Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes.

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of ß-cyclodextrin (ßCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with ßCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with ßCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: ßCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:ßCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: ßCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

Advances in the application of functional nanomaterial and cold plasma for the fresh-keeping active packaging of meat.

The most recent advancements in food science and technology include cold sterilization of food and fresh-keeping packaging. Active packaging technology has received much interest due to the photocatalytic activity (PCA) of functional nanoparticles, including titanium dioxide (TiO2) and ferric oxide (Fe2O3). However, there are still significant concerns about the toxicity and safety of these functional nanoparticles. This review emphasizes the bacteriostatic and fresh-keeping properties of functional nanoparticles as well as their packaging strategies using the ultraviolet photo-catalysis effect. High-voltage electric field cold plasma (HVEF-CP) is the most innovative method of cold-sterilizing food. HVEF-CP sterilizes by producing photoelectrons, ions, and active free radicals on food media, which come into contact with the bacteria's surface and destroy their cells. Next, this review also assesses the photocatalytic activity and bacteriostasis kinetics of nanosized TiO2 and Fe2O3 in poultry, beef, and lamb. In addition, this review also emphasizes the importance of exploiting the complex interaction processes between TiO2 and Fe2O3, along with dietary components and their utilization in the fresh meat industry.

Genome-Based Analysis of the Potential Bioactivity of the Terrestrial Streptomyces vinaceusdrappus Strain AC-40.

Streptomyces are factories of antimicrobial secondary metabolites. We isolated a Streptomyces species associated with the Pelargonium graveolens rhizosphere. Its total metabolic extract exhibited potent antibacterial and antifungal properties against all the tested pathogenic microbes. Whole genome sequencing and genome analyses were performed to take a look at its main characteristics and to reconstruct the metabolic pathways that can be associated with biotechnologically useful traits. AntiSMASH was used to identify the secondary metabolite gene clusters. In addition, we searched for known genes associated with plant growth-promoting characteristics. Finally, a comparative and pan-genome analysis with three closely related genomes was conducted. It was identified as Streptomyces vinaceusdrappus strain AC-40. Genome mining indicated the presence of several secondary metabolite gene clusters. Some of them are identical or homologs to gene clusters of known metabolites with antimicrobial, antioxidant, and other bioactivities. It also showed the presence of several genes related to plant growth promotion traits. The comparative genome analysis indicated that at least five of these gene clusters are highly conserved through rochei group genomes. The genotypic and phenotypic characteristics of S. vinaceusdrappus strain AC-40 indicate that it is a promising source of beneficial secondary metabolites with pharmaceutical and biotechnological applications.

Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis.

In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8-150.5 µM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.

The Antiviral Effects of Jasminin via Endogenous TNF-α and the Underlying TNF-α-Inducing Action.

Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-ß were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.

Potentials of orally supplemented selenium-enriched Lacticaseibacillus rhamnosus to mitigate the lead induced liver and intestinal tract injury.

Lead is a metal that exists naturally in the Earth's crust and is a ubiquitous environmental contaminant. The alleviation of lead toxicity is important to keep human health under lead exposure. Biosynthesized selenium nanoparticle (SeNPs) and selenium-enriched Lactobacillus rhamnosus SHA113 (Se-LRS) were developed in this study, and their potentials in alleviating lead-induced injury to the liver and intestinal tract were evaluated in mice by oral administration for 4 weeks. As results, oral intake of lead acetate (150 mg/kg body weight per day) caused more than 50 times and 100 times lead accumulation in blood and the liver, respectively. Liver function was seriously damaged by the lead exposure, which is indicated as the significantly increased lipid accumulation in the liver, enhanced markers of liver function injury in serum, and occurrence of oxidative stress in liver tissues. Serious injury in intestinal tract was also found under lead exposure, as shown by the decrease of intestinal microbiota diversity and occurrence of oxidative stress. Except the lead content in blood and the liver were lowered by 52% and 58%, respectively, oral administration of Se-LRS protected all the other lead-induced injury markers to the normal level. By the comparison with the effects of normal L. rhamnosus SHA113 and the SeNPs isolated from Se-LRS, high protective effects of Se-LRS can be explained as the extremely high efficiency to promote lead excretion via feces by forming insoluble mixture. These findings illustrate the developed selenium-enriched L. rhamnosus can efficiently protect the liver and intestinal tract from injury by lead.

