in T-75 flasks to a confluence of 80% before being plated onto 96-well plates. After 24 hours of acclimation, astrocytes were treated with various doses of hydrogen peroxide (H2O2) (0.1, 0.25, 0.5 and 1 µM) and resveratrol (25, 50, 75, 100 µM), respectively. Cell viability was determined 24 hours later using Alamar Blue Assay. Treatment of astrocytes with 0.5 mM H2O2, left 65% of astrocytes non-viable whereas treatment of astrocytes with 0.1 mM H2O2 had no effect on astrocytes viability; whereas 1 mM, H2O2 caused total loss of astrocyte viability. Resveratrol treatment at 75 µM and 100 µM has reduced 0.5 mM H2O2-induced cytotoxicity in astrocytes by 50%. Immunostaining with GFAP also confirmed these findings about the cytoprotective effects of resveratrol in astrocytes exposed to H2O2. These results suggest that resveratrol could be a potential neuroprotective agent in TBI due to its antioxidant properties. Further studies are needed to evaluate the long- term effects of resveratrol in animal models of TBI.
Apr 2014 DOI 10.14302/issn.2377-2549.jndc-13-329
Kumar Dinda AmitCorresponding author
Department of Pathology, All India Institute of Medical Sciences,Ansari Nagar, New Delhi-110029 (INDIA)
The aim of the study was to synthesize sub-100nm poly-ε-caprolactone nanoparticles (PCL NP), load them with the mycobacterial protein, ESAT 6 and study the resulting immune responses in CD4+ and CD8+ T cells when incubated with human peripheral blood monocyte derived macrophages that had internalized the PCL NP. The synthesized PCL NP were characterized for size, shape and charge. They were found to be about 60nm in size with spherical shape. MTT assay revealed that the particles were perfectly biocompatible when tested in vitro on THP1 human monocytic cell line. The particles had a slow protein release kinetics and did not degrade appreciably even after 30 days in buffer solution. ELISA was used to quantify the cytokine response of CD4+ and CD8+ T cells when incubated with the monocyte derived macrophages as antigen presenting cells. The result of antigen presentation assay revealed that the antigen loaded PCL NP enhanced Th1 and CD8+ T cell responses significantly compared to the pure antigen. Thus we conclude that PCL NP of 60nm size can be effectively tested as a vaccine adjuvant with resulting activation of Th1/Th2 immunity as well as cytotoxic T cell response.
Jan 2014 DOI 10.14302/issn.2328-0182.japst-12-183
D. Mahajan SupriyaCorresponding author
Department of Medicine, Division of Allergy, Immunology, and Rheumatology,
Gold nanorods (GNRs) are plasmonic nanostructures by virtue of their size-dependent optical properties, offer a bionanotechnology platform in areas of bioimaging, drug delivery etc for disease diagnosis, prognosis, and therapy. GNRs are more sensitive to changes in local environments, and offer strong scattering and absorption efficiencies thus providing opportunities to integrate multiple imaging modes and therapeutic strategies. The hydrodynamic size of these GNR under physiological condition is <100 nm, making them ideal as intracellular delivery agents. RNA interference using small inhibitory RNA (siRNA) has become a powerful tool to downregulate mRNA levels by cellular nucleases that become activated when a sequence homology between the siRNA and a respective mRNA molecule is detected. siRNA is used to silence genes involved in the pathogenesis of various diseases and holds a promising option for the development of novel therapeutic strategies in neurological dysregulation such as that observed in drug addiction. However, a major challenge in gene therapy continues to be effective delivery of siRNA and its sustained release at targeted sites. Previously, we have shown the GNR coated with poly (diallyldimethyl ammoniumchloride) (GNR-PDDAC) electrostatically complexed to the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) siRNA forming a GNR-nanoplex that was able to effectively silence the DARPP-32 gene expression in dopaminergic neuronal (DAN) cell cultures in- vitro. The current report, explores if modification of the surface coating properties of the GNRs with different surface coatings namely, amino terminated polyethylene glycol (GNR-PEG), polyethyleneimine (GNR-PEI) and Chitosan (GNR-CIT) alters their stability, cytotoxicity and DARPP-32 gene silencing efficiency in-vitro dopaminergic neuronal (DAN) cell cultures with the goal of determining the most suitable surface coating for the GNR that would provide a GNR-nanoplex with the most stability, least cytotoxicity and most efficacious gene silencing.