Impact of de-branched starch molecules and fatty acid complexes on the attenuation of ageing-induced cognitive impairment.

BACKGROUND: Ageing and associated cognitive impairments are becoming serious issues around the world. In this study, the physiological properties of three kinds of complexes of fatty acid (capric, stearic and oleic acid, respectively) and de-branched starch molecules were investigated via a d-galactose-induced ageing model. This study revealed differences in the regulation of cognitive impairment and brain damage following intervention of different complexes, which might highlight a potent approach for the prevention of this chronic disease. RESULTS: Data indicated that three complexes improved response time and cognitive function and the bio-parameter markers associated with oxidative stress in ageing rats. Among them, the complexes prepared from de-branched starch-oleic acid showed a greater improvement compared to others. In addition, de-branched starch-capric acid complex showed a higher improvement in the morphology of colon cells and hippocampal neuronal cells. The consumption of de-branched starch-capric acid and -oleic acid complexes generated more short-chain fatty acids in the gut. More importantly, the complexation of de-branched starch with either caprate or stearate enhanced gut Akkermansia. Therefore, it was proposed that the richness in Akkermansia and gut metabolites might be associated with reduced damage of the hippocampal neuronal cells induced by the ageing progress. Moreover, the AMPK (AMP-activated protein kinase) pathway was activated in liver in de-branched starch-capric acid complex diet. In summary, de-branched starch-capric acid complex exhibited a greater effect on the attenuation of ageing-induced cognitive impairment. CONCLUSION: This study might highlight a new approach for intervening in the cognitive impairment during the ageing progress via a food supply. © 2023 Society of Chemical Industry.

Association of gut microbiota characteristics and metabolites reveals the regulation mechanisms under cadmium consumption circumstance.

BACKGROUND: Cadmium is a non-biodegradable heavy metal with a long biological half-life. Although its negative impact on human health has been previously reported, the association of cadmium consumption overdose with changes in the gut microbiota and its corresponding metabolites has not been fully elucidated so far. RESULTS: Cadmium consumption overdose led to a reduced body weight gain accompanied by an enhanced level of the proinflammatory cytokine tumor necrosis factor-α, interleukin-6, and histamine in the serum of the rats in comparison with normal rats. Furthermore, hepatotoxicity was also observed to be induced by cadmium, which was consistent with abnormal hepatic activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and oxidative stress. In contrast, Lactobacillus rhamnosus-fermented Ganoderma lucidum (FGL) slice supplementation improved the aforementioned physiological properties. More importantly, microbiome and metabolites analysis indicated cadmium exposure significantly reduced the generation of short-chain fatty acids in the gut, particularly butyrate. However, rats in the FGL group had the highest level of butyrate in the feces, characterized with significantly enriched probiotics (Lactobacillus, Bifidobacterium) and butyrate-producing bacteria (Roseburia). CONCLUSION: The targeted regulation of the gut microbial community and its metabolites might be the essential association for attenuating body dysfunction induced by cadmium. The supplementation of FGL, as evidenced in this study, might highlight a novel approach to this field. © 2022 Society of Chemical Industry.

Hitting the sweet spot: A systematic review of the bioactivity and health benefits of phenolic glycosides from medicinally used plants.

Phenolic acid and flavonoid glycosides form a varied class of naturally occurring compounds, characterised by high polarity-resulting from the glycone moiety-and the presence of multiple phenol functionalities, which often leads to strong antioxidant activity. Phenolic glycosides, and in particular flavonoid glycosides, may possess strong bioactive properties with broad spectrum activity. This systematic literature review provides a detailed overview of 28 studies examining the biological activity of phenolic and flavonoid glycosides from plant sources, highlighting the potential of these compounds as therapeutic agents. The activity of glycosides depends upon the biological activity type, identity of the aglycone and the identity and specific location of the glycone moiety. From studies reporting the activity of both glycosides and their respective aglycones, phenolic glycosides appear to generally be a storage/reserve pool of precursors of more bioactive compounds. The glycosylated compounds are likely to be more bioavailable compared to their aglycone forms, due to the presence of the sugar moieties. Hydrolysis of the glycoside in the in vivo environment would release the free aglycone, potentiating their biological activity. However, further high-quality studies are needed to firmly establish the clinical efficacy of glycosides from many of the plant species studied.

