Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: In the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated. METHODS: Laboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day. RESULTS: The results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p < 0.05). In addition, the patients in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in TNF-α level in the treatment group, while a 31% increase in this cytokine level in the placebo was observed (p > 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved. CONCLUSIONS: In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS. TRIAL REGISTRATION: Iranian Registry of Clinical Trials RCT20170731035423N2 . Registered on June 12, 2020.

Nanoadjuvants Produced by Advanced Nanochelating Technology in the Inactivated-Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine Formulation: Preliminary Results on Cytokines and IgG Responses.

Despite the great success of vaccines in various infectious diseases, most current vaccines are not effective enough, and on the contrary, clinically approved alum adjuvants cannot induce sufficient immune responses, including a potent cellular immune response to confer protection. In this study, we used Nanochelating Technology to develop novel nanoadjuvants to boost the potency of the alum-adjuvanted inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. BALB/c mice were immunized twice over 2 weeks with different doses of adjuvanted-vaccine formulations and immune responses were assessed. The analysis results of IFN-γ and IL-17 cytokines demonstrated the effectiveness of the nanoadjuvants produced by the Nanochelating Technology in shifting the alum-based vaccine toward a stronger Th1 pattern. In addition, these nanoadjuvants improved IL-2 cytokine response, which shows the efficacy of these novel formulations in inducing specific T lymphocyte proliferation. Using these nanoadjuvants increased IL-10 cytokine secretion that may be representative of a better immunoregulatory impact and may also potentially prevent immunopathology responses. Moreover, specific IgG titer analysis revealed the potency of these nanoadjuvants in improving humoral immune responses. The enzyme-linked immunosorbent assay of receptor-binding domain (RBD)-specific IgG response showed that the developed novel formulations induced strong IgG responses against this protein. This study shows that the nanostructures produced by the Advanced Nanochelating Technology have potent adjuvant effects on alum-based SARS-CoV-2 vaccines to not only compensate for alum weakness in inducing the cellular immune responses by smart regulation of the immune system but also significantly improve the humoral and cellular immune responses simultaneously.

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma.

Introduction: The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects. Case presentation: A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days). Conclusion: The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal). Trial registration: IRCT20200502047277N2. Registered 10 May 2020-Retrospectively registered, https://eng.irct.ir/trial/48110.

Trends of Colorectal Cancer Incidence, Prevalence and Mortality in Worldwide From 1990 to 2017.

Background: Colorectal cancer is a major health problem both in developing and developed countries. This cancer is among the top three commonly diagnosed cancers in males and females. In this context, assessing the Incidence, Prevalence and Mortality Rate trend of this cancer is of great importance. Methods: We used the data from the GBD 2017 study to assess the global trend of 3 important indicators of colorectal cancer burden and to examine the relationship between trends of these indicators with Human Development Index (HDI). We used the multivariate mixed effects modeling framework with time and HDI as the covariates. Results: Trend analysis of colorectal cancer burden indicators showed a rather steady trend for mortality rate, while it revealed increasing slopes for both the incidence and prevalence rates. In addition, our findings showed a direct relationship between prevalence and incidence rates of this cancer and HDI level and indirect association between mortality rate and level of HDI. Conclusion: There were significant changes in indicators of colorectal cancer during the study period. The inverse relationship between mortality due to this cancer and socio-economic status of the countries indicated an urgent need for screening the patients and promoting the level of care in countries with lower levels of HDI.

Organic Acid-Based Chelate Trace Mineral Supplement Improves Broiler Performance, Bone Composition, Immune Responses, and Blood Parameters.

