內(nèi)容: Thrombin blockers have been shown to be effective for various pathological conditions, but their use is limited due to the potential for serious bleeding adverse effects. This study introduced a novel bioactive peptide (P-2-CG) from oyster, that mitigated thrombin-mediated barrier dysfunction and prothrombotic phenotypes in human pulmonary microvascular endothelial cells (HPMECs). P-2-CG significantly attenuated the increase in endothelial monolayer permeability induced by thrombin through the possible attenuation of RhoA activation and it promoted barrier recovery by enhancing endothelial cell adhesion. Additionally, P-2-CG was found to decrease the pro-thrombotic phenotype induced by thrombin in HPMEC by reducing the extrinsic trigger tissue factor mRNA expression, which resulted in prolonged plasma clotting time, decreased Factor Xa activation, and reduced thrombin generation. Moreover, P-2-CG inhibited thrombosis efficiently by blocking intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression via tyrosine phosphorylation of nuclear factor-κB p65. P-2-CG inhibits thrombin mediated inflammation and provides a potential therapeutic option for treating endothelial dysfunction and thrombosis.

內(nèi)容: The main proteases (Mpros) are hydrolases playing essential roles in the replication of β-coronaviruses including SARS-CoV-2. Herein, a highly efficient strategy was developed for discovering the Mpro inactivators from crude plant extract integrating target-based biochemical assay and chemoproteomic approaches. Firstly, Pu-erh tea was found to potently suppress SARS-CoV-2 Mpro in a time-dependent manner. Next, global chemical analysis coupling with peptide-modification profiling were used to identify the cysteine-modified constituents in Pu-erh tea. The results suggested that seven constituents in Pu-erh tea could modify SARS-CoV-2 Mpro, which turned out that epigallocatechin, gallocatechin and gallic acid were the most efficacious Mpro inactivators. Further investigations demonstrated that epigallocatechin and gallocatechin could inactivate SARS-CoV-2 Mpro via blocking the formation of the homodimers. Collectively, this work proposed a novel and practical strategy for highly efficient discovery of time-dependent inhibitors of SARS-CoV-2 Mpro from plant extracts, while 3 constituents in Pu-erh tea have emerged as robust SARS-CoV-2 Mpro inactivators.

內(nèi)容: Obesity caused by poor eating habits has become a global public health issue and harms human health. Rosmarinic acid (RA) is a natural active substance with many biological functions like antioxidant. However, the function of RA’s lipid-lowering effect and mechanism are not entirely clear. This study aimed to explore the effect of RA on obesity and its action mechanism in Caenorhabditis elegans. RA not only alleviated intestinal inflammation and change the composition of unsaturated fatty acid, but also decreased fat storage and adjusted the size and quantity of fat droplets without threatening development and reproduction or affecting energy intake. In addition, RA improved the integrity of intestinal barrier function in C. elegans. RNA sequencing and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) comprehensively revealed that the lipid-lowering mechanism mediated by RA might involve lipid metabolism and anti-inflammatory pathways. Among them, RA regulates lipid metabolism by reducing fat synthesis through SBP-1 and increasing fatty acid β-oxidation via NHR-49. Furthermore, the anti-inflammatory pathway was associated with RA’s enhancement of the ratio of unsaturated fatty acid and alleviation of inflammatory reactions caused by Pseudomonas aeruginosa (PAO1). Therefore, RA regulated lipid metabolism and relieved inflammation, which had the potential for dietary supplements or functional foods.

內(nèi)容: People living long-term in areas with UV will cause premature photoaging. An abnormal reduction in autophagy is a key feature of photoaging, and p38 MAPK has been regarded as a key regulator of autophagy. Isothiocyanate is one of the main active components of Moringa oleifera Lam. seeds. Studies have reported that M. oleifera Lam. seeds isothiocyanate (MITC) has anticancer, anti-inflammatory, cardiometabolic repair, nervous system protection, blood lipid regulation and diabetes prevention properties. However, the molecular mechanisms of MITC with protective effects against skin photoaging have not been studied thus far. In this study, we aimed to evaluate the antiphotoaging activity of MITC and to investigate the effect of p38 MAPK-dependent autophagy in vivo and in vitro models of photoaging. In this research we found that MITC can reverse the intracellular reactive oxygen species (ROS) content and inhibit the activation of p38 MAPK to improve the autophagy level, reduce the expression of matrix metalloproteinases (MMPs), and finally protect against photoaging by UV. Our results will uncover the molecular mechanisms of MITC that play a role in the protective effects against skin photoaging, provide helpful information for developing MITC as an anti-photoaging plant material and improve the utilization of M. oleifera Lam. seeds.

