Faecalibacterium prausnitzii Supplementation Prevents Intestinal Barrier Injury and Gut Microflora Dysbiosis Induced by Sleep Deprivation.

Sleep deprivation (SD) leads to impaired intestinal barrier function and intestinal flora disorder, especially a reduction in the abundance of the next generation of probiotic Faecalibacterium prausnitzii (F. prausnitzii). However, it remains largely unclear whether F. prausnitzii can ameliorate SD-induced intestinal barrier damage. A 72 h SD mouse model was used in this research, with or without the addition of F. prausnitzii. The findings indicated that pre-colonization with F. prausnitzii could protect against tissue damage from SD, enhance goblet cell count and MUC2 levels in the colon, boost tight-junction protein expression, decrease macrophage infiltration, suppress pro-inflammatory cytokine expression, and reduce apoptosis. We found that the presence of F. prausnitzii helped to balance the gut microbiota in SD mice by reducing harmful bacteria like Klebsiella and Staphylococcus, while increasing beneficial bacteria such as Akkermansia. Ion chromatography analysis revealed that F. prausnitzii pretreatment increased the fecal butyrate level in SD mice. Overall, these results suggested that incorporating F. prausnitzii could help reduce gut damage caused by SD, potentially by enhancing the intestinal barrier and balancing gut microflora. This provides a foundation for utilizing probiotics to protect against intestinal illnesses.

Age-Dependent Inflammatory Microenvironment Mediates Alveolar Regeneration.

Lung aging triggers the onset of various chronic lung diseases, with alveolar repair being a key focus for alleviating pulmonary conditions. The regeneration of epithelial structures, particularly the differentiation from type II alveolar epithelial (AT2) cells to type I alveolar epithelial (AT1) cells, serves as a prominent indicator of alveolar repair. Nonetheless, the precise role of aging in impeding alveolar regeneration and its underlying mechanism remain to be fully elucidated. Our study employed histological methods to examine lung aging effects on structural integrity and pathology. Lung aging led to alveolar collapse, disrupted epithelial structures, and inflammation. Additionally, a relative quantification analysis revealed age-related decline in AT1 and AT2 cells, along with reduced proliferation and differentiation capacities of AT2 cells. To elucidate the mechanisms underlying AT2 cell functional decline, we employed transcriptomic techniques and revealed a correlation between inflammatory factors and genes regulating proliferation and differentiation. Furthermore, a D-galactose-induced senescence model in A549 cells corroborated our omics experiments and confirmed inflammation-induced cell cycle arrest and a >30% reduction in proliferation/differentiation. Physiological aging-induced chronic inflammation impairs AT2 cell functions, hindering tissue repair and promoting lung disease progression. This study offers novel insights into chronic inflammation's impact on stem cell-mediated alveolar regeneration.

Structure, Biological Functions, Separation, Properties, and Potential Applications of Milk Fat Globule Membrane (MFGM): A Review.

BACKGROUND: The milk fat globule membrane (MFGM) is a thin film that exists within the milk emulsion, suspended on the surface of milk fat globules, and comprises a diverse array of bioactive components. Recent advancements in MFGM research have sparked a growing interest in its biological characteristics and health-related functions. Thorough exploration and utilization of MFGM as a significant bioactive constituent in milk emulsion can profoundly impact human health in a positive manner. Scope and approach: This review comprehensively examines the current progress in understanding the structure, composition, physicochemical properties, methods of separation and purification, and biological activity of MFGM. Additionally, it underscores the vast potential of MFGM in the development of additives and drug delivery systems, with a particular focus on harnessing the surface activity and stability of proteins and phospholipids present on the MFGM for the production of natural emulsifiers and drug encapsulation materials. KEY FINDINGS AND CONCLUSIONS: MFGM harbors numerous active substances that possess diverse physiological functions, including the promotion of digestion, maintenance of the intestinal mucosal barrier, and facilitation of nerve development. Typically employed as a dietary supplement in infant formula, MFGM's exceptional surface activity has propelled its advancement toward becoming a natural emulsifier or encapsulation material. This surface activity is primarily derived from the amphiphilicity of polar lipids and the stability exhibited by highly glycosylated proteins.

Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier.

BACKGROUND: Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown. METHODS: Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs. RESULTS: The expression levels of inflammation-related markers (diamine oxidase, D-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1ß) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs. CONCLUSIONS: S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.

Analysis of composition and source of the key aroma compounds in stir-fried pepper tallow.

Stir-fried pepper tallow is widely used in cooking due to its special flavor, particularly in hot-pot dishes. However, the composition and source of the key aroma compounds in stir-fried pepper tallow are poorly understood, resulting in uneven quality. Here, the key aroma compounds were screened using flavor dilution factors (FD) and odor activity values (OAVs). A total of 41 odorants compounds were identified. Of these, 20 compounds with FD ≥ 8 were aroma-active compounds. Furthermore, among these 20 compounds, 15 with OAVs ≥ 1were the key aroma-active compounds and most of these (13 out of 15 odorants) were produced from pepper. Glycosides in pepper are the precursors of the most of these key aroma compounds. It may be possible to improve the flavor quality of stir-fried pepper tallow by hydrolyzing glycosides. These findings should help to establish a standard to assess and improve the quality of stir-fried pepper tallow.

Efficacy of Bifidobacterium animalis subsp. lactis BL-99 in the treatment of functional dyspepsia: a randomized placebo-controlled clinical trial.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

Emulsion stability of hydroxybutyl chitosan as emulsifier at low pH: Effects of the degree of substitutions of hydroxybutyl groups.

Keeping the stability of emulsions at low pH is necessary for their successful applications in food and delivery systems. To achieve this goal, hydroxybutyl chitosan (HBC) with three degrees of substitution (DSs) was used as an emulsifier to investigate the effect of HBC structure on the emulsion stability. The DSs of HBC-5, HBC-10, and HBC-20 were 0.66, 1.51, and 2.19, respectively. The stability of oil-in-water emulsions against creaming/coalescence was positively correlated with the DS. As pH decreased to 2, HBC-20-stabilized emulsions were most stable without creaming or coalescence. After 30 days of storage, no changes in the droplet sizes of HBC-20-stabilized emulsions were observed, whereas the droplet sizes of HBC-5/10- stabilized emulsions significantly increased at low pH. The stability of HBC-20- stabilized emulsions at low pH was attributed to the higher surface activity and electrostatic repulsion. Our research revealed that the emulsion stability of HBC under low pH conditions can be controlled by the density of the hydroxybutyl groups in HBC. In vitro digestion further revealed the excellent stability of HBC-20-stabilized emulsions in simulated gastric fluid, which highlighted the enormous potential of HBC-20 to protect liposoluble drugs and nutrients from the extreme pH environment.

CO2 electrocatalytic reduction to ethylene and its application outlook in food science.

The efficient conversion of CO2 is considered to be an important step toward carbon emissions peak and carbon neutrality. Presently, great efforts have been devoted to the study of efficient nanocatalysts, electrolytic cell, and electrolytes to achieve high reactivity and selectivity in the electrochemical reduction of CO2 to mono- and multi-carbon (C2+) compounds. However, there are very few reviews focusing on highly reactive and selective ethylene production and application in the field of electrochemical carbon dioxide reduction reaction (CO2RR). Ethylene is a class of multi-carbon compounds that are widely applied in industrial, ecological, and agricultural fields. This review focuses especially on the convertibility of CO2 reduction to generate ethylene technology in practical applications and provides a detailed summary of the latest technologies for the efficient production of ethylene by CO2RR and suggests the potential application of CO2RR systems in food science to further expand the application market of CO2RR for ethylene production.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

BACKGROUND: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. RESULTS: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. CONCLUSION: This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

Plasmalogen Improves Memory Function by Regulating Neurogenesis in a Mouse Model of Alzheimer's Diseases.

