Concomitant oral intake of purified clinoptilolite tuff (G-PUR) reduces enteral lead uptake in healthy humans.

Lead exposure can cause substantial organ damage. Enteral lead absorption may be reduced by concomitant intake of clinoptilolite tuff, a zeolite from natural sources. This study aimed to assess the effect of purified clinoptilolite tuff (G-PUR) on enteral lead uptake in adults using stable lead isotope 204Pb as a tracer. In this randomized, placebo-controlled, double-blind, parallel-group study, 42 healthy participants were randomized to receive oral G-PUR 2.0 g, 2 * 2.0 g, or placebo, together with 2.5 µg of 204Pb in water. The enrichment of 204Pb caused by the tracer in blood and urine was measured by mass spectrometry. G-PUR was well tolerated. The mean maximum 204Pb enrichment of 0.505% of total blood lead was significantly higher (p < 0.0001) in the placebo group compared to G-PUR 2.0 g (0.073%) or G-PUR 2 * 2.0 g (0.057%) group. Normalized 204Pb AUC0-192 was 86.5, 11.9, and 8.5% * h without and with G-PUR 2.0 g, and G-PUR 2 * 2.0 g, respectively (p < 0.0001 vs. placebo). This smaller 204Pb exposure was paralleled by a reduced urinary excretion in subjects receiving G-PUR. Concomitant oral intake of purified clinoptilolite tuff reduced enteral uptake of 204Pb in healthy humans by approximately 90%. The reduced bioavailability is demonstrable by a decrease of 204Pb tracer enrichment in blood and urine.Trial registration: clinicaltrials.gov identifier: NCT04138693, registered 24/10/2019.

Investigation of a Novel Multicomponent Mycotoxin Detoxifying Agent in Amelioration of Mycotoxicosis Induced by Aflatoxin-B1 and Ochratoxin A in Broiler Chicks.

The present study was designed to determine the efficacy of a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (Clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls and silymarin against the deleterious effects of Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) in broiler chicks. A total of 160 one-day-old Ross 308® broiler chicks were randomly allocated in four treatment groups, with four replicates, according to the following experimental design for 42 days. Group A received a basal diet; Group B received a basal diet contaminated with AFB1 and OTA at 0.1 mg/kg and 1 mg/kg, respectively; Group C received a basal diet contaminated with AFB1 and OTA and MMDA at 1 g/kg feed, and Group D received a basal diet contaminated with AFB1 and OTA and MMDA at 3 g/kg feed. Results showed that ingested mycotoxins led to significant (p ≤ 0.05) reduction in body weight and feed conversion from 25 days of age, induced histopathological changes, increased the pH of the intestinal content, and altered the biochemical profile of birds with significantly (p ≤ 0.05) increased aspartate aminotransferase (AST) values (p ≤ 0.05). On the other hand, the supplementation of MMDA significantly (p ≤ 0.05) improved the feed conversion ratio (FCR) during the second part of the study, diminished biochemical alterations, reduced pH in jejunal and ileal content, and E. coli counts in the caeca of birds (p ≤ 0.05). It may be concluded that the dietary supplementation of the MMDA partially ameliorated the adverse effects of AFB1 and OTA in broilers and could be an efficient tool in a mycotoxin control program.

Efficacy of New Zeolite-Based Hemostatic Gauze in a Gunshot Model of Junctional Femoral Artery Hemorrhage in Swine.

