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1.
The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease.
Wu, Q, Luo, Y, Lu, H, Xie, T, Hu, Z, Chu, Z, Luo, F
Foods (Basel, Switzerland). 2024;(6)
Abstract
Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, and it is a multifactorial disease of the intestinal mucosa. Oxidative stress damage and inflammation are major risk factors for IBD. Vitamin E has powerful antioxidant and anti-inflammatory effects. Our previous work and other investigations have shown that vitamin E has a positive effect on the prevention and treatment of IBD. In this paper, the source and structure of vitamin E and the potential mechanism of vitamin E's role in IBD were summarized, and we also analyzed the status of vitamin E deficiency in patients with IBD and the effect of vitamin E supplementation on IBD. The potential mechanisms by which vitamin E plays a role in the prevention and treatment of IBD include improvement of oxidative damage, enhancement of immunity, maintenance of intestinal barrier integrity, and suppression of inflammatory cytokines, modulating the gut microbiota and other relevant factors. The review will improve our understanding of the complex mechanism by which vitamin E inhibits IBD, and it also provides references for doctors in clinical practice and researchers in this field.
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2.
Associations between Life's Essential 8 and abdominal aortic calcification among US Adults: a cross-sectional study.
Liu, Q, Xiang, H, Chen, S, Ouyang, J, Liu, H, Zhang, J, Chai, Y, Gao, P, Zhang, X, Fan, J, et al
BMC public health. 2024;(1):1090
Abstract
BACKGROUND Cardiovascular health (CVH) and abdominal aortic calcification (AAC) are closely linked to cardiovascular disease (CVD) and related mortality. However, the relationship between CVH metrics via Life's Essential 8 (LE8) and AAC remains unexplored. METHODS The study analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) cohort, which included adults aged 40 or above. The research used the LE8 algorithm to evaluate CVH. Semi-quantitative AAC-24 scoring techniques were employed to assess AAC, categorized into no calcification, mild to moderate calcification, and severe calcification. RESULTS The primary analysis involved 2,478 participants. Following adjustments for multiple factors, the LE8 score exhibited a significant association with ACC risk (Mild-moderate ACC: 0.87, 95% CI: 0.81,0.93; Severe ACC: 0.77, 95% CI: 0.69,0.87, all P < 0.001), indicating an almost linear dose-response relationship. Compared to the low CVH group, the moderate CVH group showed lower odds ratios (OR) for mild-moderate and severe calcification (OR = 0.78, 95% CI: 0.61-0.99, P = 0.041; OR = 0.68, 95% CI: 0.46-0.99, P = 0.047, respectively). Moreover, the high CVH group demonstrated even lower ORs for mild-moderate and severe calcification (OR = 0.46, 95% CI: 0.31, 0.69, P < 0.001; OR = 0.29, 95% CI: 0.14, 0.59, P = 0.001, respectively). Interactions were found between chronic kidney disease (CKD) condition, history of CVD, marital status and CVH metrics to ACC. Participants without CKD exhibited a more pronounced negative association between the CVH metric and both mild-moderate and severe ACC. Those lacking a history of CVD, and never married/widowed/divorced/separated showed a stronger negative association between the CVH metric and severe ACC. CONCLUSIONS The novel CVH metrics demonstrated an inverse correlation with the risk of AAC. These findings suggest that embracing improved CVH levels may assist in alleviating the burden of ACC.
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3.
Magnetic two-dimensional nanocomposites for multimodal antitumor therapy: a recent review.
