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1.
Int J Biol Macromol ; : 132889, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844288

RESUMO

HZMP-1 is a new polysaccharide isolated from Huang Zhen mycoplasm that contains seven monosaccharides, and it has an average molecular weight of 16.817 kDa. Its structural characteristics indicate that the surface of HZMP-1 is dense and rough, with some irregular protrusions. Animal experiments have shown that HZMP-1 can enhance liver protection, affect lipid-lowering indicators by reducing those related to lipid accumulation and damage in the serum and liver, upregulate genes that accelerate liver lipid oxidation and transport, downregulate genes that promote lipid deposition in the liver, increase the expression of lipid degradation proteins in the liver, and reduce the expression of lipid synthesis proteins. The improvement effect of HZMP-1 on NAFLD was further demonstrated using metabolomics methods. The results of this study indicated that HZMP-1 extracted from Huang Zhen mycoplasm significantly alleviates HFD-induced NAFLD in mice and has good potential for preventing and treating NAFLD.

3.
Front Plant Sci ; 15: 1260591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567126

RESUMO

Introduction: Low-temperature stress negatively impacts rice yield, posing a significant risk to food security. While previous studies have explored the physiological and linear gene expression alterations in rice under low-temperature conditions, the changes in competing endogenous RNA (ceRNA) networks remain largely unexamined. Methods: We conducted RNA sequencing on two japonica rice varieties with differing cold-tolerance capabilities to establish ceRNA networks. This enabled us to investigate the transcriptional regulatory network and molecular mechanisms that rice employs in response to low-temperature stress. Results: We identified 364 differentially expressed circular RNAs (circRNAs), 224 differentially expressed microRNAs (miRNAs), and 12,183 differentially expressed messenger RNAs (mRNAs). WRKY family was the most prominent transcription factor family involved in cold tolerance. Based on the expression patterns and targeted relationships of these differentially expressed RNAs, we discerned five potential ceRNA networks related to low-temperature stress in rice: osa-miR166j-5p from the miR166 family was associated with cold tolerance; osa-miR528-3p and osa-miR156j-3p were linked to stress response; and osa-miR156j-3p was involved in the antioxidant system. In addition, Os03g0152000 in the antioxidant system, as well as Os12g0491800 and Os05g0381400, correlated with the corresponding stress response and circRNAs in the network. A gene sequence difference analysis and phenotypic validation of Os11g0685700 (OsWRKY61) within the WRKY family suggested its potential role in regulating cold tolerance in rice. Discussion and conclusion: We identified Os11g0685700 (OsWRKY61) as a promising candidate gene for enhancing cold tolerance in japonica rice. The candidate miRNAs, mRNAs, and circRNAs uncovered in this study are valuable targets for researchers and breeders. Our findings will facilitate the development of cold-tolerant rice varieties from multiple angles and provide critical directions for future research into the functions of cold-tolerance-related miRNAs, mRNAs, and circRNAs in rice.

4.
Foods ; 13(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38672866

RESUMO

Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (<23 AA) were successfully identified by LC-MS/MS from goat milk hydrolysates (hydrolyzed by papaian plus proteinase K). Then, 105 potential DPP-IV inhibitory peptides were screened using PeptideRanker, the ToxinPred tool, Libdock, iDPPIV-SCM, and sequence characteristics. After ADME, physicochemical property evaluation, and a literature search, 12 candidates were efficiently selected and synthesized in vitro for functional validation. Two peptides (YPF and LLLP) were found to exert relatively high in vitro chemical system (IC50 = 368.54 ± 12.97 µM and 213.99 ± 0.64 µM) and in situ (IC50 = 159.46 ± 17.40 µM and 154.96 ± 8.41 µM) DPP-IV inhibitory capacities, and their inhibitory mechanisms were further explored by molecular docking. Our study showed that the formation of strong non-bonding interactions with the core residues from the pocket of DPP-IV (such as ARG358, PHE357, GLU205, TYR662, TYR547, and TYR666) might primarily account for the DPP-IV inhibitory activity of two identified peptides. Overall, the two novel DPP-IV inhibitory peptides rapidly identified in this study can be used as functional food ingredients for the control of diabetes.

5.
Food Chem ; 449: 139244, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583397

RESUMO

This study aimed to investigate the effects of edible gum addition on moisture changes in freeze-dried restructured strawberry blocks (FRSB), which involved five groups: the control, 1.2% guar gum, 1.2% gelatin, 1.2% pectin, and the composite group with 0.5% guar gum, 0.5% gelatin, and 0.45% pectin. The results indicated that the drying rates of the five groups of FRSB presented similar early acceleration and later deceleration trends. Moisture content in FRSB was linearly predicted by peak area of low field nuclear magnetic resonance with R2 higher than 0.90 for all the five groups. The FRSB samples in the gelatin and composition groups formed a denser porous structure and had a lower hygroscopicity after four days of storage. This study provides a theoretical basis for controlling the processing of FRSB.


