To solve the problem of insufficient low-carbon operational motivation among cold chain logistics enterprises due to the high investment costs of low-carbon assets and considering the promotional effect of environmental regulatory policies and green credit, an evolutionary game model was constructed for the government, cold chain logistics enterprises, and financial institutions. The stability strategies of each participating entity and the stability of the system equilibrium point were analyzed, and the relevant conclusions were verified through numerical simulations. The research results indicated the following: (1) the initial willingness of the three parties to participate increased, the low-carbon operation of cold chain logistics enterprises and the speed of green credit services provided by financial institutions accelerated, and the rate of strict government regulation slowed down. (2) Moderate subsidies and taxes were conducive to the joint participation of the three parties. (3) Increasing the subsidy for green credit provided positive incentives for financial institutions to provide green credit services, while reducing credit interest rates accelerated the low-carbon operation rate of cold chain logistics enterprises.
Quality improvement is an international priority, and quality education and training are important parts of hospital quality management. The aim of this study was to understand the knowledge, attitudes and practices (KAP) and its influencing factors related to quality training in medical staff. A questionnaire survey was conducted by convenience sampling to assess the KAP of quality training in Taizhou Enze Medical Center. Principal component analysis was used to extract factors from the questionnaire. Descriptive statistics (frequency, median, mean), Kendall grade correlation analysis, and Mann-Whitney U tests were used to analyze the data. A total of 205 staff members participated in the questionnaire survey. For the 5 factors of the KAP scale, the highest score was factor F4, recognition and support for quality training (mean = 90.55, median = 100), followed by factor F3, perceived benefits (mean = 84.46, median = 85.65). Relatively lower scores were found for factor F2, quality knowledge learning and mastery (mean = 63.09, median = 63.89), and F5, quality management practices and sharing (mean = 82.07, median = 75.00). There was a correlation between the 5 factors. The scores of F2 (quality knowledge learning and mastery) for staff with senior professional titles were higher than those for staff with intermediate professional titles or below. The score of F3 (perceived benefits of quality training) in medical technicians and nurses was higher than in doctors and administrative personnel. Our findings showed that the respondents' attitude toward quality training was positive, but their knowledge mastery and practice behaviors should be further improved. Occupational category and professional title were the influencing factors of the quality training KAP. Therefore, hospital should conduct quality management training at a wider scope according to the competency requirements of different groups, and further optimize the improvement and innovation system.
Health Knowledge, Attitudes, Practice , Hospitals, General , Tertiary Care Centers , Humans , Cross-Sectional Studies , Male , Female , Adult , Surveys and Questionnaires , Quality Improvement , Middle Aged , Attitude of Health Personnel , Medical Staff, Hospital , China
Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1ß, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 µM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.
The delicate balance between ischemic and bleeding risks is a significant consideration in the administration of antiplatelet therapy. Clopidogrel and prasugrel, both members of the thienopyridine class of antiplatelet drugs, are well established for their variability in individual responsiveness and for a high number of bleeding events, respectively. The current study focuses on evaluating the pharmacokinetics and pharmacodynamics of a series of deuterated clopidogrel derivatives, leveraging insights gained from the structure-pharmacokinetic relationships in the development of thienopyridine drugs. Our approaches were based on the molecular skeleton of clopidogrel and adopted the C2-pharmacophore design from prasugrel. The selected C2-pharmacophore distinguishes itself from the acetyloxy substituent of prasugrel by exhibiting a moderated hydrolysis rate, resulting in a gentler formation of the active metabolite. An excessive and burst release of the active metabolite are therefore to be avoided, as it is believed to be associated with an increased risk of bleeding. Our proposed structural modification maintains the hydrolysis-sensitive methyl ester of clopidogrel but replaces it with a deuterated methyl group, which has been shown to effectively reduce metabolic deactivation. The evaluation of the clopidogrel derivatives has been primarily based on the criteria related to the exposure to active metabolites. Three promising compounds demonstrate higher biotransformation efficiency, similar Cmax, delayed Tmax, enhanced antiplatelet activity, and a lower risk of bleeding compared to clopidogrel, when administered at a dosage resulting in a similar exposure to the active metabolites. Significance Statement The pharmacokinetics and pharmacodynamics of a series of newly designed clopidogrel derivatives were assessed to validate the rationale for their structural modifications. Three promising compounds displayed balanced pharmacokinetics, characterized by slower deactivation compared to clopidogrel and a more gradual bioactivation than prasugrel. Under similar exposure to active metabolites, these compounds have demonstrated enhanced antiplatelet activity and a diminished risk of bleeding compared to clopidogrel. The D3-clopidogrel-ozagrel conjugate was found to exert a synergistic therapeutic effect.