Yuan, Y, Chen, B, Song, L, An, X, Zhang, Q, Lu, H, Li, CM, Guo, C
Journal of materials chemistry. B. 2024;(6):1404-1428
Abstract
Magnetic two-dimensional nanocomposites (M2D NCs) that synergistically combine magnetic nanomedicine and 2D nanomaterials have emerged in multimodal antitumor therapy, attracting great interest in materials science and biomedical engineering. This review provides a summary of the recent advances of M2D NCs and their multimodal antitumor applications. We first introduce the design and fabrication of M2D NCs, followed by discussing new types of M2D NCs that have been recently reported. Then, a detailed analysis and discussions about the different types of M2D NCs are presented based on the structural categories of 2D NMs, including 2D graphene, transition metal dichalcogenides (TMDs), transition metal carbides/nitrides/carbonitrides (MXenes), black phosphorus (BP), layered double hydroxides (LDHs), metal organic frameworks (MOFs), covalent organic frameworks (COFs) and other 2D nanomaterials. In particular, we focus on the synthesis strategies, magnetic or optical responsive performance, and the versatile antitumor applications, which include magnetic hyperthermia therapy (MHT), photothermal therapy (PTT), photodynamic therapy (PDT), drug delivery, immunotherapy and multimodal imaging. We conclude the review by proposing future developments with an emphasis on the mass production and biodegradation mechanism of the M2D NCs. This work is expected to provide a comprehensive overview to researchers and engineers who are interested in such a research field and promote the clinical translation of M2D NCs in practical applications.
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4.
Association of the triglyceride-glucose index with all-cause and cardiovascular mortality in patients with cardiometabolic syndrome: a national cohort study.
Liu, Q, Zhang, Y, Chen, S, Xiang, H, Ouyang, J, Liu, H, Zhang, J, Chai, Y, Zhan, Z, Gao, P, et al
Cardiovascular diabetology. 2024;(1):80
Abstract
OBJECTIVE This study aimed to evaluate the association of triglyceride-glucose (TyG) index with all-cause and cardiovascular mortality risk among patients with cardiometabolic syndrome (CMS). METHODS We performed a cohort study of 5754 individuals with CMS from the 2001-2018 National Health and Nutrition Examination Survey. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models assessed the associations between TyG index and mortality . Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS Over a median follow-up of 107 months, 1201 all-cause deaths occurred, including 398 cardiovascular disease-related deaths. The multivariate Cox proportional hazards regression model showed a positive association between the TyG index and all-cause and cardiovascular mortality. Each one-unit increase in the TyG index was associated with a 16% risk increase in all-cause mortality (HR: 1.16, 95% CI 1.03, 1.31, P = 0.017) and a 39% risk increase in cardiovascular mortality (HR: 1.39, 95% CI 1.14, 1.71, P = 0.001) after adjusting for confounders. The restricted cubic splines revealed a U-shaped association between the TyG index and all-cause (P for nonlinear < 0.001) and cardiovascular mortality (P for nonlinear = 0.044), identifying threshold values (all-cause mortality: 9.104; cardiovascular mortality: 8.758). A TyG index below these thresholds displayed a negative association with all-cause mortality (HR: 0.58, 95% CI 0.38, 0.90, P = 0.015) but not with cardiovascular mortality (HR: 0.39, 95% CI 0.12, 1.27, P = 0.119). Conversely, a TyG index exceeding these thresholds was positively associated with all-cause and cardiovascular mortality (HR: 1.35, 95% CI 1.17, 1.55, P < 0.001; HR: 1.54, 95% CI 1.25, 1.90, P < 0.001, respectively). Notably, a higher TyG index (≥ threshold values) was significantly associated with increased mortality only among individuals aged under 55 compared to those with a lower TyG index (< threshold values). CONCLUSIONS The TyG index demonstrated a U-shaped correlation with all-cause and cardiovascular mortality in individuals with CMS. The thresholds of 9.104 and 8.758 for all-cause and cardiovascular mortality, respectively, may be used as intervention targets to reduce the risk of premature death and cardiovascular disease.
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5.
Fucoidan-based antibody-free magnetic nanoparticle for on-site detection of waterborne SARS-CoV-2.