Assuntos
Fragaria , Liofilização , Galactanos , Gelatina , Mananas , Pectinas , Gomas Vegetais , Água , Galactanos/química , Gomas Vegetais/química , Mananas/química , Gelatina/química , Pectinas/química , Fragaria/química , Água/química , Frutas/química
6.
Helicobacter ; 29(2): e13066, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468575

RESUMO

BACKGROUND: SHP1 has been documented as a tumor suppressor and it was thought to play an antagonistic role in the pathogenesis of Helicobacter pylori infection. In this study, the exact mechanism of this antagonistic action was studied. MATERIALS AND METHODS: AGS, MGC803, and GES-1 cells were infected with H. pylori, intracellular distribution changes of SHP1 were first detected by immunofluorescence. SHP1 overexpression and knockdown were then constructed in these cells to investigate its antagonistic roles in H. pylori infection. Migration and invasion of infected cells were detected by transwell assay, secretion of IL-8 was examined via ELISA, the cells with hummingbird-like alteration were determined by microexamination, and activation of JAK2/STAT3, PI3K/Akt, and ERK pathways were detected by immunoblotting. Mice infection model was established and gastric pathological changes were evaluated. Finally, the SHP1 activator sorafenib was used to analyze the attenuating effect of SHP1 activation on H. pylori pathogenesis in vitro and in vivo. RESULTS: The sub-localization of SHP1 changed after H. pylori infection, specifically that the majority of the cytoplasmic SHP1 was transferred to the cell membrane. SHP1 inhibited H. pylori-induced activation of JAK2/STAT3 pathway, PI3K/Akt pathway, nuclear translocation of NF-κB, and then reduced EMT, migration, invasion, and IL-8 secretion. In addition, SHP1 inhibited the formation of CagA-SHP2 complex by dephosphorylating phosphorylated CagA, reduced ERK phosphorylation and the formation of CagA-dependent hummingbird-like cells. In the mice infection model, gastric pathological changes were observed and increased IL-8 secretion, indicators of cell proliferation and EMT progression were also detected. By activating SHP1 with sorafenib, a significant curative effect against H. pylori infection was obtained in vitro and in vivo. CONCLUSIONS: SHP1 plays an antagonistic role in H. pylori pathogenesis by inhibiting JAK2/STAT3 and PI3K/Akt pathways, NF-κB nuclear translocation, and CagA phosphorylation, thereby reducing cell EMT, migration, invasion, IL-8 secretion, and hummingbird-like changes.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Animais , Camundongos , Proteínas de Bactérias/metabolismo , Antígenos de Bactérias/metabolismo , Helicobacter pylori/fisiologia , NF-kappa B/metabolismo , Interleucina-8/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Infecções por Helicobacter/patologia , Sorafenibe/metabolismo , Células Epiteliais/metabolismo
7.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396991

RESUMO

Low-temperature chilling is a major abiotic stress leading to reduced rice yield and is a significant environmental threat to food security. Low-temperature chilling studies have focused on physiological changes or coding genes. However, the competitive endogenous RNA mechanism in rice at low temperatures has not been reported. Therefore, in this study, antioxidant physiological indices were combined with whole-transcriptome data through weighted correlation network analysis, which found that the gene modules had the highest correlation with the key antioxidant enzymes superoxide dismutase and peroxidase. The hub genes of the superoxide dismutase-related module included the UDP-glucosyltransferase family protein, sesquiterpene synthase and indole-3-glycerophosphatase gene. The hub genes of the peroxidase-related module included the WRKY transcription factor, abscisic acid signal transduction pathway-related gene plasma membrane hydrogen-ATPase and receptor-like kinase. Therefore, we selected the modular hub genes and significantly enriched the metabolic pathway genes to construct the key competitive endogenous RNA networks, resulting in three competitive endogenous RNA networks of seven long non-coding RNAs regulating three co-expressed messenger RNAs via four microRNAs. Finally, the negative regulatory function of the WRKY transcription factor OsWRKY61 was determined via subcellular localization and validation of the physiological indices in the mutant.


