ABSTRACT
Bacterial small molecule metabolites such as adenosine-diphosphate-d-glycero-ß-d-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)- and uridine-diphosphate (UDP)-heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)-dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the ß-d-manno-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
Subject(s)
Heptoses , Nucleotidyltransferases , Pathogen-Associated Molecular Pattern Molecules , Animals , Humans , Mice , Amino Acid Motifs , Archaea/enzymology , Bacteria/enzymology , Bacteria/metabolism , Heptoses/biosynthesis , Heptoses/immunology , Immunity, Innate , Nucleotidyltransferases/chemistry , Nucleotidyltransferases/classification , Nucleotidyltransferases/genetics , Pathogen-Associated Molecular Pattern Molecules/immunology , Pathogen-Associated Molecular Pattern Molecules/metabolism , Protein Kinases/metabolism , Viruses/enzymologyABSTRACT
It has been suggested that dietary intake of lipids and fatty acids may influence cognitive function, however, the effect of lard intake during pregnancy and postpartum periods on cognitive function of mother remains to be elucidated. We investigated the effect and mechanism of consuming soybean oil (SO), the mixed oil of lard and soybean oil at the ratio of 1:1 (LS) and lard oil (LO) during the pregnancy and postpartum periods on cognitive function of the maternal mice. All pregnant C57BL/6JNifdc mice were fed with soybean oil diet during day 0-10 (the day when vaginal plugs appeared in female mice was recorded as day 0), and then randomly assigned to SO, LS and LO groups (n = 10) from day 11 to day 44. The time in center zone and the number of times to enter in center zone were significantly higher in the SO group than in the LO group detected by the open-field test. The levels of neuroglial cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex and pyroptosis related proteins in brain of the LO group were significantly higher than those in the SO group. RNA-sequencing results showed that the calcium signaling pathway related genes in brain, including Adcy8, Ntsr1, Trhr, Oxtr, Htr5b and Camk2d levels significantly higher in the LO group than in the SO group. Lipidomic analysis indicated that PG 18:2_18:2, PG 20:5_22:6, and CL 12:0_16:0_22:3_22:5 of glycerophospholipid metabolism in brain significantly connected with Htr5b of calcium signaling pathway. In conclusion, the intake of lard during the pregnancy and postpartum periods is detrimental to the cognitive function of maternal mice, which probably due to changes in the composition of fatty acid in the brain, thereby activating neuroinflammation via calcium signaling pathway in brain.
ABSTRACT
The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.
Subject(s)
Congenital Microtia , Electrocardiography , Humans , Congenital Microtia/epidemiology , Male , Female , Retrospective Studies , Adolescent , Child , Adult , Young Adult , Incidence , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/physiopathology , China/epidemiologyABSTRACT
BACKGROUND: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen. METHODS: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years. RESULTS: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT. CONCLUSION: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.
Subject(s)
Transgender Persons , Adult , Female , Humans , Male , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Asian People , Blood Glucose/metabolism , Body Fat Distribution , Body Mass Index , Case-Control Studies , China/epidemiology , East Asian People , Estrogens/blood , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/metabolism , Obesity/blood , Retrospective Studies , Sex Reassignment Procedures , Transsexualism/drug therapy , Transsexualism/bloodABSTRACT
Antineutrophil cytoplasmic antibody vasculitis-associated interstitial lung disease (AAV-ILD) is a potentially life-threatening disease. However, very little research has been done on the condition's mortality risk. Hence, our objective is to find out the factors influencing the prognosis of AAV-ILD and employ these findings to create a nomogram model. Patients with AAV-ILD who received treatment at the First Affiliated Hospital of Zhengzhou University during the period from March 1, 2011, to April 1, 2022 were selected for this research. The development of nomogram entailed a synergistic integration of univariate, Lasso, and multivariate Cox regression analyses. Internal validation ensued through bootstrap techniques involving 1000 re-sampling iterations. Discrimination and calibration were assessed utilizing Harrell's C-index, receiver operating characteristic (ROC) curve, and calibration curve. Model performance was evaluated through integrated discrimination improvement (IDI), net reclassification improvement (NRI), and likelihood ratio test. The net benefit of the model was evaluated using decision curve analysis (DCA). A cohort comprising 192 patients was enrolled for analysis. Throughout observation period, 32.29% of the population died. Key factors such as cardiac involvement, albumin, smoking history, and age displayed substantial prognostic relevance in AAV-ILD. These factors were incorporated to craft a predictive nomogram. Impressively, the model exhibited robust performance, boasting a Harrell's C index of 0.826 and an AUC of 0.940 (95% CI 0.904-0.976). The calibration curves depicted a high degree of harmony between predicted outcomes and actual observations. Significantly enhancing discriminative ability compared to the ILD-GAP model, the nomogram was validated through the IDI, NRI, and likelihood ratio test. DCA underscored the superior predictive value of the predictive model over the ILD-GAP model. The internal validation further affirmed this efficacy, with a mean Harrell's C-index of 0.815 for the predictive model. The nomogram model can be employed to predict the prognosis of patients with AAV-ILD. Moreover, the model performance is satisfactory. In the future, external datasets could be utilized for external validation.
