Gastrodin exerts perioperative myocardial protection by improving mitophagy through the PINK1/Parkin pathway to reduce myocardial ischemia-reperfusion injury.

BACKGROUND: Although blood flow is restored after treatment of myocardial infarction (MI), myocardial ischemia and reperfusion (I/R) can cause cardiac injury, which is a leading cause of heart failure. Gastrodin (GAS) exerts protective effects against brain, heart, and kidney I/R. However, its pharmacological mechanism in myocardial I/R injury (MIRI) remains unclear. PURPOSE: GAS regulates autophagy in various diseases, such as acute hepatitis, vascular dementia, and stroke. We hypothesized that GAS could repair mitochondrial damage and regulate autophagy to protect against MIRI. STUDY DESIGN: Male C57BL/6 mice and H9C2 cells were subjected to I/R and hypoxia-reoxygenation (H/R) injury after GAS administration, respectively, to assess the impact of GAS on cardiomyocyte phenotypes, heart, and mitochondrial structure and function. The effect of GAS on cardiac function and mitochondrial structure in patients undergoing cardiac surgery has been observed in clinical practice. METHODS: The effects of GAS on cardiac structure and function, mitochondrial structure, and expression of related molecules in an animal model of MIRI were evaluated using immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy, western blotting, and gene sequencing. Its effects on the morphological, molecular, and functional phenotypes of cardiomyocytes undergoing H/R were observed using immunohistochemical staining, real-time quantitative PCR, and western blotting. RESULTS: GAS significantly reduces myocardial infarct size and improves cardiac function in MIRI mice in animal models and increases cardiomyocyte viability and reduces cardiomyocyte damage in cellular models. In clinical practice, myocardial injury was alleviated with better cardiac function in patients undergoing cardiac surgery after the application of GAS; improvements in mitochondria and autophagy activation were also observed. GAS primarily exerts cardioprotective effects through activation of the PINK1/Parkin pathway, which promotes mitochondrial autophagy to clear damaged mitochondria. CONCLUSION: GAS can promote mitophagy and preserve mitochondria through PINK1/Parkin, thus indicating its tremendous potential as an effective perioperative myocardial protective agent.

Effect and mechanism of polyphenols containing m-dihydroxyl structure on 2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine (PhIP) formation in chemical models and roast pork patties.

2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine (PhIP) is a prevalent heterocyclic amine (HAA) found in heated processed meat. This study investigated the inhibitory impact of eight different types of polyphenols containing m-dihydroxyl structure on PhIP formation through a chemical model system. The structure-activity relationship and potential sites of action of polyphenols containing m-dihydroxyl structure were also analyzed. Then, the mechanism of inhibiting PhIP formation by kaempferol, naringenin and quercetin was speculated by UPLC-MS. Results showed that 8 kinds of polyphenols containing m-dihydroxyl structure had significant (P < 0.05) inhibition on the formation of PhIP in the chemical model system in a dose-dependent manner. In addition, PhIP was most significantly inhibited by naringenin at the same concentration, followed by kaempferol and quercetin (83.27%, 80.81% and 79.26%, respectively). UPLC-MS results speculated that kaempferol, naringenin, and quercetin formed a new admixture via an electrophilic aromatic substitution reaction with the intermediate product phenylacetaldehyde, preventing the formation of PhIP.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Exome-Based Amino Acid Optimization: A Dietary Strategy to Satisfy Human Nutritional Demands and Enhance Muscle Strength in Breast Tumor Mice Undergoing Chemotherapy.

Breast cancer patients undergoing chemotherapy often experience muscle wasting and weakness, which impact their quality of life. A potential solution lies in customizing amino acid compositions based on exome-derived formulations (ExAAs). The study hypothesized that tailoring dietary amino acids using ExAAs could enhance muscle health. Theoretical amino acid requirements were calculated from the genome's exome region, and a breast cancer mouse model undergoing paclitaxel treatment was established. The mice were supplemented with a cancer-specific nutritional formula (QJS), and the effects of QJS and amino acid-adjusted QJS (adjQJS) were compared. Both formulations improved the nutritional status without compromising tumor growth. Notably, adjQJS significantly enhanced muscle strength compared to QJS (1.51 ± 0.25 vs. 1.30 ± 0.08 fold change, p < 0.05). Transcriptome analysis revealed alterations in complement and coagulation cascades, with an observed upregulation of C3 gene expression in adjQJS. Immune regulation also changed, showing a decrease in B cells and an increase in monocytes in skeletal muscle with adjQJS. Importantly, adjQJS resulted in a notable increase in Alistipes abundance compared to QJS (10.19 ± 0.04% vs. 5.03 ± 1.75%). This study highlights the potential of ExAAs as valuable guide for optimizing amino acid composition in diets for breast cancer patients undergoing chemotherapy.

