Momordica charantia Bioactive Components: Hypoglycemic and Hypolipidemic Benefits Through Gut Health Modulation.

Momordica charantia (MC), a member of the Cucurbitaceae family, is well known for its pharmacological activities that exhibit hypoglycemic and hypolipidemic properties. These properties are largely because of its abundant bioactive compounds and phytochemicals. Over the years, numerous studies have confirmed the regulatory effects of MC extract on glycolipid metabolism. However, there is a lack of comprehensive reviews on newly discovered MC-related components, such as insulin receptor-binding protein-19, adMc1, and MC protein-30 and triterpenoids 3ß,7ß,25-trihydroxycucurbita-5,23(E)-dien-19-al, and the role of MC in gut microbiota and bitter taste receptors. This review offers an up-to-date overview of the recently reported chemical compositions of MC, including polysaccharides, saponins, polyphenolics, peptides, and their beneficial effects. It also provides the latest updates on the role of MC in the regulation of gut microbiota and bitter taste receptor signaling pathways. As a result, this review will serve as a theoretical basis for potential applications in the creation or modification of MC-based nutrient supplements.

Heterologous expression and enzymatic characteristics of sulfatase from Lactobacillus plantarum dy-1.

Barley, rich in bioactive components including dietary fiber, polyphenolic compounds and functional proteins, exhibits health benefits such as regulating glucose and lipid metabolism. Previous studies have found that the content and composition of free phenolic acids in barley may be significantly changed by fermentation with the laboratory patented strain Lactobacillus plantarum dy-1 (L. p dy-1), but the mechanism of enzymatic release of phenolic acid remains to be elucidated. Based on this, this study aimed to identify the key enzyme in L. p dy-1 responsible for releasing the bound phenolic acid and to further analyze its enzymatic properties. The Carbohydrate-Active enZYmes database revealed that L. p dy-1 encodes 7 types of auxiliary enzymes, among which we have identified a membrane sulfatase. The enzyme gene LPMS05445 was heterologous to that expressed in E. coli, and a recombinant strain was induced to produce the target protein and purified. The molecular weight of the purified enzyme was about 59.9 kDa, with 578.21 U mg-1 enzyme activity. The optimal temperature and pH for LPMS05445 expression were 40 °C and 7.0, respectively. Furthermore, enzymatic hydrolysis by LPMS05445 can obviously change the surface microstructure of dietary fiber from barley bran and enhance the release of bound phenolic acid, thereby increasing the free phenolic acid content and improving its physiological function. In conclusion, sulfatase produced by Lactobacillus plantarum dy-1 plays a key role in releasing bound phenolic acids during the fermentation of barley.

Long noncoding RNA GPRC5D-AS1 in renal cell carcinoma: a molecular mechanism study.

Background: Clear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses. Methods: Small interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS11 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [ß-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting. Results: Compared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in ß-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group. Conclusions: Silencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal cancer cell line 786-0, which can be weakened by the overexpression of lncRNA GPRC5D-AS1.

Changes in the structural, physicochemical and functional properties and in vitro fecal fermentation characteristics of barley dietary fiber fermented by Lactiplantibacillus plantarum dy-1.

Fermentation is an effective method for improving the nutritional quality and functional characteristics of grains. This study investigated changes in the structural, physicochemical, and functional properties of fermented barley dietary fiber (FBDF) exerted by Lactiplantibacillus plantarum dy-1 (Lp. plantarum dy-1) as well as its in vitro fecal fermentation characteristics. Lp. plantarum dy-1 fermentation remarkably changed the structure of FBDF, including the microstructure and monosaccharide components, correlating with improved water or oil retaining and cholesterol adsorption capacities. Additionally, Lp. plantarum dy-1 fermentation significantly (p < 0.05) promoted the release of bound phenolics from 6.24 mg g-1 to 6.93 mg g-1 during in vitro digestion, contributing to the higher antioxidant capacity and inhibitory activity of α-amylase and pancreatic lipase compared with those of raw barley dietary fiber (RBDF). A total of 14 phenolic compounds were detected in the supernatants of digestion and fermentation samples. During colonic fermentation, FBDF significantly increased the production of acetate, propionate, and butyrate (p < 0.05), inhibited the growth of Escherichia-Shigella, and promoted the abundance of SCFA-producing microbiota such as Faecalibacterium and Prevotella_9. In conclusion, Lp. plantarum dy-1 fermentation enhanced the physicochemical properties and in vitro fermentation characteristics of barley dietary fiber, representing a promising bioprocessing technology for modifying barley bran.