Subject(s)
Anilides , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Lung Diseases, Interstitial , Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Nomograms , Lung Diseases, Interstitial/diagnosis , China/epidemiologyABSTRACT
BACKGROUND: Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. METHODS: A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. RESULTS: The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). CONCLUSION: ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis.
Subject(s)
Deglutition Disorders , Delirium , Ischemic Stroke , Adult , Humans , Female , Aged , Male , Cohort Studies , Retrospective Studies , Critical Illness , Intensive Care UnitsABSTRACT
Osteoporosis has become one of the major diseases that threaten the health of middle-aged and elderly people, and with the growth of an ageing population, more and more people are affected by osteoporosis these days. In recent years, intestinal flora has been found to affect the host immune system, and an overactive immune system is closely related to bone resorption. Probiotics can effectively improve bone density and strength, reduce bone loss, and improve osteoporosis, but their mechanism of action and relationship with intestinal microbiota are still unclear. In this study, two strains of Bifidobacterium (Bifidobacterium bifidum FL228.1 and Bifidobacterium animalis subsp. Lactis F1-7) that can alleviate intestinal inflammation were screened based on previous experiments. Through the construction of an ovariectomized mouse model, the improvement of osteoporosis by Bifidobacterium was detected, and the influence of Bifidobacterium on intestinal immunity was explored. The results show that Bifidobacterium treatment significantly improved bone mineral density (BMD), bone volume/total volume ratio (BV/TV), and trabecular number (Tb·N), and effectively suppressed bone loss. Furthermore, Bifidobacterium treatment could inhibit the expression of inflammatory cytokines in the gut, alleviate gut inflammation, and thus suppress excessive osteoclast generation. Its mechanism of action includes factors that protect the mucosal barrier, including occludin, ZO-1, claudin-2, and MUC2, and the reduction of pro-inflammatory M1 macrophages. B. bifidum FL228.1 increased the abundance of beneficial bacteria in the colon, including Lactobacillus and Colidextribacter. B. animalis F1-7 increased the abundance of Bifidobacterium and decreased the abundance of Desulfovibrio and Ruminococcus in the colon. These research findings expand our understanding of the gut-bone axis and provide new guidance for the development of probiotic-based therapies for osteoporosis in the future.
Subject(s)
Bifidobacterium animalis , Osteoporosis , Probiotics , Humans , Mice , Animals , Aged , Middle Aged , Bifidobacterium/metabolism , Cytokines/metabolism , Inflammation , Bifidobacterium animalis/metabolism , Osteoporosis/therapy , EstrogensABSTRACT
Bone morphogenetic protein (BMP) signaling plays a vital role in differentiation, organogenesis, and various cell processes. As a member of TGF-ß superfamily, the BMP initiation usually accompanies crosstalk with other signaling pathways and simultaneously activates some of them. It is quite challenging to solely initiate an individual pathway. In this study, an opsin-free optical method to specifically activate BMP receptors (BMPR) and subsequent pSmad1/5/8 cascades by a single-time scan of a tightly-focused femtosecond laser in the near infrared range is reported. Via transient two-photon excitation to intrinsic local flavins near the cell membrane, the photoactivation drives conformational changes of preformed BMPR complexes to enable their bonding and phosphorylation of the GS domain in BMPR-I by BMPR-II. The pSmad1/5/8 signaling is initiated by this method, while p38 and pSmad2 are rarely perturbed. Based on a microscopic system, primary adipose-derived stem cells in an area of 420 â × 420 µm2 are photoactivated by a single-time laser scanning for 1.5 s and exhibit pSmad1/5/8 upregulation and osteoblastic differentiation after 21 days. Hence, an opsin-free, specific, and noninvasive optical method to initiate BMP signaling, easily accomplished by a two-photon microscope system is reported.
