ABSTRACT
Gut microbiota-derived microbial compounds may link to the pathogenesis of colorectal cancer (CRC). However, the role of the host-microbiome in the incidence and progression of CRC remains elusive. We performed 16S rRNA sequencing, metabolomics, and proteomic studies on samples from 85 CRC patients who underwent colonoscopy examination and found two distinct changed patterns of microbiome in CRC patients. The relative abundances of Catabacter and Mogibacterium continuously increased from intramucosal carcinoma to advanced stages, whereas Clostridium, Anaerostipes, Vibrio, Flavonifractor, Holdemanella, and Hungatella were significantly altered only in intermediate lesions. Fecal metabolomics analysis exhibited consistent increases in bile acids, indoles, and urobilin as well as a decrease in heme. Serum metabolomics uncovered the highest levels of bilin, glycerides, and nucleosides together with the lowest levels of bile acids and amino acids in the stage of intermediate lesions. Three fecal and one serum dipeptides were elevated in the intermediate lesions. Proteomics analysis of colorectal tissues showed that oxidation and autophagy through the PI3K/Akt-mTOR signaling pathway contribute to the development of CRC. Diagnostic analysis showed multiomics features have good predictive capability, with AUC greater than 0.85. Our overall findings revealed new candidate biomarkers for CRC, with potentially significant diagnostic and prognostic capabilities.
Subject(s)
Colorectal Neoplasms , Feces , Gastrointestinal Microbiome , Metabolomics , Proteomics , RNA, Ribosomal, 16S , Humans , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Proteomics/methods , Feces/microbiology , Feces/chemistry , Metabolomics/methods , Male , RNA, Ribosomal, 16S/genetics , Female , Middle Aged , Aged , Signal Transduction , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/blood , MultiomicsABSTRACT
Sodium-ion batteries (SIBs) present a promising avenue for next-generation grid-scale energy storage. However, realizing all-climate SIBs operating across a wide temperature range remains a challenge due to the poor electrolyte conductivity and instable electrode interphases at extreme temperatures. Here, we propose a comprehensively balanced electrolyte by pairing carbonates with a low-freezing-point and low-polarity ethyl propionate solvent which enhances ion diffusion and Na+-desolvation kinetics at sub-zero temperatures. Furthermore, the electrolyte leverages a combinatorial borate- and nitrile-based additive strategy to facilitate uniform and inorganic-rich electrode interphases, ensuring excellent rate performance and cycle stability over a wide temperature range from -45 °C to 60 °C. Notably, the Na||sodium vanadyl phosphate cell delivers a remarkable capacity of 105â mAh g-1 with a high rate of 2â C at -25 °C. In addition, the cells exhibit excellent cycling stability over a wide temperature range, maintaining a high capacity retention of 84.7 % over 3,000 cycles at 60 °C and of 95.1 % at -25 °C over 500 cycles. The full cell also exhibits impressive cycling performance over a wide temperature range. This study highlights the critical role of electrolyte and interphase engineering for enabling SIBs that function optimally under diverse and extreme climatic environments.
ABSTRACT
Rapeseed polyphenols have cardiovascular protective effects. Sinapine, one main rapeseed polyphenol, possesses antioxidative, anti-inflammatory, and antitumor properties. However, no research has been published about the role of sinapine in alleviating macrophage foaming. This study aimed to reveal the macrophage foaming alleviation mechanism of sinapine by applying quantitative proteomics and bioinformatics analyses. A new approach was developed to retrieve sinapine from rapeseed meals by using hot-alcohol-reflux-assisted sonication combined with anti-solvent precipitation. The sinapine yield of the new approach was significantly higher than in traditional methods. Proteomics was performed to investigate the effects of sinapine on foam cells, and it showed that sinapine can alleviate foam cell formation. Moreover, sinapine suppressed CD36 expression, enhanced the CDC42 expression, and activated the JAK2 and the STAT3 in the foam cells. These findings suggest that the action of sinapine on foam cells inhibits cholesterol uptake, activates cholesterol efflux, and converts macrophages from pro-inflammatory M1 to anti-inflammatory M2. This study confirms the abundance of sinapine in rapeseed oil by-products and elucidates the biochemical mechanisms of sinapine that alleviates macrophage foaming, which may provide new perspectives for reprocessing rapeseed oil by-products.