Zhu, J, Lu, H, Lin, Q, Zhang, T, Chen, G, Zhou, Y, Sui, G
The Science of the total environment. 2024;:168619
Abstract
The portable and sensitive point-of-care-test (POCT) method is in urgent need to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for ensuring public health and safety. However, detection of trace number of pathogens in real water sample from the environment still faces challenges, because complex environment disruptors can rapidly degrade targets. Herein, magnetic beads coated with fucoidan and polydopamine (Fuc-PDA-MBs) were introduced as the capture carrier for pretreatment of samples. Fucoidan, a sulfated polysaccharide, can recognize the SARS-CoV-2 spike (S1) protein receptor-binding domain (S1 RBD) and was chosen for replacement of antibody in enrichment. Environmental water seeded with SARS-CoV-2 spike pseudovirus was applied to test performance of Fuc-PDA-MBs method. Under optimal conditions, the use of Fuc-PDA-MBs showed average 76 % capture efficiency at SARS-CoV-2 spike pseudovirus concentration ranging from 107.62 to 104.34 gene copies (gc)/L. Compared with Electronegative filtration (ENF), Fuc-PDA-MBs showed better virion sorption effectiveness. Fuc-PDA-MBs also validated by raw contaminated urban wastewater and showed high recovery results for SARS-CoV-2 variants. To rapidly detect virus in POCT, nucleic acid extraction-free Loop-Mediated Isothermal Amplification (LAMP) was used for simplifying experimental process. The Fuc-PDA-MBs-LAMP assay showed the quantitation limit of sample (LOQ) was 105.49 gc/L. The whole procedure could be completed within 90 min, including 30 min for virus pre-enrichment, 10 min nucleic acid release and 45 min LAMP analysis. Compared with regular antibody-based immunodetection, this integrated system provides broad-spectrum, economic way to detect SARS-CoV-2 mutants in complex environments and also adaptable for high throughput test, which might be used for on-site early warning of SARS-CoV-2 outbreaks in developing area.
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6.
Construction of an exosome-associated miRNA-mRNA regulatory network and validation of FYCO1 and miR-17-5p as potential biomarkers associated with ovarian cancer.
Chen, L, Lai, L, Zheng, L, Wang, Y, Lu, H, Chen, Y
Translational cancer research. 2024;(2):1052-1067
Abstract
BACKGROUND The occurrence and development of several human physiological processes are significantly influenced by the competing endogenous RNA (ceRNA) network. The aim of the present study was to construct a microRNA (miRNA)-mRNA network associated with exosomes in ovarian cancer (OV), and experimental validation of key target genes. METHODS By exploring the Gene Expression Omnibus (GEO) database, we analyzed the RNAs from 226 samples to identify differentially expressed miRNAs (DEMs) and genes (DEGs) that showed differential expression as OV progressed. Subsequently, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on the DEGs. Furthermore, we constructed a miRNA-mRNA network that pertains to exosomes in OV using DEMs and DEGs. Moreover, we validated the expression levels of mRNAs in the miRNA-mRNA network using Gene Expression Profiling Interactive Analysis (GEPIA2). Ultimately, luciferase reporter assay was used to identify the potential target relationship between FYVE and coiled-coil domain containing 1 (FYCO1) and miRNAs. RESULTS Our analysis screened a total of 14 DEMs and 101 DEGs, and the DEGs were mainly enriched in DNA replication or repair, amino acid biosynthesis and carbon metabolism. Furthermore, a miRNA-mRNA network was constructed including 3 miRNAs (hsa-miR-17-5p, hsa-miR-20b-5p and hsa-miR-20a-5p) and 2 mRNAs, FYCO1 and purine rich element binding protein A (PURA). Finally, the 2 mRNAs in this miRNA-mRNA network were verified by GEPIA2 using The Cancer Genome Atlas (TCGA) database. Among them, only FYCO1 showed significant different expression of mRNA in OV and normal tissue, while the prognosis of FYCO1 in OV remains controversial due to different database. Interestingly, FYCO1 was identified as the target of hsa-miR-17-5p. CONCLUSIONS By constructing a novel network of miRNA-mRNA, we can gain new understanding of the molecular mechanisms that drive exosomes in OV. Targeting FYCO1, which originates from exosomes, may hold promise as a diagnostic marker for OV.
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7.
Management of an Esophago-pleural Fistula after Emergent Endoscopic Variceal Injectional Sclerotherapy: A Case Report And Literature Review.
Lu, H, Li, T, Xia, Y, Shao, L, Yu, S, Xu, L
Internal medicine (Tokyo, Japan). 2024;(7):937-941
Abstract
A 48-year-old man developed sudden-onset haematemesis and melena after decompensated posthepatitic cirrhosis. Endoscopic variceal injectional sclerotherapy was emergently performed. However, the patient developed esophago-pleural fistula, empyema, and liver failure. He thus received symptomatic treatments and nasojejunal feedings, which failed to restore the nutrition as the gastroesophageal reflux exacerbated the hydrothorax. Percutaneous endoscopic gastro-jejunal (PEG-J) was therefore carefully performed for enteral nutrition support. The patient had recovered from the fistula at a six-month follow-up, which allowed the resumption of an oral diet. Our literature review revealed that PEG-J is a feasible approach to treating esophago-pleural fistula, a rare but lethal complication of endoscopic sclerotherapy.
