Discovery of a class of glycosaminoglycan lyases with ultrabroad substrate spectrum and their substrate structure preferences.

Glycosaminoglycan (GAG) lyases are often strictly substrate specific, and it is especially difficult to simultaneously degrade GAGs with different types of glycosidic bonds. Herein, we found a new class of GAG lyases (GAGases) from different bacteria. These GAGases belong to polysaccharide lyase 35 family and share quite low homology with the identified GAG lyases. The most surprising thing is that GAGases can not only degrade three types of GAGs: HA, CS and HS, but even one of them can also degrade alginate. Further investigation of structural preferences revealed that GAGases selectively act on GAG domains composed of non/6-O-/N-sulfated hexosamines and d-glucoronic acids, as well as on alginate domains composed of d-mannuronic acids. Additionally, GAG lyases were once speculated to have evolved from alginate lyases, but no transitional enzymes have been found. The discovery of GAGases not only broadens the category of GAG lyases, provides new enzymatic tools for the structural and functional studies of GAGs with specific structures, but also provides candidates for the evolution of GAG lyases.

Armillariella tabescens-derived polysaccharides alleviated â±°-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway.

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans-A Pilot Study.

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group-except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.

A Comparison and Safety Evaluation of Micellar versus Standard Vitamin D3 Oral Supplementation in a Randomized, Double-Blind Human Pilot Study.

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.

Predicting brain edema and outcomes after thrombectomy in stroke: Frontal delta/alpha ratio as an optimal quantitative EEG index.

OBJECTIVE: We aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). METHODS: A total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. RESULTS: Significantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. CONCLUSIONS: QEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SIGNIFICANCE: QEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.

Burden and trends of infectious disease mortality attributed to air pollution, unsafe water, sanitation, and hygiene, and non-optimal temperature globally and in different socio-demographic index regions.

BACKGROUND: Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. METHODS: This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. RESULTS: In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65-69, 75-79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. CONCLUSIONS: Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Global, regional and national trends and impacts of natural floods, 1990-2022.

Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings: From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion: Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation.

Roles of Pseudomonas aeruginosa siderophores in interaction with prokaryotic and eukaryotic organisms.

Pseudomonas aeruginosa is an opportunistic pathogen that produces two types of siderophores, pyoverdine and pyochelin, that play pivotal roles in iron scavenging from the environment and host cells. P. aeruginosa siderophores can serve as virulence factors and perform various functions. Several bacterial and fungal species are likely to interact with P. aeruginosa due to its ubiquity in soil and water as well as its potential to cause infections in plants, animals, and humans. Siderophores produced by P. aeruginosa play critical roles in iron scavenging for prokaryotic species (bacteria) and eukaryotic hosts (fungi, animals, insects, invertebrates, and plants) as well. This review provides a comprehensive discussion of the role of P. aeruginosa siderophores in interaction with prokaryotes and eukaryotes as well as their underlying mechanisms of action. The evolutionary relationship between P. aeruginosa siderophore recognition receptors, such as FpvA, FpvB, and FptA, and those of other bacterial species has also been investigated.

Inhibition of BMP-mediated SMAD pathway supports the pluripotency of pig embryonic stem cells in the absence of feeder cells.

Here, we examined the effects of the BMP signaling pathway inhibitor LDN-193189 on the pluripotency of porcine embryonic stem cells (ESCs) in the absence of feeder cells using molecular and transcriptomic techniques. Additionally, the effects of some extracellular matrix components on porcine ESC pluripotency were evaluated to develop an optimized and sustainable feeder-free culture system for porcine ESCs. Feeder cells were found to play an important role in supporting the pluripotency of porcine ESCs by blocking trophoblast and mesodermal differentiation through the inhibition of the BMP pathway. Additionally, treatment with LDN-193189, an inhibitor of the BMP pathway, maintained the pluripotency and homogeneity of porcine ESCs for an extended period in the absence of feeder cells by stimulating the secretion of chemokines and suppressing differentiation, based on transcriptome analysis. Conclusively, these results suggest that LDN-193189 could be a suitable replacement for feeder cells in the maintenance of porcine ESC pluripotency during culture. Additionally, these findings contribute to the understanding of pluripotency gene networks and comparative embryogenesis.