Generation of a nitric oxide signaling pathway in mesenchymal stem cells promotes endothelial lineage commitment.

Enhancing differentiation of mesenchymal stem cells (MSCs) to endothelial cells may improve their ability to vascularize tissue and promote wound healing. This study describes a novel role for nitric oxide (NO) in reprogramming MSCs towards an endothelial lineage and highlights the role of Wnt signaling and epigenetic modification by NO. Rat MSCs were transduced with lentiviral vectors expressing endothelial nitric oxide synthase (pLV-eNOS) and a mutated caveolin gene (pLV-CAV-1F92A ) to enhance NO generation resulting in increased in vitro capillary tubule formation and endothelial marker gene expression. An exogenous source of NO could also stimulate CD31 expression in MSCs. NO was associated with an arterial-specific endothelial gene expression profile of Notch1, Dll4, and Hey2 and significantly reduced expression of venous markers. Wnt signaling associated with NO was evident through increased gene expression of Wnt3a and ß-catenin protein, and expression of the endothelial marker Pecam-1 could be significantly reduced by treatment with the Wnt signaling inhibitor Dkk-1. The role of NO as an epigenetic modifier was evident with reduced gene expression of the methyltransferase, DNMT1, and bisulfite sequencing of the endothelial Flt1 promoter region in NO-producing MSCs showed significant demethylation compared to control cells. Finally, subcutaneous implantation of NO-producing MSCs seeded in a biomaterial scaffold (NovoSorb®) resulted in survival of transplanted cells and the formation of blood vessels. In summary, this study describes, NO as a potent endothelial programming factor which acts as an epigenetic modifier in MSCs and may provide a novel platform for vascular regenerative therapy.

Phenolic Compounds with Antioxidant Properties from Canola Meal Extracts Inhibit Adipogenesis.

The extraction of phenolic compounds from canola meal produces functional health products and renders the canola meal a more digestible animal feed. The extracted phenolics may have novel bioactivity worth investigation. In this study, several solvents were evaluated for their ability to extract phenolic compounds from canola meal: water (WE) and various 80% organic solvent/water mixtures of methanol (ME), acetone (AE), ethanol (EE), butanol (BE), chloroform (CE) and hexane (HE). The in vitro antioxidant and anti-obesity properties of various extracts were investigated. Anti-obesity properties were studied using adipogenic differentiation inhibition of a murine mesenchymal stem cell line (C3H10T1/2) and a pancreatic lipase inhibition assay. AE, ME, and BE showed significant (p < 0.05) adipogenesis and pancreatic lipase inhibitory activities and may have more pharmacological properties. AE down-regulated the gene expression of the major adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), correlating to phenolic content in a dose-dependent manner. The chemical characterization of AE revealed the presence of sinapic acid, ferulic acid, and kaempferol derivatives as main bioactive phenols.

Regulation of hyperglycemia in diabetic mice by autolysates from ß-mannanase-treated brewer's yeast.

BACKGROUND: Diabetes mellitus is a serious chronic disease, characterized by hyperglycemia. This study administered either ß-mannanase-treated yeast cell autolysis supernatant (YCS) or yeast cell-wall residues after autolysis (YCR) to investigate their influence on the alleviation of diabetes in a diabetic mouse model. RESULTS: Application of either YCS or YCR led to body weight gain, blood glucose reduction, and an improvement in lipid composition in the diabetic mice. Administration of YCS was more effective in inhibiting oxidative stress than YCR. The expression of PPARα and CPT1α was enhanced, improving lipid biosynthesis, and Trx1 and HIF-1-α genes were downregulated due to the activation of thioredoxin following the interventions, indicating that the processes of lipid metabolism and oxidative stress were heavily involved in the reduction of diabetic characteristics following the interventions. The current study revealed that consumption of YCR also led to a reduction in hyperglycemia, this being associated with its richness in mineral elements, such as chromium and selenium. CONCLUSION: This study may highlight the potential of both YCS and YCR as functional ingredients in dietary formula for improving diabetic syndromes. © 2019 Society of Chemical Industry.