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8.
Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial.
Zhan, Y, Lin, Z, Liang, J, Sun, R, Li, Y, Lin, B, Ge, F, Lin, L, Lu, H, Su, L, et al
EClinicalMedicine. 2024;:102359
Abstract
BACKGROUND Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. METHODS This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. FINDINGS Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95-428.68 h]) than that of Placebo (271.33 h [IQR 219.00-529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07-1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. INTERPRETATION Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. FUNDING This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.
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9.
Small-molecule autocatalysis drives compartment growth, competition and reproduction.
Lu, H, Blokhuis, A, Turk-MacLeod, R, Karuppusamy, J, Franconi, A, Woronoff, G, Jeancolas, C, Abrishamkar, A, Loire, E, Ferrage, F, et al
Nature chemistry. 2024;(1):70-78
Abstract
Sustained autocatalysis coupled to compartment growth and division is a key step in the origin of life, but an experimental demonstration of this phenomenon in an artificial system has previously proven elusive. We show that autocatalytic reactions within compartments-when autocatalysis, and reactant and solvent exchange outpace product exchange-drive osmosis and diffusion, resulting in compartment growth. We demonstrate, using the formose reaction compartmentalized in aqueous droplets in an emulsion, that compartment volume can more than double. Competition for a common reactant (formaldehyde) causes variation in droplet growth rate based on the composition of the surrounding droplets. These growth rate variations are partially transmitted after selective division of the largest droplets by shearing, which converts growth-rate differences into differences in droplet frequency. This shows how a combination of properties of living systems (growth, division, variation, competition, rudimentary heredity and selection) can arise from simple physical-chemical processes and may have paved the way for the emergence of evolution by natural selection.
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10.
Epidermolysis Bullosa: Two rare case reports of COL7A1 and EBS-GEN SEV KRT14 variants with review of literature.
Ali, FM, Zhou, J, Wang, M, Wang, Q, Sun, L, Mshenga, MM, Lu, H
BMC pediatrics. 2024;(1):242
Abstract
EPIDERMOLYSIS Bullosa is a rare hereditary skin condition that causes blisters. Genes encoding structural proteins at or near the dermal-epidermal junction are mutated recessively or dominantly, and this is the primary cause of EB. Herein, two Chinese boys were diagnosed with the condition, each with a different variant in a gene that serves as a reference for EB genetic counseling. Skincare significantly impacted their prognosis and quality of life. CASE PRESENTATION Two Chinese boys, with phenotypically normal parents, have been diagnosed with distinct blister symptoms, one with Dominant Dystrophic Epidermolysis Bullosa and the other with a severe form of Epidermolysis Bullosa Simplex. The first patient had a G-to-A variant in the COL7A1 allele, at nucleotide position 6163 which was named "G2055A". The proband is heterozygous for Dystrophic Epidermolysis Bullosa due to a COL7A1 allele with a glycine substitution at the triple helix domain. A similar variant has been discovered in his mother, indicating its potential transmission to future generations. Another patient had severe Epidermolysis Bullosa Simplex with a rare c.377T > A variant resulting in substitution of amino acid p.Leu126Arg (NM_000526.5 (c.377T > G, p.Leu126Arg) in the Keratin 14 gene. In prior literature, Keratin 14 has been associated with an excellent prognosis. However, our patient with this infrequent variant tragically died from sepsis at 21 days old. There has been a reported occurrence of the variant only once. CONCLUSION Our study reveals that Epidermolysis Bullosa patients with COL7A1 c.6163G > A and KRT14 c.377T>A variants have different clinical presentations, with dominant forms of Dystrophic EB having milder phenotypes than recessive ones. Thus, the better prognosis in the c.6163G > A patient. Furthermore, c.377T>A patient was more prone to infection than the patient with c.6163G>A gene variant. Genetic testing is crucial for identifying the specific variant responsible and improving treatment options.