Multiple databases analyzed the prognosis prediction of renin secretion pathway-related genes in renal clear cell carcinoma and immunotherapy.

Background: Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumour and its progression is associated with the renin secretion pathway, so this study aimed to develop a prognostic model based on renin secretion pathway-related genes. Methods: First, 453 renin secretion pathway-related genes were acquired [|log fold change (FC)| >1.5, false discovery rate (FDR) <0.05] from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The data were combined and further screened for 188 genes associated with ccRCC prognosis (P<0.05) by univariate independent prognostic analysis. These genes were subjected to least absolute shrinkage and selection operator regression to identify potential prognostic genes to construct the prognostic model. The stability of the model was externally validated. Combined risk scores and clinical information were used to create nomograms to accurately reflect patient survival. The model-related genes were further mined for subsequent analysis. Results: A prognostic model of six renin secretion pathway genes (IGFBP3, PLAUR, CHKB-CPT1B, HOXA13, CDH13, and CDC20) was developed. Its reliability in predicting disease prognosis was confirmed by survival analysis, receiver operating characteristic (ROC) curve analysis and a risk curve. The nomogram and calibration curve showed good accuracy. The immune-related analyses revealed that the low-risk group would benefit more from immunotherapy. Conclusions: The prognostic model of ccRCC based on six renin secretion pathway-related genes can be used to guide the precise treatment of ccRCC patients.

Effects of Lactiplantibacillus plantarum dy-1 fermentation on multi-scale structure and physicochemical properties of barley starch.

The effects of fermentation on barley starch were studied using Lactiplantibacillus plantarum dy-1. Changes in multi-scale structure and physicochemical properties of barley starch were studied. The chain structure results revealed that fermentation could increase the content of short chain and medium short chain by breaking down long amylopectin side chains in barley and increase amylose content by debranching amylopectin. Also, fermentation promoted the arrangement of short chains into short order structure, leading to the enhancement of hydrogen bond interaction. Furthermore, it improved the helical structure content and relative crystallinity of barley starch by degrading the amorphous structure of barley starch. In terms of physicochemical properties, fermentation inhibited the hydration characteristics of barley starch, thus improving its thermal stability. It also enhanced shear stability, resistance to short-term aging and digestion, and improved gel texture properties. These findings offer potential for the processing and nutritional regulation of fermented barley products.

Construction of a polymer-based fluorescent probe with dual responsive sites for monitoring changes of lysosomal viscosity.

As highly dynamic organelles, lysosomes are involved in various physiological processes. The viscosity of lysosomes plays critical roles in maintaining their normal physiological function and abnormal variations of viscosity are associated with many diseases. Monitoring the changes of lysosomal viscosity could contribute to understanding lysosome-related physiological and pathological processes. In this work, based on an indole fluorophore and fluorescent polymer, poly(2-hydroxyethyl methacrylate) (PHEM), a new polymeric fluorescent probe, In-PHEM, with dual responsive sites for tracking changes of lysosomal viscosity is presented. In-PHEM showed excellent fluorescence properties and high photostability. With this robust probe, the variation of the lysosomal viscosity in cells under different physiological conditions, including inducer stimulation, the process of starvation and apoptosis, was monitored using dual-channel imaging. Therefore, this work may provide a powerful tool for monitoring changes of lysosomal viscosity and helping to understand the relationship between the viscosity changes of lysosomes and their related diseases.

Cinnamaldehyde Alleviates the Oxidative Stress of Caenorhabditis elegans in the Presence of Lactic Acid.

Cinnamaldehyde is an excellent natural antioxidant with high antioxidant activity, but its function in food or human digestive tract under acidic conditions remains to be studied. The effects of cinnamaldehyde in the presence of lactic acid on oxidative stress of Caenorhabditis elegans and the underlying molecular mechanisms were investigated in the present study. Results showed that cinnamaldehyde with or without lactic acid exhibited good antioxidant ability, represented by high SOD and CAT activities in C. elegans, while lactic acid exerted no effect on the antioxidant enzymes. Trace elements, like Cu, Fe, or Se, are important for the activities of antioxidant enzymes. Data of metal elements analysis revealed that cinnamaldehyde made big differences on the levels of Mn, Cu, Se of worms compared with single lactic acid treatment. Moreover, mechanistic study suggested that in the presence of lactic acid, cinnamaldehyde could enhance the expressions of akt-2, age-1 to increase the antioxidant activities. In addition, we found that lactic acid was able to change the metabolic profile of cinnamaldehyde in C. elegans, characterized by nucleosides and amino acids, which were involved in the purine metabolism, the biosynthesis, and metabolism of some amino acids, etc. This study provides a theoretical basis for further revealing the functional activity and mechanism of cinnamaldehyde under acidic conditions.