Organic acid-based trace minerals are known to have more bioavailability, possibly due to fewer antagonism reactions in the lumen. A 42-day study was conducted to assess the supplementation of manganese (Mn), zinc (Zn), selenium (Se), iron (Fe), and copper (Cu) from different sources. To that end, a total of 1248-day-old As-hatched Arbor Acres chickens were examined for performance, histology, bone integrity, and plasma biochemical parameters. Experimental groups were as follows: basal diet supplying 50, 75, 100, and 120% of trace mineral requirements using an inorganic trace mineral supplement (ITM50, ITM75, ITM100, ITM120); basal diet supplying 33, 66, and 100% of trace mineral requirements using an organic acid-based trace mineral supplement (OAT33, OAT66, OAT100); plus a basal diet supplying 100% of trace mineral requirements using an amino acid-based chelated trace mineral supplement (ATM100%) as control positive. According to results, birds' fed OAT66 had the highest (P < 0.05) average daily body weight gain (ADG), average daily feed intake (ADFI), and lower feed conversion ratio (FCR). Feeding OAT66 increased (P < 0.05) villus length to crypt depth ratio, compared to OAT33 and ITM100 by 26% and 19%, respectively. The relative weight of the bursa enhanced by 22% in birds' receiving OAT supplement, compared to those received ITM supplement (P < 0.05). The plasma uric acid was reduced by 42% (P < 0.001) in birds fed with OAT66 and OAT100 when compared to those fed ITM50. Overall, our results indicated that the same performance could be achieved by using lower levels of organic trace minerals.

Effect of advanced chelate compounds-based mineral supplement in laying hen diet on the performance, egg quality, yolk mineral content, fatty acid composition, and oxidative status.

The study aimed to determine the efficiency of advanced chelate compounds-based trace minerals (OTM) in laying hens. Laying hens (240, 32 weeks old) were assigned to one of the following five groups: NOTM (no added trace minerals), CONTM (standard mineral salts), and three experimental groups in which chelates were used to replace 33, 66, and 100% of mineral salts (OTM33, OTM66, and OTM100, respectively). Each treatment had six replicates with eight hens per replicate. After 18 weeks, performance and physicochemical properties of eggs in all experimental groups was better than those in the NOTM group. Among the treatments, OTM66 and OTM100 produced the best results in terms of laying performance, yolk PUFA/SFA ratio, Zn and Se contents, and malondialdehyde concentration in both serum and yolk. In conclusion, up to 66% OTM supplementation was beneficial for performance, lipid and mineral composition of yolk, and oxidative status.

Combining cell therapy with human autologous Schwann cell and bone marrow-derived mesenchymal stem cell in patients with subacute complete spinal cord injury: safety considerations and possible outcomes.

BACKGROUND: Cellular transplantations have promising effects on treating spinal cord injury (SCI) patients. Mesenchymal stem cells (MSCs) and Schwann cells (SCs), which have safety alongside their complementary characteristics, are suggested to be the two of the best candidates in SCI treatment. In this study, we assessed the safety and possible outcomes of intrathecal co-transplantation of autologous bone marrow MSC and SC in patients with subacute traumatic complete SCI. METHODS: Eleven patients with complete SCI (American Spinal Injury Association Impairment Scale (AIS); grade A) were enrolled in this study during the subacute period of injury. The patients received an intrathecal autologous combination of MSC and SC and were followed up for 12 months. We assessed the neurological changes by the American Spinal Injury Association's (ASIA) sensory-motor scale, functional recovery by spinal cord independence measure (SCIM-III), and subjective changes along with adverse events (AE) with our checklist. Furthermore, electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 months, and 1 year after the intervention. RESULTS: Light touch AIS score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients, and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients). SCIM III total scores (21.2 ± 13.3) and all its sub-scores ("respiration and sphincter management" (15 ± 9.9), "mobility" (9.5 ± 13.3), and "self-care" (6 ± 1.4)) had statistically significant changes after cell injection. Our findings support that the most remarkable positive, subjective improvements were in trunk movement, equilibrium in standing/sitting position, the sensation of the bladder and rectal filling, and the ability of voluntary voiding. Our safety evaluation revealed no systemic complications, and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo-meningocele. CONCLUSION: The present study showed that autologous SC and bone marrow-derived MSC transplantation at the subacute stage of SCI could reveal statistically significant improvement in sensory and neurological functions among the patients. It appears that using this combination of cells is safe and effective for clinical application to spinal cord regeneration during the subacute period.

Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment.

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.

A Trend Study of Preterm Infant Mortality Rate in Developed and Developing Countries over 1990 to 2017.