Adult hippocampal neurogenesis (AHN) is associated with hippocampus-dependent cognitive function, and its initiation is attributed to neural stem cells (NSCs). Dysregulated AHN has been identified in Alzheimer's disease (AD) and may underlie impaired cognitive function in AD. Modulating the function of NSCs and stimulating AHN are potential ways to manipulate AD. Plasmalogen (PLA) are a class of cell membrane glycerophospholipids which exhibit neuroprotective properties. However, the effect of PLA on altered AHN in AD has not been investigated. In our study, PLA(10µg/mL) -attenuated Aß (1-42) (5µM) induced a decrease in NSC viability and neuronal differentiation of NSCs, partially through regulating the Wnt/ß-catenin pathway. Additionally, AD mice were supplemented with PLA (67mg/kg/day) for 6 weeks. PLA treatment improved the impaired AHN in AD mice, including increasing the number of neural stem cells (NSCs) and newly generated neurons. The memory function of AD mice was also enhanced after PLA administration. Therefore, it was summarized that PLA could regulate NSC differentiation by activating the Wnt/ß-catenin pathway and ameliorate AD-related memory impairment through up-regulating AHN.

Nobiletin Mitigates D-Galactose-Induced Memory Impairment via Improving Hippocampal Neurogenesis in Mice.

Memory impairment is a characteristic of brain aging, and it is associated with a decrease in neurogenesis. Therefore, enhancing neurogenesis is a potential method for mitigating brain aging. Nobiletin (NOB) is a natural polymethoxylated flavonoid derived from citrus peels. It acts as an antioxidant, enhances anti-inflammation, and displays neuroprotective properties. However, the mechanism of NOB on brain aging has not been elucidated. In this study, D-galactose-induced aging mice were treated with NOB (100 mg/kg/day) for 10 weeks. NOB administration attenuated D-galactose-induced memory impairment and restored hippocampal neurogenesis, including the number of newborn neurons and neural stem cells in mice. Furthermore, it downregulated the pro-inflammatory mediators IL-1 ß, IL-6, and pP65 (by 42.2%, 22.9%, and 46.4% of those in the D-galactose treated group, respectively) in the hippocampus and blocked microglia and astrocyte activation. In vitro, NOB inhibited D-galactose-induced inflammatory responses in BV2 cells, and the conditioned medium prepared from NOB- and D-galactose-co-treated BV2 cells elevated the viability (90.3% of control) and differential ability (94.9% of control) of C17.2 cells, compared to the D-galactose-treated group alone. It was concluded that NOB could restore memory impairment via the improvement of neurogenesis by ameliorating neuroinflammation in the hippocampus. Overall, NOB is a potential candidate neurogenesis enhancer for improving brain function.

The regulation of Insulin/IGF-1 signaling by miR-142-3p associated with human longevity.

MicroRNAs (miRNAs) have been demonstrated to modulate life span in the invertebrates C. elegans and Drosophila by targeting conserved pathways of aging, such as insulin/IGF-1 signaling (IIS). However, a role for miRNAs in modulating human longevity has not been fully explored. Here we investigated novel roles of miRNAs as a major epigenetic component of exceptional longevity in humans. By profiling the miRNAs in B-cells from Ashkenazi Jewish centenarians and 70-year-old controls without a longevity history, we found that the majority of differentially expressed miRNAs were upregulated in centenarians and predicted to modulate the IIS pathway. Notably, decreased IIS activity was found in B cells from centenarians who harbored these upregulated miRNAs. miR-142-3p, the top upregulated miRNA, was verified to dampen the IIS pathway by targeting multiple genes including GNB2, AKT1S1, RHEB and FURIN . Overexpression of miR-142-3p improved the stress resistance under genotoxicity and induced the impairment of cell cycle progression in IMR90 cells. Furthermore, mice injected with a miR-142-3p mimic showed reduced IIS signaling and improved longevity-associated phenotypes including enhanced stress resistance, improved diet/aging-induced glucose intolerance, and longevity-associated change of metabolic profile. These data suggest that miR-142-3p is involved in human longevity through regulating IIS-mediated pro-longevity effects. This study provides strong support for the use of miR-142-3p as a novel therapeutic to promote longevity or prevent aging/aging-related diseases in human.

YTHDC2-mediated m6A mRNA modification of Id3 suppresses cisplatin resistance in non-small cell lung cancer.