Subject(s)
Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins , Bone Morphogenetic Protein Receptors , Bone Morphogenetic Proteins/metabolism , Opsins , Transforming Growth Factor beta/metabolismABSTRACT
Long non-coding RNAs (lncRNAs) play essential roles in a variety of biological processes. It has been recently reported that lncRNAs can regulate mRNA expression by binding to microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs). However, the involvement of this regulatory mechanism during cold acclimation in fish remains unclear. In this study, we constructed a ceRNA network mediated by lncRNAs in cold-acclimated zebrafish ZF4 cells through bioinformatic analysis of the mRNA, miRNA, and lncRNA profiles obtained from ZF4 cells cultured at 18 °C for 30 days. A previously uncharacterized lncRNA, MSTRG3207, was selected for further analysis. MSTRG3207 was upregulated and dre-miR-736 was downregulated during cold acclimation. MSTRG3207 was cloned by rapid amplification of cDNA ends (RACE) and functionally characterized. The binding of MSTRG3207 to dre-miR-736 was validated by dual-luciferase reporter assay. Under cold acclimation, MSTRG3207 promoted apoptosis by sponging dre-miR-736 and upregulating bbc3 and LOC101885512, two apoptotic genes targeted by dre-miR-736. Taken together, our findings indicate that MSTRG3207 upregulation promotes apoptosis by sponging dre-miR-736 during cold acclimation in fish.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Animals , Zebrafish/genetics , Zebrafish/metabolism , RNA, Long Noncoding/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Apoptosis/genetics , RNA, Messenger/genetics , Acclimatization/geneticsABSTRACT
SCOPE: People suffer from constipation caused by many factors, including constipation (Opioid-Induced Constipation, OIC) during analgesic treatment. Microorganisms may be a potent solution to this problem, but the mechanism is still unclear. METHODS AND RESULTS: Based on models in vivo and in vitro, the potential mechanism involving Bifidobacterium animalis F1-7 (B. animalis F1-7), screened in the previous studies, is explored through non-targeted metabonomics, electrophysiological experiment and molecular level docking. The results showed that B. animalis F1-7 effectively alleviates OIC and promotes the expression of chromogranin A (CGA) and 5-hydroxytryptamine (5-HT). The metabolite 13,14-dihydro-15-keto-PGE2 related to B. animalis F1-7 is found, which has a potential improvement effect on OIC at 20 mg kg BW-1 in vivo. At 30 ng mL-1 it effectively stimulates secretion of CGA/5-HT (408.95 ± 1.18 ng mL-1 ) by PC-12 cells and changes the membrane potential potassium ion current without affecting the sodium ion current in vitro. It upregulates the target of free fatty acid receptor-4 protein(FFAR4/ß-actin, 0.81 ± 0.02). CONCLUSION: The results demonstrate that metabolite 13,14-dihydro-15-keto-PGE2 participated in B. animalis F1-7 to alleviate OIC via the 5-HT pathway.
Subject(s)
Bifidobacterium animalis , Dinoprostone/analogs & derivatives , Opioid-Induced Constipation , Humans , Serotonin , Analgesics, Opioid , Constipation/chemically induced , Constipation/drug therapyABSTRACT
Ergothioneine is a naturally occurring amino acid and thiol antioxidant found in high amounts in mushrooms and fermented foods. Humans and animals acquire ergothioneine from the diet through the pH-dependent activity of a membrane transporter, the large solute carrier 22A member 4 (SLC22A4), expressed on the apical membrane of the small intestine. The SLC22A4 transporter also functions in the renal reabsorption of ergothioneine in the kidney, with avid absorption and retention of ergothioneine from the diet observed in both animals and humans. Ergothioneine is capable of scavenging a diverse range of reactive oxygen and nitrogen species, has metal chelation properties, and is predicted to directly regulate nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Although not lethal, the genetic knockout of the SLC22A4 gene in multiple organisms increases susceptibility to oxidative stress, damage and inflammation; in agreement with a large body of preclinical data suggesting the physiological function of ergothioneine is as a cellular antioxidant and cytoprotectant agent. In humans, blood levels of ergothioneine decline after the age of 60 years, and lower levels of ergothioneine are associated with more rapid cognitive decline. Conversely, high plasma ergothioneine levels have been associated with significantly reduced cardiovascular mortality and overall mortality risks. In this horizon's manuscript, we review evidence suggesting critical roles for dietary ergothioneine in healthy ageing and the prevention of cardiometabolic disease. We comment on some of the outstanding research questions in the field and consider the question of whether or not ergothioneine should be considered a conditionally essential micronutrient.