Immunomodulation Potential of Probiotics: A Novel Strategy for Improving Livestock Health, Immunity, and Productivity.

Over the past decade, the use of probiotics as feed supplements in animal production has increased considerably due to the ban on antibiotic growth promoters in livestock. This review provides an overview of the current situation, limitation, and prospects for probiotic formulations applied to livestock. Recently, the use of probiotics in livestock has been suggested to significantly improve their health, immunity, growth performance, nutritional digestibility, and intestinal microbial balance. Furthermore, it was reported that the use of probiotics in animals was helpful in equilibrating their beneficial microbial population and microbial turnover via stimulating the host immune response through specific secretions and competitive exclusion of potentially pathogenic bacteria in the digestive tract. Recently, there has been great interest in the understanding of probiotics targeted diet and its ability to compete with harmful microbes and acquire their niches. Therefore, the present review explores the most commonly used probiotic formulations in livestock feed and their effect on animal health. In summary, this article provides an in-depth knowledge about the formulation of probiotics as a step toward a better alternative to antibiotic healthy growth strategies.

Valorization of kiwi agricultural waste and industry by-products by recovering bioactive compounds and applications as food additives: A circular economy model.

Currently, agricultural production generates large amounts of organic waste, both from the maintenance of farms and crops (agricultural wastes) and from the industrialization of the product (food industry waste). In the case of Actinidia cultivation, agricultural waste groups together leaves, flowers, stems and roots while food industry by-products are represented by discarded fruits, skin and seeds. All these matrices are now underexploited and so, they can be revalued as a natural source of ingredients to be applied in food, cosmetic or pharmaceutical industries. Kiwifruit composition (phenolic compounds, volatile compounds, vitamins, minerals, dietary fiber, etc.) is an outstanding basis, especially for its high content in vitamin C and phenolic compounds. These compounds possess antioxidant, anti-inflammatory or antimicrobial activities, among other beneficial properties for health, but stand out for their digestive enhancement and prebiotic role. Although the biological properties of kiwi fruit have been analyzed, few studies show the high content of compounds with biological functions present in these by-products. Therefore, agricultural and food industry wastes derived from processing kiwi are regarded as useful matrices for the development of innovative applications in the food (pectins, softeners, milk coagulants, and colorants), cosmetic (ecological pigments) and pharmaceutical industry (fortified, functional, nutraceutical, or prebiotic foods). This strategy will provide economic and environmental benefits, turning this industry into a sustainable and environmentally friendly production system, promoting a circular and sustainable economy.

Isolation and identification of two new compounds from the seeds of Moringa oleifera and their antiviral and anti-inflammatory activities.

Eleven compounds were isolated from methanol extract taken from Moringa oleifera seeds, including two previously unknown and nine known compounds. These compounds were authenticated as a carbamate, three phenylglycosides, four phenol glycosides, two nucleosides, and one flavonoid. Their chemical structures were elucidated using 1 D/2D nuclear magnetic resonance and high resolution-MS. Antivirus activity analyses revealed that Moringa A, glucomoringin, and Vitexin possessed strong inhibitory effects against the H1N1 virus, having IC50 values in the range of IC50 = 0.26 ± 0.03, 0.98 ± 0.17, and 3.42 ± 0.37 µg/mL, respectively. Furthermore, these three compounds could decrease the levels of TNF-α, IL-6, and IL-1ß, which occur in hosts because of H1N1 infections.

Role of Food Antioxidants in Modulating Gut Microbial Communities: Novel Understandings in Intestinal Oxidative Stress Damage and Their Impact on Host Health.