Subject(s)
Brassica napus , Brassica rapa , Rapeseed Oil/metabolism , Proteomics , Macrophages/metabolism , Foam Cells/metabolism , Brassica napus/metabolism , Brassica rapa/chemistry , Anti-Inflammatory Agents/metabolism , Cholesterol/metabolism , Lipoproteins, LDL/metabolismABSTRACT
Accurately assessing the health risks of human exposure to heavy metals via water is of great importance for performing targeted health risk prevention measures. To better understand the concentration characteristics and potential harm to human health of cadmium, chromium, lead and arsenic in the main drinking water-type reservoirs of Changzhou city, we collected samples from the Haidi Reservoir, Dongjin Reservoir, Xinfushan Reservoir, Maodong Reservoir and Xiangyang Reservoir of Changzhou in the summer of 2019. The results showed that the daily average comprehensive exposure level of metals was much lower than the provisional tolerated daily intake (PTDI), i.e., Cd: 1 µg kg-1 d-1; Cr: 3 µg kg-1 d-1; Pb: 3.57 µg kg-1 d-1; and As: 2.14 µg kg-1 d-1. The comprehensive non-carcinogenic risk levels of four metals under water-drinking exposure and water-skin exposure routes ranged from 4.68E - 3 to 1.69E - 1, and the carcinogenic risk ranged from 2.09E - 5 to 7.30E - 5, which were all at acceptable risk levels. Although lead and chromium were present at acceptable health risk levels, they still represented the main pollutants of potential health risk in the local water environment from a non-carcinogenic or carcinogenic perspective, and they should be listed as the primary targets for water environmental risk management.
Subject(s)
Arsenic , Drinking Water , Metals, Heavy , Humans , Arsenic/analysis , Cadmium/analysis , Chromium , Lead , Environmental Monitoring , Metals, Heavy/analysis , Drinking Water/analysis , China , Risk AssessmentABSTRACT
BACKGROUND: Corona Virus Disease 2019 (COVID-19) is currently a worldwide pandemic and has a huge impact on public health and socio-economic development. The purpose of this study is to explore the diagnostic value of the quantitative computed tomography (CT) method by using different threshold segmentation techniques to distinguish between patients with or without COVID-19 pneumonia. METHODS: A total of 47 patients with suspected COVID-19 were retrospectively analyzed, including nine patients with positive real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR) test (confirmed case group) and 38 patients with negative RT-PCR test (excluded case group). An improved 3D convolutional neural network (VB-Net) was used to automatically extract lung lesions. Eight different threshold segmentation methods were used to define the ground glass opacity (GGO) and consolidation. The receiver operating characteristic (ROC) curves were used to compare the performance of various parameters with different thresholds for diagnosing COVID-19 pneumonia. RESULTS: The volume of GGO (VOGGO) and GGO percentage in the whole lung (GGOPITWL) were the most effective values for diagnosing COVID-19 at a threshold of - 300 HU, with areas under the curve (AUCs) of 0.769 and 0.769, sensitivity of 66.67 and 66.67%, specificity of 94.74 and 86.84%. Compared with VOGGO or GGOPITWL at a threshold of - 300 Hounsfield units (HU), the consolidation percentage in the whole lung (CPITWL) with thresholds at - 400 HU, - 350 HU, and - 250 HU were statistically different. There were statistical differences in the infection volume and percentage of the whole lung, right lung, and lobes between the two groups. VOGGO, GGOPITWL, and volume of consolidation (VOC) were also statistically different at the threshold of - 300 HU. CONCLUSIONS: Quantitative CT provides an image quantification method for the auxiliary diagnosis of COVID-19 and is expected to assist in confirming patients with COVID-19 pneumonia in suspected cases.