Evaluation of the Metabolite Profile of Fish Oil Omega-3 Fatty Acids (n-3 FAs) in Micellar and Enteric-Coated Forms-A Randomized, Cross-Over Human Study.

This study evaluated the differences in the metabolite profile of three n-3 FA fish oil formulations in 12 healthy participants: (1) standard softgels (STD) providing 600 mg n-3 FA; (2) enteric-coated softgels (ENT) providing 600 mg n-3 FA; (3) a new micellar formulation (LMF) providing 374 mg n-3 FA. The pharmacokinetics (PKs), such as the area under the plot of plasma concentration (AUC), and the peak blood concentration (Cmax) of the different FA metabolites including HDHAs, HETEs, HEPEs, RvD1, RvD5, RvE1, and RvE2, were determined over a total period of 24 h. Blood concentrations of EPA (26,920.0 ± 10,021.0 ng/mL·h) were significantly higher with respect to AUC0-24 following LMF treatment vs STD and ENT; when measured incrementally, blood concentrations of total n-3 FAs (EPA/DHA/DPA3) up to 11 times higher were observed for LMF vs STD (iAUC 0-24: 16,150.0 ± 5454.0 vs 1498.9 ± 443.0; p ≤ 0.0001). Significant differences in n-3 metabolites including oxylipins were found between STD and LMF with respect to 12-HEPE, 9-HEPE, 12-HETE, and RvD1; 9-HEPE levels were significantly higher following the STD vs. ENT treatment. Furthermore, within the scope of this study, changes in blood lipid levels (i.e., cholesterol, triglycerides, LDL, and HDL) were monitored in participants for up to 120 h post-treatment; a significant decrease in serum triglycerides was detected in participants (~20%) following the LMF treatment; no significant deviations from the baseline were detected for all the other lipid biomarkers in any of the treatment groups. Despite a lower administered dose, LMF provided higher blood concentrations of n-3 FAs and certain anti-inflammatory n-3 metabolites in human participants-potentially leading to better health outcomes.

Attenuation of biofilm and virulence factors of Pseudomonas aeruginosa by tetramethylpyrazine-gold nanoparticles.

Pseudomonas aeruginosa is often identified as the causative agent in nosocomial infections. Their adapted resistance makes them strong towards antimicrobial treatments. They protect and empower their survival behind strong biofilm architecture that works as their armor toward antimicrobial therapy. Additionally, P. aeruginosa generates virulence factors, contributing to chronic infection and recalcitrant phenotypic characteristics. The current study utilizes the benevolence of nanotechnology to develop an alternate technique to control the spreading of P. aeruginosa by limiting its biofilm and virulence development. This study used a natural compound, tetramethylpyrazine, to generate gold nanoparticles. Tetramethylpyrazine-gold nanoparticles (Tet-AuNPs) were presented in spherical shapes, with an average size of 168 ± 52.49 nm and a zeta potential of -12.22 ± 2.06 mV. The minimum inhibition concentration (MIC) of Tet-AuNPs that proved more than 90 % effective in inhibiting P. aeruginosa was 256 µg/mL. Additionally, it also shows antibacterial activities against Staphylococcus aureus (MIC, 256 µg/mL), Streptococcus mutans (MIC, 128 µg/mL), Klebsiella pneumoniae (MIC, 128 µg/mL), Listeria monocytogenes (MIC, 256 µg/mL), and Escherichia coli (MIC, 256 µg/mL). The sub-MIC values of Tet-AuNPs significantly inhibited the early-stage biofilm formation of P. aeruginosa. Moreover, this concentration strongly affected hemolysis, protease activity, and different forms of motilities in P. aeruginosa. Additionally, Tet-AuNPs destroyed the well-established mature biofilm of P. aeruginosa. The expression of genes linked with the biofilm formation and virulence in P. aeruginosa treated with sub-MIC doses of Tet-AuNPs was shown to be significantly suppressed. Gene expression studies support biofilm- and virulence-suppressing effects of Tet-AuNPs at the phenotypic level.

