Dose-response relationship of MSCs as living Bio-drugs in HFrEF patients: a systematic review and meta-analysis of RCTs.

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that MSC-based therapy is safe and effective in heart failure patients; however, its dose-response relationship has yet to be established. We aimed to determine the optimal MSC dose for treating HF patients with reduced ejection fraction (EF) (HFrEF). METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells). RESULTS: MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment. CONCLUSION: Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.

Enhancing the bioavailability and antioxidant activity of natamycin E235-ferulic acid loaded polyethylene glycol/carboxy methyl cellulose films as anti-microbial packaging for food application.

This study investigated the development of biodegradable films made from a combination of polyethylene glycol (PEG), carboxymethyl cellulose (CMC) and mixtures from natamycin and ferulic acid. The films were characterized for their surface microstructure, antioxidant activity, thermal stability, mechanical properties, permeability and antifungal/bacterial activity. The addition of natamycin and ferulic acid to the film matrix enhanced antioxidant activity, thermal stability, antimicrobial activity, reduced the water vapor permeability (WVP) to 1.083 × 10-10 g × m-1s-1Pa-1, imparted opaque color and increased opacity up to 3.131 A mm-1. The attendance of natamycin and ferulic acid inside films created a clear roughness shape with agglomerates on the surface of films and caused a clear inhibition zone for Aspergillus niger, E. coli and C. botulinum. The utilization of PG/CMC/N-F packaging material on Ras cheese had a noticeable effect, resulting in a slight decrease in moisture content from 34.23 to 29.17 %. Additionally, it helped maintain the titrable acidity within the range of 0.99 % to 1.11 % and the force required for puncture from 0.035 to 0.052 N with non-significant differences. Importantly, these changes did not significantly affect the sensory qualities of Ras cheese during the storage period.

Sodium alginate films incorporated with Lepidium sativum (Garden cress) extract as a novel method to enhancement the oxidative stability of edible oil.

This study addresses the growing interest in bio-based active food packaging by infusing Lepidium sativum (Garden cress) seeds extract (GRCE) into sodium alginate (SALG) films at varying concentrations (1, 3, and 5 %). The GRCE extract revealed six phenolic compounds, with gallic and chlorogenic acids being prominent, showcasing substantial total phenolic content (TPC) of 139.36 µg GAE/mg and total flavonoid content (TFC) of 26.46 µg RE/mg. The integration into SALG films significantly increased TPC, reaching 30.73 mg GAE/g in the film with 5 % GRCE. This enhancement extended to DPPH and ABTS activities, with notable rises to 66.47 and 70.12 %, respectively. Physical properties, including tensile strength, thickness, solubility, and moisture content, were positively affected. A reduction in water vapor permeability (WVP) was reported in the film enriched with 5 % GRCE (1.389 × 10-10 g H2O/m s p.a.). FT-IR analysis revealed bands indicating GRCE's physical interaction with the SALG matrix, with thermal stability of the films decreasing upon GRCE integration. SALG/GRCE5 effectively lowered the peroxide value (PV) of sunflower oil after four weeks at 50 °C compared to the control, with direct film-oil contact enhancing this reduction. Similar trends were observed in the K232 and K270 values.

Enhanced physical properties, antioxidant and antibacterial activity of bio-composite films composed from carboxymethyl cellulose and polyvinyl alcohol incorporated with broccoli sprout seed extract for butter packaging.

This study investigated the development of biodegradable films made from a combination of carboxymethyl cellulose (CMC), Polyvinyl alcohol (PVA), and purified extract of broccoli sprout seed (BSSE). The films were characterized for their color, physical properties, surface morphology, crystallinity, mechanical properties, and thermal properties. The addition of BSSE up to 1.4 % to the film matrix imparted opaque color and increased opacity up to 3.652. The films also became less moisture-absorbent 8.21 %, soluble 19.16 %, and permeable to water vapor 1.531 (× 10-10 g.m-1 s-1 pa-1). By utilizing 0.7 % from BSSE inside films, the surface of the films became smoother but became rough with higher concentrations 2.1 % of BSSE. Fourier transform infrared (FT-IR) analysis showed that there was physical interaction between the BSSE extract and the PV/CM matrix. The films showed good thermal stability, and the incorporation of BSSE improved their ability to preserve the acidity, TBARS, peroxide value, and total color differences of butter during cold storage.