Subject(s)
COVID-19 , Pneumonia/diagnostic imaging , Tomography, X-Ray Computed/methods , Artificial Intelligence , Humans , Retrospective Studies , SARS-CoV-2ABSTRACT
Researchers have puzzled over the phenomenon in sensorimotor timing that people tend to tap ahead of time. When synchronizing movements (e.g., finger taps) with an external sequence (e.g., a metronome), humans typically tap tens of milliseconds before event onsets, producing the elusive negative asynchrony. Here, we present 24 metronome-tapping data sets from 8 experiments with different experimental settings, showing that less negative asynchrony is associated with lower tapping variability. Further analyses reveal that this negative mean-SD correlation of asynchrony is likely to be observed for sequence types appropriate for synchronization, as indicated by the statistically negative lag 1 autocorrelation of inter-response intervals. The reported findings indicate an association between negative asynchrony and timing variability.
Subject(s)
Movement/physiology , Psychomotor Performance/physiology , Reaction Time/physiology , Time Perception/physiology , Adolescent , Female , Fingers/physiology , Humans , Male , Time Factors , Young AdultABSTRACT
OBJECTIVES: To evaluate the existing body of evidence to determine the current state of knowledge regarding the perspectives of the following groups: (1) children with cancer, (2) family caregivers, and (3) healthcare professionals, about symptoms, as well as factors that may influence the symptom reports. METHODS: A systematic search was performed for all types of studies that included the perspectives of at least two groups of participants' symptom reports. Children included anyone younger than 19 years of age who was diagnosed with any type of cancer. Electronic searches were conducted in five English databases and four Chinese databases. The appraisal of methodological quality was conducted using the GRADE criteria. Data were extracted into matrix tables. RESULTS: Thirty-three studies were included. The pediatric oncology symptoms reported by children, family caregivers, and healthcare professionals were synthesized. Findings suggested that family caregivers' symptom reports were more closely aligned with children's reports than with the healthcare professionals' reports. Influencing factors on the different symptom reports included the children's diagnosis, symptom characteristics, social-demographic factors, and family caregivers' psychosocial status. CONCLUSIONS: Children with cancer should be the primary reporters for their symptoms. When there are reporters other than the children, the potential discrepancy between the different perspectives needs to be carefully considered.
Subject(s)
Caregivers/psychology , Health Personnel/psychology , Medical Oncology/standards , Adolescent , Child , Child, Preschool , Female , Humans , MaleABSTRACT
Oral mucositis is one of the most frequent complications after chemotherapy, occurring in approximately 52 to 80% of children receiving treatment for cancer. Recently, it has been suggested that the use of low-energy laser could reduce the grade of oral mucositis and alleviate the symptoms. In 2014, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology has recommended low-level laser therapy in prevention of mucositis for hematopoietic stem cell transplantation patients because of its beneficial effects in majority of recent studies. However, the recommendation was made for adult patients, not pediatric patients. Data about the effect of low-level laser therapy in pediatric patients is limited. This study aims to synthesize the available clinical evidences on the effects of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy-induced oral mucositis (OM). A meta-analysis was performed using trials identified through the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Web of Science, China Biology Medicine (CBM), Wanfang Database, and China National Knowledge Infrastructure (CNKI). Data on occurrence, duration, and severity of oral mucositis were collected. All randomized controlled studies and clinical controlled studies comparing LLLT to routine qualified prevention or treatment during or after chemotherapy were critically appraised and analyzed. We found 8 qualified clinical trials with a total of 373 pediatric patients; the methodological quality was acceptable. After prophylactic LLLT, the odds ratio for developing OM was significantly lower compared with placebo(OR = 0.50, 95% CI 0.29 to 0.87, P = 0.01), the odds ratio for developing grade III OM or worse was statistically significantly lower compared with placebo (OR = 0.30, 95% CI (0.10, 0.90), P = 0.03), and the OM severity was statistically significantly lower compared with placebo (SMD = - 0.56, 95% CI (- 0.98, - 0.14), P = 0.009). For therapeutic LLLT, the OM severity was significantly reduced compared to routine care (SMD = - 1.18, 95% CI (- 1.52, - 0.84), P < 0.00001). Oral pain was also reduced after LLLT over routine care (MD = - 0.73, 95% CI (- 1.36, - 0.11), P = 0.02). CONCLUSION: Prophylactic LLLT reduces mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients with cancer. Therapeutic LLLT also reduces the average severity of oral mucositis and oral pain. Further research should investigate the optimal parameter of LLLT in pediatric and young patients, and studies with higher methodological quality should be performed. What is known: ⢠Low-level laser therapy (LLLT) was recommended by Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; however, evidences about LLLT on oral mucositis in pediatric and young patients were insufficient and lack supportive synthesized data. ⢠Recently, there have been several new RCTs or CCTs for pediatric patients or young adults. What is new: ⢠Prophylactic LLLT reduces the occurrence of mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients. ⢠Therapeutic LLLT reduces the average severity of oral mucositis and oral pain.