Peptides derived from lupin proteins confer potent protection against oxidative stress.

BACKGROUND: Lupin seeds are rich in proteins, which are utilized in the food industry. There is an increased interest in lupin research due to its association with health-related benefits, such as reduction of hypertension and hyperglycemia. However, studies on the peptides derived from lupin proteins are rare. RESULTS: Lupin protein hydrolysates (LPHs) were prepared by proteolysis using alcalase, trypsin and pepsin, respectively. All the hydrolysates demonstrated higher antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities compared to lupin proteins. The hydrolysates were fractionated into three fractions based on molecular weight (MW), and the peptides with MW < 3 kDa (LPH3) had the highest antioxidant and ACE inhibitory activities compared to other fractions. Cell model study revealed that LPH3 fraction had the highest protection against the generation of reactive oxygen species in HepG2 cells, which was associated with increased activities of superoxide dismutase and glutathione peroxidase through upregulation of SOD1, GPX1, GCLM, SLC7A11 and SRXN1 expression. CONCLUSIONS: The analysis of amino acid composition indicated that the peptides were characterized with high content of hydrophobic amino acids, which may be responsible for the greatest antioxidant activity. This study highlights the promising potential of lupin peptides as a functional ingredient in healthy foods. © 2018 Society of Chemical Industry.

Generation of Immortalized Equine Chondrocytes With Inducible Sox9 Expression Allows Control of Hypertrophic Differentiation.

Immortalization of chondrocytes enables long term in vitro culture; however, the chondrogenic capacity of transformed cells varies, thus highlighting the need to develop a proliferative and tuneable chondrocyte cell line where hypertrophic differentiation can be controlled. In this study the SV40 large T antigen and human telomerase reverse transcriptase were employed to immortalize pooled equine chondrocytes through lentiviral vector mediated transduction either singly or on combination. Transformed chondrocytes proliferated stably over multiple passages, but resulted in significantly lower expression of chondrocyte specific collagen II mRNA (P < 0.0001) and up regulation of the hypertrophic marker collagen X (P < 0.0001) in three dimensional cultures. A Col2a1 promoter driven GFP reporter was constructed for real time monitoring of chondrogenic differentiation and a significant increase in promoter activation was observed in cultures treated with the growth factor TGFß-3 (P < 0.05). To recapitulate the native articular chondrocyte phenotype we further transduced large T antigen immortalized chondrocytes with lentiviral vectors allowing either constitutive or doxycycline inducible expression of Sox9. In 3D cultures, the Sox9 over-expressing chondrocytes secreted significantly higher levels of extracellular matrix polysaccharide glycosaminoglycan (P < 0.05), while up-regulating collagen II and Aggrecan mRNA (P < 0.05) in both expression systems with a similar patterns observed with imunohistochemical staining. High levels of collagen X mRNA and protein were maintained with constitutive sox9 reflecting hypetrophic differentiation but significantly lower expression could be achieved with inducible Sox9. In conclusion, immortalization of equine chondrocytes results in stable proliferation but a reduction of chondrogenic potential whilst modulation of sox9 expression enabled control of hypertrophic characteristics. J. Cell. Biochem. 118: 1201-1215, 2017. © 2016 Wiley Periodicals, Inc.

Mesenchymal Stem Cells Expressing eNOS and a Cav1 Mutant Inhibit Vascular Smooth Muscle Cell Proliferation in a Rat Model of Pulmonary Hypertension.