Optimizing extraction conditions and isolation of bound phenolic compounds from corn silk (Stigma maydis) and their antioxidant effects.

During the processing of maize, Stigma maydis, also known as corn silk, is normally discarded as waste. Phytochemical research was carried out on the S. maydis to use it as a valuable source of bioactive components. This research aimed to maximize the recovery of free and bound phenolic compounds from corn silk under optimal experimental conditions. Response surface design was operated to optimize the alkaline hydrolysis extraction of bound phytochemicals from corn silk based on total phenolic content and DPPH radical scavenging activity. The optimum conditions (i.e., NaOH concentration 2 M, digestion time 135 min, digestion temperature of 37.5°C, the solid-to-solvent ratio of 1:17.5, and acetone) were obtained. The optimum parameters were used to extract the corn silk. The structures of two compounds isolated from ethyl acetate extracts were then identified as friedelin (1) and (E)-4-(4-hydroxy-3-methoxyphenyl) but-3-en-2-one (2). The DPPH, H2 O2 , and ABTS % inhibition of the compounds is as follows: compound (1) 74.81%, 76.8%, 70.33% and compound (2) 70.37%, 56.70% and 57.46%, respectively. The current study has opened previously unexplored perspectives of the composition of bound compounds in corn silk and established the foundations for more effective processing and utilization of corn waste. PRACTICAL APPLICATION: Bound phenolic compounds from corn silk under optimal experimental conditions were obtained. Corn silk can be utilized as a type of medicinal herb as well as a source of inexpensive natural antioxidants.

Composite films based on carboxy methyl cellulose and sodium alginate incorporated Thymus vulgaris purified leaves extract for food application: Assessment, antimicrobial and antioxidant properties.

The current study was conducted to develop biodegradable films with matrix composed from carboxymethyl cellulose (CMC), sodium alginate (SA) and different concentrations from Thymus vulgaris purified leaves extract (TVE). The color properties, physical properties, shape of surface, manners of crystallinity, mechanical properties and thermal properties of produced films were investigated. The continuous addition of TVE up to 1.6 % inside films matrix imparted the yellow color of extract that increased opacity to 2.98 and reduced moisture, swelling, solubility and water vapor permeability (WVP) of films up to 10.31 %, 30.17 %, 20.18 % and (1.12× 10-10 g.m-1 s-1 pa-1), respectively. Furthermore, the surface micrographs showed smoother surface after using small concentrations of TVE and turned to irregular with rough surface at higher concentrations. The FT-IR analysis indicated typically bands that demonstrated physical interaction between TVE extract and CMC/SA matrix. The fabricated films showed suitable thermal stability with decreasing trend by incorporation of TVE inside CMC/SA films. Furthermore, the developed CMC/SA/TVE2 showed significant effects on preserving the levels of moisture content, titrable acidity, force to puncture and sensory properties of cheddar cheese during cold storage days compared with commercial packaging materials.

Large batch production of Galactooligosaccharides using ß-glucosidase immobilized on chitosan-functionalized magnetic nanoparticle.