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

Risk Factors and Short-Term Outcomes of Postoperative Pulmonary Complications in Elderly Patients After Cardiopulmonary Bypass.

Objective: The risk factors of postoperative pulmonary complications (PPCs) have been extensively investigated in non-cardiac surgery and non-elderly adult patients undergoing cardiac surgery. However, data on elderly patients after cardiopulmonary bypass (CPB) is limited. This study aimed to evaluate the risk factors and short-term outcomes for PPCs in elderly patients undergoing CPB procedures. Patients and Methods: Data from 660 patients who underwent CPB over a six-year period at a tertiary care hospital were collected. The primary outcome encompassed the incidence of PPCs, including re-intubation, postoperative mechanical ventilation exceeding 48 hours, pulmonary infection, pleural effusion requiring thoracic drainage, and acute respiratory distress syndrome. Missing data were managed using multiple imputation. Univariate analysis and the multiple logistic regression method were utilized to ascertain independent risk factors for PPCs. Results: Among the 660 patients, PPCs were observed in 375 individuals (56.82%). Multiple logistic regression identified serum albumin levels <40 g/L, type of surgery, CPB duration >150 minutes, blood transfusion, and intra-aortic balloon pump use before extubation as independent risk factors for PPCs. Patients experiencing PPCs had prolonged mechanical ventilation, extended hospitalization and ICU stays, elevated postoperative mortality, and higher tracheotomy rates compared to those without PPCs. Conclusion: Elderly patients following CPB displayed a substantially high incidence of PPCs, significantly impacting their prognosis. Additionally, this study identified five prominent risk factors associated with PPCs in this population. These findings enable clinicians to better recognize patients who may benefit from perioperative prevention strategies based on these risk factors.

Polysaccharide isolated from Grifola frondosa eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T cells responses.

Myeloid derived suppressor cells (MDSCs) are known to accumulate in cancer patients and tumor-bearing mice, playing a significant role in promoting tumor growth. Depleting MDSCs has emerged as a potential therapeutic strategy for cancer. Here, we demonstrated that a fungal polysaccharide, extracted from Grifola frondosa, can effectively suppress breast tumorigenesis in mice by reducing the accumulation of MDSCs. Treatment with Grifola frondosa polysaccharide (GFI) leads to a substantial decrease in MDSCs in the blood and tumor tissue, and a potent inhibition of tumor growth. GFI treatment significantly reduces the number and proportion of MDSCs in the spleen, although this effect is not observed in the bone marrow. Further analysis reveals that GFI treatment primarily targets PMN-MDSCs, sparing M-MDSCs. Our research also highlights that GFI treatment has the dual effect of restoring and activating CD8+T cells, achieved through the downregulation of TIGIT expression and the upregulation of Granzyme B. Taken together, our findings suggest that GFI treatment effectively eliminates PMN-MDSCs in the spleen, leading to a reduction in MDSC numbers in circulation and tumor tissues, ultimately enhancing the antitumor immune response of CD8+T cells and inhibiting tumor growth. This study introduces a promising therapeutic agent for breast cancer.

Risk factors prediction of 6-month mortality after noncardiac surgery of older patients in China: a multicentre retrospective cohort study.