Background: The methylation of adenosines at the N6 position (N6-methyladenosine; m6A) is one of the most conserved internal RNA modifications. m6A can modulate the expression of oncogenes or tumor suppressor genes, as well as m6A levels and the expression and activity of m6A enzymes, thus influencing tumor progression and therapeutic response. This study investigates the role of YTHDC2-mediated m6A messenger RNA (mRNA) modification of Id3 in controlling cisplatin resistance in non-small cell lung cancer (NSCLC). Methods: The expression of the m6A reader protein YTHDC2 was detected in an NSCLC cisplatin-resistant cell line (A549/DDP) using real-time fluorescence quantitative polymerase chain reaction (qPCR). YTHDC2 overexpression plasmids were constructed and transfected into A549/DDP and A549 cells respectively. We performed qPCR and western blot (WB) to detect changes in YTHDC2 and Id3 expression, and the effects of YTHDC2 overexpression on proliferation, apoptosis, invasion, and migration of drug-resistant cells were assessed by cell counting kit-8 (CCK-8), flow cytometry, and transwell and scratch assays. The m6A modification of Id3 by YTHDC2 was clarified by m6A-immunoprecipitation-PCR (m6A-IP-PCR) assay. Results: The CLIPdb online database predicted that YTHDC2 might bind to Id3. The results of qPCR showed that YTHDC2 was downregulated in the NSCLC cisplatin-resistant cell line A549/DDP compared to the cisplatin-sensitive cell line A549. Overexpression of YTHDC2 increased the expression of Id3, and the methylation inhibitor 3-deazaadenosine abrogated the regulatory effect of YTHDC2 on Id3. YTHDC2 overexpression significantly inhibited A549/DDP cell proliferation, migration, and invasion, and promoted apoptosis by synergistically promoting the effects of Id3. m6A-IP-PCR analysis revealed that YTHDC2 could inhibit the m6A level of Id3 mRNA. Conclusions: To regulate the activity of Id3, YTHDC2 requires modifications to m6A, which ultimately inhibit cisplatin resistance in NSCLC.

Graphene-Oxide-Grafted Natural Phosphate Support as a Low-Cost Ceramic Membrane for the Removal of Anionic Dyes from Simulated Textile Effluent.

A novel natural phosphate/graphene oxide (GO) composite membrane was successfully fabricated using two steps: (i) silane chemical grafting and (ii) dip-coating of a GO solution. First, the low-cost disk ceramic support used in this work was fabricated out of Moroccan natural phosphate, and its properties were thoroughly characterized. The optimized ceramic support was sintered at 1100 °C following a specific heat treatment based on thermogravimetric analysis (TGA) and differential thermal analysis (DTA); it exhibited a permeability of 953.33 L/h·m2·bar, a porosity of 24.55%, an average pore size of 2.45 µm and a flexural strength of 22.46 MPa. The morphology analysis using SEM showed that the GO layer was homogenously coated on the crack-free Moroccan phosphate support with a thickness of 2.8 µm. The Fourier transform infrared spectrometer (FT-IR) results showed that modification with silane could improve the interfacial adhesion between the GO membrane and the ceramic support. After coating with GO on the surface, the water permeability was reduced to 31.93 L/h·m2·bar (i.e., by a factor of 142). The prepared GO/ceramic composite membrane exhibited good efficiency in the rejection of a toxic azo dye Congo Red (CR) (95.2%) and for a simulated dye effluent (87.6%) under industrial conditions. The multi-cycle filtration tests showed that the rejection rate of CR dye remained almost the same for four cycles. Finally, the flux recovery was also studied. After 1 h of water cleaning, the permeate flux recovered, increased significantly, and then remained stable.

Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment.