BACKGROUND: This work sought to (1) establish a reliable gunshot model of junctional femoral artery rupture in swine that accurately simulates field rescue conditions and (2) use the gunshot model to compare the efficacy and ease of application of zeolite nanometer hemostatic gauze with other hemostatic materials. METHODS: Thirty-six healthy landrace swine (body weight 50 ± 5 kg) were randomly divided into three groups which were treated with Combat Gauze (CG), FeiChuang hemostatic gauze (FG), or standard medical gauze (SG). A gunshot model of femoral artery hemorrhage in landrace swine was used with portable ultrasound to accurately position the wound. After the shooting, when mean arterial pressure of swine decreased by at least 30% for 10 s, wounds were pressed with standard packing (39 g) of gauze materials for 3 min to stop bleeding, then bandaged with pressure. Blood samples were taken 15 min before injury, then 10 min, 30 min, and 60 min after injury to determine hemodynamic, coagulation, and arterial blood gas indexes. Wound temperatures were taken at 5 min, 10 min, 30 min, and 60 min after injury, and survival times were recorded. The volume of blood loss and survival time were used to evaluate hemostatic effect, whereas the fill time, wound temperature, and physiological indexes were used to evaluate the safety and operation of the product. RESULTS: The CG (11.15 ± 3.09 mL/kg) and FG (12.19 ± 3.5 mL/kg) groups had significantly less blood loss than the SG group (16.8 ± 5.14 mL/kg) (P = 0.04; P = 0.039, respectively). After gauze packing, bleeding in CG (5.85 ± 1.17 mL/kg) and FG (5.37 ± 0.93 mL/kg) groups remained significantly lower than that of the SG group (6.93 ± 1.03 mL/kg) (P = 0.011; P = 0.003, respectively). Wound temperature rose with time for all groups (P < 0.001). The wound temperatures in the FG group and the CG group were significantly higher than that of the SG group (P = 004 and 0.009, respectively). Survival rates and times were not significantly different among the three groups, although the FG group had the longest average survival time (standard deviation [SD] 204.8 s), compared with the SG group (SD 177.8 s) and CG (SD 187.5 s) groups. No significant differences in hemodynamics, blood gas, and coagulation were observed among the three groups. CONCLUSIONS: The gunshot model of junctional femoral arterial hemorrhage guided by ultrasound had high accuracy for femoral arterial rupture by bullet wound and provided consistent and reproducible field-simulation conditions for comparison of hemostatic materials. FeiChuang zeolite hemostatic gauze effectively controlled bleeding as well as combat gauze, without excessive heat as found in other zeolite-based products. However, improvements to application technique, such as a packing device, are needed to improve operating time.

Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells.

Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle - zeolitic imidazolate framework-8 (nZIF-8) - that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEM⊂nZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEM⊂RGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEM⊂nZIF-8. The GEM⊂RGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 µg mL-1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEM⊂nZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively.

Effects of oral supplementation with organically modified clinoptilolite during prepartum period on colostrum quality in primiparous dairy cows.

This research paper addresses the hypothesis that an oral supplementation with organically modified clinoptilolite will improve colostrum quality in primiparous dairy cows whilst having no adverse effects on the cows' health. A total of 36 pregnant Holstein primiparous dairy cattle were randomly assigned to receive daily oral drenching, two hours following morning feeding, with 1 l of water containing either 0 g/l (n = 16) or 150 g/l (n = 20) of clinoptilolite. Treatment lasted from 24 ± 4 d prior to expected parturition until two days postpartum (pp). Colostrum was collected at 2 to 3 h, 12, 24 and 36 h pp and blood samples were collected at 24 ± 4 and 4 ± 2 d prior to parturition and 1, 2 and 7 d pp. Overall mean dry matter, fat and total protein percentage as well as IgG concentration and mass were significantly greater in colostrum collected from cattle drenched with clinoptilolite (total protein increased by 15% and IgG concentration and mass by 21 and 38% respectively at first sampling and further at second sampling). Total γ globulin and most other blood serum biochemistry parameters did not differ between cattle treated and not treated with clinoptilolite, the only exception being the fast anionic γ globulin fraction that was 17% greater at 4 ± 2 d prior to parturition and 10% lower on the 1st day pp in treated cattle. These results showed that organically modified oral clinoptilolite supplementation at 150 g/d significantly increases the IgG concentration in colostrum and has no adverse effects on the energy status, protein, lipid, and mineral metabolism in primiparous dairy cattle during prepartum period.

Montmorillonite-Enveloped Zeolitic Imidazolate Framework as a Nourishing Oral Nano-Platform for Gastrointestinal Drug Delivery.