Dietary components have an important role on the structure and function of host gut microbial communities. Even though, various dietary components, such as carbohydrates, fats, proteins, fibers, and vitamins, have been studied in depth for their effect on gut microbiomes, little attention has been paid regarding the impact of several food antioxidants on the gut microbiome. The long-term exposure to reactive oxygen species (ROS) can cause microbial dysbiosis which leads to numerous intestinal diseases such as microbiota dysbiosis, intestinal injury, colorectal cancers, enteric infections, and inflammatory bowel diseases. Recently, it has been shown that the food derived antioxidant compounds might protect the host from intestinal oxidative stress via modulating the composition of beneficial microbial species in the gut. The present review summarizes the impact of food antioxidants including antioxidant vitamins, dietary polyphenols, carotenoids, and bioactive peptides on the structure as well as function of host gut microbial communities. Several in vitro, animal model, and clinical studies indicates that food antioxidants might modify the host gut microbial communities and their health status. However, still further clarification is needed as to whether changes in certain microbial species caused by food additives may lead to changes in metabolism and immune function.

A new type of bilayer dural substitute candidate made up of modified chitin and bacterial cellulose.

In the field of neurosurgery, timely and effective repair of dura mater plays an important role in stabilizing the physiological functions of the human body. Therefore, the aim of this study is to develop a new type of bilayer membrane as a dural substitute candidate. It consists of a dense layer that prevents cerebrospinal fluid leakage and a porous layer that promotes tissue regeneration. The dense layer, a composite polysaccharid film, was composed of high molecular weight chitosan (CS) and bacterial cellulose (BC). The porous layer, a composite polysaccharid scaffold cross-linked by glutaraldehyde (GA) or citric acid (CA) respectively, was composed of O-carboxymethyl chitin (O-CMCH) and BC. The bilayer dural substitutes were characterized in terms of SEM, mechanical behavior, swelling rate, anti-leakage test, in vitro cytotoxicity, proliferation, and animal experiment. Results indicated that all prepared dural substitutes were tightly bound between layers without excessively large cavities. The porous layer showed appropriate pore size (90～200 µm) with high porous connectivity. The optimized bilayer dural substitutes showed suitable swelling rate and mechanical behavior. Furthermore, no leakage was observed during testing, no cytotoxicity effect on NIH/3T3 cells, and exhibited excellent cell proliferation promoting properties. Also, it was observed that it did not deform in the peritoneal environment of mice, and tissue inflammation was mild.

Chitin/chitosan derivatives and their interactions with microorganisms: a comprehensive review and future perspectives.

Chitosan, obtained as a result of the deacetylation of chitin, one of the most important naturally occurring polymers, has antimicrobial properties against fungi, and bacteria. It is also useful in other fields, including: food, biomedicine, biotechnology, agriculture, and the pharmaceutical industries. A literature survey shows that its antimicrobial activity depends upon several factors such as: the pH, temperature, molecular weight, ability to chelate metals, degree of deacetylation, source of chitosan, and the type of microorganism involved. This review will focus on the in vitro and in vivo antimicrobial properties of chitosan and its derivatives, along with a discussion on its mechanism of action during the treatment of infectious animal diseases, as well as its importance in food safety. We conclude with a summary of the challenges associated with the uses of chitosan and its derivatives.

Regulation of the Morphological and Physical Properties of a Soft Tissue Scaffold by Manipulating DD and DS of O-Carboxymethyl Chitin.