INTRODUCTION: Viruses have been reported as inducers of tumorigenesis. Little studies have explored the impact of the gut virome on the progression of colorectal cancer. However, there is still a problem with the repeatability of viral signatures across multiple cohorts. OBJECTIVES: The present study aimed to reveal the repeatable gut vial signatures of colorectal cancer and adenoma patients and decipher the potential of viral markers in disease risk assessment for diagnosis. METHODS: 1,282 available fecal metagenomes from 9 published studies for colorectal cancer and adenoma were collected. A gut viral catalog was constructed via a reference-independent approach. Viral signatures were identified by cross-cohort meta-analysis and used to build predictive models based on machine learning algorithms. New fecal samples were collected to validate the generalization of predictive models. RESULTS: The gut viral composition of colorectal cancer patients was drastically altered compared with healthy, as evidenced by changes in some Siphoviridae and Myoviridae viruses and enrichment of Microviridae, whereas the virome variation in adenoma patients was relatively low. Cross-cohort meta-analysis identified 405 differential viruses for colorectal cancer, including several phages of Porphyromonas, Fusobacterium, and Hungatella that were enriched in patients and some control-enriched Ruminococcaceae phages. In 9 discovery cohorts, the optimal risk assessment model obtained an average cross-cohort area under the curve of 0.830 for discriminating colorectal cancer patients from controls. This model also showed consistently high accuracy in 2 independent validation cohorts (optimal area under the curve, 0.906). Gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal area under the curve of 0.772 for discriminating patients from controls. CONCLUSION: Our findings demonstrate the gut virome characteristics in colorectal cancer and adenoma and highlight gut virus-bacterial synergy in the progression of colorectal cancer. The gut viral signatures may be new targets for colorectal cancer treatment. In addition, high repeatability and predictive power of the prediction models suggest the potential of gut viral biomarkers in non-invasive diagnostic tests of colorectal cancer and adenoma.

Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats.

Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.

Polygonatum cyrtonema Hua Polysaccharides Protect BV2 Microglia Relief Oxidative Stress and Ferroptosis by Regulating NRF2/HO-1 Pathway.

Neuronal-regulated cell death (RCD) due to the accumulation of ROS within the central nervous system (CNS) is one of the crucial causes of central system diseases. Caspase-dependent apoptosis is the only form of RCD. As research progressed, several nonapoptotic cell death pathway RCDs were identified. Ferroptosis is a nonapoptotic RCD characterized by lipid peroxidation and plasma membrane damage. Polygonatum cyrtonema Hua. Polysaccharides (PCP) are an effective antioxidant. Based on this, the protective effect and mechanism of PCP against H2O2-induced microglial injury were investigated. Furthermore, the protective mechanism of PCP against ferroptosis in microglia was explored. Our results indicated that PCP could reduce oxidative stress-induced ROS accumulation by activating the NRF2/HO-1 signaling pathway, thus attenuating RCD in microglia. Subsequent studies have revealed that PCP alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. Therefore, we hypothesized that PCP exerts antioxidative and anti-ferroptosis effects by activating the expression of the NRF2/HO-1 pathway. This facilitates new ideas for clinically effective prevention and treatment of diseases due to accumulated reactive oxygen species in the CNS. Simultaneously, PCP has the development potential as a new drug candidate for treating CNS diseases.

Glycochenodeoxycholate Affects Iron Homeostasis via Up-Regulating Hepcidin Expression.

Increasing hepcidin expression is a vital factor in iron homeostasis imbalance among patients with chronic kidney disease (CKD). Recent studies have elucidated that abnormal serum steroid levels might cause the elevation of hepcidin. Glycochenodeoxycholate (GCDCA), a steroid, is significantly elevated in patients with CKD. However, the correlation between GCDCA and hepcidin has not been elucidated. Decreased serum iron levels and increased hepcidin levels were both detected in patients with CKD in this study. Additionally, the concentrations of GCDCA in nephropathy patients were found to be higher than those in healthy subjects. HepG2 cells were used to investigate the effect of GCDCA on hepcidin in vitro. The results showed that hepcidin expression increased by nearly two-fold against control under 200 µM GCDCA treatment. The phosphorylation of SMAD1/5/8 increased remarkably, while STAT3 and CREBH remained unchanged. GCDCA triggered the expression of farnesoid X receptor (FXR), followed with the transcription and expression of both BMP6 and ALK3 (upward regulators of SMAD1/5/8). Thus, GCDCA is a potential regulator for hepcidin, which possibly acts by triggering FXR and the BMP6/ALK3-SMAD signaling pathway. Furthermore, 40 C57/BL6 mice were treated with 100 mg/kg/d, 200 mg/kg/d, and 300 mg/kg/d GCDCA to investigate its effect on hepcidin in vivo. The serum level of hepcidin increased in mice treated with 200 mg/kg/d and 300 mg/kg/d GCDCA, while hemoglobin and serum iron levels decreased. Similarly, the FXR-mediated SMAD signaling pathway was also responsible for activating hepcidin in liver. Overall, it was concluded that GCDCA could induce the expression of hepcidin and reduce serum iron level, in which FXR activation-related SMAD signaling was the main target for GCDCA. Thus, abnormal GCDCA level indicates a potential risk of iron homeostasis imbalance.