Oral administration of medicine faces physiological constraints imposed by the gastrointestinal tract (GIT) and simultaneously causes irritation to GI mucosa, which motivates us to pursue the innovation of a GI drug delivery system. Inspired by the mucosa-nutrient functions of Zinc element and smectite clay, a montmorillonite (MMT)-enveloped zeolitic imidazolate framework (M-ZIF-8) is developed in a successive one-pot fabrication of ZIF-8 encapsulated medicine, and followed MMT coating to yield a core-shell nanoplatform for GI drug delivery. ZIF-8 encapsulated medicines can maintain their intrinsic structure, and MMT layer potentiates mucous-adhesion and optimizes medicine release. Validated in gastritis and colitis models, M-ZIF-8 not only achieves efficient GI delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation inhibition, but also reduces the NSAIDs-induced GI irritation, promoting mucosal healing in GIT. Coupled with the facile construction and biocompatibility, M-ZIF-8 shows a significant advancement in GI drug delivery.

ZeOxaNMulti Trial: A Randomized, Double-Blinded, Placebo-Controlled Trial of Oral PMA-zeolite to prevent Chemotherapy-Induced Side Effects, in particular, Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most frequently reported adverse effect of oxaliplatin. In this study, we set out to evaluate the role of the panaceo-micro-activation (PMA) zeolite in the reduction of the incidence of CIPN and hematological and liver toxicity. The possible impact of the PMA-zeolite as an adjuvant therapeutic agent is based on its detoxification properties toward agents promoting the development of neuropathy (e.g., ammonium - recognized as a neurotoxic agent produced by tumors), as well as its positive impact on immunity and oxidative stress through its effects in the gastrointestinal tract. From April 2015 to October 2018, a total of 120 patients (pts) diagnosed with predominantly colorectal cancer requiring oxaliplatin-based chemotherapy were randomized to receive either the PMA-zeolite (Multizeo Med) or placebo while undergoing oxaliplatin-based chemotherapy. A nerve-conduction study (NCS) was planned at the baseline, after three and six months of chemotherapy, to evaluate CIPN. Furthermore, the evaluation of hematological and liver toxicity was performed during every cycle of chemotherapy. 70.6% and 64.3% of patients developed CIPN in the placebo and the PMA-zeolite group, respectively. Patients treated with the PMA-zeolite were able to undergo more cycles of chemotherapy (p = 0.03), which also indicates a significant improvement in tolerance to the therapy. The group treated with the PMA-zeolite showed a lower CIPN (although not statistically significant within the whole group of subjects) compared to patients receiving placebo. This advantage was, however, statistically significant in men (p = 0.047). In addition, supplementation with the PMA-zeolite resulted in a lower incidence of severe-grade hematological toxicity (trend toward statistical significance of p = 0.09 was observed). Cancer patients may benefit from the therapy with the appropriate certified zeolite-products (e.g., the PMA-zeolite) for human use in CIPN. The lower CIPN (statistically significant results in the male subgroup) was accompanied by a trend of lower incidence of severe-grade hematological toxicity. Furthermore, these benefits led to a better tolerance toward chemotherapy (increase in cycles) and allow an improved compliance with the oncological treatment protocol.

Assessment of H-ß zeolite as an ochratoxin binder for poultry.

Most of the cereal-based ingredients used in poultry feed are contaminated with ochratoxin-A (OTA). We have investigated H-ß zeolite (HBZ) as a new OTA binder for poultry, along with widely used clay mineral-based product (CM), using in vitro and in vivo methods. In vitro binding experiment was carried out using a biphasic assay, consisting of adsorption at pH 3.2 and desorption at pH 6.8. High adsorption (>98%) with less desorption (<5%) was observed for HBZ, whereas CM showed high binding (>98%) and moderate desorption (48%). In the in vitro experiments with the different simulated gastro-intestinal pH buffers, HBZ did not desorb OTA at any of the pH. Desorption of OTA was observed with CM, as the pH increases. From the in vitro kinetic and chemisorption studies, faster, stronger, and higher adsorption was observed for HBZ. Thermodynamic studies showed positive entropy (22.76 KJ/mol K) for HBZ, signifying predominant hydrophobic interactions towards OTA, whereas CM exhibited negative entropy (-3.67 KJ/mol K). The in vivo binding efficacy of HBZ and CM was tested in 5-wk-old broiler chickens. The study consisted of 4 experimental groups, each with 6 replicates having 2 birds per replicate. The groups were control, negative control (no toxin binder), T1 (HBZ at 1 kg/ton of feed), and T2(CM at 1 kg/ton of feed). Except control, all the replicates received 20 µg of OTA in the feed. Excreta samples of T1, T2, and NC contained 11.57, 7.16, and 2.78 µg of OTA respectively, which was significantly different from each other (P < 0.05). A growth performance trial was conducted in broiler chickens for 35 D. A total of 288 one-day-old birds were randomly segregated to 3 treatment groups, each with 8 replicates of 12 birds each. Treatment groups consisted of control, T1, and T2, treated with no toxin binder, HBZ, and CM at 1 kg/ton of feed, respectively. None of the treatment groups including control, affected BW gain, and feed conversion ratio (P > 0.05).