ß-glucosidase (BglA) immobilization from Thermotoga maritima on magnetic nanoparticles (MNPs) functionalized with chitosan (Cs) were efficiently investigated to improve lactose conversion and galactooligosaccharides (GOS) production. We used a batch method in order to improve the conversion of lactose to GOS. The efficiency and yield of immobilization were 79% and immobilized BglA was effectively recycled via a magnetic separation procedure through a batch-wise GOS with no activity lessening. Furthermore, analyses were done through screening kinetics of enzyme activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). Proposed methodology of immobilization shows a potential application as it is stable which was proved through many methods including pH, temperature, heat treatment, storage, and kinetics of the enzyme. GOS and residual enzyme activity showed to be 28.76 and 40.44%, respectively. However, free enzyme synthesis of GOS yield was just 24% after 12 hr. This study proposed applying magnet in the immobilization process of BglA on Cs-MNPs to produce GOS as new method for immobilizing enzyme in a biostable and cost-efficient way. PRACTICAL APPLICATIONS: This paper focus on immobilization of BglA from T. maritima onto MNPs functionalized with CS to investigate their further possibility improving lactose conversion and GOS production. Interestingly, a successful immobilization of Tm-BglA on the substrates were achieved in Cs-MNPs. The obtained results from enzyme activity, SDS-PAGE, FT-IR, and TEM showed that the high binding capacity of BglA to Cs-MNPs was successfully obtained. Furthermore, the binding efficiency calculation indicated that the immobilized BglA-Cs-MNPs conserved 40.44% of its native activity at the end of its 6th repeated use. In addition, magnetic separation technique was successfully employed for reuse of the immobilized BglA for repetitive batch-wise GOS without significant loss of activity.

Antioxidant and anti-inflammatory activities of target anthocyanins di-glucosides isolated from Syzygium cumini pulp by high speed counter-current chromatography.

High-speed counter-current chromatography (HSCCC) was utilized as an effective procedure for isolation of targeted three anthocyanins di-glucosides from Syzygium cumini (SC) pulp by using an optimized biphasic successful combination of different solvents. The resulted fractions described by HPLC/ESI-MS to be delphinidin 3,5-diglucoside (DDG), petunidin 3,5-diglucoside (PDG), and malvidin 3,5-diglucoside (MDG). A weight of 150 mg of sample yielded 7.53, 22.68, and 39.09 mg for DDG, PDG, and MDG, respectively. It was stated that the target three anthocyanins possessed strong antioxidant activities. Furthermore, MDG exhibited definite advantages for inhibition of nitric oxide release and pro-inflammatory mediators like mouse interleukin 6 (IL-6), mouse interleukin (IL-1ß) and mouse tumor necrosis factor (TNF-α) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The results propose that HSCCC can be utilized to separate highly antioxidative and anti-inflammatory natural components from SC pulp. PRACTICAL APPLICATIONS: Anthocyanins are water-soluble pigments and considered one of the groups of bioactive compounds, which generally concentrate in the skin, and often also the flesh of some fruits and vegetables as glycosides like acylglycosides and aglycones of anthocyanidins. The fully ripe fruits of SC contain anthocyanins, like as delphinidin, cyanidin, and petunidin, which supply them a distinctive color and good antioxidant characteristics. HSCCC considers a system of liquid-liquid extraction with separating large quantities of materials, using a minimum of solvent. The findings of the study would pave a separation strategy for potential large-scale preparation of anthocyanins di-glucosides standards for compounds detection and reduce the inflammation symptoms through declining the induction of pro-inflammatory cytokines such as IL-1ß, TNF-α and IL-6, which will also enhance the future notification on the structure-activity correlations of anthocyanins di-glucosides.

Effect of Chinese chives (Allium tuberosum) addition to carboxymethyl cellulose based food packaging films.

Carboxymethyl cellulose (CMC) based novel functional films containing Chinese chives root extract (CRE) at different concentrations (1, 3 and 5 % in w/w) were successfully fabricated. It was revealed by SEM that higher extract concentration triggered the formation of agglomerates within the film. Tensile strength of the films was decreased from 30.91 to 16.48 MPa. Thickness of films was increased from 43 to 84 µm, while decrease in water solubility from 77.51-52.91 %, swelling degree from 55.74 to 40.37 %, and water vapor permeability from 5.76 to 1.17 10-10 gm-1s-1 Pa-1 was observed. DPPH and ABTS radical scavenging ability of CMC-CRE films was increased from 0 to 58 % and 82 %, respectively. CMC-CRE5 film showed the highest biodegradability of 58.14 %. The film prepared by the addition of CRE into CMC also exhibited good antioxidant and antimicrobial activity indicating that it could be developed as a bio-composite food packaging material for the food industry.

Immunomodulatory Activity in vitro and in vivo of Polysaccharides from Kabuli Chickpea (Cicer arietinum L.) Hull.

