A randomized, double-blind, placebo-controlled investigation of BCc1 nanomedicine effect on survival and quality of life in metastatic and non-metastatic gastric cancer patients

Background: Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. Methods: The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. Results: In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days 95% confidence interval (CI) 82.37-265.62) than in placebo (62 days 95% CI 0-153.42); hazard ratio (HR): 0.5 95% CI 0.25-0.98; p = 0.046. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days 95% CI 393.245-664.75) than in placebo (345 days 95% CI 134.85-555.14); HR: 0.324 95% CI 0.97-1.07; p = 0.066. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of - 4.42 and - 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. Conclusion: The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1 © 2019 The Author(s)

DIBc, a nanochelating-based nano metal-organic framework, shows anti-diabetic effects in high-fat diet and streptozotocin-induced diabetic rats

Saideh Fakharzadeh,1&ndash;3 Somayeh Kalanaky,2 Maryam Hafizi,2 Mohammad Hassan Nazaran,2 Homeira Zardooz1,3 1Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 3Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Aims: Despite daily increase in diabetic patients in the world, currently approved medications for this disease, at best, only reduce its progression speed. Using novel technologies is a solution for synthetizing more efficient medicines. In the present study, we evaluated anti-diabetic effects of DIBc, a nano metal&ndash;organic framework, which is synthetized based on nanochelating technology.Methods: High-fat diet and streptozotocin-induced diabetic rats were treated by DIBc or metformin for 6 weeks.Results: DIBc decreased plasma glucose, triglyceride, cholesterol, high-density lipoprotein, and low-density lipoprotein compared with diabetic and metformin groups. In DIBc-treated rats, significant homeostasis model assessment of insulin resistance index, malondialdehyde, and tumor necrosis factor-&alpha; decrease was observed. H&amp;E staining showed increased islet number and area in DIBc-treated rats compared with diabetic controls.Conclusion: The results showed anti-diabetic effects of nanochelating-based framework. So DIBc, as a nano structure, has the capacity to be evaluated in future studies as a novel anti-diabetic agent. Keywords: DIBc, nanochelating technology, metal organic framework, diabetes, streptozotocin, high-fat diet &nbsp

Growth performance, nutrient digestibility, bone mineralization, gut morphology, and antioxidant status in meat-type turkeys receiving diets supplemented with advanced chelate compounds-based minerals

SUMMARY: The aim of this study was to examine the efficiency of dietary supplementation with advanced chelate compounds-based trace minerals (CTM) in growing turkeys. A total of 336 one-day-old turkeys were assigned to 3 dietary treatments, consisting of 8 replicates of 14 birds each. Experimental treatments included: ITM (basal diet; commercially recommended levels of inorganic TM), CTM50 (CTM replaced at 50% of ITM), and CTM100 (CTM replaced at 100% of ITM). After 112 d, body weight, average daily gain, and feed conversion ratio in turkeys fed with the ITM were also similar to those of the turkeys in the CTM50 group, but poorer (P < 0.05) than those for the CTM100 group. When compared to the ITM diet, the CTM100 diet increased ileal digestibility coefficients of crude fat, energy, ash, and phosphorus; tibia length; tibia ash, phosphorus, zinc, manganese, and copper contents; jejunal villus height, villus height/crypt depth ratio, and villus surface area; and serum total antioxidant capacity, superoxide dismutase, and catalase values (P < 0.05). The CTM50 diet also increased ileal digestibility coefficients of crude ash and phosphorus, as well as tibia ash and phosphorus contents (P < 0.05) compared to the ITM diet. These findings indicate that, while CTM supplementation at 50% of the commercially recommended levels could support growth performance, a complete replacement of ITM with equivalent levels of CTM could beneficially influence growth performance, bone mineralization, gut morphology, and antioxidant status in growing turkeys

TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo

Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine. © 2016, The Japanese Society of Hematology

The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

Saideh Fakharzadeh,1 Mohammad Ali Sahraian,2 Maryam Hafizi,1 Somayeh Kalanaky,1 Zahra Masoumi,1 Mehdi Mahdavi,1 Nasser Kamalian,3 Alireza Minagar,4 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pathology, Medical School of Tehran University of Medical Sciences, Tehran, Iran; 4Department of Neurology, LSU Health Sciences Centre, Shreveport, LA, USA Purpose: Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods: MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2)-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1&ndash;7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results: The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1&ndash;7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did&nbsp;not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal. Conclusion: These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies. Keywords: EAE, multiple sclerosis, MSc1, nanochelating technology, nanocomple

BCc1, the novel antineoplastic nanocomplex, showed potent anticancer effects in vitro and in vivo

Somayeh Kalanaky,1,2 Maryam Hafizi,1&ndash;3 Saideh Fakharzadeh,1 Mohammad Vasei,4 Ladan Langroudi,5 Ehsan Janzamin,6 Seyed Mahmoud Hashemi,7 Maryam Khayamzadeh,2 Masoud Soleimani,6 Mohammad Esmaeil Akbari,2 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Stem Cell Technology Research Center, Tehran, Iran; 4Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 6Department of Haematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 7Department of Immunology, Faculty of Medicine, Shahid Beheshti University of&nbsp;Medical Sciences, Tehran, Iran Purpose: In spite of all the efforts and researches on anticancer therapeutics, an absolute treatment is still a myth. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In this study, for the first time, we have evaluated the anticancer effects of BCc1 nanocomplex by vitro and in vivo studies, which is designed based on the novel nanochelating technology.Methods: Human breast adenocarcinoma cell line (MCF-7) and mouse embryonic fibroblasts were used for the in vitro study. Antioxidant potential, cell toxicity, apoptosis induction, and CD44 and CD24 protein expression were evaluated after treatment of cells with different concentrations of BCc1 nanocomplex. For the in vivo study, mammary tumor-bearing female Balb/c mice were treated with different doses of BCc1 and their effects on tumor growth rate and survival were evaluated.Results: BCc1 decreased CD44 protein expression and increased CD24 protein expression. It&nbsp;induced MCF-7 cell apoptosis but at the same concentrations did not have negative effects on mouse embryonic fibroblasts viability and protected them against oxidative stress. Treatment with nanocomplex increased survival and reduced the tumor size growth in breast cancer-bearing balb/c mice.Conclusion: These results demonstrate that BCc1 has the capacity to be assessed as a new anticancer agent in complementary studies. Keywords: BCc1, cancer, nanotechnology, nanochelating technology, nanocomple