Metabolomics reveals the effects of Lactiplantibacillus plantarum dy-1 fermentation on the lipid-lowering capacity of barley ß-glucans in an in vitro model of gut-liver axis.

Bioactive polysaccharides known as the biological response modifiers, can directly interact with intestinal epithelium cells (IEC) and regulate key metabolic processes such as lipid metabolism. Here, the coculture of Caco-2/HT29 monolayer (>400 Ω × cm2) and HepG2 cells was developed to mimic the gut-liver interactions. This system was used to investigate the effects of raw and fermented barley ß-glucans (RBG and FBG) on lipid metabolism by directly interacting with IEC. Both RBG and FBG significantly and consistently reduced the lipid droplets and triacylglycerol levels in monoculture and coculture of HepG2 overloaded with oleic acid. Notably, FBG significantly and distinctly elevated PPARα (p < 0.05) and PPARα-responsive ACOX-1 (p < 0.01) gene expressions, promoting lipid degradation in cocultured HepG2. Moreover, the metabolomics analyses revealed that FBG had a unique impact on extracellular metabolites, among them, the differential metabolite thiomorpholine 3-carboxylate was significantly and strongly correlated with PPARα (r = -0.68, p < 0.01) and ACOX-1 (r = -0.76, p < 0.01) expression levels. Taken together, our findings suggest that FBG-mediated gut-liver interactions play a key role in its lipid-lowering effects that are superior to those of RBG. These results support the application of Lactiplantibacillus fermentation for improving hypolipidemic outcomes.

Heterologous expression and characterization of an endoglucanase from Lactobacillus plantarum dy-1.

The structure and function of ß-glucan in barley have been reported to change significantly after fermentation with Lactobacillus plantarum dy-1, but little information is available to explain this phenomenon. The Carbohydrate-Active enZYmes database revealed that L. plantarum dy-1 encodes 158 types of glycosidic hydrolases, among which we have identified an endoglucanase. Therefore, we conducted a heterologous expression of this endoglucanase gene, namely Lpeg14265. The pH of 6.0 and the temperature of 60 °C were optimal for LPEG14265. The physiological activities of ß-glucan, such as the capacity to adsorb cholesterol or to block α-amylase and α-glucosidase, increased as a result of enzymatic hydrolysis of LPEG14265, which also caused a significant change in the microstructure of barley bran. Based on these findings, it was concluded that barley bran, a by-product of agriculture, may be processed with LPEG14265 to reveal its potential value, which could have applications in the brewing and feed industries, among others.

Metabolomics Reveal the Regulatory Effect of Polysaccharides from Fermented Barley Bran Extract on Lipid Accumulation in HepG2 Cells.

Barley bran has potential bioactivities due to its high content of polyphenols and dietary fiber, etc. Fermentation has been considered as an effective way to promote the functional activity of food raw materials. In this study, polysaccharides from barley bran extract fermented by Lactiplantibacillus plantarum dy-1 (FBBE-PS) were analyzed, and its effects on lipid accumulation and oxidative stress in high-fat HepG2 cells induced by sodium oleate were evaluated. The results showed that the molecular weight decreased and monosaccharide composition of polysaccharides changed significantly after fermentation. In addition, 50 µg/mL FBBE-PS could reduce the triglyceride (TG) content and reaction oxygen species (ROS) level in high-fat HepG2 cells by 21.62% and 30.01%, respectively, while increasing the activities of superoxide dismutase (SOD) and catalase (CAT) represented by 64.87% and 22.93%, respectively. RT-qPCR analysis revealed that FBBE-PS could up-regulate the lipid metabolism-related genes such as ppar-α, acox-1 and cpt-1α, and oxidation-related genes such as nrf2, ho-1, nqo-1, sod1, cat, etc. The metabolomics analysis indicated that FBBE-PS could alleviate lipid deposition by inhibiting the biosynthesis of unsaturated fatty acids, which is consistent with the downregulation of scd-1 expression. It is demonstrated that fermentation can alter the properties and physiological activities of polysaccharides in barley bran, and FBBE-PS exhibited an alleviating effect on lipid deposition and oxidative stress in high-fat cells.