內(nèi)容: Morin is a functional flavonoid commonly found in human diet. Compared to being used solely, it is evident that morin can be more effective as a drug adjuvant. However, research on the combined effect and its corresponding mechanism is limited. Here, we found that morin significantly potentiated the inhibitory effects of the natural compound celastrol on the proliferation of lung cancer cells. Morin and celastrol synergistically exhibit marked apoptosis induction in lung cancer cells, accompanied by changes in the abundance of apoptosis-related proteins. Transcriptome analyses revealed that the combination of morin and celastrol had a significant impact on the number of differentially expressed genes in lung cancer cells. Among these genes, BIRC3 was one of the most significantly different ones, which plays a crucial role in the process of tumor resistance to apoptosis. In addition, several genes identified are primarily associated with intracellular signal transduction pathways, specifically the NF-κB signaling pathway. Importantly, the treatment combining morin and celastrol in tumor-bearing mice results in a synergistic effect that significantly suppressed tumor growth. These findings indicate that morin could be a promising functional adjuvant, and the combination of morin and celastrol has potential for the treating lung cancer.

內(nèi)容: Tropomyosin (TM) is the predominant allergenic protein in shrimp, which has induced IgE-mediated food allergy reactions. In this study, Lit v 1 was purified from Penaeus vannamei muscles, which were glycosylated by pectic oligosaccharides. The results showed that di-galacturonic acid (DGA) and galacturonic acid (GA) induced the unfolding of the primary protein structure of TM, and changed α-helical structure, and IgE binding capacity. In addition, compared with TM-sensitized BALB/c mice, GA-modified TM (GA-TM) and DGA-modified TM (DGA-TM) were insufficient to stimulate sensitization, and significantly reduced the hypersecretion of IgE, IgG1, HIS, and IL-4, up-regulated IgG2a and IFN-γ levels to improve imbalanced Th1/Th2, Treg/Th17 immunity, and promoted mRNA expression of tight junction proteins. Together, this study confirmed that glycosylation modification alleviated sensitization by altering TM structure, reducing IgE binding allergic inflammatory response, and regulating cytokine immune balance. Overall, these results indicated that glycosylation modification was a promising method for decreasing the allergenic reactivity of allergic proteins.

內(nèi)容: This paper aimed to explore the mechanism of tetrapeptide Val-Thr-Pro-Tyr (VTPY) in improving alcoholic gastric injury. VTPY has the potential to enhance the growth and movement of normal human gastric epithelial cells (GES-1). Following ethanol-induced impairment, VTPY effectively improved migration of GES-1 and human umbilical vein endothelial cells (HUVEC) cells, enhanced angiogenesis, eliminated cellular and mitochondrial reactive oxygen species (ROS), inhibited excessive mitochondrial division, enhanced F-actin polymerization and mitochondrial respiratory capacity. To counteract excessive mitochondrial fission, VTPY primarily restores the mitochondria dynamics by reducing the expression of Drp1 and Fis1, while increasing Mfn2. Further studies utilizing inhibitors clarifies that the inhibition of excessive mitochondrial fission can markedly reduce F-actin depolymerization, consequently enhancing cell migration. Additionally, VTPY can inhibit the apoptosis pathway by maintaining potential of mitochondrial membrane, preventing the release of mitochondrial cytochrome c, bolstering the levels of Bcl-XL, while reducing the levels of Bax and cleaved-caspase-3. Further investigations using inhibitors demonstrates that excessive mitochondrial fission could activate apoptotic pathway. However, VTPY counteracts this effect and enhance cells viability. Further evidence suggests that VTPY effectively improves ulcer index and pathologic changes, relieves inflammation, enhances the balance of oxidation and anti-oxidation, promotes angiogenesis, improves the expression of mitochondrial dynamics factors, blocks apoptotic pathway, and subsequently ameliorates gastric damage in mice through Fis-1/Bcl-2 pathway.

