Different depths of food restriction and high-fat diet refeeding in mice impact host obesity and metabolic phenotypes with correlative changes in the gut microbiota.

Overweight and obesity affect almost 2 billion adults worldwide, and food restriction (FR) is commonly used to reduce body fat. Whether refeeding (Re) after FR at different ages and to different degrees leads to overweight and its possible mechanisms are uncertain. In this study, adult and young mice were both restricted to 15% and 40% of their casual food intake, and then were fed 60% high-fat chow (FR15%-Re, FR40%-Re), whereas the control groups(CON) consumed high-fat or normal food throughout, respectively. The results of the study suggest that mild FR-heavy feeding may lead to more significant abnormal fat accumulation, liver damage, and increased recruitment of intestinal inflammatory factors and immune cells in mice of different ages and involves multiple types of alterations in the gut microbiota. Further fecal transplantation experiments as well as serum and liver enzyme-linked immunosorbent assay experiments preliminarily suggest that the link between lipid metabolism and inflammatory responses and the gut microbiota may be related to the regulation of the gut and live by Lipopolysaccharides(LPS) and Peroxisome Proliferator-Activated Receptor-Alpha(PPAR-α). In addition, our study may also serve as a reference for studying obesity prevention and treatment programs at different ages.

Targeting Nrf2 by bioactive peptides alleviate inflammation: expanding the role of gut microbiota and metabolites.

Inflammation is a complex process that usually refers to the general response of the body to the harmful stimuli of various pathogens, tissue damage, or exogenous pollutants. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense against oxidative damage and toxicity by expressing genes related to oxidative stress response and drug detoxification. In addition to its antioxidant properties, Nrf2 is involved in many other important physiological processes, including inflammation and metabolism. Nrf2 can bind the promoters of antioxidant genes and upregulates their expressions, which alleviate oxidation-induced inflammation. Nrf2 has been shown to upregulate heme oxygenase-1 expression, which promotes NF-κB activation and is closely related with inflammation. Nrf2, as a key factor in antioxidant response, is closely related to the expressions of pro-inflammatory factors, NF-κB pathway and cell metabolism. Bioactive peptides come from a wide range of sources and have many biological functions. Increasing evidence indicates that bioactive peptides have potential anti-inflammatory activities. This article summarized the sources, absorption and utilization of bioactive peptides and their role in alleviating inflammation via Nrf2 pathway. Bioactive peptides can also regulate gut microbiota and alter metabolites, which regulates the Nrf2 pathway through novel pathway and supplement the anti-inflammatory mechanisms of bioactive peptides. This review provides a reference for further study on the anti-inflammatory effect of bioactive peptides and the development and utilization of functional foods.

An active peptide from yak inhibits hypoxia-induced lung injury via suppressing VEGF/MAPK/inflammatory signaling.

Pulmonary vascular remodeling and inflammation play an important role in the hypoxic-induced lung diseases. Our previous investigations showed that peptide from yak milk residues could alleviate inflammation. In this study, our results suggest that peptide (LV) from yak milk residues peptide had protective effect of lung in the animal models of hypoxic-induced lung injury. LV Gavage could improve pulmonary vascular remodeling in the lung tissues of hypoxic mice. A comprehensive analysis of metabolomics and transcriptomics revealed that 5-KETE, 8,9-EET, and 6-keto-prostaglandin F1a might be potential targets to prevent lung injury in the hypoxic mice. These metabolites can be regulated by MAPK/VEGF and inflammatory pathways. Our data indicated that LV treatment could inhibit apoptosis and inflammation via Nrf2/NF-κB/MAPK/PHD-2 pathway and protected hypoxic-induced lung epithelial cells injury. Taken together, our results suggest that LV provides a novel therapeutic clue for the prevention of hypoxia-induced lung injury and inflammation-related lung diseases.

Protein of yak milk residue: Structure, functionality, and the effects on the quality of non-fat yogurt.