RESEARCH BACKGROUND: Polysaccharides isolated from plants, fungi and bacteria are associated with immunomodulatory effects. Chickpea hull, which is regarded as food industrial waste, contains considerable amount of antioxidants and bioactive compounds. EXPERIMENTAL APPROACH: In the present study, we investigated the immunomodulatory activity of polysaccharides from kabuli chickpea (Cicer arietinum L.) hull (CHPS). In vitro study was conducted with RAW264.7 cell line while in vivo study was carried out using specific pathogen-free BALB/c mouse animal model. RESULTS AND DISCUSSION: In in vitro test with RAW264.7 murine macrophage cells, the three purified fractions of chickpea hull polysaccharides showed potent immunomodulatory activity. Sample CHPS-3 showed stronger effect on cell viability, promoted the phagocytosis index to a greater extent and had the best effect on acid phosphatase activity. Moreover, it was found that CHPS-3 significantly (p<0.05) enhanced the secretion of nitrogen monoxide and cytokine (interleukins IL-6, IL-1ß and tumor necrosis factor-alpha (TNF-α)) levels. In in vivo study, CHPS-3 improved thymus and spleen indices in cyclophosphamide-induced immunodeficient mice. Increased activities of lysozyme, catalase, superoxide dismutase and glutathione peroxidase, serum haemolysin content and total antioxidant capacity were observed, while the amount of malondialdehyde in the liver decreased. NOVELTY AND SCIENTIFIC CONTRIBUTION: The results suggest that chickpea hull polysaccharides enhanced the immune activity and could be developed as the ingredient of functional foods.

Production and characterization of CMC-based antioxidant and antimicrobial films enriched with chickpea hull polysaccharides.

In the present study, polysaccharides from chickpea hull (CHPS) were incorporated into carboxymethyl cellulose (CMC) for the development of CMC-based films. The physical and mechanical properties, color, transmittance, antioxidant and antimicrobial activities were investigated, and differential scanning calorimetry (DSC), Fourier transform-infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA) were applied to study the potential interaction, structure and thermal stabilization of the prepared films. The results revealed that some physical and mechanical properties of films, like moisture content, elongation at break and water vapor permeability, were decreased. While thickness, swelling ratio, water solubility and tensile strength were significantly increased (p < 0.05) compared with control film. Furthermore, the films exhibited potential antioxidant effects on DPPH and ABTS free radicals. The results of scanning electron microscopy showed rough and heterogeneous morphology for CMC-CHPS films while control film exhibited smooth, homogenous and compact structure. FT-IR results reflected good interaction of chemical groups and bonds between CMC and CHPS. DSC results showed that glass transition temperature increased significantly (p < 0.05) from 82.68 to 90.39 °C compared with control of 78.21 °C. Thermal stability of all films was improved, indicating that the films could be used as biocomposite materials for packaging of food products.

Volumetric bone mineral density of the tibia is not increased in subjects with radiographic knee osteoarthritis.

OBJECTIVES: Radiographic osteoarthritis (ROA) has previously been shown to be associated with an increase in areal bone mineral density (BMD) as assessed by dual energy X-ray absorptiometry (DXA). Here we have assessed volumetric bone density, size and strength by peripheral quantitative computed tomography (pQCT) in a large population-based cohort study in which knee radiographs were available. METHODS: Two hundred and ninety-five men and 288 women from the MRC Hertfordshire Cohort Study underwent weight bearing extended knee X-rays and bone density measurement of the ipsi-lateral knee using pQCT. RESULTS: Increasing radiographic grade in men but not women was associated with an increase in tibial total area at 38% site and cortical area at 14% site, but not with volumetric BMD. The tibial fracture loads as well as tibial polar strength strain index at 38% site were also increased. There were no significant associations of tibia bone area, BMD or strength with radiographic grade in women. CONCLUSION: ROA is not associated with an increase in volumetric BMD as assessed by pQCT. It is, however, associated with a significant increase in bone area and strength, indicating that the association between ROA and areal BMD is mediated through bone size rather than volumetric BMD.