BACKGROUND: This study aimed to investigate the effect of bone marrow derived mesenchymal stem cells (rBMSCs) transduced with lentiviral vectors expressing endothelial nitric oxide synthase (eNOS) and/or a mutant caveolin-1(F92A-Cav1), on the pulmonary haemodynamics and structure in a rat model of pulmonary arterial hypertension (PAH). METHODS: Pulmonary arterial hypertension was induced with monocrotaline (MCT) in 60 adult male Wistar rats prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1, eNOS and/or F92A-Cav1. Changes in pulmonary haemodynamics, right ventricular hypertrophy index (RVHI), and serum nitric oxide (NO) were evaluated. Ultrastructure changes in lung tissues were observed by transmission electron microscopy. Expression of Kruppel-like factor 4 (KLF4), p53, P21, eNOS, and alpha-smooth muscle actin were evaluated by real time PCR, western blotting or immunohistochemistry. RESULTS: Treatment of PAH rats with gene modified rBMSCs (eNOS +/- Cav1 F92A) decreased right ventricular systolic pressure and improved pulmonary haemodynamics. The protein of alpha-smooth muscle actin expression was decreased whilst KLF4, p53, P21, eNOS expression, and serum NO concentration was elevated. The survival rate of rats in the treatment groups was also improved, after 35 days of observation. CONCLUSION: Intravenous delivery of rBMSCs expressing eNOS/F92A-Cav1 to PAH rats inhibits pulmonary vascular smooth muscle cell proliferation, and improves pulmonary haemodynamics, vascular remodelling and short-term survival. Activation of KLF4-p53 signalling pathway may be involved in these beneficial effects.

Functional enrichment of mannanase-treated spent brewer yeast.

In this study, the effect of Bacillus amyloliquefaciens-produced ß-mannanase on the nutrient diffusion (release) and antioxidant activity of spent brewer yeast (SBY) was investigated. Three pretreatments were performed: (1) autolysis at 50°C for 24 h; (2) autolysis at 50°C for 24 h, with the addition of ß-mannanase during the autolysis; (3) autolysis at 50°C for 24 h, and the ß-mannanase was added for another 12 h treatment. The pretreatments with the addition of ß-mannanase caused significant cell wall degradation, markedly increased the yield of SBY extracts. More importantly, this study found that polysaccharides were degraded to be oligosaccharides with a considerable reduction in molecular weights. Meanwhile, pretreatment with the enzyme also exhibited a higher antioxidant activity in SBY extract compared to autolysis itself. The current study indicated that pretreatment (3) had a better effect than pretreatment (2) in terms of improving in antioxidant activity in SBY extract. These improved characteristics of SBY extracts isolated through enzymatic treatment appear to show promising features for their prospective use as natural functional agents.

Deep-fried oil consumption in rats impairs glycerolipid metabolism, gut histology and microbiota structure.

BACKGROUND: Deep frying in oil is a popular cooking method around the world. However, the safety of deep-fried edible oil, which is ingested with fried food, is a concern, because the oil is exposed continuously to be re-used at a high temperature, leading to a number of well-known chemical reactions. Thus, this study investigates the changes in energy metabolism, colon histology and gut microbiota in rats following deep-fried oil consumption and explores the mechanisms involved in above alterations. METHODS: Deep-fried oil was prepared following a published method. Adult male Wistar rats were randomly divided into three groups (n = 8/group). Group 1: basal diet without extra oil consumption (control group); Group 2: basal diet supplemented with non-heated canola oil (NEO group); Group 3: basal diet supplemented with deep-fried canola oil (DFEO group). One point five milliliters (1.5 mL) of non-heated or heated oil were fed by oral gavage using a feeding needle once daily for 6 consecutive weeks. Effect of DFEO on rats body weight, KEGG pathway regarding lipids metabolism, gut histology and gut microbiota were analyzed using techniques of RNA sequencing, HiSeq Illumina sequencing platform, etc. RESULTS: Among the three groups, DFEO diet resulted in a lowest rat body weight. Metabolic pathway analysis showed 13 significantly enriched KEGG pathways in Control versus NEO group, and the majority of these were linked to carbohydrate, lipid and amino acid metabolisms. Comparison of NEO group versus DFEO group, highlighted significantly enriched functional pathways were mainly associated with chronic diseases. Among them, only one metabolism pathway (i.e. glycerolipid metabolism pathway) was found to be significantly enriched, indicating that inhibition of this metabolism pathway (glycerolipid metabolism) may be a response to the reduction in energy metabolism in the rats of DFEO group. Related gene analysis indicated that the down-regulation of Lpin1 seems to be highly associated with the inhibition of glycerolipid metabolism pathway. Histological analysis of gastrointestinal tract demonstrated several changes induced by DFEO on intestinal mucosa with associated destruction of endocrine tissue and the evidence of inflammation. Microbiota data showed that rats in DFEO group had the lowest proportion of Prevotella and the highest proportion of Bacteroides among the three groups. In particular, rats in DFEO group were characterized with higher presence of Allobaculum (Firmicutes), but not in control and NEO groups. CONCLUSION: This study investigated the negative effect of DFEO on health, in which DFEO could impair glycerolipid metabolism, destroy gut histological structure and unbalance microbiota profile. More importantly, this is the first attempt to reveal the mechanism involved in these changes, which may provide the guideline for designing health diet.