The purpose of this study was to compare the structural and functional of protein from yak milk residue, which collected from different elevations (MRP1 and MRP2) in Tibet, as well as their potential for enhancing the quality of non-fat yogurt. The results showed that MRP1 exhibited higher levels of ß-sheet, turbidity, particle size, and gel properties. MRP2 had better flexibility, emulsification, foaming, water/oil absorption capacity. The addition of MRP1 (3%) could improve texture and sensory properties of yogurt. Although MRP2 yogurt had higher hardness, gumminess, chewiness and water holding capacity, poor mouthfeel. Rheological test showed that MRPs yogurt exhibited typical gel-like and shear-thinning behavior. Moreover, the fortification of non-fat yogurts with MRP1 brought the formation of larger protein clusters with a more tightly knit network of smaller pores. These results indicate that MRP1 can be used as a fat substitute to improve the quality of non-fat yogurt.

Extraction, structures, biological effects and potential mechanisms of Momordica charantia polysaccharides: A review.

Momordica charantia L. is a kind of vegetable with medicinal value. As the main component of the vegetable, Momordica charantia polysaccharides (MCPs) mainly consist of galactose, galacturonic acid, xylose, rhamnose, mannose and the molecular weight range is 4.33 × 103-1.16 × 106 Da. MCPs have been found to have various biological activities in recent years, such as anti-oxidation, anti-diabetes, anti-brain injury, anti-obesity, immunomodulatory and anti-inflammation. In this review, we systematically summarized the extraction methods, structural characteristics and physicochemical properties of MCPs. Especially MCPs modulate gut microbiota and cause the alterations of metabolic products, which can regulate different signaling pathways and target gene expressions to exert various functions. Meanwhile, the potential structure-activity relationships of MCPs were analyzed to provide a scientific basis for better development or modification of MCPs. Future researches on MCPs should focus on industrial extraction and molecular mechanisms. In East Asia, Momordica charantia L. is used as both food and medicine. It is not clear whether MCP has its unique biological effects. Further study on the difference between MCPs and other food-derived polysaccharides will be helpful to the development and potential application of Momordica charantia L.

Characterization of lipid composition and nutritional quality of yak ghee at different altitudes: A quantitative lipidomic analysis.

Efficient and comprehensive analysis of lipid profiles in yak ghee samples collected from different elevations is crucial for optimal utilization of these resources. Unfortunately, such research is relatively rare. Yak ghee collected from three locations at different altitudes (S2: 2986 m; S5: 3671 m; S6: 4508 m) were analyzed by quantitative lipidomic. Our analysis identified a total of 176 lipids, and 147 s lipid of them were upregulated and 29 lipids were downregulated. These lipids have the potential to serve as biomarkers for distinguishing yak ghee from different altitudes. Notably, S2 exhibited higher levels of fatty acids (21:1) and branched fatty acid esters of hydroxy fatty acids (14:0/18:0), while S5 showed increased levels of phosphatidylserine (O-20:0/19:1) and glycerophosphoric acid (19:0/22:1). S6 displayed higher levels of triacylglycerol (17:0/20:5/22:3), ceramide alpha-hydroxy fatty acid-sphingosine (d17:3/34:2), and acyl glucosylceramides (16:0-18:0-18:1). Yak ghee exhibited a high content of neutralizing glycerophospholipids and various functional lipids, including sphingolipids and 21 newly discovered functional lipids. Our findings provide insights into quantitative changes in yak ghee lipids during different altitudes, development of yak ghee products, and screening of potential biomarkers.

Pathological Interplay and Clinical Complications between COVID-19 and Cardiovascular Diseases: An Overview in 2023.