BACKGROUND: Preterm birth is the most important in children under 5 yr mortality. In this study, we used the Global Burden of Disease Data (GBD) to evaluate the trend of preterm infant mortality rate for all countries from 1990 to 2017 and to assess the effect of development factors on this trend. METHODS: The preterm infant mortality rate data from 196 countries of the world, from 1990 to 2017, were extracted from the GBD database. To study the trend of preterm infant mortality rate, a mixed-effects log-linear regression model was fitted separately for each IHME super-region. In the next step of data analysis, the development factor was included in the model to determine its effect on this trend for all countries under study. RESULTS: The average rate mortality rate has declined about 2% per year throughout the world over the mentioned period. The highest and lowest decreasing trends were observed in high-income countries (about 4.0%) and Sub-Saharan Africa (about 1.0%), respectively. Including the effect of development factor in the mentioned model revealed that in 1990, the rate of preterm infant mortality in developed countries was 2.2 times of this rate in developing countries and this rate ratio has increased to 2.69 in year 2017. CONCLUSION: Although the preterm infant mortality rate were decreasing in all super regions, there is a remarkable gap in this rate between developing and developed countries yet. Therefore, preventative strategies are needed to reduce preterm birth and its burden, especially in the developing world.

Lactation responses of Holstein dairy cows to supplementation with a combination of trace minerals produced using the advanced chelate compounds technology.

Advanced chelate compounds technology is a novel technology that introduces a new generation of chelates to deliver trace elements better by polymerization of organic acids. In the present study, the over-supplementation effect of Bonzaplex7 supplement, which is designed based on the aforementioned technology, was evaluated on milk yield of dairy Holstein cattle through two experiments. In the first experiment (exp. I), 24 primiparous dairy cows were randomly assigned to one of 3 groups: (1) without over-supplementation (control); (2) daily allowance of 7 g/cow Bonzaplex7 containing Co (12 mg), Cr (3.5 mg), Cu (126 mg), Fe (56 mg), Mn (196 mg), Se (2 mg), and Zn (357 mg) (Bonzaplex7); and (3) daily allowance of the same amounts of all of the trace minerals in amino acid complex form (AA). In the second experiment (exp. II), 170 multiparous dairy cows received either 7 g/day/cow Bonzaplex7 (85 cows, test) or no additional supplement (85 cows, NS). In exp. I, the milk yields in control, Bonzaplex7, and AA were 34.30, 36.46, and 35.83 kg/day, respectively (P = 0.528). No significant differences in milk composition were detected among the groups. In exp. II, however, higher milk fat and energy-corrected milk yield were observed in test compared with NS. Both Bonzeplex7 and AA elevated the plasma concentrations of Cu, Mn, and Se. The results provided evidence that supplementing dairy cows with a combination of trace minerals which produced using the advanced chelate compounds technology has a potential to improve milk fat and to decrease disease susceptibility under stressed conditions.

Effect of advanced chelate technology based trace minerals on growth performance, mineral digestibility, tibia characteristics, and antioxidant status in broiler chickens.

BACKGROUND: Compared to the corresponding source of inorganic trace minerals (TM), chelated supplements are characterized by better physical heterogeneity and chemical stability and appear to be better absorbed in the gut due to possibly decreased interaction with other feed components. METHODS: This study was designed in broiler chickens to determine the effects of replacing inorganic trace minerals (TM) with an advanced chelate technology based supplement (Bonzachicken) on growth performance, mineral digestibility, tibia bone quality, and antioxidant status. A total of 625 male 1-day-old broiler chickens were allocated to 25 pens and assigned to 5 dietary treatments in a completely randomized design. Chelated TM (CTM) supplement was compared at 3 levels to no TM (NTM) or inorganic TM. A corn-soy-based control diet was supplemented with inorganic TM at the commercially recommended levels (ITM), i.e., iron, zinc, manganese, copper, selenium, iodine, and chromium at 80, 92, 100, 16, 0.3, 1.2, and 0.1 mg/kg, respectively, and varying concentration of CTM, i.e., match to 25, 50, and 100% of the ITM (diets CTM25, CTM50, and CTM100, respectively). RESULTS: Diets CTM50 and CTM100 increased average daily gain (ADG), European performance index (EPI), and tibia length compared to the NTM diet (P < 0.05). Broilers fed the CTM100 diet had lowest overall FCR and serum malondialdehyde level and highest EPI, tibia ash, zinc, manganese, and copper contents, and serum total antioxidant capacity (P < 0.05). The apparent ileal digestibilities of phosphorus and zinc were lower in the ITM group compared with the CTM25 and CTM50 groups (P < 0.05). Broiler chickens fed any of the diets, except diet CTM25, exhibited higher serum glutathione peroxidase and superoxide dismutase activities than those fed the NTM diet, where the best glutathione peroxidase activity was found for CTM100 treatment (P < 0.05). CONCLUSIONS: These results indicate that while CTM supplementation to 25 and 50% of the commercially recommended levels could support growth performance, bone mineralization, and antioxidant status, a totally replacing ITM by equivalent levels of CTM could also improve performance index and glutathione peroxidase activity of broiler chickens under the conditions of this study.