BACKGROUND: Identifying the risk factors associated with perioperative mortality is crucial, particularly in older patients. Predicting 6-month mortality risk in older patients based on large datasets can assist patients and surgeons in perioperative clinical decision-making. This study aimed to develop a risk prediction model of mortality within 6 months after noncardiac surgery using the clinical data from 11 894 older patients in China. MATERIALS AND METHODS: A multicentre, retrospective cohort study was conducted in 20 tertiary hospitals. The authors retrospectively included 11 894 patients (aged ≥65 years) who underwent noncardiac surgery between April 2020 and April 2022. The least absolute shrinkage and selection operator model based on linear regression was used to analyse and select risk factors, and various machine learning methods were used to build predictive models of 6-month mortality. RESULTS: The authors predicted 12 preoperative risk factors associated with 6-month mortality in older patients after noncardiac surgery. Including laboratory-associated risk factors such as mononuclear cell ratio and total blood cholesterol level, etc. Also including medical history associated risk factors such as stroke, history of chronic diseases, etc. By using a random forest model, the authors constructed a predictive model with a satisfactory accuracy (area under the receiver operating characteristic curve=0.97). CONCLUSION: The authors identified 12 preoperative risk factors associated with 6-month mortality in noncardiac surgery older patients. These preoperative risk factors may provide evidence for a comprehensive preoperative anaesthesia assessment as well as necessary information for clinical decision-making by anaesthesiologists.

Remote ischemic preconditioning reduces mitochondrial apoptosis mediated by calpain 1 activation in myocardial ischemia-reperfusion injury through calcium channel subunit Cacna2d3.

Remote Ischemic Preconditioning (RIPC) can reduce myocardial ischemia-reperfusion injury, but its mechanism is not clear. In order to explore the mechanism of RIPC in myocardial protection, we collected myocardial specimens during cardiac surgery in children with tetralogy of Fallot for sequencing. Our study found RIPC reduces the expression of the calcium channel subunit cacna2d3, thereby impacting the function of calcium channels. As a result, calcium overload during ischemia-reperfusion is reduced, and the activation of calpain 1 is inhibited. This ultimately leads to a decrease in calpain 1 cleavage of Bax, consequently inhibiting increased mitochondrial permeability-mediated apoptosis. Notably, in both murine and human models of myocardial ischemia-reperfusion injury, RIPC inhibiting the expression of the calcium channel subunit cacna2d3 and the activation of calpain 1, improving cardiac function and histological outcomes. Overall, our findings put forth a proposed mechanism that elucidates how RIPC reduces myocardial ischemia-reperfusion injury, ultimately providing a solid theoretical foundation for the widespread clinic application of RIPC.

Mental health changes in elderly patients undergoing non-cardiac surgery during the COVID-19 pandemic in China.

BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.

Comparison of Neuroprotection and Regulating Properties on Gut Microbiota between Selenopeptide Val-Pro-Arg-Lys-Leu-SeMet and Its Native Peptide Val-Pro-Arg-Lys-Leu-Met In Vitro and In Vivo.

Selenopeptides are promising candidates for intervening in neuroinflammation; however, the key role of selenium (Se) in selenopeptides remains poorly understood. To address this gap, we compared the neuroprotective effects of selenopeptide Val-Pro-Arg-Lys-Leu-SeMet (namely, Se-P1) and its native peptide Val-Pro-Arg-Lys-Leu-Met (namely, P1). Our results demonstrate that Se-P1 treatment exhibits superior antioxidant and antineuroinflammatory effects in PC12 cells and lipopolysaccharide (LPS)-injured mice compared to P1. Moreover, the administration of Se-P1 and P1 resulted in a shift in the gut microbiota composition. Notably, during LPS-induced injury, Se-P1 treatment demonstrated greater stability in maintaining gut microbiota composition compared to P1 treatment. Specifically, Se-P1 may have a positive impact on gut microbiota dysbiosis by modulating inflammatory-related bacteria such as enhancing Lactobacillus abundance while reducing that of Lachnospiraceae_NK4A136_group. Furthermore, the alteration of metabolites induced by Se-P1 treatment exhibited a significant correlation with gut microbiota, subsequently modulating the inflammatory-related metabolic pathways including histidine metabolism, lysine degradation, and purine metabolism. These findings suggest that organic Se contributes to the bioactivities of Se-P1 in mitigating neuroinflammation in LPS-injured mice compared to P1. These findings hold significant value for the development of potential preventive or therapeutic strategies against neurodegenerative diseases and introduce novel concepts in selenopeptide nutrition and supplementation recommendations.