BACKGROUND: The coronavirus disease 2019 (COVID-19) involves all organs of the body, of which the interaction with cardiovascular diseases is the most important. SUMMARY: Numerous studies have reported that COVID-19 patients complicated with cardiovascular comorbidities (hypertension, coronary heart disease, chronic heart failure (HF), cerebrovascular disease) are more likely to develop into critical illness and have higher mortality. Conversely, COVID-19 may also cause myocardial injury in patients through various pathological mechanisms such as direct virus attack on cardiomyocytes, overactivation of immune response, microthrombus formation, which may lead to fatal acute ST-segment elevation myocardial infarction, arrhythmia, acute worsening of chronic HF, etc. In addition, the symptoms of the so-called long-COVID may remain in some patients who survived the acute viral infection. Positional tachycardia has been widely reported, and cardiovascular autonomic disorders are thought to play a pathogenic role. KEY MESSAGE: The review summarizes the interaction between COVID-19 and cardiovascular disease in terms of pathological mechanism, clinical features, and sequelae. Therapeutic and rehabilitation programs after COVID-19 infection are compiled and need to be further standardized in the future.

Exploration on anti-hypoxia properties of peptides: a review.

Peptides are important components of human nutrition and health, and considered as safe, nontoxic, and easily absorbed potential drugs. Anti-hypoxia peptides are a kind of peptides that can prevent hypoxia or hypoxia damage. In this paper, the sources, preparations, and molecular mechanisms of anti-hypoxia peptides were systemically reviewed. The combination of bioinformatics, chemical synthesis, enzymatic hydrolysis, and microbial fermentation are recommended for efficient productions of anti-hypoxic peptides. The mechanisms of anti-hypoxic peptides include interference with glycolytic process and HIF-1α pathway, mitochondrial apoptosis, and inflammatory response. In addition, bioinformatics analysis, including virtual screening and molecular docking, provides an alternative or auxiliary method for exploring the potential anti-hypoxic activities and mechanisms of peptides. The potential challenges and prospects of anti-hypoxic peptides are also discussed. This paper can provide references for researchers in this field and promote further research and clinical applications of anti-hypoxic peptides in the future.

Targeting gut-liver axis by dietary lignans ameliorate obesity: evidences and mechanisms.

An imbalance between energy consumption and energy expenditure causes obesity. It is characterized by increased adipose accumulation and accompanied by chronic low-grade inflammation. Many studies have suggested that the gut microbiota of the host mediates the relationship between high-fat diet consumption and the development of obesity. Diet and nutrition of the body are heavily influenced by gut microbiota. The alterations in the microbiota in the gut may have effects on the homeostasis of the host's energy levels, systemic inflammation, lipid metabolism, and insulin sensitivity. The liver is an important organ for fat metabolism and gut-liver axis play important role in the fat metabolism. Gut-liver axis is a bidirectional relationship between the gut and its microbiota and the liver. As essential plant components, lignans have been shown to have different biological functions. Accumulating evidences have suggested that lignans may have lipid-lowering properties. Lignans can regulate the level of the gut microbiota and their metabolites in the host, thereby affecting signaling pathways related to fat synthesis and metabolism. These signaling pathways can make a difference in inhibiting fat accumulation, accelerating energy metabolism, affecting appetite, and inhibiting chronic inflammation. It will provide the groundwork for future studies on the lipid-lowering impact of lignans and the creation of functional meals based on those findings.

Dietary Polysaccharides Exert Anti-Fatigue Functions via the Gut-Muscle Axis: Advances and Prospectives.

Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency, and quality of life. Fatigue is also a common symptom of several serious diseases such as Parkinson's, Alzheimer's, cancer, etc. However, the contributing mechanisms are not clear, and there are currently no official recommendations for the treatment of fatigue. Some dietary polysaccharides are often used as health care supplements; these have been reported to have specific anti-fatigue effects, with minor side effects and rich pharmacological activities. Dietary polysaccharides can be activated during food processing or during gastrointestinal transit, exerting unique effects. This review aims to comprehensively summarize and evaluate the latest advances in the biological processes of exercise-induced fatigue, to understand dietary polysaccharides and their possible molecular mechanisms in alleviating exercise-induced fatigue, and to systematically elaborate the roles of gut microbiota and the gut-muscle axis in this process. From the perspective of the gut-muscle axis, investigating the relationship between polysaccharides and fatigue will enhance our understanding of fatigue and may lead to a significant breakthrough regarding the molecular mechanism of fatigue. This paper will provide new perspectives for further research into the use of polysaccharides in food science and food nutrition, which could help develop potential anti-fatigue agents and open up novel therapies for sub-health conditions.