The effect of feed supplementation with Transcarpathian zeolite (clinoptilolite) on the concentrations of acute phase proteins and cytokines in the serum and hepatic tissue of chickens.

The aim of the this study was to determine the effect of different levels of Transcarpathian zeolite (clinoptilolite) on selected indicators of the immune response in chickens by assessing the concentrations of the acute phase proteins haptoglobin, C-reactive protein (CRP), serum amyloid A, transferrin, and alpha-1-acid glycoprotein and the cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-2, and IL-10 in the serum and hepatic tissues of chickens. The study was conducted on 450 one-day-old male Ross 308 chickens. The total rearing period was 42 D. The samples of blood and liver were collected before the start of the study (day 0) and on day 42, after rearing was completed. ELISA kits specific for chicken CRP, haptoglobin, alpha-1-acid glycoprotein, serum amyloid A, transferrin, TNF-α, IFN-γ, IL-2, and IL-10 were used to determine the levels of acute phase proteins and cytokines in the serum and liver homogenates. The results of immunological tests suggest that for long-term maintenance of homeostasis in chickens, the addition of 2% zeolite as a feed additive is most beneficial. The results indicate that 3% clinoptilolite induce production of Th1 pro-inflammatory cytokines, increasing the synthesis of IL-2, IFN-γ, and TNF-α. The high concentration of IL-10 after the use of zeolite in conjunction with the high concentration of IL-2, TNF-α, and IFN-γ indicates a reduction in the intensity of inflammatory processes, the enhancement of the humoral immune response, and the simultaneous inhibition of the production of Th1-type cytokines. The increase of CRP concentration in conjunction with high concentrations of pro- and anti-inflammatory cytokines in the birds from the group receiving 3% clinoptilolite demonstrates indicates that it can influence the development of local inflammatory processes and enhance immune regulation in birds. Our research has shown that clinoptilolite influences on an increase in birds' resistance to infection, as confirmed by clinical observations and anatomopathological examination and by the increase in the synthesis of acute phase proteins with immunoregulatory properties.

Effects of dietary clinoptilolite on reproductive performance, serum progesterone and insulin-like growth factor-1 concentrations in dairy cows during pregnancy and lactation.

The objective of this study was to evaluate the effects of dietary zeolite clinoptilolite on re- productive performance, serum progesterone and insulin-like growth factor 1 (IGF-1) concentra- tions in 78 Holstein Friesian (HF) cows during pregnancy and lactation. The cows were divided into two groups comprising 40 (control group; CON) and 38 (CPL group) cows. To assess repro- ductive performance of HF cows the following variables were registered: the interval from calv- ing to first insemination (days open to first service, DFS), the interval from calving to pregnancy (days open to pregnancy, DOP), and the number of services per pregnancy (NSP). The average values of progesterone (5.64±0.59 ng/mL vs. 5.16±0.64 ng/mL) were not statistically different (p⟨0.05) and IGF-1 levels (400.17±17.72 ng/mL vs. 348.36±20.39 ng/mL) were higher in the CON than in the CPL group which received 50 g of clinoptilolite twice a day. However, in the CPL group ovarian cyclity resumed on days 40 and 60 postpartum. In addition, DFS (p⟨0.05) and DOP (p>0.05) were shorter in the CPL than in the CON group (115.1±19.9 and 137.5±36.3 days vs. 124.2±17.3 and 143.8±33.5 days, respectively). During 305 days of lactation, milk production was higher in the CPL vs. CON (8325.5±628.8 kg vs. 8050±586.8 kg). The NSP was lower in the CPL than in CON group (1.91 vs. 2.14). The dietary clinoptilolite supplement had a positive in- fluence on milk yield, exhibited modulating effects on endocrine status of dairy cows, and im- proved reproductive performance, with the decreased NSP, and fewer DFS and DOP.