Calpain: the regulatory point of myocardial ischemia-reperfusion injury.

Calpain is a conserved cysteine protease readily expressed in several mammalian tissues, which is usually activated by Ca2+ and with maximum activity at neutral pH. The activity of calpain is tightly regulated because its aberrant activation will nonspecifically cleave various proteins in cells. Abnormally elevation of Ca2+ promotes the abnormal activation of calpain during myocardial ischemia-reperfusion, resulting in myocardial injury and cardiac dysfunction. In this paper, we mainly reviewed the effects of calpain in various programmed cell death (such as apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, and parthanatos) in myocardial ischemia-reperfusion. In addition, we also discussed the abnormal activation of calpain during myocardial ischemia-reperfusion, the effect of calpain on myocardial repair, and the possible future research directions of calpain.

Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria.

Histidine-rich protein II (HRPII) is secreted by Plasmodium falciparum during the blood stage of malaria infection. High plasma levels of HRPII are associated with cerebral malaria, a severe and highly fatal complication of malaria. HRPII has been shown to induce vascular leakage, the hallmark of cerebral malaria, in blood-brain barrier (BBB) and animal models. We have discovered an important mechanism for BBB disruption that is driven by unique features of HRPII. By characterizing serum from infected patients and HRPII produced by P. falciparum parasites in culture, we found that HRPII exists in large multimeric particles of 14 polypeptides that are richly laden with up to 700 hemes per particle. Heme loading of HRPII is required for efficient binding and internalization via caveolin-mediated endocytosis in hCMEC/D3 cerebral microvascular endothelial cells. Upon acidification of endolysosomes, two-thirds of the hemes are released from acid-labile binding sites and metabolized by heme oxygenase 1, generating ferric iron and reactive oxygen species. Subsequent activation of the NLRP3 inflammasome and IL-1ß secretion resulted in endothelial leakage. Inhibition of these pathways with heme sequestration, iron chelation, or anti-inflammatory drugs protected the integrity of the BBB culture model from HRPII:heme. Increased cerebral vascular permeability was seen after injection of young mice with heme-loaded HRPII (HRPII:heme) but not with heme-depleted HRPII. We propose that during severe malaria infection, HRPII:heme nanoparticles in the bloodstream deliver an overwhelming iron load to endothelial cells to cause vascular inflammation and edema. Disrupting this process is an opportunity for targeted adjunctive therapies to reduce the morbidity and mortality of cerebral malaria.

Effect of oil exposure stages on the heat resistance of Salmonella enterica serovar Enteritidis phage type 30 in peanut flour.

The oil in low-moisture foods (LMFs) shows protective effects on bacteria during thermal processing. However, the circumstances under which this protective effect strengthens remain unclear. This study aimed to understand which step of the oil exposure to bacterial cells (inoculation, isothermal inactivation, or recovery and enumeration step) in LMFs can enhance their heat resistance. Peanut flour (PF) and defatted PF (DPF) were selected as the oil-rich and oil-free LMF models. Salmonella enterica Enteritidis Phage Type 30 (S. Enteritidis) was inoculated into four designated PF groups representing different oil exposure stages. It was isothermally treated to obtain heat resistance parameters. At a constant moisture content (aw,25°C = 0.32 ± 0.02) and controlled aw,85°C (0.32 ± 0.02), S. Enteritidis exhibited significantly high (p < 0.05) D values in oil-rich sample groups. For instance, the heat resistance values of S. Enteritidis in the PF-DPF and DPF-PF groups were D80°C of 138.22 ± 7.45 min and 101.89 ± 7.82 min; however, the D80°C in the DPF-DPF group was 34.54 ± 2.07 min. The oil addition after the thermal treatment also helped injured bacterial recovery in the enumeration. For instance, the D80°C, D85°C, and D90°C values in the DFF-DPF oil groups were 36.86 ± 2.30, 20.65 ± 1.23, and 7.91 ± 0.52 min, respectively, which were higher than those in the DPF-DPF group at 34.54 ± 2.07, 17.87 ± 0.78, and 7.10 ± 0.52 min. We confirmed that the oil protected S. Enteritidis in PF in all three stages: desiccation process, heat treatment, and recovery of bacterial cells in plates.