Subject(s)
Antineoplastic Agents/adverse effects , Low-Level Light Therapy , Stomatitis/radiotherapy , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Severity of Illness Index , Stomatitis/chemically induced , Stomatitis/prevention & control , Treatment Outcome , Young AdultABSTRACT
In this study, the effect of high hydrostatic pressure (HHP) on antigenicity, free sulfhydryl group (SH) content, hydrophobicity (Ho), fluorescence intensity and circular dichroism data of soybean ß-conglycinin was studied. The antigenicity of soybean ß-conglycinin was decreased significantly at pressures 200-400 MPa. The antigenicity inhibition rate of ß-conglycinin declined from 92.72 to 55.15%, after being treated at 400 MPa for 15 min. Results indicated that free sulphydryl (SH) groups and surface Ho of ß-conglycinin were significantly increased at pressures 200-400 MPa and 5-15 min, whereas these properties decreased at the treatments above 400 MPa and 15 min. The maximum fluorescence intensity was noticed at 400 MPa and 15 min. The circular dichroism data analysis revealed that the amount of ß-turns and unordered structure significantly increased, while the content of α-helix1 and ß-strand1 noticeably decreased. These results provide evidence that HHP-induced the structural modification of ß-conglycinin and could alter the antigenicity of ß-conglycinin.
ABSTRACT
SCOPE: The cannabidiol (CBD) in hemp oil has important pharmacological activities. Accumulating evidence suggests that CBD is beneficial in the cardiovascular system and has been applied as a health supplement for atherosclerosis. However, the mechanism remains unclear. METHODS AND RESULTS: This study investigates the impact of CBD on foam cell formation, cholesterol homeostasis, and lipid metabolism in macrophages. CBD elevates the levels of peroxisome proliferator-activated receptor gamma (PPARγ) and its associated targets, such as ATP binding transporter A1/G1 (ABCA1/ABCG1), thus reducing foam cell formation, and increasing cholesterol efflux within macrophages. Notably, the upregulation of ABCA1 and ABCG1 expression induced by CBD is found to be attenuated by both a PPARγ inhibitor and PPARγ small interfering RNA (siRNA). Moreover, transfection of PPARγ siRNA results in a decrease in the inhibitory effect of CBD on foam cell formation and promotion of cholesterol efflux. Through lipidomics analysis, the study finds that CBD significantly reverses the enhancement of ceramide (Cer). Correlation analysis indicates a negative association between Cer level and the expression of ABCA1/ABCG1. CONCLUSION: This study confirms that CBD can be an effective therapeutic candidate for atherosclerosis treatment by activating PPARγ, up-regulating ABCA1/ABCG1 expression, and down-regulating Cer level.