Effects of dietary chitosan and nano-chitosan loaded clinoptilolite on growth and immune responses of rainbow trout (Oncorhynchus mykiss).

In this study, rainbow trout Oncorhynchus mykiss weighing 27.75 ± 0.34 g were orally subjected to eight experimental diets each in three replicates containing varying amounts of chitosan and nano-chitosan (0.05, 0.5 and 5 g kg-1) loaded in clinoptilolite (14.28 g kg-1) for 70 days; and the growth and immune responses were evaluated. Results showed that growth parameters in fish fed diets chit + clin2, chit + clin3, nchit + clin1, nchit + clin2 and nchit + clin3 were significantly higher than in fish fed the control diet. All feeds, except chit + clin3, and nchit + clin3, significantly increased the total protein level. Feeds containing chit + clin2, nchit + clin1, and nchit + clin2 significantly elevated serum lysozyme activity compared with the control group. All treatments, except chit + clin3, and nchit + clin3 exhibited higher serum immunoglobulin (Ig) level than control one. In contrast, diet nchit + clin1 significantly unregulated the expression of Ig M gene in fish head-kidney compared to other groups. Additionally, all feeds, except clinoptilolite, and nchit + clin3, significantly improved the serum complement activity. Diets chit + clin2, nchit + clin1, and nchit + clin2 also significantly elevated antibacterial activity against Yersinia ruckeri compared with the control diet. Expression of inducible nitric oxide synthase (iNOS) gene in fish fed diets clinoptilolite, chit + clin1, chit + clin3, nchit + clin1, nchit + clin2, and nchit + clin3 was significantly higher than the control diet. All diets, except clinoptilolite, increased IL-1ß gene expression compared to the control group. Present results suggest that diets supplemented with nchit + clin, especially at 0.05 g kg-1 nano-chitosan inclusion, could improve growth performance and immune parameters of rainbow trout.

Feeding synthetic zeolite to transition dairy cows alters neutrophil gene expression.

Synthetic zeolites are used to control the availability of dietary minerals (e.g., Ca, Mg, and P) in dairy cows. Due to calcium demand increasing with lactation onset, most cows become hypocalcemic immediately postpartum, which likely contributes to poorer immune function because calcium is important for immune cell signaling. To overcome postpartum hypocalcemia, we fed transition cows synthetic zeolite A (sodium aluminosilicate) precalving and hypothesized that it would alter calcium and thus neutrophil function during the transition period. Multiparous Holstein-Friesian cows in late gestation were randomly allocated to an untreated control group (n = 10) or a treatment group in which each cow received 500 g of zeolite A daily (n = 10) for 14 d prior to the expected calving date (actual duration = 17 ± 3 d prepartum). The cows grazed pasture, and each was supplemented with 2 kg/d of maize silage (dry matter basis), with or without zeolite, until calving. Blood samples for neutrophil isolation and analysis of plasma indicators of mineral status, energy status, liver function, and inflammation were collected pretreatment (covariate; d -19); on d -14 and -7 precalving; on the day of calving (d 0); and on d 1, 4, 7, and 28 postcalving. Neutrophils were isolated and gene expression was analyzed using microfluidic gene expression arrays. Neutrophil respiratory burst was assessed using stimulation with phorbol 12-myristate 13-acetate and flow cytometry. Plasma calcium and phosphorus revealed a treatment by time interaction; cows offered zeolite had greater plasma calcium concentrations at d 0, 1, and 4 postcalving and plasma phosphorus concentrations were lower in zeolite-treated cows during the precalving period until d 1 postcalving compared with control animals. Zeolite treatment downregulated neutrophil gene expression of CXCR4 and S100A8 and tended to lower gene expression for other immune mediators (CXCR1, IFNG, S100A12, and S100A9) compared with the control. Zeolite treatment did not affect neutrophil respiratory burst or expression of the other genes investigated. Plasma concentrations of cytokine IL-6 were reduced with zeolite treatment, which was most evident immediately postcalving (d 0, 1, and 7). Overall, feeding zeolite precalving had few effects on neutrophil gene expression and function; however, the lower gene expression of neutrophil inflammatory mediators may be due to altered availability of dietary minerals prepartum and indicates that zeolite A may control inflammation during the transition period.