Evaluation of Blood and Liver Cytotoxicity and Apoptosis-necrosis Induced by Nanochelating Based Silver Nanoparticles in Mouse Model.

This study aimed to evaluate the in-vitro and in-vivo biological activities of newly synthesized nanochelating based silver nanoparticles (AgNPs) in mouse model. Nanochelating technology was used to design and synthesize the AgNPs. The animals studies were including the lethal dose (LD50) determination by the intraperitoneal administration in mice, and determination of liver enzymes levels and hematological parameters. Flow cytometry analysis was used to quantitatively determine apoptosis and necrotic cells in-vitro. The NPs A and NPs B have LD50 = 250 mg/kg and LD50 = 350 mg/kg, respectively and classified as non-toxic. In general, minor alterations were observed in levels of liver enzymes as indicative of liver damage. For blood parameters several factors associated with significant changes in AgNPs treated animals. Regarding animals weight, combination therapy showed more effective to maintain animals weight losses after infection. Flow cytometry results showed that AgNPs induced cell apoptosis-necrosis depends on AgNP size, concentration and exposure time. Cells damage due to AgNPs (A) with lower size (20-25 nm) were relatively more than cells exposed to AgNPs (B) (30-35 nm). The findings support the potent antibacterial activities of nanochelating based AgNPs. Also, the present study showed that nanochelating based AgNPs induce a moderate level of apoptosis/necrosis in mice, and affected several clinical parameters like blood parameters, liver enzymes, and body weight with no definite signs of toxicity.

GFc7 as a Smart Growth Nanofactor for ex vivo Expansion and Cryoprotection of Humans' Hematopoietic Stem Cells.

BACKGROUND: Nowadays, smart synthesized nanostructures have attracted wide attention in the field of stem cell nanotechnology due to their effect on different properties of stem cells. METHODS: GFc7 growth nanofactor was synthesized based on nanochelating technology as an iron-containing copper chelator nanocomplex. The effect of this nanocomplex on the expansion and differentiation of hematopoietic stem cells (HSCs) as well as its performance as a cryoprotectant was evaluated in the present study. RESULTS: The results showed that the absolute count of CD34+ and CD34+CD38- cells on days 4, 7, 10 and 13; the percentage of lactate dehydrogenase enzyme on the same days and CD34+CXCR4 population on day 10 were significantly increased when they were treated with GFc7 growth nanofactor in a fetal bovine serum (FBS)-free medium. This medium also led to delayed differentiation in HSCs. One noticeable result was that CD34+CD38- cells cultured in an FBS medium were immediately differentiated into CD34+CD38+ cells, while CD34+CD38- cells treated with GFc7 growth nanofactor in FBS medium did not show such an immediate significant differentiation. De-freezing GFc7-treated CD34+ cells, which were already frozen according to cord blood bank protocols, showed a higher percentage of cell viability and a larger number of colonies according to colony-forming cell assay as compared to control. CONCLUSION: It can be claimed that treating HSCs with GFc7 growth nanofactor leads to quality and quantity improvement of HSCs, both in terms of expansion in vitro and freezing and de-freezing processes.

Using Nanochelating Technology for Biofortification and Yield Increase in Rice.