Subject(s)
ATP Binding Cassette Transporter 1 , ATP Binding Cassette Transporter, Subfamily G, Member 1 , Cannabidiol , Cholesterol , Foam Cells , Homeostasis , Lipid Metabolism , PPAR gamma , Foam Cells/drug effects , Foam Cells/metabolism , Cannabidiol/pharmacology , Cholesterol/metabolism , ATP Binding Cassette Transporter 1/metabolism , ATP Binding Cassette Transporter 1/genetics , PPAR gamma/metabolism , PPAR gamma/genetics , Lipid Metabolism/drug effects , ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics , Animals , Homeostasis/drug effects , Mice , RAW 264.7 Cells , Ceramides/metabolismABSTRACT
The core of the concept of nature-based solutions (NBS) is ecological protection, which is the same direction as China's double-carbon goal and has attracted much attention in China. Ecological ditch sewage treatment technology has been widely used in controlling agricultural non-point source pollution because of its advantages of high pollutant removal efficiency and low energy consumption. Suppose the NBS concept of sustainable management, restoration, and ecological protection is integrated into the research and development and application of ecological ditch technology. In that case, it can not only improve the effective removal of pollutants, achieve the purpose of recycling water resources and nutrient elements, but also realize economic, environmental, and social benefits. This paper describes the ecosystem service functions provided by ecological ditches in detail, evaluates their economic values through literatures review, so as to raise people's awareness of natural resource conservation and realize the sustainable management of ecological ditches.
Subject(s)
Environmental Pollutants , Non-Point Source Pollution , Humans , Ecosystem , Agriculture , Technology , China , Conservation of Natural ResourcesABSTRACT
Inflammation plays a critical role in the development of numerous diseases. Cannabidiol (CBD), found in hemp, exhibits significant pharmacological activities. Accumulating evidence suggests that CBD has anti-inflammatory and cardiovascular protection effects, but the potential mechanisms require further exploration. In this study, we aimed to reveal the mechanisms of CBD against high-fat, high-cholesterol (HFC) diet-induced inflammation combining metabolomics with network pharmacology. First, plasma lipidomics results indicated that oxidized lipids could serve as potential biomarkers for HFC diet-induced inflammation, and CBD reversed the elevated levels of oxidized lipids. The HFC diet was also found to enhance intestinal permeability, facilitating the entry of lipopolysaccharides (LPSs) into the circulatory system and subsequently increasing systemic inflammation. Additionally, cell metabolomic results indicated that CBD could reverse 10 important differential metabolites in LPS-induced RAW 264.7 cells. Using network pharmacology, we identified 49 core targets, and enrichment analysis revealed that arachidonic acid was the most significantly affected by CBD, which was closely associated with inflammation. Further integrated analysis focused on three key targets, including PTGS2, ALOX5, and ALOX15. Molecular docking showed high affinities between key targets and CBD, and qPCR further demonstrated that CBD could reverse the mRNA expression of these key targets in RAW 264.7 cells. Collectively, this finding integrates lipidomics and metabolomics with network pharmacology to elucidate the anti-inflammatory effects of CBD and validates key therapeutic targets.