Assuntos
MicroRNAs , Oryza , RNA Longo não Codificante , Oryza/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Antioxidantes , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Redes Reguladoras de Genes , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Peroxidases/genética , Superóxido Dismutase/genética
8.
Nano Lett ; 24(6): 2094-2101, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315573

RESUMO

Prelithiation plays a crucial role in advancing the development of high-energy-density batteries, and ultrathin lithium (UTL) has been proven to be a promising anode prelithiation reagent. However, there remains a need to explore an adjustable, efficient, and cost-effective method for manufacturing UTL. In this study, we introduce a method for producing UTL with adjustable thicknesses ranging from 1.5 to 10 µm through blade coating of molten lithium on poly(vinylidene fluoride)-modified copper current collectors. By employing the transfer-printing method, prelithiated graphite and Si-C composite electrodes are prepared, which exhibit significantly improved initial Coulombic efficiencies of 99.60% and 99.32% in half-cells, respectively. Moreover, the energy densities of Li(NiCoMn)1/3O2 and LiFePO4 full cells assembled with the prelithiated graphite electrodes increase by 13.1% and 23.6%, respectively.

9.
Int J Biol Macromol ; 259(Pt 1): 129191, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184042

RESUMO

Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides were screened and identified from yak hemoglobin for the first time by in silico analysis, molecular docking, and in vitro evaluation. Results showed that yak hemoglobin had a high potential to produce DPP-IV inhibitory peptides based on the sequence alignment and bioactive potential evaluation. Furthermore, "pancreatic elastase + stem bromelain" was the optimal combined-enzymatic strategy by simulated proteolysis. Additionally, 25 novel peptides were found from its simulated hydrolysate, among which 10 peptides had high binding affinities with DPP-IV by molecular docking. Most of these peptides were also in silico characterized with favorable physicochemical properties and biological potentials, including relatively low molecular weight, high hydrophobicity, several net charges, good water solubility, nontoxicity, acceptable sensory quality, and good human intestinal absorption. Finally, six novel DPP-IV inhibitory peptides were identified via in vitro assessment, among which EEKA (IC50 = 235.26 µM), DEV (IC50 = 339.45 µM), and HCDKL (IC50 = 632.93 µM) showed the strongest capacities. The hydrogen bonds and electrostatic attractions formed with core residues within the S2 pocket of DPP-IV could be mainly responsible for their inhibition performances. This work provided a time-saving method and broadened application for yak by-products development as sources of functional foods.


Assuntos
Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV , Animais , Bovinos , Humanos , Simulação de Acoplamento Molecular , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/química , Peptídeos/química , Hemoglobinas
10.
Small ; 20(7): e2306227, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37806748

RESUMO

γ-valerolactone (GVL) is a key value-added chemical catalytically produced from levulinic acid (LA), an important biomass derivative platform chemical. Here an ultra-efficient 3D Ru catalyst generated by in situ reduction of RuZnOx nanoboxes is reported; the catalyst features a well-defined structure of highly dispersed in situ oxide-derived Ru (IOD-Ru) clusters (≈1 nm in size) spatially confined within the 3D nanocages with rich mesopores, which guarantees a maximized atom utilization with a high exposure of Ru active sites as well as a 3D accessibility for substrate molecules. The IOD-Ru exhibits ultrahigh performance for the hydrogenation of LA into GVL with a record-breaking turnover frequency (TOF) up to 59400 h-1 , 14 times higher than that of the ex situ reduction of RuZnOx nanoboxes catalyst. Structural characterizations and theoretical calculations collectively indicate that the defect-rich and coordination-unsaturated IOD-Ru sites can boost the activation of the carbonyl group in LA with a significantly lowered energy barrier of hydrogenation.

11.
Plant Phenomics ; 5: 0098, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791248

RESUMO

Plant phenomics aims to perform high-throughput, rapid, and accurate measurement of plant traits, facilitating the identification of desirable traits and optimal genotypes for crop breeding. Salvia miltiorrhiza (Danshen) roots possess remarkable therapeutic effect on cardiovascular diseases, with huge market demands. Although great advances have been made in metabolic studies of the bioactive metabolites, investigation for S. miltiorrhiza roots on other physiological aspects is poor. Here, we developed a framework that utilizes image feature extraction software for in-depth phenotyping of S. miltiorrhiza roots. By employing multiple software programs, S. miltiorrhiza roots were described from 3 aspects: agronomic traits, anatomy traits, and root system architecture. Through K-means clustering based on the diameter ranges of each root branch, all roots were categorized into 3 groups, with primary root-associated key traits. As a proof of concept, we examined the phenotypic components in a series of randomly collected S. miltiorrhiza roots, demonstrating that the total surface of root was the best parameter for the biomass prediction with high linear regression correlation (R2 = 0.8312), which was sufficient for subsequently estimating the production of bioactive metabolites without content determination. This study provides an important approach for further grading of medicinal materials and breeding practices.