內(nèi)容: Milk fat globules (MFG) are the primary source of energy and functional factor in dairy-based products. To evaluate the suitability of commercial MFG substitutes for infant and adult consumers, the lipolysis properties and regulatory factors in digesting bovine, caprine, and human MFG were compared. The lipolysis kinetic models of bovine and caprine MFG are comparable, with bovine MFG displaying the highest degree of lipolysis (50.21%) during gastric digestion in infants, resulting in the production short-chain saturated fatty acids. Caprine MFG has a high rate of lipolysis due to its weak phospholipid-glycoprotein layer, which is prominent in both infants’ and adults’ digestion. The effects of consuming bovine and caprine MFG for adults are comparable in terms of lipolysis properties and nutritional value of fatty acid. After gastrointestinal digestion, human MFG has the highest digestibility (93.98%). The advantages of human MFG include its phospholipid structure, exogenous lipase, and lipolysis-regulating proteins. This study provides recommendation for the selection of milk fat substitutes and improvements in commercial dairy.

內(nèi)容: Defatted hickory meal (DHM), a by-product of hickory oil production, is a protein source rich in essential amino acids. In this study, the functional properties of DHM hydrolysate (DHMH) were assessed using in vitro and in vivo assays in context to its antioxidant and memory-enhancing effects. To induce memory impairment, D-galactose (D-gal) was administered to mice at a dose of 120 mg/kg body weight per day, and DHMH was orally administered at doses of 300, 600, and 1 000 mg/kg body weight per day for 8 weeks. DHMH treatment led to improved memory performance in D-gal-induced memory-impaired mice, as observed in the Morris water maze test. Furthermore, DHMH mitigated the accumulation of amyloid β1-42 triggered by D-gal exposure. Notably, high-dose DHMH significantly reduced the elevation of pro-inflammatory markers, including tumor necrosis factor alpha, interleukin 1β, and interleukin 6. Additionally, DHMH prevented the decline in total superoxide dismutase activity, glutathione peroxidase activity, and glutathione levels, while reducing malondialdehyde content in D-gal-induced mice, indicative of its antioxidant properties. Moreover, DHMH treatment effectively prevented histological alterations in neurons within the hippocampal CA1 area induced by D-gal. Collectively, our findings suggest that DHMH may counteract memory dysfunctions resulting from oxidative stress injury in the brain, positioning it as a potential candidate for use as a functional food.

內(nèi)容: The role of S-layer proteins (SLP), which form the outermost layer of cell walls in lactic acid bacteria (LAB), plays a crucial role in regulating immune-stimulating activity, thereby closely influencing LAB’s ability to boost host immunity. In this study, the heterologous expression, purification, and characterization of Lactobacillus acidophilus CICC6074-derived slpX protein and the molecular mechanism of its anti-inflammatory effect on LPS-induced RAW264.7 cells were investigated. Initially, the PCR results were shown to successfully clone the slpX DNA sequence by homologous recombination to obtain the pet-32a-slpX recombinant plasmid. SDS-PAGE results revealed that slpX protein with a molecular weight of 54 kDa was successfully obtained under 0.7 mmol/L IPTG-induced conditions, which was further demonstrated by western blot (WB) and LC-MS/MS. ELISA, WB and molecular docking results indicated that slpX protein can inhibit LPS-induced cellular inflammatory responses by linking to TLR4 and MD2 via hydrogen bonding and increasing the levels of anti-inflammatory factor IL-10 and decreasing the levels of inflammatory factors (TNF-α, IL-6, NO) and ROS via MAPK and NF-κB signaling pathways. The study is essential for the preparation of pure slpX protein and revealing its anti-inflammatory molecular mechanism.