Paenibacillus soyae sp. nov., isolated from the rhizosphere of soya bean.

A Gram-positive, facultatively anaerobic, agar-hydrolytic and rod-shaped bacterium with peritrichous flagellation, designated strain SCIV0701T, was isolated from soya bean rhizosphere soil collected from Bazhong, Sichuan Province, PR China and characterized by using polyphasic taxonomy. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SCIV0701T belonged to the genus Paenibacillus, and showed highest similarity to Paenibacillus nanensis MX2-3T (97.59 %), Paenibacillus paeoniae M4BSY-1T (97.45 %) and Paenibacillus pinisoli NB5T (97.45 %). The average nucleotide identity values and in silico DNA-DNA hybridization scores between strain SCIV0701T and P. nanensis MX2-3T, P. paeoniae M4BSY-1T and P. pinisoli NB5T were lower than recommended thresholds of 95% and 70 %, respectively, for species delineation. Menaquinone-7 was the predominant respiratory quinone. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified phospholipids and one unidentified aminophospholipid. The major fatty acids were anteiso-C15 : 0, C16 : 00 and iso-C16 : 0. Physiological and biochemical features differentiated strain SCIV0701T from the closely related Paenibacillus species. Based on the results of polyphasic taxonomic analysis, strain SCIV0701T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus soyae sp. nov. is proposed. The type strain is SCIV0701T (=GDMCC 1.2482T=JCM 34672T).

Selenium-enriched foods and their ingredients: As intervention for the vicious cycle between autophagy and overloaded stress responses in Alzheimer's disease.

Dysfunctional autophagy induced by excessive reactive oxygen species (ROS) load and inflammation accelerates the development of Alzheimer's disease (AD). Recently, there has been an increasing interest in selenium-enriched ingredients (SEIs), such as selenoproteins, selenoamino acids and selenosugars, which could improve AD through antioxidant and anti-inflammation, as well as autophagy modulating effects. This review indicates that SEIs eliminate excessive ROS by activating the nuclear translocation of nuclear factor erythroid2-related factor 2 (Nrf2) and alleviate inflammation by inhibiting the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa-B (NF-κB) pathway. Furthermore, they can activate the adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, and subsequently promote amyloid beta (Aß) clearance and reduce memory impairments. SEIs are ubiquitous in many plants and microorganisms, such as Brassicaceae vegetables, yeast, and mushroom. Enzymatic hydrolysis, as well as physical processing, such as thermal, high pressure and microwave treatment, are the main techniques to modify the properties of dietary selenium. This work highlights the fact that SEIs can inhibit inflammation and oxidative stress and provides evidence that supports the potential use of these dietary materials to be a novel strategy for improving AD.

Effects of probiotics on hypertension.

Emerging data have suggested that probiotics had good potential in regulating intestinal flora and preventing hypertension. Some studies in human and animal models have demonstrated probiotic intervention could attenuate hypertension, regulate intestinal flora to increase the abundance of beneficial bacteria, and regulate intestinal microbial metabolites such as trimethylamine oxide, short-chain fatty acids, and polyphenols. However, there is still some debate as to whether probiotics exert effective benefits. These recently published reviews did not systematically expound on the heterogeneity between the effect and mechanism of probiotics with different types, doses, and carriers to exert antihypertensive effects, as well as the possible application of probiotics in the prevention and treatment of hypertension in food and clinic. Here we try to systematically review the association between hypertension and intestinal microflora, the effect of probiotics and their metabolites on hypertension, and the recent research progress on the specific mechanism of probiotics on hypertension. In addition, we also summarized the potential application of probiotics in antihypertension. Future challenges include elucidating the functions of metabolites produced by microorganisms and their downstream pathway or molecules, identifying specific strains, not just microbial communities, and developing therapeutic interventions that target hypertension by modulation of gut microbes and metabolites.