Effect of zeolite supplementation on the dynamics of some trace elements and pigmentation of rumen in growing lambs.

A study was conducted to investigate the effect of feeding complete feed as total mixed ration (TMR) with two levels of zeolite on copper (Cu), iron (Fe), and zinc (Zn) status and rumen color of growing Naemi lambs. Twenty-four growing lambs (25 ± 2.1 kg body weight) were individually kept in separate pens with ad libitum feed and water. The lambs were randomly distributed to three treatments as follow: control, TMR diet only; T1, TMR with 1% zeolite daily; T2, TMR with 2% zeolite daily. The trial was lasted for 56 days. Four lambs from each treatment were slaughtered and tissue (liver, kidney, meat, and rumen tissues) and rumen fluid samples were collected. A significantly (P < 0.05) high concentration of Fe was found in T2 in blood and rumen fluid samples of lambs supplemented with zeolite. In the meat tissue, significantly (P < 0.05) high concentration of Zn was found in the treatment groups compared with the control, while Cu concentration decreased significantly (P < 0.05) in T1. In addition, rumen dark color was reduced in the zeolite-supplemented groups. We concluded that supplementation of zeolite at the rate of 1 or 2% did not appear to have any adverse effects on the blood profile of trace elements. Moreover, under these two levels of zeolite, discoloration of the rumen was significantly reduced in response to the supplementation of zeolite.

Effects of in-feed clinoptilolite treatment on serum metabolic and antioxidative biomarkers and acute phase response in dairy cows during pregnancy and early lactation.

The objective of this study was to evaluate the effects of in-feed clinoptilolite (CPL) on serum metabolic and antioxidative biomarkers, acute phase proteins and reproductive performance in cows during pregnancy and lactation. A total of 78 Holstein-Friesian cows were randomly assigned into two groups: the treatment group, cows fed CPL (n = 38) which received 50 g of powdered CPL twice a day from day 180 before parturition to day 60 postpartum; and the control group (n = 40). Blood samples were taken on days 180, 90, 60, 30 and 10 before parturition, on day of calving and on days 5, 12, 19, 26, 33, 40 and 60 postpartum, and were analysed for metabolic biomarkers: glucose, triglycerides, total cholesterol, high density lipoprotein cholesterol, non-esterified fatty acids, beta-hydroxybutyrate (BHB), antioxidative biomarkers and acute phase proteins: paraoxonase-1 (PON1), apolipoprotein A-I, haptoglobin (Hp) and serum amyloid A (SAA). CPL supplementation increased concentration of glucose and significantly decreased (P < .05) level of BHB during puerperium. The SAA concentration in CPL-fed cows was significantly decreased (P < .05) on days 33, 40 and 60 postpartum as well as Hp concentration on days 0 and 12 postpartum. The results of this study suggest that the CPL-fed cows may have improved metabolic status due to the tendency of greater glucose levels and decreased BHB values during early lactation. In addition, acute phase response was lower (P < .05) in CPL-fed cows. Such an outcome might be attributed to the effect of dietary CPL on intensity and severity of the negative energy balance and inflammatory response in dairy cows.

Antimicrobial activity of Titanium dioxide and Zinc oxide nanoparticles supported in 4A zeolite and evaluation the morphological characteristic.