Subject(s)
Anti-Inflammatory Agents , Cannabidiol , Diet, High-Fat , Inflammation , Lipidomics , Metabolomics , Mice, Inbred C57BL , Network Pharmacology , Animals , Cannabidiol/pharmacology , Mice , Diet, High-Fat/adverse effects , Inflammation/metabolism , Inflammation/drug therapy , Male , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , RAW 264.7 Cells , Humans , Cholesterol/metabolism , Molecular Docking Simulation , Arachidonate 5-Lipoxygenase/metabolism , Arachidonate 5-Lipoxygenase/genetics , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolismABSTRACT
BACKGROUND: Children and adolescents may experience a variety of subjective adverse events (AEs) caused by cancer treatment. The identification of distinct groups of patients is crucial for guiding symptomatic AE management interventions to prevent AEs from worsening. OBJECTIVE: The aim of this study was to identify subgroups of children with cancer experiencing similar patterns of subjective toxicities and evaluate differences among these subgroups in demographic and clinical characteristics. METHODS: A cross-sectional survey was conducted of 356 children in China with malignancies who received chemotherapy within the past 7 days using the pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events. A latent class analysis (LCA) was conducted to identify subgroups of patients with distinct profiles of symptomatic AE occurrence. RESULTS: Nausea (54.5%), anorexia (53.4%), and headache (39.3%) were the top 3 AEs children experienced. Nearly all participants (97.8%) experienced ≥1 core AEs, and 30.3% experienced ≥5 AEs. The LCA results identified 3 subgroups ("high gastrotoxicity and low neurotoxicity" [53.2%], "moderate gastrotoxicity and high neurotoxicity" [23.6%], and "high gastrotoxicity and high neurotoxicity" [22.8%]). The subgroups were differentiated by monthly family per-capita income, time since diagnosis, and Karnofsky Performance Status score. CONCLUSIONS: Children experienced multiple subjective toxicities during chemotherapy, especially gastrotoxicity and neurotoxicity. Heterogeneity was found in the LCA in the patients' toxicities. The prevalence of toxicities could be distinguished by the children's characteristics. IMPLICATIONS FOR PRACTICE: The results showing different subgroups in our study may assist clinical staff in focusing on patients with higher toxicities to provide effective interventions.
Subject(s)
Neoplasms , Adolescent , Humans , Child , Cross-Sectional Studies , Latent Class Analysis , Neoplasms/drug therapy , Patient Reported Outcome Measures , Nausea/chemically inducedABSTRACT
Sodium-ion batteries (SIBs) hold great promise for next-generation grid-scale energy storage. However, the highly instable electrolyte/electrode interphases threaten the long-term cycling of high-energy SIBs. In particular, the instable cathode electrolyte interphase (CEI) at high voltage causes persistent electrolyte decomposition, transition metal dissolution, and fast capacity fade. Here, this work proposes a balanced principle for the molecular design of SIB electrolytes that enables an ultra-thin, homogeneous, and robust CEI layer by coupling an intrinsically oxidation-stable succinonitrile solvent with moderately solvating carbonates. The proposed electrolyte not only shows limited anodic decomposition thus leading to a thin CEI, but also suppresses dissolution of CEI components at high voltage. Consequently, the tamed electrolyte/electrode interphases enable extremely stable cycling of Na3V2O2(PO4)2F (NVOPF) cathodes with outstanding capacity retention (>90%) over 3000 cycles (8 months) at 1 C with a high charging voltage of 4.3 V. Further, the NVOPF||hard carbon full cell shows stable cycling over 500 cycles at 1 C with a high average Coulombic efficiency (CE) of 99.6%. The electrolyte also endows high-voltage operation of SIBs with great temperature adaptability from -25 to 60 °C, shedding light on the essence of fundamental electrolyte design for SIBs operating under harsh conditions.
ABSTRACT
Cardiovascular diseases are caused by hypercholesterolemia. Astaxanthin (AST) has been reported to exhibit antioxidant and anti-inflammatory properties. However, its bioavailability is poor because of low solubility and instability. In order to improve the bioavailability of AST, we developed an intestinal-responsive composite carrier termed as "liposomes in micropheres" incorporating N-succinyl-chitosan (NSC)-poly(ethylene glycol) (PEG) liposomes that functionalized by neonatal Fc receptors (FcRn) into hydrogels of sodium alginate (SA) and carboxymethyl chitosan (CMCS). In the AST NSC/HSA-PEG liposomes@SA/CMCS microspheres, the AST's encapsulation efficiency (EE) was 96.26% (w/w) and its loading capacity (LC) was 6.47% (w/w). AST NSC/HSA-PEG liposomes had stability in the gastric conditions and achieved long-term release of AST in intestinal conditions. Then, AST NSC/HSA-PEG liposomes@SA/CMCS bind to intestinal epithelial cell targets by the neonatal Fc receptor. In vitro permeation studies show that there was a 4-fold increase of AST NSC/HSA-PEG liposomes@SA/CMCS in AST permeation across the intestinal epithelium. Subsequent in vivo experiments demonstrated that the composite carrier exhibited a remarkable mucoadhesive capacity, allowing for extended intestinal retention of up to 12 h, and it displayed deep penetration through the mucus layer, efficiently entering the intestinal villi epithelial cells, and enhancing the absorption of AST and its bioavailability in vivo. And oral administration of AST NSC/HSA-PEG liposomes@SA/CMCS could effectively prevent hypercholesterolemia caused by a high-fat, high-cholesterol diet (HFHCD). These advancements highlight the potential of NSC/HSA-PEG liposomes@SA/CMCS composite carriers for targeted and oral uptake of hydrophobic bioactives.