Nickel-Catalyzed Directed Cross-Electrophile Coupling of Phenolic Esters with Arylmethyl Trimethylammonium Triflates.

In this context, we successfully utilize polycyclic aryl-activated alkyl ammonium triflates as the electrophilic aryl-activated alkylating agent in the nickel-catalyzed hydroxyl- or sulfonamide-directed cross-electrophile coupling reaction with an array of phenyl benzoates, allowing for the synthesis of various aryl ketones under mild conditions.

Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis.

BACKGROUND: Multiple myeloma is a clonal disorder of malignant plasma cells that comprises approximately 10% of hematologic malignancies. The aim of this study was to investigate the efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: Data mining was conducted in March 2022 across PubMed, EMBASE and ClinicalTrials.gov. All published RCTs which assessed efficacy and toxicity of carfilzomib-based regimens treatment for transplant-ineligible patients with newly diagnosed multiple myeloma when compared with a bortezomib-based regimens were included. RESULTS: Our meta-analysis showed that the overall response rate (ORR) (Odds ratio = 1.33, 95% CI 1.05-1.69, P = .02) was significantly higher in the carfilzomib-based regimens group than in the bortezomib-based regimens group. However, the difference in ORR did not translate into improvements in progression-free survival (PFS), overall survival (OS) and complete response rate (CRR). Adverse events of grade 3 or worse that occurred with a higher incidence in the carfilzomib-based regimens group compared with the bortezomib-based regimens group were dyspnea, hypertension, acute kidney injury, and heart failure. CONCLUSIONS: The carfilzomib-based regimens did not improve PFS, OS and CRR compared with the bortezomib-based regimens in transplant-ineligible patients with newly diagnosed multiple myeloma, and they showed higher toxicity.

Biological functions of active ingredients in quinoa bran: Advance and prospective.

Quinoa is known to be a rich source of nutrients and bioactive components. Quinoa bran, used mainly as animal feed in processing by-products, is also a potential source of bioactive ingredients being conducive to human health. The importance of nutrition and function of quinoa seed has been discussed in many studies, but the bioactive properties of quinoa bran often are overlooked. This review systemically summarized the progress in bioactive components, extraction, and functional investigations of quinoa bran. It suggests that chemically assisted electronic fractionation could be used to extract albumin from quinoa bran. Ultrasound-assisted extraction method is a very useful method for extracting phenolic acids, triterpene saponins, and flavonoids from quinoa bran. Based on in vitro and in vivo studies for biological activities, quinoa bran extract exhibits a wide range of beneficial properties, including anti-oxidant, anti-diabetes, anti-inflammation, anti-bacterial and anti-cancer functions. However, human experiments and action mechanisms need to investigate. Further exploring quinoa bran will promote its applications in functional foods, pharmaceuticals, and poultry feed in the future.

Antiaging Effects of Dietary Polysaccharides: Advance and Mechanisms.

Aging is a process in which the various physiological functions of the body gradually deteriorate and eventually lead to death. During this process, the body's resistance to external stresses gradually decreases and the aging-related diseases gradually are increased. Polysaccharides are a group of active substances extracted from living organisms and are widely found in plants, animals, and microorganisms. In the last decade, a variety of natural polysaccharides from functional and medicinal foods have attracted considerable interest for their beneficial effects in the prevention of chronic diseases such as cancers, diabetes, and neurodegenerative diseases. Interestingly, these polysaccharides have also been found to delay aging by reducing oxidative damage, inhibiting telomere shortening, and being anti-inflammatory in different animal models of aging. These reviews summarized the progresses in effects of polysaccharides on antiaging and the potential mechanisms and especially focused on the signaling pathways involved in the antiaging functions. Finally, the applications and prospects of the antiaging effects of polysaccharides are discussed.