Subject(s)
Ergothioneine , Healthy Aging , Symporters , Humans , Animals , Middle Aged , Ergothioneine/metabolism , Antioxidants/metabolism , Organic Cation Transport Proteins/genetics , Organic Cation Transport Proteins/metabolism , Symporters/genetics , DietABSTRACT
BACKGROUND: Diabetes mellitus erectile dysfunction (DMED) is one of common complications of diabetes. We aimed to investigate the potential efficacy of methyl protodioscin (MPD) in DMED and explored the underlying mechanism. METHODS: Diabetic mice were induced by streptozotocin, while vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were stimulated with high glucose. MPD was administrated in vitro and in vivo to verify its efficacy on DMED. The interaction of c-Myc and AKAP12 was determined by luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS: c-Myc and AKAP12 were upregulated in penile tissues in DMED mice. In high glucose-stimulated VSMCs or VECs, MPD intervention enhanced cell viability, inhibited apoptosis, decreased c-Myc and AKAP12, as well as elevated p-eNOS Ser1177. MPD-induced apoptosis inhibition, AKAP12 reduction and p-eNOSSer1177 elevation were reversed by AKAP12 overexpression. c-Myc functioned as a positive regulator of AKAP12. Overexpression of c-Myc reversed the effects induced by MPD in vitro, which was neutralized by AKAP12 silencing. MPD ameliorated erectile function in diabetic mice via inhibiting AKAP12. CONCLUSIONS: MPD improved erectile dysfunction in streptozotocin-caused diabetic mice by regulating c-Myc/AKAP12 pathway, indicating that MPD could be developed as a promising natural agent for the treatment of DMED.
Subject(s)
Diabetes Mellitus, Experimental , Erectile Dysfunction , Male , Rats , Humans , Mice , Animals , Erectile Dysfunction/etiology , Erectile Dysfunction/genetics , Diabetes Mellitus, Experimental/metabolism , Down-Regulation , Endothelial Cells/metabolism , Streptozocin , Rats, Sprague-Dawley , Glucose , Cell Cycle Proteins/metabolism , A Kinase Anchor Proteins/genetics , A Kinase Anchor Proteins/metabolismABSTRACT
The Mg alloy vascular clip has biodegradability and good biocompatibility, which can improve the convenience and safety of clinical application. However, the Mg alloy vascular clip also has some disadvantages, such as an unreasonable structure design and a degradation rate which is too fast. In this study, the process of clamping blood vessels with a biodegradable Mg alloy (Mg-Zn-Nd-Zr and Mg-Zn-Nd) general V-type vascular clip was simulated by finite element simulation software (Abaqus). A new type of vascular clip, the P-type vascular clip, was analyzed and investigated through simulation. The differences between Mg alloy vascular clips of V-type and P-type were analyzed by finite element simulation. In addition, the effects of Zr element on the mechanical properties and corrosion resistance of P-type vascular clips were also investigated to improve the mechanical stability. The results show that during the V-type vascular clip closure of Mg-Zn-Nd-Zr alloy, this clip has some problems, such as uneven distribution of blood vessel stress, crevices in blood vessels and stress concentration. The improved P-type vascular clip has uniform closure, and there is no gap in the blood vessel, which can effectively avoid stress concentration. The improved P-type vascular clip is well closed and can effectively avoid stress concentration. The corrosion resistance of the Mg-Zn-Nd-Zr alloy P-type clip was better than that of the Mg-Zn-Nd alloy P-type clip (degradation rate of 2.02 mm/y and 2.61 mm/y on the 7th day, respectively). Mg-Zn-Nd-Zr alloy The P-type vascular clip remained closed even on the 7th day, which could meet the requirements of clinical application.