To improve the biocompatibility/biodegradability as well as to lower the cost of the popular glycosaminoglycan/collagen scaffold, a monocomponent's polysaccharide scaffold based on biomimetic chemical modification of chitin from lower organisms was developed creatively. O-Carboxymethyl chitin (O-CMCH) was prepared by chloroacetic acid substitution of alkalized chitin. The cross-linked O-CMCH soft tissue scaffold was constructed by a sol-gel freeze-drying method. The key parameters of the O-CMCH molecular structure, the degree of deacetylation (DD), and the degree of substitution (DS) were used to regulate the morphology and physical properties of the scaffold. The optimized scaffolds were implanted subcutaneously in mice, and the inflammation reaction of surrounding tissues, dermal tissue growth, and scaffold degradation were observed dynamically by light microscopy and scanning electron microscopy. The results showed that the micropores of the scaffold constructed by O-CMCH with DD = 0.53 and DS = 0.61 were uniformly distributed and in communication with each other, and the pore size was 100-150 µm, with high porosity (93.52 ± 4.68%), high swelling ratio (1402 ± 70%), and high skeleton cross-linking degree (93.4 ± 4.6%). Its tensile strength reached 0.183 ± 0.009 MPa, and its elongation at break was 18.7 ± 0.9%. Furthermore, it could be degraded to less than 10% after 16 days in phosphate buffer solution (pH = 7.4) with 0.2 mg/mL lysozymes (≥ 20 000 U/mg). The early inflammation after implanting the optimized scaffolds in mice showed no difference compared with the control. The scaffold material induced dermal tissues to grow over it and was degraded gradually in vivo. The optimized scaffold regulated by DD and DS of O-CMCH possessed suitable morphology and physical properties for soft tissue engineering technology and exhibited a high applicable value.

Antibacterial and antioxidant activity of exopolysaccharide mediated silver nanoparticle synthesized by Lactobacillus brevis isolated from Chinese koumiss.

Recently, silver nanoparticles gain significant attention due to their applications in various fields. The aim of present study was to develop the eco-friendly, cost effective, and simple method to biosynthesized the silver nanoparticle using sliver nitrate as precursor. In this study, we investigated the physical characterization and biotechnological applications of biosynthesized silver nanoparticle using exopolysaccharide of probiotic Lactobacillus brevis MSR104 isolated from Chinese koumiss. Biosynthesized silver nanoparticles were characterized using the fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction analysis, and elemental analyzer. The achieved results indicate that silver nanoparticles varied in sized with an average size of 45 nm. The X-ray diffraction analysis results showed that the silver nanoparticles have a crystalline nature. The results of antimicrobial assay indicated that the silver nanoparticles exhibited outstanding antimicrobial activity in dose dependent manner against both Gram's negative as well as Gram's positive. The antioxidant results indicate that the silver nanoparticles showed excellent scavenging rate against DPPH free radicals (81.4 ±â€¯1.2%) and nitric oxide free radicals (75.06 ±â€¯0.4%). Furthermore, the results of MTT assay revealed that the AgNPs significantly reduced the percentage of live HT-29 cells at higher concentration. This study concluded that the newly synthesized silver nanoparticles have antibacterial, antioxidant, and anticancer applications in agricultural and food industries.

Anti-tumor potential of cell free culture supernatant of Lactobacillus rhamnosus strains isolated from human breast milk.

Lactobacilli rhamnosus has been characterized as a probiotic and plays an important role in human health by stimulating the supplement of nutrients, preventing the colonization of pathogens, and influencing the immune system. This study investigated the anticancer activity of the three Lactobacillus rhamnosus strains SHA111, SHA112, and SHA113 isolated from human breast milk. The cell-free supernatant of a liquid culture of the three strains showed excellent antioxidant activities against DPPH free radicals, superoxide anion radicals, and hydroxyl radicals; furthermore, significant anticancer activity was found on cervix cancer cells (HeLa) via cytotoxicity and induction of apoptosis. RT-qPCR and western blot analysis showed the induction of apoptosis was achieved via the up-regulation of BAD, BAX, Caspase3, Caspase8, Caspase9, and down-regulation of BCL-2 genes in HeLa cells. The results suggest that these strains have potential anticancer capability.

Chitosan and its derivatives: synthesis, biotechnological applications, and future challenges.