Epigallocatechin Gallate (EGCG) Decorating Soybean Seed Ferritin as a Rutin Nanocarrier with Prolonged Release Property in the Gastrointestinal Tract.

The instability and low bioavailability of polyphenols limit their applications in food industries. In this study, epigallocatechin gallate (EGCG) and soybean seed ferritin deprived of iron (apoSSF) were fabricated as a combined double shell material to encapsulate rutin flavonoid molecules. Firstly, due to the reversible assembly characteristics of phytoferritin, rutin was successfully encapsulated within apoSSF to form a ferritin-rutin complex (FR) with an average molar ratio of 28.2: 1 (rutin/ferritin). The encapsulation efficiency and loading capacity of rutin were 18.80 and 2.98 %, respectively. EGCG was then bound to FR to form FR-EGCG composites (FRE), and the binding number of EGCG was 27.30 ± 0.68 with a binding constant K of (2.65 ± 0.11) × 10(4) M(-1). Furthermore, FRE exhibited improved rutin stability, and displayed prolonged release of rutin in simulated gastrointestinal tract fluid, which may be attributed to the external attachment of EGCG to the ferritin cage potentially reducing enzymolysis in GI fluid. In summary, this work demonstrates a novel nanocarrier for stabilization and sustained release of bioactive polyphenols.

Effect of Ganoderma lucidum spores intervention on glucose and lipid metabolism gene expression profiles in type 2 diabetic rats.

BACKGROUND: The fruiting body of Ganoderma lucidum has been used as a traditional herbal medicine for many years. However, to the date, there is no detailed study for describing the effect of G. lucidum spores on oxidative stress, blood glucose level and lipid compositions in animal models of type 2 diabetic rats, in particular the effect on the gene expression profiles associated with glucose and lipid metabolisms. METHODS: G. lucidum spores powder (GLSP) with a shell-broken rate >99.9 % was used. Adult male Sprague-Dawley rats were randomly divided into three groups (n = 8/group). Group 1: Normal control, normal rats with ordinary feed; Group 2: Model control, diabetic rats with ordinary feed without intervention; Group 3: GLSP, diabetic rats with ordinary feed, an intervention group utilizing GLSP of 1 g per day by oral gavages for 4 consecutive weeks. Type 2 diabetic rats were obtained by streptozocin (STZ) injection. The changes in the levels of glucose, triglycerides, total cholesterol and HDL-cholesterol in blood samples were analyzed after GLSP intervention. Meanwhile, gene expressions associated with the possible molecular mechanism of GLSP regulation were also investigated using a quantitative RT-PCR. RESULTS: The reduction of blood glucose level occurred within the first 2 weeks of GLSP intervention and the lipid synthesis in the diabetic rats of GLSP group was significantly decreased at 4 weeks compared to the model control group. Furthermore, it was also found that GLSP intervention greatly attenuated the level of oxidative stress in the diabetic rats. Quantitative RT-PCR analysis showed up-regulation of lipid metabolism related genes (Acox1, ACC, Insig-1 and Insig-2) and glycogen synthesis related genes (GS2 and GYG1) in GLSP group compared to model control group. Additionally, there were no significant changes in the expression of other genes, such as SREBP-1, Acly, Fas, Fads1, Gpam, Dgat1, PEPCK and G6PC1. CONCLUSION: This study might indicate that GLSP consumption could provide a beneficial effect in terms of lowering the blood glucose levels by promoting glycogen synthesis and inhibiting gluconeogenesis. Meanwhile, GLSP treatment was also associated with the improvement of blood lipid compositions through the regulation of cholesterol homeostasis in the type 2 diabetic rats.