ABSTRACT
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder worldwide. According to several previous studies, the treatment of patients with NAFLD using medicinal and food-homologous substances has consistent effects on the levels of blood lipids and blood glucose and liver function. OBJECTIVE: This systematic review was conducted to investigate the impact of medicinal and food homologous substances on blood lipid and glucose levels as well as liver function in patients with NAFLD. METHODS: A thorough search was conducted in eight databases, including China Science and Technology Journal Database (VIP), Chinese National Knowledge Infrastructure(CNKI), China Biomedical Literature Database (SinoMed), Wanfang Database, PubMed, Cochrane Library, Web of Science and Embase, for articles published from database inception until June 24, 2023. The methodological quality of the included studies was evaluated utilizing Cochrane Randomized Trial Risk Bias Tool, Edition 2 and GRADE methodology for assessment. RESULTS: A total of 13 randomized controlled trials, involving 829 patients with NAFLD, were included in the analysis, these studies included a total of 9 medicinal and food homologous substances. In the 13 studies, hawthorn (2), sea buckthorn (1), ginger (2), turmeric (4) (1 with chicory seeds), cinnamon (1), cardamom (1), purslane (1) and saffron (1) were included. The results of the included studies showed that medicinal and food homologous substances could improve high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FBG) and liver enzyme levels in patients with NAFLD to a certain extent, but the effect of turmeric on TC, liver enzyme levels is controversial. CONCLUSION: In patients with NAFLD, dietary intervention using medicinal and food homologous substances can ameliorate blood lipid and blood glucose levels and liver enzymes to some extent. In clinical work, medicinal and food homologous substances can be used to provide patients with NAFLD with a safe and effective dietary plan to help prevent and treat disease onset and progression.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Blood Glucose , Randomized Controlled Trials as Topic , Lipids , Seeds , Cholesterol, HDLABSTRACT
BACKGROUND: Interprofessional education (IPE) is crucial for effective clinical practice but remains challenging to be implemented. The IPE activity using virtual simulation (VS) may potentially solve the time and space challenges of in-person interprofessional simulations. Using shared VS resources may increase the popularity of virtual teaching in conditions of limited resources. OBJECTIVES: Using shared resources, this study aimed to design and implement a VS-based IPE activity for undergraduate healthcare students, exploring the effects. DESIGN: A quasi-experimental design was used, with assessments conducted before and after the activity. SETTINGS: One university and its affiliated hospitals in south China. PARTICIPANTS: Forty-two undergraduate students majoring in nursing, clinical medicine, and rehabilitation therapy participated in this study. METHODS: A test composed of ten questions was used to evaluate knowledge of rehabilitation. The Chinese version of Critical Thinking Disposition Inventory (CTDI-CV) and the Chinese version of Assessment of Interprofessional Team Collaboration in Student Learning Scale (AITCS-II (Student)-CV) were used to evaluate critical thinking and interprofessional collaboration. Participants' opinions about the activity were assessed, considering satisfaction, perceived effectiveness, the ease of shared VS platform use, and suggestions about the activity. RESULTS: Significant improvements were shown in pre- and post-test total scores on knowledge of rehabilitation, mean scores for overall critical thinking disposition, and mean item scores on overall interprofessional team collaboration. CONCLUSIONS: The study provides a reference for designing and implementing VS-based IPE but the effects of this innovative pedagogy on students' rehabilitation knowledge, critical thinking, and interprofessional collaboration ability still need to be further confirmed. Most of the students gave positive feedback on the activity. Technical issues should be addressed to decrease their impacts on the VS practice experience.
Subject(s)
Rehabilitation Nursing , Students, Health Occupations , Humans , Interprofessional Relations , Interprofessional Education , Computer Simulation , Attitude of Health PersonnelABSTRACT
Hypoxia induces profound modifications in the gene expression program of eukaryotic cells due to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One significant consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. Drosophila melanogaster is strongly resistant to oxygen fluctuations; however, the mechanisms allowing specific mRNA to be translated into hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated into hypoxia by a mechanism involving a CA-rich motif present in its 3' untranslated region. Furthermore, we identified the cap-binding protein eIF4EHP as a main factor involved in 3'UTR-dependent translation under hypoxia. In accordance with this observation, we show that eIF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to LDH production and Drosophila adaptation to oxygen variations.
Subject(s)
Drosophila melanogaster , Hypoxia , Animals , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Hypoxia/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Drosophila/genetics , Drosophila/metabolism , Oxygen/metabolism , 3' Untranslated Regions , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Protein BiosynthesisABSTRACT
The complex microflora of traditional fermented milk is crucial to milk coagulation mainly through acid and protease production; however, it is still unclear which microbes and proteases significantly influence the texture of Ayran, a Kazakh artisanal fermented milk in Xinjiang, China. In this study, fifty-nine samples of Ayran were collected and investigated on texture properties. Finally, six Ayran samples with different texture features were screened out, and the taxonomic and functional attributes of their microbiota were characterized by metagenomics. The results showed that the hardness of the fermented milk in Yili Kazakh Autonomous Prefecture was significantly higher than that in other pasture areas. Lactobacillus and Lactococcus were the core genera that affected the coagulation quality of milk. Furthermore, we found that the proline iminopeptidase pip (EC 3.4.11.5) gene of Lactobacillus helveticus and Limosilactobacillus fermentum and the dipeptidase E pepE (EC 3.4.13.21) gene of Lactococcus lactis were most associated with the coagulation quality of fermented milk. Furthermore, positive correlations were observed among the hardness of fermented milk, the activity of the proteases, and the corresponding functional gene expressions.