Iron is a vital microelement that plays an important role in plant metabolism. Consuming a large amount of chemical fertilizers increases the risk factors of neoplastic diseases such as heavy metals and harmful components in crops edible parts. Therefore, utilizing novel technologies to increase yields without requiring more chemical fertilizers seems essential. In this regard, nanotechnology holds considerable potentials for creating valuable outputs in agriculture. The effect of nano chelated iron fertilizer, which is synthesized based on novel nanochelating technology, on agronomic traits and yield of rice were evaluated in the present study. A randomized complete block experiment was conducted with 3 replicates. The treatments were: T0 (control), T1 (2.5 g/L foliar application twice at nursery with a one-week interval), T2 (foliar application at tillering + T1), T3 (foliar application at booting + T1), T4 (foliar application at tillering and booting + T1), T5 (8 kg/ha soil application at tillering + T1), T6 (8 kg/ha soil application at booting + T1), T7 (4 kg/ha soil application at tillering + 4 kg/ha soil application at booting + T1). Nano chelated iron fertilizer increased biological yield by 27% and decreased hollow grain number by 254%; in addition, it raised protein content by 13%. This fertilizer also led to increase in nitrogen, phosphorus, potassium, iron and zinc concentrations in white rice by 46%, 43%, 41%, 25% and 50%, respectively. Nanochelating technology can decrease the need for chemical fertilizers; additionally, this technology has the capability to bio-fortify crops with vital micronutrients.

Neuroprotective Effect of New Nanochelating-Based Nano Complex, ALZc3, Against Aß (1-42)-Induced Toxicity in Rat: a Comparison with Memantine.

PURPOSE: The current drugs for Alzheimer's disease (AD) are only used to slow or delay the progression of the pathology. So using a novel technology is a necessity to synthesize more effective medications to control this most common cause of dementia. In this study, using nanochelating technology, ALZc3 was synthesized and its therapeutic effects were evaluated in comparison with memantine on a well-known rat model of AD, which is based on Amyloid-ßeta (Aß) injection into the brain. MATERIALS AND METHODS: Aß (1-42) was injected bilaterally into the CA1 area of the hippocampus of male rats and then animals were treated daily by oral administration of Alz-C3, memantine or their vehicles. Activities of antioxidant enzymes catalase and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels, as well as Bax/Bcl-2 ratio, caspase-3 activation, and TNF-α expression were evaluated 7 days after Aß injection. Finally, learning and memory of the rats were assessed by Morris water maze test. RESULTS: ALZc3 and memantine improved memory impairment and antioxidant activity and reduced TNF-α expression, caspase-3 activity and Bax/Bcl-2 ratio in the rat's hippocampus. The results showed a superiority of ALZC3 compared to memantine in reducing caspase-3, increasing CAT activity in Aß (1-42)-injected groups and improving apoptosis factor in healthy mice. CONCLUSION: These results indicated that ALZc3 could significantly prevent the memory impairment and Aß (1-42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.

Effects of BCc1 nanoparticle and its mixture with doxorubicin on survival of murine 4T1 tumor model.

Background: Our previous findings showed that BCc1, a nanoparticle designed based on nanochelating technology, can be considered a new anti-cancer nanoparticle if confirmed by complementary studies. Goal: In the present study, we investigated the effects of the BCc1 nanoparticle alone on some gene expressions influencing the apoptosis pathway, and also the effect of the mixture of BCc1 nanoparticle and doxorubicin on survival. Method: Using an in vitro study, the effects of the BCc1 nanoparticle on Bax, Bcl2, p53, Caspase7 and p21 gene expressions were assessed after a 24-h treatment using real-time PCR in MCF-7 and MEFs; in addition, using an in vivo study, 4T1 tumor-bearing female Balb/c mice were treated with different doses of the BCc1 nanoparticle and doxorubicin alone and together and then their mean and median survival was evaluated. Result: The results showed that the BCc1 nanoparticle increased gene expressions of RB, p53, Caspase7, p21, and Bax and decreased gene expressions of Bcl2 in MCF-7 significantly, but no change was observed in MEFs expressions. The findings revealed that the BCc1 nanoparticle, when used orally, had the highest mean and median survival time. A mixture of a high dose of the BCc1 nanoparticle (1 mg/kg) and a low dose of doxorubicin (0.1 mg/kg) showed synergistic effects on enhanced life span, while doxorubicin dose was prescribed approximately 50 times less than the murine applicable dose (5 mg/kg). Conclusion: Our results demonstrated that the BCc1 nanoparticle not only has the potential to become a novel nanomedicine for cancer therapy, but it can also provide the basis of a new medicine for cancer management when mixed with a lower applicable dose of doxorubicin.