Effect of Carbetocin on Postpartum Hemorrhage after Vaginal Delivery: A Meta-Analysis.

Background: The efficacy of oxytocin and carbetocin in preventing postpartum hemorrhage (PPH) in women with vaginal delivery has been controversial. This study is aimed at conducting a meta-analysis that compares the efficacy of carbetocin and oxytocin in the prevention of PPH among women with vaginal delivery. Methods: Literature was retrieved from PubMed, Medline, Embase, CENTRAL, and CNKI databases. The randomized controlled trials (RCTs) that compare the efficacy of carbetocin and oxytocin to prevent PPH were searched. Data from the included literatures were extracted by two researchers, including author, title, publication date, study type, study number, the incidence of PPH, number of patients requiring additional uterotonics, and number of patients requiring blood transfusion. Jadad scale was used to evaluate the quality of the included RCTs. The Chi-square test was adopted for the heterogeneity test. A fixed-effect model was used for analysis if heterogeneity did not exist between literatures. If heterogeneity exists between literatures, a random-effect model was used for analysis. The source of heterogeneity was explored by subgroup analysis and sensitivity analysis. Results: The incidence of PPH in the carbetocin group was lower than that in the oxytocin group (OR = 0.62, 95% CI (0.46, 0.84), Z = 3.14, P = 0.002). There was no heterogeneity among studies (χ 2 = 7.29, P = 0.12, I 2 = 45%) and no significant publication bias (P > 0.05). The proportion of women requiring additional uterotonics in the carbetocin group was lower than that in the oxytocin group (OR = 0.41, 95% CI (0.29, 0.56), Z = 5.34, P < 0.00001). There was no heterogeneity among studies (χ 2 = 0.82, P = 0.84, I 2 = 0%) and no significant publication bias (P > 0.05). There was no significant difference in the proportion of women needing blood transfusion between the carbetocin group and the oxytocin group (OR = 0.92, 95% CI (0.66, 1.29), Z = 0.46, P = 0.64). There was no heterogeneity among studies (χ 2 = 3.06, P = 0.55, I 2 = 0%) and no significant publication bias (P > 0.05). Conclusion: Carbetocin is superior to oxytocin in preventing PPH among women with vaginal delivery and can be widely used in clinical practice.