Study on mechanism underlying the acceleration of pitting corrosion of B30 copper-nickel alloy by sulfate-reducing bacteria in seawater.

In this paper, the relationship between the pitting corrosion formation of B30 copper-nickel (CuNi) alloy and the metabolism of sulfate-reducing bacteria (SRB) was investigated. Combined with the influence of temperature during the actual operation of the cooling systems, the evolution law of the alloy passivation film was analyzed, and the mechanism of SRB promoting the accelerated development of B30 CuNi alloy pitting corrosion was revealed. The results show that SRB significantly promoted the pitting formation and development of B30 CuNi alloy. The maximum pitting depth was 3.9 µm in the sterile system and 15.3 µm with SRB, which was 3.9 times higher than that of sterile system. The loose porous Cu2S film formed by SRB metabolites and copper matrix was easily penetrated by corrosive anions, which promoted copper dissolution and led to pit nucleation. The sulfide adsorbed on the surface prevented or delayed the passivation of B30 CuNi alloy by blocking the adsorption site of O atom, and the corrosion nuclei continued to grow. The non-uniformity caused by the film peeling accelerated the longitudinal development of pitting corrosion, and the expansion and coalescence of adjacent pits caused the transverse development of pitting corrosion. Temperature had a certain influence on the SRB and the formation of B30 CuNi alloy passivation film. The passivation film was formed rapidly at 50 °C with poor quality and the passivation property of Cu2O film was weakened. With the increase of temperature, the pitting potential of sterile system negative shifted from 0.447 to 0.360 V (vs. SCE), while SRB system from 0.340 to 0.198 V (vs. SCE), and the pitting resistance decreased. The passivation film with defects and the Cu2S reduced the barrier efficiency of the film and accelerated the pitting corrosion of B30 CuNi alloy.

Boosting Excited-State Energy Transfer by Anchoring Dipole Orientation in Binary Thermally Activated Delayed Fluorescence/J-Aggregate Assemblies.

Förster resonance energy transfer (FRET) has been widely applied in fluorescence imaging, sensing and so on, while developing useful strategy of boosting FRET efficiency becomes a key issue that limits the application. Except optimizing spectral properties, promoting orientation factor (κ2) has been well discussed but rarely utilized for boosting FRET. Herein, we constructed binary nano-assembling of two thermally activated delayed fluorescence (TADF) emitters (2CzPN and DMAC-DPS) with J-type aggregate of cyanine dye (C8S4) as doping films by taking advantage of their electrostatic interactions. Time-resolved spectroscopic measurements indicated that 2CzPN/Cy-J films exhibit an order of magnitude higher kFRET than DMAC-DPS/Cy-J films. Further quantitative analysing on kFRET and kDET indicated higher orientation factor (κ2) in 2CzPN/Cy-J films play a key role for achieving fast kFRET, which was subsequently confirmed by anisotropic measurements. Corresponding DFT/TDDFT calculation revealed strong "two-point" electrostatic anchoring in 2CzPN/Cy-J films that is responsible for highly orientated transitions. We provide a new strategy for boosting FRET in nano-assemblies, which might be inspired for designing FRET-based devices of sensing, imaging and information encryption.

Multidimensional Frailty Instruments Can Predict Acute Exacerbations Within One Year in Patients with Stable Chronic Obstructive Pulmonary Disease: A Retrospective Longitudinal Study.

Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People's Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P<0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663-0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693-0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.

Reduced graphene oxide/MXene hybrid decorated graphite felt as an effective electrode for vanadium redox flow battery.