Suppression of dedifferentiation and hypertrophy in canine chondrocytes through lentiviral vector expression of Sox9 and induced pluripotency stem cell factors.

OBJECTIVES: Prolonged in vitro culture of primary articular chondrocytes results in dedifferentiation to a fibroblast-like cell with reduced expression of the Sox9 transcription factor and the extracellular matrix protein collagen II. The ability to genetically-modify chondrocytes to allow both proliferation and maintenance of an articular phenotype may provide increased numbers of appropriate cells for regeneration of large cartilage defects. RESULTS: Canine chondrocytes were expanded in monolayer culture and transduced with a lentiviral vector expressing Sox9 or in combination with a multicistronic lentiviral vector expressing the four induced pluripotency stem (iPS) cell factors, Oct4, Klf4, Sox2 and c-Myc (OSKM). 3D pellet cultures of transduced cells in the presence of TGFß-3 revealed increased pellet size and higher levels of total glycosaminoglycan in both Sox9 and Sox9+ OSKM co-transduced chondrocytes compared to untransduced and green fluorescent protein expressing controls. Immunohistochemical detection of Sox9 and collagen II was evident in transduced cells (Sox9, OSKM, or Sox9+ OSKM) with very low levels in untransduced chondrocytes, demonstrating a dedifferentiated state (P < 0.01). The marker for chondrocyte hypertrophy, collagen X was highly expressed in Sox9 transduced chondrocytes but lower in OSKM or Sox9+ OSKM cells (P < 0.05). CONCLUSION: A combination of Sox9 and OSKM gene delivery to canine chondrocytes allows continuous proliferation in monolayer culture with a higher expression of col2a1 without an increase in the hypertrophy marker collagen X in 3D pellet cultures.

A paper-based scaffold for enhanced osteogenic differentiation of equine adipose-derived stem cells.

OBJECTIVES: We investigated the applicability of single layer paper-based scaffolds for the three-dimensional (3D) growth and osteogenic differentiation of equine adipose-derived stem cells (EADSC), with comparison against conventional two-dimensional (2D) culture on polystyrene tissue culture vessels. RESULTS: Viable culture of EADSC was achieved using paper-based scaffolds, with EADSC grown and differentiated in 3D culture retaining high cell viability (>94 %), similarly to EADSC in 2D culture. Osteogenic differentiation of EADSC was significantly enhanced in 3D culture, with Alizarin Red S staining and quantification demonstrating increased mineralisation (p < 0.0001), and an associated increase in expression of the osteogenic-specific markers alkaline phosphatase (p < 0.0001), osteopontin (p < 0.0001), and runx2 (p < 0.01). Furthermore, scanning electron microscopy revealed a spherical morphology of EADSC in 3D culture, compared to a flat morphology of EADSC in 2D culture. CONCLUSIONS: Single layer paper-based scaffolds provide an enhanced environment for the in vitro 3D growth and osteogenic differentiation of EADSC, with high cell viability, and a spherical morphology.

Endothelial progenitor cells and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterised by lung endothelial cell dysfunction and vascular remodelling. A number of studies now suggest that endothelial progenitor cells (EPCs) may induce neovascularisation and could be a promising approach for cell based therapy for PAH. On the contrary EPCs may contribute to pulmonary vascular remodelling, particularly in end-stage pulmonary disease. This review article will provide a brief summary of the relationship between PAH and EPCs, the application of the EPCs to PAH and highlight the potential clinical application of the EPCs cell therapy to PAH.