[A Propensity Score Matching Study of Autologous Hematopoietic Stem Cell Transplantation and New Drug Chemotherapy for Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To compare the clinical efficacy, survival, and prognosis of autologous hematopoietic stem cell transplantation (ASCT) with new drug chemotherapy in the treatment of newly diagnosed multiple myeloma (NDMM) in the new drug era. METHODS: The clinical data of 149 patients with NDMM treated with new drug induction regimen in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2012 to December 2019 were retrospectively analyzed. Twenty-four patients who received ASCT were in ASCT group, and 125 patients who did not receive ASCT were in non-ASCT group. The median follow-up time was 43 (1-90) months. The propensity score matching (PSM) method was used to balance confounding factors, then depth of response, overall survival (OS), and progression-free survival (PFS) between the two groups were compared and subgroup analysis was performed. RESULTS: After matching, the covariates were balanced between the two groups. Fifty-one patients (15 cases in ASCT group and 36 cases in non-ASCT group) were included. ASCT patients had a better complete response (CR) rate than non-ASCT patients receiving maintenance therapy (93.3% vs 42.3%, P=0.004), while there were no statistical differences in deep response rate and overall response rate (ORR) between the two groups (93.3% vs 65.4%, P=0.103; 93.3% vs 96.2%, P=1.000). Before matching, the 3 and 5-year PFS rate and median PFS (mPFS) in ASCT group and non-ASCT group were [89.6% vs 66.5%, P=0.024; 69.8% vs 42.7%; non-response (NR) vs 51.0 months], and the 3 and 5-year OS rate and median OS (mOS) were (100% vs 70.6%, P=0.002; 92.3% vs 49.6%; NR vs 54.0 months). After matching, the 3 and 5-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.6% vs 61.7%, P=0.182; 62.7% vs 45.7%; NR vs 51.0 months), the 3 and 5-year OS rate and mOS were (100% vs 65.6%, P=0.018; 88.9% vs 46.9%; NR vs 51.0 months). Subgroup analysis showed that patients with mSMART 3.0 high risk stratification, the 3-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.3% vs 41.5%, P=0.091; NR vs 34.0 months), and the 3-year OS rate and mOS were (100% vs 41.5%, P=0.034; NR vs 34.0 months). Patients with mSMART 3.0 standard risk stratification, the 3-year PFS rate and OS rate in ASCT group and non-ASCT group were (83.3% vs 76.8%, P=0.672; 100% vs 87.2%, P=0.155). The 3-year PFS and OS rate in MM patients who achieved deep response within 3 months after transplantation compared with non-ASCT patients who achieved deep response after receiving maintenance therapy were (83.1% vs 56.7%, P=0.323; 100% vs 60.5%, P=0.042), and the 3-year PFS and OS rate in patients who achieved overall response in both groups were (83.1% vs 62.5%, P=0.433; 100% vs 68.1%, P=0.082). After matching, Cox multivariate regression analysis showed that mSMART 3.0 risk stratification and ASCT were independent prognostic factors for OS. CONCLUSION: In the new drug era, ASCT can increase CR rate and prolong OS of NDMM patients. ASCT patients who are mSMART 3.0 high risk stratification or achieved deep response within 3 months after transplantation have better OS than non-ASCT patients receiving new drug chemotherapy. ASCT and mSMART 3.0 risk stratification are independent prognostic factors for OS in NDMM patients.

Bioactive Peptide F2d Isolated from Rice Residue Exerts Antioxidant Effects via Nrf2 Signaling Pathway.

Studies have shown that the peroxidation caused by oxygen free radicals is an important reason of vascular endothelial dysfunction and multiple diseases. In this study, active peptides (F2ds) were isolated from the fermentation product of rice dregs and its antioxidant effects were approved. Human umbilical vein endothelial cells (HUVECs) stimulated by H2O2 were used to evaluate the antioxidation effect and its molecular mechanism in the oxidative stress model. F2d protected H2O2-induced damage in HUVECs in a dosage-dependent manner. F2d can reduce the expression of Keap1, promote the expression of Nrf2, and activate the downstream target HO-1, NQO1, etc. It means F2d can modulate the Nrf2 signaling pathway. Using Nrf2 inhibitor ML385 to block the Nrf2 activation, the protective function of F2d is partially lost in the damage model. Our results indicated that F2d isolated from rice exerts antioxidant effects via the Nrf2 signaling pathway in H2O2-induced damage, and the work will benefit to develop functional foods.

Integrative Analysis of Gene Expression Through One-Class Logistic Regression Machine Learning Identifies Stemness Features in Multiple Myeloma.

Tumor progression includes the obtainment of progenitor and stem cell-like features and the gradual loss of a differentiated phenotype. Stemness was defined as the potential for differentiation and self-renewal from the cell of origin. Previous studies have confirmed the effective application of stemness in a number of malignancies. However, the mechanisms underlying the growth and maintenance of multiple myeloma (MM) stem cells remain unclear. We calculated the stemness index for samples of MM by utilizing a novel one-class logistic regression (OCLR) machine learning algorithm and found that mRNA expression-based stemness index (mRNAsi) was an independent prognostic factor of MM. Based on the same cutoff value, mRNAsi could stratify MM patients into low and high groups with different outcomes. We identified 127 stemness-related signatures using weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional annotation and pathway enrichment analysis indicated that these genes were mainly involved in the cell cycle, cell differentiation, and DNA replication and repair. Using the molecular complex detection (MCODE) algorithm, we identified 34 pivotal signatures. Meanwhile, we conducted unsupervised clustering and classified the MM cohorts into three MM stemness (MMS) clusters with distinct prognoses. Samples in MMS-cluster3 possessed the highest stemness fractions and the worst prognosis. Additionally, we applied the ESTIMATE algorithm to infer differential immune infiltration among the three MMS clusters. The immune core and stromal score were significantly lower in MMS-cluster3 than in the other clusters, supporting the negative relation between stemness and anticancer immunity. Finally, we proposed a prognostic nomogram that allows for individualized assessment of the 3- and 5-year overall survival (OS) probabilities among patients with MM. Our study comprehensively assessed the MM stemness index based on large cohorts and built a 34-gene based classifier for predicting prognosis and potential strategies for stemness treatment.