Subject(s)
Cultured Milk Products , Lactobacillus helveticus , Cultured Milk Products/microbiology , Metagenomics , Bacteria , Peptide Hydrolases/geneticsABSTRACT
SCOPE: Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. METHODS AND RESULTS: In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. CONCLUSION: The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.
Subject(s)
Food Hypersensitivity , Probiotics , Animals , Mice , Toll-Like Receptor 4/metabolism , Leukocytes, Mononuclear , Th1 Cells , Allergens , Th2 Cells , Interferon-gamma/metabolism , Probiotics/pharmacology , Signal Transduction , Mice, Inbred BALB C , Ovalbumin , Cytokines/metabolismABSTRACT
Osteoarthritis (OA) is the most common joint disease primarily characterized by cartilage degeneration. Milk-derived extracellular vesicles (mEVs) were reported to inhibit catabolic and inflammatory processes in the cartilage of OA patients. However, the current therapies target the advanced symptoms of OA, and it is significant to develop a novel strategy to inhibit the processes driving OA pathology. In this study, we investigated the therapeutic potential of mEVs in alleviating OA in vivo. The results revealed that mEVs ameliorated cartilage degeneration by increasing hyaline cartilage thickness, decreasing histological Osteoarthritis Research Society International (OARSI) scores, enhancing matrix synthesis, and reducing the expression of cartilage destructive enzymes in the destabilization of medial meniscus (DMM) mice. In addition, the disturbed gut microbiota in DMM mice was partially improved upon treatment with mEVs. It was observed that the pro-inflammatory bacteria (Proteobacteria) were reduced and the potential beneficial bacteria (Firmicutes, Ruminococcaceae, Akkermansiaceae) were increased. mEVs could alleviate the progression of OA by restoring matrix homeostasis and reshaping the gut microbiota. These findings suggested that mEVs might be a potential therapeutic dietary supplement for the treatment of OA.
Subject(s)
Cartilage, Articular , Extracellular Vesicles , Gastrointestinal Microbiome , Osteoarthritis , Mice , Animals , Menisci, Tibial/metabolism , Menisci, Tibial/pathology , Chondrocytes/metabolism , Milk/metabolism , Mice, Inbred C57BL , Osteoarthritis/drug therapy , Extracellular Vesicles/metabolism , Administration, Oral , Cartilage, Articular/pathology , Disease Models, AnimalABSTRACT
Acidic postconditioning by transient CO2 inhalation applied within minutes after reperfusion has neuroprotective effects in the acute phase of stroke. However, the effects of delayed chronic acidic postconditioning (DCAPC) initiated during the subacute phase of stroke or other acute brain injuries are unknown. Mice received daily DCAPC by inhaling 5%/10%/20% CO2 for various durations (three cycles of 10- or 20-min CO2 inhalation/10-min break) at days 3-7, 7-21, or 3-21 after photothrombotic stroke. Grid-walk, cylinder, and gait tests were used to assess motor function. DCAPC with all CO2 concentrations significantly promoted motor functional recovery, even when DCAPC was delayed for 3-7 days. DCAPC enhanced the puncta density of GAP-43 (a marker of axon growth and regeneration) and synaptophysin (a marker of synaptogenesis) and reduced the amoeboid microglia number, glial scar thickness and mRNA expression of CD16 and CD32 (markers of proinflammatory M1 microglia) compared with those of the stroke group. Cerebral blood flow (CBF) increased in response to DCAPC. Furthermore, the mRNA expression of TDAG8 (a proton-activated G-protein-coupled receptor) was increased during the subacute phase of stroke, while DCAPC effects were blocked by systemic knockout of TDAG8, except for those on CBF. DCAPC reproduced the benefits by re-expressing TDAG8 in the peri-infarct cortex of TDAG8-/- mice infected with HBAAV2/9-CMV-TDAG8-3flag-ZsGreen. Taken together, we first showed that DCAPC promoted functional recovery and brain tissue repair after stroke with a wide therapeutic time window of at least 7 days after stroke. Brain-derived TDAG8 is a direct target of DCAPC that induces neuroreparative effects.