Barley ß-glucan inhibits digestion of soybean oil in vitro and lipid-lowering effects of digested products in cell co-culture model.

The effect of barley ß-glucan on soybean oil digestion characteristics before and after fermentation was studied in an in vitro-simulated gastrointestinal digestion model. The addition of barley ß-glucan made the system more unstable, the particle size increased significantly, and confocal laser imaging showed that it was easier to form agglomerates. The addition of barley ß-glucan increased the proportion of unsaturated fatty acids in digestion products, and reduced digestibility of soybean oil. In a co-culture model of Caco-2/HT29 and HepG2 cells, the effects of digestive products of soybean oil and barley ß-glucan before and after fermentation on lipid metabolism in HepG2 cells were investigated. The results showed that adding only soybean oil digestion products significantly increased triglycerides (TG) content and lipid accumulation in basolateral HepG2 cells. When fermented barley ß-glucan was added, lipid deposition was significantly decreased, and the lipid-lowering activity was better than that of unfermented barley ß-glucan.

Health-promoting properties of barley: A review of nutrient and nutraceutical composition, functionality, bioprocessing, and health benefits.

Barley is one of the world's oldest cereal crops forming an important component of many traditional diets. Barley is rich in a variety of bioactive phytochemicals with potentially health-promoting effects. However, its beneficial nutritional attributes are not being fully realized because of the limited number of foods it is currently utilized in. It is therefore crucial for the food industry to produce novel barley-based foods that are healthy and cater to customers' tastes. This article reviews the nutritional and functional characteristics of barley, with an emphasis on its ability to improve glucose/lipid metabolism. Then, recent trends in barley product development are discussed. Finally, current limitations and future research directions in glucolipid modulation mechanisms and barley bioprocessing are discussed.

Application of environmental-safe fermentation with Saccharomyces cerevisiae for increasing the cinnamon biological activities.

The effect of fermentation by Saccharomyces cerevisiae on biological properties of cinnamon (Cinnamomum cassia) was investigated. The study demonstrated that the extract of S. cerevisiae-fermented cinnamon (S.C.FC) has antioxidants higher than non-fermented one. The optimum results for antioxidant yield were noted with 107 CFU S. cerevisiae/10 g cinnamon and 70 mL of dH2O at pH 6 and incubated for 3 d at 35 °C. Under optimum conditions, ABTS, DPPH, and H2O2 radical-scavenging activity increased by 43.8, 61.5, and 71.9%, respectively. Additionally, the total phenols and flavonoids in S.C.FC were increased by 81.3 and 415% compared by non-fermented one. The fermented cinnamon had antimicrobial activity against L. monocytogenes, S. aureus, E. coli, S. typhi, and C. albicans. Also, the anti-inflammatory properties were increased from 89 to 92% after fermentation. The lyophilized extract of S.C.FC showed positive effect against Huh7 cancer cells which decreased by 31% at the concentration of 700 µg/mL. According to HPLC analysis, p-hydroxybenzoic acid, gentisic acid, catechin, chlorogenic acid, caffeic acid, and syringic acid were increased by 116, 33.2, 59.6, 50.6, 1.6, and 16.9%, respectively. Our findings suggest the applicability of cinnamon fermentation using S. cerevisiae as a useful tool for processing functional foods to increase their antioxidant and anti-inflammatory content.

Purification and Identification of Lipid-Lowering Protein from Barley Extract after Lactiplantibacillus plantarum dy-1 fermentation.

Previous studies have found that the protein in barley extract fermented by Lactiplantibacillus plantarum dy-1 has the ability to inhibit lipid accumulation. However, the isolation, purification, and structural identification of the protein with lipid-lowering activity were still needed. In the present study, barley protein fermented by L. plantarum dy-1 with the optimal lipid-lowering ability was isolated and purified in three steps: using ammonium sulfate precipitation, anion-exchange chromatography, and size-exclusion chromatography. Combined with the model of HepG2 cells induced by oleic acid, the results showed that the pure protein LFBEP-C1 had the best lipid-lowering potential. Furthermore, our research found that LFBEP-C1 enriched the content of hydrophobic amino acids in LFBEP-C1. Ultraviolet spectroscopy analysis indicated that the glycosidic bond in LFBEP-C1 was an O-type glycosidic bond. The FTIR and circular dichroism spectra indicated that α-helix and random coil were the main secondary structures of LFBEP-C1. Mass spectrometry determined the theoretical molecular weight of LFBEP-C1 as 48 kDa, and its amino acid coverage was 63%. These findings suggest that the protein LFBEP-C1 with the best lipid-lowering activity was isolated and purified, and its structural characteristics were identified.