Vanadium redox flow battery (VRFB) is a highly suitable technology for energy storage and conversion in the application of decoupling energy and power generation. However, the sluggish reaction kinetics of redox couples is one of the bottlenecks hindering the commercialization of VFFBs. Developing efficient electrode is a promising method to improve the battery performance. In this work, a reduced graphene oxide/Mxene hybrid-decorated graphite felt (rGO/Mxene@GF) is designed to facilitate the kinetics of redox reaction. The electrocatalytic activity and mass transfer of the prepared electrode are investigated through experiment and simulation methods. The results indicate that the favorable mass transfer and the synergistic effect between rGO and Ti3C2Tx Mxene remarkably improve the performance of electrode. The flow cell with rGO/Mxene@GF delivers a good stability up to 100 cycles with a coulombic, voltage, and energy efficiency of 91.6%, 82.7%, and 75.8%, respectively, at a current density of 80 mA cm-2. These findings suggest that the as-prepared rGO/Mxene@GF holds a good application potential in VRFB and provides a promising approach to design efficient electrode for electrochemical devices.

Bactericidal effect of water-washing methods on Vibrio vulnificus contaminated in a raw fish Konosirus punctatus: water type, temperature, and pH.

This study aimed to evaluate a method for effectively reducing Vibrio vulnificus contamination in fish based on the type of washing water and method. Texture profiles and sensory evaluations were performed to determine the effect of the developed method on the quality and preference of the samples. The selected fish sample was Konosirus punctatus, which is mainly consumed in Asian countries. Various factors that could affect the survival rate of V. vulnificus were reviewed, including water type, temperature, exposure time, organic acids, pH, and washing methods. As a result, immersion and washing with filtered water with pH adjusted to 4.0 using acetic acid showed a high bactericidal effect of 2.5 log MPN/100 g. Furthermore, this method showed no statistically significant effect on the texture and sensory characteristics of fish. The results of the present study suggest a simple and effective method for preventing V. vulnificus infection in raw fish.

α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction.

The epithelium lining the intestinal tract serves a multifaceted role. It plays a crucial role in nutrient absorption and immune regulation and also acts as a protective barrier, separating underlying tissues from the gut lumen content. Disruptions in the delicate balance of the gut epithelium trigger inflammatory responses, aggravate conditions such as inflammatory bowel disease, and potentially lead to more severe complications such as colorectal cancer. Maintaining intestinal epithelial homeostasis is vital for overall health, and there is growing interest in identifying nutraceuticals that can strengthen the intestinal epithelium. α-Ketoglutarate, a metabolite of the tricarboxylic acid cycle, displays a variety of bioactive effects, including functioning as an antioxidant, a necessary cofactor for epigenetic modification, and exerting anti-inflammatory effects. This article presents a comprehensive overview of studies investigating the potential of α-ketoglutarate supplementation in preventing dysfunction of the intestinal epithelium.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Rheumatoid Arthritis Symptoms via Shuttling Proteins.

Our prior investigations have evidenced that bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study aims to conduct a comprehensive analysis of the proteomics between BMSCs and BMSCs-Exos, and to further elucidate the potential therapeutic effect of BMSCs-Exos on RA, so as to establish a theoretical framework for the prevention and therapy of BMSCs-Exos on RA. The 4D label-free LC-MS/MS technique was used for comparative proteomic analysis of BMSCs and BMSCs-Exos. Collagen-induced arthritis (CIA) rat model was used to investigate the therapeutic effect of BMSCs-Exos on RA. Our results showed that some homology and differences were observed between BMSCs and BMSCs-Exos proteins, among which proteins highly enriched in BMSCs-Exos were related to extracellular matrix and extracellular adhesion. BMSCs-Exos can be taken up by chondrocytes, promoting cell proliferation and migration. In vivo results revealed that BMSCs-Exos significantly improved the clinical symptoms of RA, showing a certain repair effect on the injury of articular cartilage. In short, our study revealed, for the first time, that BMSCs-Exos possess remarkable efficacy in alleviating RA symptoms, probably through shuttling proteins related to cell adhesion and tissue repair ability in CIA rats, suggesting that BMSCs-Exos carrying expressed proteins may become a useful biomaterial for RA treatment.