LITAF acts as a novel regulator for pathological cardiac hypertrophy.

Pathological hypertrophy generally progresses to heart failure. Exploring effective and promising therapeutic targets might lead to progress in preventing its detrimental outcomes. Our current knowledge about lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) is mainly limited to regulate inflammation. However, the role of LITAF in other settings that are not that relevant to inflammation, such as cardiac remodeling and heart failure, remains largely unknown. In the present study, we found that the expression of LITAF decreased in hypertrophic hearts and cardiomyocytes. Meanwhile, LITAF protected cultured neonatal rat cardiomyocytes against phenylephrine-induced hypertrophy. Moreover, using LITAF knockout mice, we demonstrated that LITAF deficiency exacerbated cardiac hypertrophy and fibrosis compared with wild-type mice. Mechanistically, LITAF directly binds to the N-terminal of ASK1, thus disrupting the dimerization of ASK1 and blocking ASK1 activation, ultimately inhibiting ASK1-JNK/p38 signaling over-activation and protecting against cardiac hypertrophy. Furthermore, AAV9-mediated LITAF overexpression attenuated cardiac hypertrophy in vivo. Conclusions: Our findings uncover the novel role of LITAF as a negative regulator of cardiac remodeling. Targeting the interaction between LITAF and ASK1 could be a promising therapeutic strategy for pathological cardiac remodeling.

Peptides Isolated from Yak Milk Residue Exert Antioxidant Effects through Nrf2 Signal Pathway.

Food-derived bioactive peptides are considered as the important sources of natural bioactive ingredients. Approximately 3094 peptides were identified by nESI-LC-MS/MS in the hydrolyzed yak milk residue. Peptide KALNEINQF (T10) is the strongest antioxidant peptide. The damage model of H2O2-induced human umbilical vein endothelial cells (HUVECs) was used to evaluate the antioxidant effect. After treatment with 25, 50, or 100 µg/mL T10 peptide, T10 obviously decreased H2O2-induced damage and increased the cell survival. Comparing with the H2O2-induced damage group, superoxide dismutase (SOD) activities were significantly increased 1.03, 1.1, and 1.33 times, and glutathione reductase (GR) activities were significantly increased 1.11, 1.30, and 1.43 times, respectively. Malondialdehyde (MDA) also reduced 1.41, 1.54, and 1.72 times, respectively. T10 inhibited H2O2-induced apoptosis in HUVECs, and protein expressions of the apoptosis-related genes bcl-2 and bax were increased and decreased by 1.95 and 1.44 times, respectively, suggesting T10 decreases apoptosis of the mitochondria-dependent pathway. Comparing with the H2O2-induced damage group, the RNA expressions of Nrf2, HO-1, and NQO1 were significantly increased by 2.00, 2.11, and 1.94 times; the protein expressions of p-Nrf2, HO-1, and NQO1 were significantly increased by 2.67, 1.73, and 1.04 times; and Keap1 was downregulated by 3.9 and 1.32 times, respectively. T10 also regulated the Nrf2 pathway and expressions of related genes (Keap1, HO-1, and NQO1), and blocking the Nrf2 pathway in the model decreased the protective effect of T10. Taken together, T10 peptide isolated from yak milk residue has a protective effect against H2O2-induced damage in HUVECs and the molecular mechanisms are involved in the regulation of Nrf2 signaling pathway and cell apoptosis.