In this study, the antimicrobial activity of titanium dioxide (TiO2), zinc oxide (ZnO), and TiO2/ZnO nanoparticles supported into 4A zeolite (4A z) was assessed. Based on antimicrobial experiments, minimum inhibitory concentration (MIC90), minimum bactericidal concentration (MBC), fractional inhibitory concentration (FIC) and disc diffusion test were determined after 24 h of contact with the prepared nanocomposites. These results are in agreements with the results of disc diffusion test. During the experiments, the numbers of viable bacterial cells of Staphylococcus aureus, Pseudomonas fluorescens, Listeria monocytogenes and Escherichia coli O157:H7 decreased significantly. The crystallinity and morphology of nanoparticles were investigated by X-ray diffraction patterns (XRD), elemental mapping at the microstructural level by scanning electron microscopy (SEM) with energy dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM). As a result, it was demonstrated that TiO2/ZnO nanoparticles supported in 4A zeolite could lead to an optimum activity as antimicrobial agents.

A New Calcium Oral Controlled-Release System Based on Zeolite for Prevention of Osteoporosis.

Osteoporosis, a systemic skeleton disease, can be prevented by increasing calcium levels in serum via administration of calcium salts. However, traditional calcium-based formulations have not appeared to be effective, hence the purpose of the present work has been to prepare and test in vitro/vivo a formulation able to gradually release calcium during transit over the GI tract, thus increasing bioavailability and reducing daily dose, and hence, side effects. Calcium controlled-release granules based on zeolite and Precirol® were prepared. In the best case, represented by granules sized 1.2 mm, containing 20% Precirol®, 19% zeolite, 60% calcium (granule), the release lasted ≈6 h. The release is controlled by diffusion of calcium ions through the aqueous channels forming within granules, once these come into contact with physiological fluids. Such a diffusion is hindered by the interaction of calcium ions with the negatively charged surface of the zeolite. Ovariectomy was used to make rats osteopenic. For in vivo studies, rats were divided into the following groups. Sham: not treated; ova: ovariectomized (ova); CaCl2 1.0 g: ova, treated with 1.0 g/die Ca2+; CaCl2 0.5 g: ova, treated with 0.5 g/die Ca2+; granule 1.0 g, or granule 0.5 g: ova, treated with granules equivalent to 1.0 g/die or 0.5 g/die Ca2+ in humans. Ca2+ amounts in femur bone and bone marrow, femur mechanical characteristics, and femur medullary canalicule diameter were measured and the same efficacy rank order was obtained: ova < CaCl2 0.5 g < CaCl2 1.0 g < granule 0.5 g ≈ granule 1.0 g ≈ sham. The results show promise of an effective prevention of osteoporosis, based on a controlled-rate administration of a calcium dose half that administered by the current therapy, with reduced side effects.

An aluminum adjuvant-integrated nano-MOF as antigen delivery system to induce strong humoral and cellular immune responses.

Metal-organic frameworks (MOFs) have high surface area, tunable pore size, and high loading capacity, making them promising for drug delivery. However, their synthesis requires organic solvents, high temperature and high pressure that are incompatible with biomacromolecules. Zeolitic imidazole frameworks (ZIF-8) which forms through coordination between zinc ions and 2-methylimidazole (MeIM) have emerged as an advanced functional material for drug delivery due to its unique features such as high loading and pH-sensitive degradation. In this study, we took advantage of a natural biomineralization process to create aluminum-containing nanoZIF-8 particles for antigen delivery. Without organic solvents or stabilizing agent, nanoparticles (ZANPs) were synthesized by a mild and facile method with aluminum, model antigen ovalbumin (OVA) and ZIF-8 integrated. A high antigen loading capacity (%) of 30.6% and a pH dependent antigen release were achieved. A Toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides (CpG) was adsorbed on the surface of ZANPs (hereafter CpG/ZANPs) to boost the immune response. After subcutaneous injection in vivo, CpG/ZANPs targeted lymph nodes (LNs), where their cargo was efficiently internalized by LN-resident antigen-presenting cells (APCs). ZANPs decomposition in lysosomes released antigen into the cytoplasm and enhanced cross-presentation. Moreover, CpG/ZANPs induced strong antigen-specific humoral and cytotoxic T lymphocyte responses that significantly inhibited the growth of EG7-OVA tumors while showing minimal cytotoxicity. We demonstrate that ZANPs may be a safe and effective vehicle for the development of cancer vaccines.

FA-PEG decorated MOF nanoparticles as a targeted drug delivery system for controlled release of an autophagy inhibitor.