Natural products as a source of Coronavirus entry inhibitors.

The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate entry, the coronavirus spike glycoprotein interacts with angiotensin converting enzyme 2 (ACE2) on respiratory epithelial cells. Blocking this interaction and consequently viral replication may be an effective strategy for treating infection, however further research is needed to better characterize candidate molecules with antiviral activity before progressing to animal studies and clinical trials. In general, antiviral drugs are developed from purely synthetic compounds or synthetic derivatives of natural products such as plant secondary metabolites. While the former is often favored due to the higher specificity afforded by rational drug design, natural products offer several unique advantages that make them worthy of further study including diverse bioactivity and the ability to work synergistically with other drugs. Accordingly, there has recently been a renewed interest in natural product-derived antivirals in the wake of the COVID-19 pandemic. This review provides a summary of recent research into coronavirus entry inhibitors, with a focus on natural compounds derived from plants, honey, and marine sponges.

Splice variants of the Alzheimer's disease beta-secretase, BACE1.

Cleavage of the amyloid precursor protein by enzymes commonly referred to as ß- and γ-secretase constitute an important process in the pathogenesis of Alzheimer's disease (AD). The regulation of this process is therefore an important subject of investigation. Numerous sources of endogenous regulation have been identified, and one of these is the relative abundance and regulation of splice variants of the ß-secretase, BACE1 (ß-site amyloid precursor protein cleaving enzyme 1). In this review, we will briefly discuss the main characteristics of BACE1, review the different variants of this enzyme that have been identified to date, and highlight their possible implication in AD.

Structurally Orientated Rheological and Gut Microbiota Fermentation Property of Mannans Polysaccharides and Oligosaccharides.

Three mannan polysaccharides and their oligosaccharides were investigated in terms of physicochemical characteristics and effects on gut microbiota. Oligosaccharides from guar gum had the fastest fermentation kinetics for SCFAs generation at the initial stage, while the locust bean of both polymers and oligosaccharides demonstrated the lowest SCFAs through the whole fermentation process. In contrast, konjac gum steadily increased SCFAs and reached its maximum level at 24 h fermentation, indicating its fermentation character may be associated with its rheological properties. Compared to their corresponding polysaccharides, all the oligosaccharides demonstrated a faster fermentation kinetics, followed by an enriched abundance of propionate-producing bacterial Prevotella and a decreased abundance of Megamonas and Collinsella. Meanwhile, oligosaccharides reduced the Firmicutes/Bacteroidota ratio as well as the abundance of Bacteroidetes and Escherichia-Shigella. The fermentation of konjac substrate significantly promoted the abundance of butyrate-producing bacterial Faecalibacterium. In contrast, although the fermentation of locust bean and guar gum substrates benefited Bifidobacterium abundance due to their similar structure and monosaccharides composition, the fermentation of locust bean gum led to greater Bifidobacterium than the others, which may be associated with its higher mannose composition in the molecules. Interestingly, the partial hydrolysis of the three polysaccharides slightly reduced their prebiotic function.

Mapping the metabolic characteristics of probiotic-fermented Ganoderma lucidum and its protective mechanism against Cd-induced nephrotoxicity.

An animal model of Cd-induced kidney damage was designed to investigate the nephroprotective potential of the probiotic-fermented Ganoderma lucidum (FGL) via metabonomic analysis. The results showed that FGL enhanced sugar and amino acid metabolism. The interaction of Ganoderma lucidum (GL) and probiotics efficiently elevated short-chain fatty acid production following gut microbiota fermentation. The current data revealed that the FGL intervention alleviated Cd-induced nephrotoxicity via elevating the activity of antioxidant enzymes and decreasing the levels of pro-inflammatory and apoptotic factors. Based on transcriptome analysis, FGL intervention mediated renal dysfunction via decreasing the expressions of Nos2, Tnfsf14, S100a9, Map3k6 and Hk3, which were involved in oxidative stress, inflammatory response and the apoptosis process. The current study highlights a new approach for achieving positive nephroprotection via natural product intervention.