Subject(s)
Chitosan , Hypercholesterolemia , Infant, Newborn , Humans , Liposomes/chemistry , Microspheres , Xanthophylls , Chitosan/chemistry , Drug Carriers/chemistry , Administration, OralABSTRACT
Antibiotics are useful for treating infections caused by bacteria, but they have negative effects on the host body. The goal of this study was to determine whether antibiotics alter the metabolic phenotype of the host. We found that taking antibiotics reduced the diversity and richness of gut microbiota and affected the composition of the microbiome, which in turn altered the metabolic profiles of plasma and fecal samples. Additionally, plasma and fecal metabolites and gut microbiota genera showed a significant association. The most significant pathways related to the gut dysbiosis induced by antibiotics including purine, pentose, and glucuronate metabolism, histidine, ascorbate and alternate, lysine degradation, and fatty acid biosynthesis. The relationship between gut microbiota and altered metabolites of plasma and feces provides information about bacterial action, which is useful for designing new microbiota-based disease prevention and treatment interventions.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Humans , Gastrointestinal Microbiome/genetics , Anti-Bacterial Agents/adverse effects , Dysbiosis/chemically induced , Dysbiosis/metabolism , Dysbiosis/microbiology , MetabolomeABSTRACT
BACKGROUND: Chimeric antigen receptor T-cell therapy-related severe cytokine release syndrome (sCRS) has seriously affected the life safety of patients. OBJECTIVE: To explore the influencing factors of sCRS in children with B-cell hematological malignancies and build a risk prediction model. METHODS: The study recruited 115 children with B-cell hematological malignancies who received CD19- and CD22-targeted chimeric antigen receptor T-cell therapy. A nomogram model was established based on symptomatic adverse events and highly accessible clinical variables. The model discrimination was evaluated by the area under the receiver operating characteristic curve. The calibration of our model was evaluated by the calibration curve and Hosmer-Lemeshow test. The bootstrap self-sampling method was used to internally validate. RESULTS: Thirty-seven percent of the children experienced sCRS. Indicators included in the nomogram were tumor burden before treatment, thrombocytopenia before pretreatment, and the mean value of generalized muscle weakness and headache scores. The results showed that the area under the receiver operating characteristic curve was 0.841, and the calibration curve showed that the probability of sCRS predicted by the nomogram was in good agreement with the actual probability of sCRS. The Hosmer-Lemeshow test indicated that the model fit the data well (χ2 = 5.759, P = .674). The concordance index (C-index) obtained by internal validation was 0.841 (0.770, 0.912). CONCLUSIONS: The nomogram model constructed has a good degree of discrimination and calibration, which provides a more convenient and visual evaluation tool for identifying the sCRS. IMPLICATIONS FOR PRACTICE: Incorporation of patient-reported outcomes into risk prediction models enables early identification of sCRS.