A zeolitic imidazolate framework (ZIF-8) with high loading capacity and pH-responsive properties, an important subclass of metal-organic frameworks (MOFs), has become a promising material for drug delivery. A multifunctional drug delivery system (DDS) was designed in this work for effective targeting delivery of chloroquine diphosphate (CQ) as an autophagy inhibitor. The ZIF-8 nanoparticles encapsulating CQ (CQ@ZIF-8 NPs) were fabricated by a simple one-pot method and were then decorated with methoxy poly(ethylene glycol)-folate (FA-PEG), a special identifier of cancer cells, to form FA-PEG/CQ@ZIF-8. The target identification of FA-PEG/CQ@ZIF-8 NPs, compared with CQ@ZIF-8 NPs, leads to an increasing number of NPs being internalized into HeLa cells, which decreases the loss of drugs and results in high cytotoxicity of CQ for cancer cells. The lower viabilities of HeLa cells (cancer cells) and higher viabilities of HEK293 cells (healthy cells) treated with FA-PEG/CQ@ZIF-8 NPs show that the special target for cancer cells results from the combinations of folic acid and folate receptors on the surface of HeLa cells. The quantitative measurements of autophagy-related proteins and the detection of autophagy flux in HeLa cells suggest that the autophagosome formation and autophagy flux are appreciably blocked after the cells are treated with FA-PEG/CQ@ZIF-8 NPs. The ZIF-8 can disintegrate only under low pH conditions, resulting in fast and full release of CQ. The pH-responsive and tumor-targeted properties of the NPs can control the drug release and enhance the efficiency of autophagy inhibition. It indicates that the FA-PEG/CQ@ZIF-8 NPs combining target identification with controlled drug release can be used as a novel model for discussing targeted cancer therapy and inhibiting the autophagy of cancer cells.

Does supplemental zeolite (clinoptilolite) affect growth performance, meat texture, oxidative stress and production of polyunsaturated fatty acid of Turkey poults?

BACKGROUND: Following the ban on the use of growth factors, the use of zeolite in poultry feed could be a solution to obtain healthier food products that are more demanded by the consumer. METHODS: Zeolite (Clinoptilolite) was added to turkey male and female feed at concentrations 1% or 2% and was evaluated for its effectiveness on performance of the production. The turkeys were given free and continuous access to a nutritionally non-limiting diet (in meal form) that was either a basal diet or a 'Zeolite supplemented-diet' (the basal diet supplemented with clinoptilolite at a level of 1% or 2%). RESULTS: It was found that adding zeolite in the turkey diet had a positive effect on growth performance and increased weight gain compared to the control. In addition, zeolite treatment had a positive effect on oxidative stress and organoleptic parameters that were measured. It was found that adding zeolite in the turkey diet reduced the MDA level in the liver and in the meat, as compared to the control. Quality of meat was measured as a significantly increase (p < 0.05) in pH for male meat, indicated that the zeolite could maintain the quality of longer period. The adding of zeolite in the turkey diet increased level of polyunsaturated fatty acid. CONCLUSION: This study showed the significance of using zeolite, as a feed additive for turkey, as part of a comprehensive program to improve growth performance and oxidative stress parameters and to increase level of polyunsaturated fatty acid on the turkey body.

Hollow Mesoporous Silica@Zeolitic Imidazolate Framework Capsules and Their Applications for Gentamicin Delivery.

We have synthesized hollow mesoporous silica (HMS) at a zeolitic imidazolate framework (ZIF) capsule that can be used as a drug delivery system for gentamicin (GM). The GM is first loaded into HMS. Then, the outer surface of the GM/HMS is coated with uniformed ZIF nanoparticles (denoted as GM/HMS@ZIF). The GM/HMS@ZIF has been successfully prepared and acts as a capsule for GM. The GM/HMS@ZIF shows a good biocompatibility and a good cellular uptake in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. The GM is released slowly within 10 h under acidic conditions, which is used to simulate the pH of the endosome and lysosome compartments. The in vivo assay shows that the signal from fluorescein isothiocyanate (FITC) can be observed after 15 days, when the mice were injected with FITC/HMS@ZIF. This opens new opportunities to construct a delivery system for GM via one controlled low dose and sustained release for the therapy of Ménière's disease.