BACKGROUND: Ulcerative colitis (UC) is associated with intestinal macrophage infiltration due to disruption of the mucosal barrier and bacterial invasion. Therefore, it is crucial to identify therapeutic agents capable of attenuating the macrophage-induced inflammatory response to preserve mucosal homeostasis and immune tolerance. The modified Zhenwu decoction (CDD-2103) is a novel herbal formulation developed based on the principles of Traditional Chinese medicine. To date, there are no clinically approved herbal formulations for UC with a well-known mechanism of action on macrophages. PURPOSE: The objective of this study was to systematically investigate the inhibitory effect of the active fraction of CDD-2103 in a mouse model of chronic colitis and delineate the mechanisms underlying its inhibitory action. METHODS: CDD-2103 was extracted into four fractions using organic solvents with increasing polarity. A chronic 49-day dextran sulfate sodium (DSS)-induced colitis mice model, closely resembling human clinical conditions, was used to examine the effect of CDD-2103 on chronic colitis. To confirm the effect of CDD-2103 on macrophages in this chronic colitis model, adoptive macrophage transfer and CCL2 supplementation were conducted. The mechanisms of action of CDD-2103 were further elucidated utilizing bone marrow-derived macrophages (BMDMs). Transcriptome analysis was conducted to gain insights into the underlying mechanism of action of CDD-2103 in BMDMs. RESULTS: Our in vitro and in vivo findings demonstrated that the ethanol-enriched fraction of CDD-2103 exhibited significant anti-inflammatory effects, leading to the suppression of colitis severity. This effect was associated with diminished accumulation of colonic macrophages in the lamina propria of CDD-2103-intervened colitis mice. Specifically, CDD-2103 inhibited CCR2/L2-mediated proinflammatory macrophage infiltration into the colon without affecting macrophage proliferation. Mechanistically, CDD-2103 inhibited Fyn expression-mediated p38 MAPK activation and subsequently suppressed CCR2 expression in BMDMs. CONCLUSIONS: Collectively, our study supports the potential use of CDD-2103 to limit macrophage infiltration, thereby reducing inflammation during UC treatment. CDD-2103 and the components in the ethanolic fraction are promising candidates for the development of novel drugs for UC management. Additionally, our study underscores Fyn-mediated CCR2 expression as a potential therapeutic target for the management of UC.
High polymerization persimmon tannin has been reported to have lipid-lowering effects. Unfortunately, the poor solubility restricts its application. This research aimed to investigate the effect and mechanism of inulin on solubilizing of persimmon tannin. Furthermore, we examined whether the addition of inulin would affect the attenuated obesity effect of persimmon tannin. Transmission electron microscope (TEM), Isothermal titration calorimetry (ITC) and Fourier transform infrared spectroscopy (FT-IR) results demonstrated that inulin formed a gel-like network structure, which enabled the encapsulation of persimmon tannin through hydrophobic and hydrogen bond interactions, thereby inhibiting the self-aggregation of persimmon tannin. The turbidity of the persimmon tannin solution decreased by 56.2â¯%, while the polyphenol content in the supernatant increased by 60.0â¯%. Furthermore, biochemical analysis and 16s rRNA gene sequencing technology demonstrated that persimmon tannin had a significant anti-obesity effect and improved intestinal health in HFD-fed mice. Moreover, inulin was found to have a positive effect on enhancing the health benefits of persimmon tannin, including improving hepatic steatosis and gut microbiota dysbiosis. it enhanced the abundance of beneficial core microbes while decreasing the abundance of harmful bacteria. Our findings expand the applications of persimmon tannin in the food and medical sectors.
Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.
OBJECTIVE: Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage. Notably, the knockout of transient receptor potential channel 6 (TRPC6) has shown promise in alleviating renal fibrosis. However, the regulatory impact of TRPC6 on renal fibrosis remains unclear. METHODS: In vivo, TRPC6 knockout (TRPC6-/-) mice and age-matched 129 SvEv (WT) mice underwent unilateral renal ischemia-reperfusion (uIR) injury surgery on the left renal pedicle or sham operation. Kidneys and serum were collected on days 7, 14, 21, and 28 after euthanasia. In vitro, primary tubular epithelial cells (PTECs) were isolated from TRPC6-/- and WT mice, followed by treatment with transforming growth factor ß1 (TGFß1) for 72 h. The anti-fibrotic effect of TRPC6-/- and the underlying mechanisms were assessed through hematoxylin-eosin staining, Masson staining, immunostaining, qRT-PCR, and Western blotting. RESULTS: Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFß1. TRPC6-/- alleviated renal fibrosis by reducing the expression of fibrotic markers (Col-1, α-SMA, and vimentin), as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro. Additionally, we found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3ß) signaling pathway, a pivotal player in renal fibrosis, was down-regulated following TRPC6 deletion. CONCLUSION: These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3ß pathway. Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.
Activating multielectron reactions of sodium superionic conductor (NASICON)-type cathodes toward higher energy density remains imperative to boost their application feasibility. However, multisodium storage with high stability is difficult to achieve due to the sluggish reaction kinetics, irreversible phase transitions, and negative structural degradation. Herein, a kind of NASICON-type Na2.5V1.5Ti0.5(PO4)3/C (NVTP-0.5) hierarchical microsphere consisting of abundant primary nanoparticles is designed, realizing a reversible 3.2-electron reaction with high stability. The optimized NVTP-0.5 cathode demonstrates an ultrahigh discharge capacity of 192.42 mAh g-1, energy density of up to 497.3 Wh kg-1 at 20 mA g-1, and capacity retention ratio of 94.1% after 1000 cycles at 1 A g-1. Additionally, the NVTP-0.5 cathode delivers excellent tolerance to extreme temperatures while also achieving a high-energy density of 400 Wh kg-1 (based on the cathode mass) in a full-cell configuration. Systematic in situ/ex situ analysis results confirm the multisodium storage processes of NVTP-0.5 involving successive redox reactions (V2+/V3+, Ti3+/Ti4+, and V3+/V4+ redox couples) and reversible structure evolution (solid-solution and biphasic mechanisms), which contribute to the high capacity and excellent cycling stability. This work indicates that the rational regulation of components with different functions can unlock more possibilities for the development of NASICON-type cathodes.
Effective capture of radioactive iodine from nuclear fuel reprocessing is of great importance for public safety as well as the secure utility of nuclear energy. In this work, a hydrophobic nanosheet silicalite-1 (NSL-1) zeolite with an adjustable size was developed for efficient iodine (I2) and methyl iodide (CH3I) adsorption. The optimized all-silica zeolite NSL-1 exhibits an excellent I2 uptake capacity of 553 mg/g within 45 min and a CH3I uptake capacity of 262 mg/g within 1 h. Benefiting from the reduced thickness and enhanced porosity, microporous NSL-1 possesses enhanced iodine adsorption capacity and fast adsorption kinetics, which is a considerable high value among inorganic materials. Unexpectedly, the remarkable characters of high hydrophobicity, acid-resistance and anti-oxidation endow it a higher iodine uptake capacity than traditional aluminosilicate zeolites. More importantly, the high uptake selectivity toward I2 possessed by NSL-1 owing to its hydrophobic skeleton under simulated dynamic conditions. The low cost, facile and scalable synthesis of NSL-1 further highlights great prospects for applications in the nuclear industry. This work provides useful insights for designing efficient adsorbents for iodine capture.