Whole-plant foods and their macromolecules: untapped approaches to modulate neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Recently, sustained neuroinflammatory response in microglia and astrocytes has been found to cause the deposition of amyloid beta plaques and the hyperphosphorylation of tau protein, thereby accelerating AD progression. The lipoxin A4-transcription factor nuclear factor-kappa B and mitogen-activated protein kinase pathways have been shown to play important roles in the regulation of inflammatory processes. There is growing research-based evidence suggesting that dietary whole-plant foods, such as mushrooms and berries, may be used as inhibitors for anti-neuroinflammation. The beneficial effects of whole-plant foods were mainly attributed to their high contents of functional macromolecules including polysaccharides, polyphenols, and bioactive peptides. This review provides up-to-date information on important molecular signaling pathways of neuroinflammation and discusses the anti-neuroinflammatory effects of whole-plant foods. Further, a critical evaluation of plants' macromolecular components that have the potential to prevent and/or relieve AD is provided. This work will contribute to better understanding the pathogenetic mechanism of neuroinflammation in AD and provide new approaches for AD therapy.

A Ganoderma lucidum polysaccharide F31 alleviates hyperglycemia through kidney protection and adipocyte apoptosis.

In this paper, we reported an excellent hypoglycemic effect of a Ganoderma lucidium polysaccharide F31 with efficacies between 45 and 54 %, approaching to that of liraglutide (52 %). Significantly, F31 reduced the body weight gains and food intakes. F31 decreased 4 key compounds, consisting of adenosine, adenosine, galactitol and glycerophosphocholine and elevated 8 key compounds, including arginine, proline, arachidonic acid, creatine, aspartic acid, leucine, phenylalanine and ornithine, which protected kidney function. Also, apoptosis was promoted by F31 in epididymal fat through increasing Caspase-3, Caspase-6 and Bax and decreasing Bcl-2. On 3 T3-L1 preadipocyte cells, F31 induced early apoptosis through reducing mitochondrial membrane potential. Finally, a molecular docking was performed to reveal a plausible cross-talk between kidney and epididymal fat through glycerophosphorylcholine-Bax axis. Overall, F31 alleviated hyperglycemia through kidney protection and adipocyte apoptosis in db/db mice. This work may provide novel insights into the hypoglycemic activity of polysaccharides.

Gut Microbiome Is Associated With the Response to Chemoradiotherapy in Patients With Non-small Cell Lung Cancer.

PURPOSE: To explore the dynamic change of gut microbiota and its predictive role in progression-free survival (PFS) in non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Forty-one patients with NSCLC in 2 phase 2 trials (NCT02573506 and NCT03006575) were analyzed. A total of 102 fecal samples were collected at 3 time points (T0, before CCRT; T1, 2 weeks after the initiation of CCRT; and T2, the end of CCRT). Gut microbiota composition and functionality were analyzed by 16S rRNA gene sequencing and shotgun metagenomics, respectively. Alpha diversity, taxonomic composition, and KEGG functional pathways were compared between patients in the long-PFS group (PFS ≥11.0 months) and short-PFS group (PFS <11.0 months). A random forest classifier was constructed to identify microbial signature related to PFS. Clinical and microbial factors potentially predictive of PFS were assessed in the univariate and multivariate Cox regression analysis. RESULTS: The abundance of Bacteroidota and Proteobacteria increased, while the abundance of Firmicutes decreased after CCRT. Shannon index (P = .006) and PD index (P = .022) were significantly higher in the long-PFS group than for those in the short-PFS group at T1. The PFS-prediction microbial signature at T1 included unclassified members of the Lanchospiraceae spp., such as NK4A136 and UCG-003 groups, Dorea sp., various strains from within the Eubacterium hallii and E. siraeum groups, and an unclassified member of the Muribaculaceae, which yielded an area under the ROC curve of 0.87. These discriminatory genera mostly belong to phylum Firmicutes/family Clostridia. Multivariate analysis indicated PD index (HR = 8.036, P = .016) and the abundance of Dorea sp. at T1 (HR = 4.186, P = .043) were independent predictors of PFS. The KEGG pathways at T1 overrepresented in the long-PFS group included fatty acid metabolism, fatty acid biosynthesis, and arginine biosynthesis. Those overrepresented in the short-PFS group included lipopolysaccharide biosynthesis, ascorbate and aldarate metabolism, and biosynthesis of vancomycin group antibiotics. CONCLUSIONS: Gut microbiota composition and functionality at 2 weeks after the initiation of CCRT were associated with PFS in NSCLC. Further research is needed to confirm these results.