Chitosan is a naturally occurring biodegradable as well as a non-toxic polymer generated from chitin through alkaline deacetylation reaction, and it is insoluble in organic/inorganic solvents and water. Furthermore, chitosan is one of the most plentiful cationic polymers in natural surroundings. Due to its non-toxicity and biocompatibility, chitosan is extensively employed in industrial, biomedical, food, pharmaceutical, environmental, and agricultural industry. Chitosan-based biomaterials exhibit great potential in various biotechnological applications, such as anti-hypertensive therapy, anti-oxidant, anti-microbial, anti-allergic, immunostimulant, cancer therapy, delivery of genetic materials, delivery of bone morphogenetic type-2, wound healing, treatment of wastewater, hypocholesterolemic, and bio-imaging. Therefore, this review mainly focuses on the biotechnological potential of chitosan and its derivatives as well as presents the potential of chitosan-based biomaterial/pharmaceutical for the prevention of various life-threating chronic disorders.

Origination, change, and modulation of geriatric disease-related gut microbiota during life.

The age-related changes in the diversity and composition of the gut microbiota are well described in recent studies. These changes have been suggested to be influenced by age-associated weakening of the immune system and low-grade chronic inflammation, resulting in numerous age-associated pathological conditions. Gut microbiota homeostasis is important throughout the life of the host by providing vital functions to regulate various immunological functions and homeostasis. Based on published results, we summarize the relationship between the gut microbiota and aging-related diseases, especially Parkinson's disease, immunosenescence, rheumatoid arthritis, bone loss, and metabolic syndrome. The change in composition of the gut microbiota and gut ecosystem during life and its influence on the host immunologic and metabolic phenotype are also analyzed to determine factors that affect aging-related diseases. Approaches to maintain host health and prevent or cure geriatric diseases are also discussed.

Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk.

Lactic acid bacteria have been categorized as probiotics and play a crucial role in human health by stimulating the supply of nutrients, shaping the immune system, and preventing the colonization of pathogenic microbes. This study investigated the mechanisms for the action of three potential probiotic Lactobacillus strains: Lactobacillus casei SR1, Lactobacillus casei SR2, and Lactobacillus paracasei SR4 isolated from human breast milk. These Lactobacillus strains were identified via 16S DNA sequencing and characterized via biochemical assays including acid resistance, bile resistance, antioxidant activity, and antibiotic susceptibility. The bioactivity of the cell-free culture supernatant (CFCS) secreted by these strains on the cervix cancer (HeLa) cell line was also evaluated via cytotoxicity assay and apoptosis analysis. The mechanism of anticancer activity was also investigated via RT-qPCR and western blotting. The results demonstrated that these newly isolated Lactobacillus strains from human milk displayed noticeable probiotic characteristics such as excellent antibiotic susceptibility, outstanding antioxidant activity, and promising resistance to low pH and high concentration of bile salts. The results of the conducted bioactivity assays verified that the CFCSs had acceptable anticancer effects on cervix cancer (HeLa) cells by upregulating the expression of apoptotic genes BAX, BAD, caspase3, caspase8, and caspase9 and by downregulating the expression of the BCl-2 gene. Overall, these results indicate that the Lactobacillus strains isolated from human breast milk could be considered as a topical medication with a potential therapeutic index due to their efficacy against cervix cancer cells.

Impact of dietary compounds on cancer-related gut microbiota and microRNA.

Cancer is one of the most common causes of death worldwide. Extensive research has been conducted on cancer; regardless, the link between cancer and diet remains undetermined. Recent studies have emphasized the importance of miRNAs in cancer-associated pathways from the perspective of dietary modulation. We highlighted the recent data on dietary modulation of gut microbiota and miRNAs related to cancer on the basis of recently published results. The targets of miRNAs are oncogenes or tumor suppressors that mediate the progression and initiation of carcinogenesis. Different miRNAs display complex expression profiles in response to dietary manipulation. Various dietary components, such as fatty acids, resveratrol, isothiocyanate, and curcumin, have been effectively used in cancer prevention and treatment. This potency is attributed to the capability of these components to alter miRNA expression, thereby modulating the vital pathways involved in metastasis, invasion, apoptosis, tumor growth, and cell proliferation.