A series of Ir(III)-naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4'-CH2ONPX)](PF6) (Ir-NPX-1-3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1-3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1-3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1-3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) -NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.
BACKGROUND: Fillers are popular substances for the correction of tear trough deformity. Despite well-documented complications increasing gradually, standardized treatment algorithm for deformity secondary to improper injection is still limited. METHODS: Between April 2020 and April 2023, a total of 22 patients with filler-associated tear trough deformity with static bulges or dynamic swells after injection of tear trough were enrolled. For patients who received hyaluronic acid (HA) and unknown fillers, hyaluronidase dissolution was performed. For patients who received non-HA fillers and unknown fillers that failed to dissolve, a magnetic resonance imaging (MRI) examination was conducted. Surgical approaches were selected based on the filler distribution and the condition of the lower eyelid. Ligament releasement and fat transposition were accomplished when fillers were excised. Aesthetic outcomes were evaluated by double-blind examiners using the Global Aesthetic Improvement Scale after patients were followed up. RESULTS: In total, the study included 3 patients with simple static deformities, 1 patient with simple dynamic, and 18 patients with both. Fourteen patients underwent transconjunctival surgery and 8 patients underwent transcutaneous surgery, among which 18 patients underwent hyaluronidase dissolution and 8 patients underwent MRI prior to surgery. A total of 4 patients with self-limited complications recovered after conservative treatment. 90.9% of patients expressed satisfaction or high satisfaction with the treatment results. CONCLUSION: Filler-associated tear trough deformities could be classified into static and dynamic deformities, which could appear separately or simultaneously. Treatment of deformities should be based on characteristics of fillers, in which MRI could serve as a promising tool. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.
COVID-19 , RNA Editing , SARS-CoV-2 , Humans , COVID-19/genetics , COVID-19/virology , SARS-CoV-2/genetics , Adenosine/metabolism , Inosine/metabolism , Inosine/genetics , Transcriptome , Eye/metabolism , Eye/virology
This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were included, with 34 assigned to the ceftriaxone group and 171 to the penicillin group. The median age of patients was 56 years, with an interquartile range of 49-62 years, and 137 of them (66.8%) were male. Between 3 and 6 months after treatment, 13 patients (38.2%) in the ceftriaxone group and 82 patients (48.0%) in the penicillin group demonstrated effective treatment based on the clinical and laboratory parameters. The crude odds ratio (OR) was 0.672 (95% confidence interval [CI]: 0.316-1.428, P = 0.301), indicating no significant difference in effectiveness between the two groups. Thirty patients (17.5%) in the penicillin group and six patients (17.6%) in the ceftriaxone group did not experience successful outcomes. Notably, no serious adverse effects were reported in both the groups. There was no significant difference in the effectiveness of ceftriaxone and aqueous crystalline penicillin G in treating ocular syphilis. The administration of ceftriaxone without requiring hospitalization presents a convenient and safe alternative treatment option for ocular syphilis.