ABSTRACT
Introduction: Cannabidiol (CBD) has important pharmacological activity, which includes antispasmodic, antioxidant, antithrombotic, and antianxiety properties. CBD has been applied as a health supplement to atherosclerosis. However, CBDs effect on gut microbiota and metabolic phenotype is unclear. Materials and Methods: We constructed a high production of cardiovascular risk factors, such as trimethylamine-N-oxide (TMAO) and phenylacetylglutamine (PAGln), in a mouse model using Clostridium sporogenes colonization. We used 16S ribosomal RNA (rRNA) gene sequencing and ultra-high performance liquid chromatography-quadrupole time-of flight mass spectrometry-based metabolomics to evaluate the effect of CBD on gut microbiota and plasma metabolites. Results: CBD decreased the levels of creatine kinase (CK), alanine transaminase (ALT), and low-density lipoprotein cholesterol and markedly increased high-density lipoprotein cholesterol. Furthermore, CBD treatment increased the abundance of beneficial bacteria, which include Lachnospiraceae_NK4A136 and Blautia in the gut, but it decreased the levels of TMAO and PAGln in the plasma. Conclusion: CBD might have beneficial effects for cardiovascular protection.
ABSTRACT
BACKGROUND: The original English Pediatric Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) captures symptomatic adverse events (AEs) in cancer clinical trials from the perspective of pediatric patients. A Chinese version was needed to encourage the use of the Pediatric PRO-CTCAE among Chinese pediatric oncology patients. OBJECTIVE: This study translated and linguistically validated a simplified Chinese version of the Pediatric PRO-CTCAE for oncological patients aged 7 to 18 years. METHODS: Following the Functional Assessment of Chronic Illness Therapy translation methodology, 130 questions were translated into Chinese. Semistructured cognitive interviews investigated the comprehensibility and clarity of terms for symptoms, attributes, and response options. Two rounds of interviews were conducted with 48 native Chinese-speaking children aged 7 to 18 years who were undergoing chemotherapy or radiotherapy treatment. RESULTS: Most items, response options, and recall periods were well understood by children across the age range in round 1. Nineteen items posed comprehension difficulties for 9 participants and were revised and retested without further difficulties. CONCLUSIONS: The Pediatric PRO-CTCAE was successfully developed and linguistically validated among Chinese oncology patients. The results indicated that the Chinese Pediatric PRO-CTCAE was semantically and conceptually equivalent to the English version. IMPLICATIONS FOR PRACTICE: The availability of the simplified Chinese Pediatric PRO-CTCAE will facilitate the generation of patient-reported outcome data about symptomatic AEs for children with cancer in China and thus improve our understanding of children's experience of treatment-related symptoms.
Subject(s)
Neoplasms , Patient Reported Outcome Measures , United States , Humans , Child , National Cancer Institute (U.S.) , Surveys and Questionnaires , Neoplasms/drug therapy , Neoplasms/diagnosis , China , CognitionABSTRACT
Astaxanthin (AST) has outstanding antioxidant and anti-inflammation bioactivities, but the low biocompatibility and stability limit its application in foods. In this study, N-succinyl-chitosan (NSC)-coated AST polyethylene glycol (PEG)-liposomes were constructed to enhance the biocompatibility, stability, and intestinal-targeted migration of AST. The AST NSC/PEG-liposomes were uniform in size, had larger particles, greater encapsulation efficiency, and better storage, pH, and temperature stability than the AST PEG-liposomes. AST NSC/PEG-liposomes exerted stronger antibacterial and antioxidant activities against Escherichia coli and Staphylococcus aureus than AST PEG-liposomes. The NSC coating not only protects AST PEG-liposomes from gastric acid but also prolongs the retention and sustained release of AST NSC/PEG-liposomes depending on the intestinal pH. Moreover, caco-2 cellular uptake studies showed that AST NSC/PEG-liposomes had higher cellular uptake efficiency than AST PEG-liposomes. And AST NSC/PEG-liposomes were taken up by caco-2 cells through clathrin mediated endocytic, macrophage pathways and paracellular transport pathway. These results further proved that AST NSC/PEG-liposomes delayed the release and promoted the intestinal absorption of AST. Hence, AST PEG-liposomes coated with NSC could potentially be used as an efficient delivery system for therapeutic AST.