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

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-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-α decrease was observed. H&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.

Effects of water supplementation of an organic acid-trace mineral complex on production and slaughter parameters, intestinal histomorphology, and macronutrient digestibility in growing ostriches.

An experiment was conducted to study the effect of water supplementation of organic acid-chelated trace minerals (OTM) on production traits, carcass characteristics, intestinal histomorphology, and nutrient digestibility in African ostrich chicks from 8 to 12 mo of age. A total of 20 growing ostriches, with almost similar body weight (73.4 to 75.8 kg), were individually distributed in outdoor paddocks of ≈ 24 m2 and were randomly allocated into 1 of the following 4 treatments: (1) control/basal diet, (2) low OTM (basal diet + 100 mg/bird/day OTM powder in water), (3) medium OTM (basal diet + 1 g/bird/day OTM powder in water), and (4) high OTM (basal diet + 2 g/bird/day OTM powder in water). The body weight gain and feed conversion efficiency were greater (P < 0.05) in ostriches receiving medium-OTM treatment compared to control during the overall phase of the experiment. Although whole carcass yield, the yield of parts, and the relative weights of internal organs were not affected by experimental treatments, supplementation of higher amounts of OTM (medium- and high-OTM) resulted in a decrease (P < 0.05) in the subcutaneous and abdominal fat contents. Medium- and high-OTM treatments increased (P < 0.05) the villus height/crypt depth ratio in the jejunum and ileum compared with control and low-OTM treatments. Moreover, ostriches receiving the medium-OTM had also higher total tract apparent digestibility of energy (P = 0.048), ether extract (P = 0.050), crude fiber (P = 0.063), and higher AMEn (P = 0.094) than the control group. Overall, supplementation of OTM at the level of 1 g/bird/day to the drinking water of growing ostriches fed diets containing the recommended levels of inorganic trace minerals could beneficially affect productive performance, nutrient digestibility, and intestinal morphology.

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.

Growth Performance, Mineral Digestibility, and Blood Characteristics of Ostriches Receiving Drinking Water Supplemented with Varying Levels of Chelated Trace Mineral Complex.

The effects of water supplementation of chelated trace minerals (CTM, which is named Bonzaplex designed with chelate compounds technology) on growth performance, apparent total tract digestibility (ATTD) of minerals, and some blood metabolites, TM, and antioxidant enzyme values in African ostriches were investigated from 8 to 12 months of age. A total of 20 8-month-old ostriches (five birds in five replicate pens) was randomly allocated into one of the following four treatments: (1) control (basal diet + tap water), (2) low CTM (basal diet +100 mg/bird/day CTM powder in tap water), (3) medium CTM (basal diet +1 g/bird/day CTM powder in tap water), and (4) high CTM (basal diet +2 g/bird/day CTM powder in tap water). Compared with control, medium CTM improved (P < 0.05) daily weight gain and ATTD of phosphorous, zinc, and copper in 12-month-old ostriches. Furthermore, the feed conversion ratio was lower, and ATTD of magnesium was higher in the medium- and high-CTM groups than that in the control group (P < 0.05). At the end of the trial, ostriches receiving high-CTM treatment exhibited the lower (P < 0.05) serum triglyceride and very low-density lipoprotein cholesterol concentrations and higher copper levels compared to those of the control treatment. Supplementation of higher amounts of CTM (medium and high CTM) also increased the activity of serum superoxide dismutase (P < 0.05). No differences were detected for other blood parameters including glucose, total protein, albumin, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, iron, magnesium, and glutathione peroxidase values. In conclusion, supplementation of CTM at the level of 1 g/bird/day to the drinking water can be recommended for improving growth performance, mineral absorption, and antioxidant status of ostriches fed diets containing the recommended levels of inorganic TM.