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.

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.

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.

Ameliorative effect of a nano chromium metal-organic framework on experimental diabetic chronic kidney disease.

Metal-Organic Frameworks (MOFs) are a new class of crystalline porous structures which can be used as a novel structure in diverse fields of medical science. Several studies have shown that chromium supplementation can be effective in amelioration of biochemical parameters of diabetes and its renal complications. Therefore, a chromium-containing MOF (DIFc) was synthetized by nanochelating technology in the present study and then its effect on biochemical indices in diabetic rats was evaluated. Diabetes was induced by high-fat diet consumption and streptozotocin (35 mg/kg) injection and then the treatment started 8 weeks after disease induction and continued for 8 weeks. The results showed that DIFc treatment decreased HOMA-IR index, blood urea nitrogen, uric acid and malondialdehyde in plasma samples. This nano MOF also reduced albumin, malondialdehyde and 8-isoprostane in urine specimen, while it increased creatinine clearance. In conclusion, DIFc MOF demonstrated promising results in the present study, indicating that it can be developed and evaluated in future investigations with the aim of designing a novel agent for management of diabetes and its renal complications.

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.

Nanochelating based nanocomplex, GFc7, improves quality and quantity of human mesenchymal stem cells during in vitro expansion.

INTRODUCTION: Human mesenchymal stem cells (hMSCs) have been approved for therapeutic applications. Despite the advances in this field, in vitro approaches are still required to improve the essential indices that would pave the way to a bright horizon for an efficient transplantation in the future. Nanotechnology could help to improve these approaches. Studies signified the important role of iron in stem cell metabolism and efficiency of copper chelation application for stem cell expansion METHODS: For the first time, based on novel Nanochelating technology, we design an iron containing copper chelator nano complex, GFc7 and examined on hMSCs during in vitro expansion. In this study, the hMSCs were isolated, characterized and expanded in vitro in two media (with or without GFc7). Then proliferation, cell viability, cell cycle analysis, surface markers, HLADR, pluripotency genes expression, homing and antioxidative defense at genes and protein expression were investigated. Also we analyzed the spontaneous differentiation and examined osteogenic and lipogenic differentiation. RESULTS: GFc7 affected the expression of key genes, improving both the stemness and fitness of the cells in a precise and balanced manner. We observed significant increases in cell proliferation, enhanced expression of pluripotency genes and homing markers, improved antioxidative defense, repression of genes involved in spontaneous differentiation and exposing the hMSCs to differentiation medium indicated that pretreatment with GFc7 increased the quality and rate of differentiation. CONCLUSIONS: Thus, GFc7 appears to be a potential new supplement for cell culture medium for increasing the efficiency of transplantation.