A catalog of 48,425 nonredundant viruses from oral metagenomes expands the horizon of the human oral virome.

The human oral cavity is a hotspot of numerous, mostly unexplored, viruses that are important for maintaining oral health and microbiome homeostasis. Here, we analyzed 2,792 publicly available oral metagenomes and proposed the Oral Virus Database (OVD) comprising 48,425 nonredundant viral genomes (≥5 kbp). The OVD catalog substantially expanded the known phylogenetic diversity and host specificity of oral viruses, allowing for enhanced delineation of some underrepresented groups such as the predicted Saccharibacteria phages and jumbo viruses. Comparisons of the viral diversity and abundance of different oral cavity habitats suggested strong niche specialization of viromes within individuals. The virome variations in relation to host geography and properties were further uncovered, especially the age-dependent viral compositional signatures in saliva. Overall, the viral genome catalog describes the architecture and variability of the human oral virome, while offering new resources and insights for current and future studies.

A2DS2 Score Combined With Clinical and Neuroimaging Factors Better Predicts Stroke-Associated Pneumonia in Hyperacute Cerebral Infarction.

OBJECTIVE: To investigate the predictors of stroke-associated pneumonia (SAP) and poor functional outcome in patients with hyperacute cerebral infarction (HCI) by combining clinical factors, laboratory tests and neuroimaging features. METHODS: We included 205 patients with HCI from November 2018 to December 2019. The diagnostic criterion for SAP was occurrence within 7 days of the onset of stroke. Poor outcome was defined as a functional outcome based on a 3-months MRS score >3. The relationship of demographic, laboratory and neuroimaging variables with SAP and poor outcome was investigated using univariate and multivariate analyses. RESULTS: Fifty seven (27.8%) patients were diagnosed with SAP and 40 (19.5%) developed poor outcomes. A2DS2 score (OR = 1.284; 95% CI: 1.048-1.574; P = 0.016), previous stroke (OR = 2.630; 95% CI: 1.122-6.163; P = 0.026), consciousness (OR = 2.945; 95% CI: 1.514-5.729; P < 0.001), brain atrophy (OR = 1.427; 95% CI: 1.040-1.959; P = 0.028), and core infarct volume (OR = 1.715; 95% CI: 1.163-2.528; P = 0.006) were independently associated with the occurrence of SAP. Therefore, we combined these variables into a new SAP prediction model with the C-statistic of 0.84 (95% CI: 0.78-0.90). Fasting plasma glucose (OR = 1.404; 95% CI: 1.202-1.640; P < 0.001), NIHSS score (OR = 1.088; 95% CI: 1.010-1.172; P = 0.026), previous stroke (OR = 4.333; 95% CI: 1.645-11.418; P = 0.003), SAP (OR = 3.420; 95% CI: 1.332-8.787; P = 0.011), basal ganglia-dilated perivascular spaces (BG-dPVS) (OR = 2.124; 95% CI: 1.313-3.436; P = 0.002), and core infarct volume (OR = 1.680; 95% CI: 1.166-2.420; P = 0.005) were independently associated with poor outcome. The C-statistic of the outcome model was 0.87 (95% CI: 0.81-0.94). Furthermore, the SAP model significantly improved discrimination and net benefit more than the A2DS2 scale, with a C-statistic of 0.76 (95% CI: 0.69-0.83). CONCLUSIONS: After the addition of neuroimaging features, the models exhibit good differentiation and calibration for the prediction of the occurrence of SAP and the development of poor outcomes in HCI patients. The SAP model could better predict the SAP, representing a helpful and valid tool to obtain a net benefit compared with the A2DS2 scale.