Improving the antioxidant and anticancer potential of Cinnamomum cassia via fermentation with Lactobacillus plantarum.

This study designed to investigate effect of fermentation by Lactobacillus plantarum on antioxidant and anticancer properties of Cinnamomum cassia aqueous solution. The optimum condition to produce high antioxidant activity was 107 CFU L. plantarum/10 g cinnamon at pH6 after 3 days of incubation at 35 °C. Fermented cinnamon showed an increase in ABTS, DPPH and H2O2 by 24.63, 58.31 and 60.27%, respectively over the control. Also, the total phenolic and flavonoid contents were increased, 8.15 to 11.40 mg GAE/g and 0.43 to 2.61 mg QE/g, respectively. The gallic acid, p-hydroxybenzoic acid, catechin and chlorogenic acid were increased by 37, 404, 11 and 98%, respectively. Also, anticancer activity was developed after fermentation. The increased antioxidant activity of fermented cinnamon could be attributed to the increase of some phenolics and flavonoids. Hence, cinnamon fermentation using L. plantarum is able to enhance its antioxidant and anticancer activities without producing toxic substances.

Saponins from bitter melon reduce lipid accumulation via induction of autophagy in C. elegans and HepG2 cell line.

Saponins from bitter melon (BMS) are well-known to have various biological activities, especially in the field of fat-lowering. However, many gaps remain in our knowledge of BMS-induced fat reduction and health benefits. Here, we aimed to investigate the precise mechanism of BMS in alleviating fat accumulation in C. elegans and HepG2 cell line. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by phosphatidylethanolamine (PE) increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS largely depended on daf-16/FoxO1 and hlh-30/TFEB mediated lipophagy to reduce fat deposition. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of autophagy-related proteins, such as the phosphorylated AMPK and LC3B. In conclusion, our results elucidated the underlying mechanism of bitter melon saponins interfering with lipid metabolism from the autophagy point of view, which provide new insights into a nutraceutical to mitigate obesity.

Recent Developments in Fermented Cereals on Nutritional Constituents and Potential Health Benefits.

Fermentation is one of the most economical and safe methods to improve the nutritional value, sensory quality and functional characteristics of raw materials, and it is also an important method for cereal processing. This paper reviews the effects of microbial fermentation on cereals, focusing on their nutritional value and health benefits, including the effects of fermentation on the protein, starch, phenolic compounds contents, and other nutrient components of cereals. The bioactive compounds produced by fermented cereals have positive effects on health regulation. Finally, the future market development of fermented cereal products is summarized and prospected.

Transcriptomics reveals the anti-obesity mechanism of Lactobacillus plantarum fermented barley extract.

Fermentation by lactic acid bacteria can improve the nutritional value and biological function of cereal. Our previous studies have confirmed that Lactobacillus plantarum fermented barley extract (LFBE) can alleviate obesity caused by high-fat diet (HFD) in rats, while the precise mechanism remains unclear. Herein, we explored the effect of LFBE on the adipose tissue in obese rats and its mechanism via transcriptomics technology. Results showed that administration of LFBE in obese rats for 8 weeks significantly alleviated weight gain, reduced fasting blood glucose, and inhibited lipid accumulation. Transmission electron microscope (TEM) observation of adipose tissue found that LFBE held the ability to maintain mitochondria integrity and functionality. Transcriptomics analysis revealed that LFBE increased the expressions of mitochondrial ß-oxidized-related genes, while inhibiting the expressions of fatty acid synthesis-related genes. Furthermore, KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis and western blotting studies confirmed that LFBE mainly enhanced the energy consumption of adipocytes through the phosphorylation of AMP-Activated Protein Kinase (AMPK) and the mitochondrial proliferation pathway regulated by peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC1α). Taken together, these findings indicated that LFBE could ameliorate HFD-induced obesity by activating AMPK/PGC1α axis regulated signaling pathways.