Introduction: Taurine has a prominent lipid-lowering effect on hyperlipidemia. However, a comprehensive analysis of the effects of taurine on endogenous metabolites in hyperlipidemia has not been documented. This study aimed to explore the impact of taurine on multiple metabolites associated with hyperlipidemia. Methods: The hyperlipidemic mouse model was induced by high-fat diet (HFD). Taurine was administered via oral gavage at doses of 700 mg/kg/day for 14 weeks. Evaluation of body weight, serum lipid levels, and histopathology of the liver and adipose tissue was performed to confirm the lipid-lowering effect of taurine. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabonomics analyses of serum, urine, feces, and liver, coupled with multivariate data analysis, were conducted to assess changes in the endogenous metabolites. Results and discussion: Biochemical and histological examinations demonstrated that taurine administration prevented weight gain and dyslipidemia, and alleviated lipid deposition in the liver and adipose tissue in hyperlipidemic mice. A total of 76 differential metabolites were identified by UPLC-MS-based metabolomics approach, mainly involving BAs, GPs, SMs, DGs, TGs, PUFAs and amino acids. Taurine was found to partially prevent HFDinduced abnormalities in the aforementioned metabolites. Using KEGG database and MetaboAnalyst software, it was determined that taurine effectively alleviates metabolic abnormalities caused by HFD, including fatty acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, diacylglycerol metabolism, amino acid metabolism, bile acid and taurine metabolism, taurine and hypotaurine metabolism. Moreover, DGs, GPs and SMs, and taurine itself may serve as active metabolites in facilitating various anti-hyperlipidemia signal pathways associated with taurine. This study provides new evidence for taurine to prevent hyperlipidemia.
Background: Impaired kidney function is frequently observed in patients following cardiopulmonary bypass (CPB). Our group has previously linked blood transfusion to acute declines in S-nitroso haemoglobin (SNO-Hb; the main regulator of tissue oxygen delivery), reductions in intraoperative renal blood flow, and postoperative kidney dysfunction. While not all CPB patients receive blood, kidney injury is still common. We hypothesized that the CPB procedure itself may negatively impact SNO-Hb levels leading to renal dysfunction. Materials and methods: After obtaining written informed consent, blood samples were procured immediately before and after CPB, and on postoperative day (POD) 1. SNO-Hb levels, renal function (estimated glomerular filtration rate; eGFR), and plasma erythropoietin (EPO) concentrations were quantified. Additional outcome data were extracted from the patients' medical records. Results: Twenty-seven patients were enroled, three withdrew consent, and one was excluded after developing bacteremia. SNO-Hb levels declined after surgery and were directly correlated with declines in eGFR (R=0.48). Conversely, plasma EPO concentrations were elevated and inversely correlated with SNO-Hb (R=-0.53) and eGFR (R=-0.55). Finally, ICU stay negatively correlated with SNO-Hb concentration (R=-0.32). Conclusion: SNO-Hb levels are reduced following CPB in the absence of allogenic blood transfusion and are predictive of decreased renal function and prolonged ICU stay. Thus, therapies directed at maintaining or increasing SNO-Hb levels may improve outcomes in adult patients undergoing cardiac surgery.
In this study, the influence of total sn-2 palmitic triacylglycerols (TAGs) and ratio of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on the metabolic changes were investigated in Sprague-Dawley rats. Metabolomics and lipidomics profiling analysis indicated that increasing the total sn-2 palmitic TAGs and OPL to OPO ratio in HMFS could significantly influence glycine, serine and threonine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid metabolism, bile acid biosynthesis, and taurine and hypotaurine metabolism pathways in rats after 4 weeks of feeding, which were mainly related to lipid, bile acid and energy metabolism. Meanwhile, the up-regulation of taurine, L-tryptophan, and L-cysteine, and down-regulations of lysoPC (18:0) and hypoxanthine would contribute to the reduction in inflammatory response and oxidative stress, and improvement of immunity function in rats. In addition, analysis of targeted biochemical factors also revealed that HMFS-fed rats had significantly increased levels of anti-inflammatory factor (IL-4), immunoglobulin A (IgA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px), and decreased levels of pro-inflammatory factors (IL-6 and TNF-α) and malondialdehyde (MDA), compared with those of the control fat-fed rats. Collectively, these observations present new in vivo nutritional evidence for the metabolic regulatory effects of the TAG structure and composition of human milk fat substitutes on the host.
Fat Substitutes , Milk, Human , Rats, Sprague-Dawley , Triglycerides , Animals , Milk, Human/chemistry , Triglycerides/metabolism , Humans , Rats , Fat Substitutes/pharmacology , Male , Lipid Metabolism/drug effects , Glycerides/metabolism , Glycerides/pharmacology , Metabolomics/methods , Lipidomics , Oxidative Stress/drug effects , Female
The organic matter molecular mechanism by which combined hydrothermal carbonization (co-HTC) of municipal sludge (MS) and agricultural wastes (rice husk, spent mushroom substrate, and wheat straw) reduces the inhibitory effects of aqueous phase (AP) products on pak choi (Brassica campestris L.) growth compared to HTC of MS alone is not clear. Fourier-transform ion cyclotron resonance mass spectrometry was used to characterize the differences in organic matter at the molecular level between AP from MS HTC alone (AP-MS) and AP from co-HTC of MS and agricultural waste (co-Aps). The results showed that N-bearing molecules of AP-MS and co-Aps account for 70.6 % and 54.2 %-64.1 % of all molecules, respectively. Lignins were present in the highest proportion (56.3 %-78.5 %) in all APs, followed by proteins and lipids. The dry weight of co-APs hydroponically grown pak choi was 31.6 %-47.6 % higher than that of the AP-MS. Molecules that were poorly saturated and with low aromaticity were preferentially consumed during hydroponic treatment. Molecules present before and after hydroponics were defined as resistant molecules; molecules present before hydroponics but absent after hydroponics were defined as removed molecules; and molecules absent before hydroponics but present after hydroponics were defined as produced molecules. Large lignin molecules were broken down into more unsaturated molecules, but lignins were the most commonly resistant, removed, and produced molecules. Correlation analysis revealed that N- or S-bearing molecules were phytotoxic in the AP. Tannins positively influenced the growth of pak choi. These results provide new insights into potential implementation strategies for liquid fertilizers produced from AP arising from HTC of MS and agricultural wastes.
Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.
Emodin , Fibrosis , Mitochondria , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Renal Insufficiency, Chronic , Animals , Emodin/pharmacology , Emodin/therapeutic use , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Fibrosis/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism , Male , Rats , Rats, Sprague-Dawley , Homeostasis/drug effects , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Ureteral Obstruction/pathology , Ureteral Obstruction/drug therapy , Transforming Growth Factor beta1/metabolism , Cell Line
A significant gap exists in the demand for safe and effective drugs for inflammatory bowel disease (IBD), and its associated intestinal fibrosis. As oxidative stress plays a central role in the pathogenesis of IBD, astaxanthin (AST), a good antioxidant with high safety, holds promise for treating IBD. However, the application of AST is restricted by its poor solubility and easy oxidation. Herein, different protein-based nanoparticles (NPs) are fabricated for AST loading to identify an oral nanovehicle with potential clinical applicability. Through systematic validation via molecular dynamics simulation and in vitro characterization of properties, whey protein isolate (WPI)-driven NPs using a simple preparation method without the need for cross-linking agents or emulsifiers were identified as the optimal carrier for oral AST delivery. Upon oral administration, the WPI-driven NPs, benefiting from the intrinsic pH sensitivity and mucoadhesive properties, effectively shielded AST from degradation by gastric juices and targeted release of AST at intestinal lesion sites. Additionally, the AST NPs displayed potent therapeutic efficacy in both dextran sulfate sodium (DSS)-induced acute colitis and chronic colitis-associated intestinal fibrosis by ameliorating inflammation, oxidative damage, and intestinal microecology. In conclusion, the AST WPI NPs hold a potential therapeutic value in treating inflammation and fibrosis in IBD.