12.
Int J Biol Macromol ; 253(Pt 6): 127312, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37827416

RESUMO

The angiotensin I-converting enzyme (ACE)-inhibitory peptide SQPK was selected by in silico digestion and virtual screening from goat ß-casein, and its effect and regulatory mechanism on function of endothelial cells was further evaluated. The results showed that SQPK exhibited relatively good ACE inhibition capacity (IC50 = 452.7 µg/mL). Treatment with 25 µg/mL SQPK for 12 h significantly elevated nitric oxide (NO) production, stimulated eNOS expression (p < 0.05) and affected the transcriptomic profiling of EA. Hy926 cells. In particular, SQPK stimulated the expression of genes encoding inflammatory cytokines (CXCL1/2 and IL6) but depressed encoding mesenchymal markers (FN1 and CNN3). Furthermore, SQPK modified the expression of genes involved in endothelial-to-mesenchymal transition (EndMT). Therefore, the selected peptide SQPK may exert potential protective effects on the function of endothelial cells by inhibiting the EndMT.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Caseínas , Animais , Caseínas/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Células Endoteliais/metabolismo , Cabras/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo
13.
Acta Trop ; 247: 107012, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37659685

RESUMO

BACKGROUND: Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the recommended oral treatment for schistosomiasis. The main pathologic manifestation of schistosomiasis is liver injury. However, the role and interactions of various RNA molecules in the effect of PZQ on the liver after S. japonicum infection have not been elucidated. RESULTS: In this study, C57BL/6 mice were randomly divided into the control group, infection group, and PZQ treatment group. Total RNA was extracted from the livers of the mice. High-throughput whole transcriptome sequencing was performed to detect the RNA expression profiles in the three groups. A co-expression gene-interaction network was established based on the significant differentially expressed genes in the PZQ treatment group; messenger RNA (mRNA) Cyp4a14 was identified as a critical hub gene. Furthermore, competitive endogenous RNA networks were constructed by predicting the specific binding relations between mRNA and long noncoding (lnc) RNA and between lncRNA and microRNA (miRNA) of Cyp4a14, suggesting the involvement of the H19/miR-130b-3p/Cyp4a14 regulatory axis. Dual luciferase reporter assay result proved the specific binding of miR-130b-3p with Cyp4a14 3'UTR. CONCLUSIONS: Our findings indicate the involvement of the H19/miR-130b-3p/Cyp4a14 axis in the effect of PZQ on the liver after S. japonicum infection. Moreover, the expression of mRNA Cyp4a14 could be regulated by the bonding of miR-130b-3p with 3'UTR of Cyp4a14. The findings of this study could provide a novel perspective to understand the host response to PZQ against S. japonicum in the future.


Assuntos
MicroRNAs , Esquistossomose Japônica , Animais , Camundongos , Camundongos Endogâmicos C57BL , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Esquistossomose Japônica/tratamento farmacológico , Regiões 3' não Traduzidas , Fígado , MicroRNAs/genética , RNA Mensageiro , Transcriptoma
14.
Molecules ; 28(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37570706

RESUMO

The development of efficient electrocatalysts for hydrogen evolution reactions is an extremely important area for the development of green and clean energy. In this work, a precursor material was successfully prepared via electrodeposition of two doping elements to construct a co-doped cobalt hydroxide electrocatalyst (Ru-Co(OH)2-Se). This approach was demonstrated to be an effective way to improve the performance of the hydrogen evolution reaction (HER). The experimental results show that the material exhibited a smaller impedance value and a larger electrochemically active surface area. In the HER process, the overpotential was only 109 mV at a current density of 10 mA/cm2. In addition, the doping of selenium and ruthenium effectively prevented the corrosion of the catalysts, with the (Ru-Co(OH)2-Se) material showing no significant reduction in the catalytic performance after 50 h. This synergistic approach through elemental co-doping demonstrated good results in the HER process.

15.
Adv Sci (Weinh) ; 10(26): e2301872, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37395639

RESUMO

The increasing demand for clean energy conversion and storage has increased interest in hydrogen production via electrolytic water splitting. However, the simultaneous production of hydrogen and oxygen in this process poses a challenge in extracting pure hydrogen without using ionic conducting membranes. Researchers have developed various innovative designs to overcome this issue, but continuous water splitting in separated tanks remains a desirable approach. This study presents a novel, continuous roll-to-roll process that enables fully decoupled hydrogen evaluation reaction (HER) and oxygen evolution reaction (OER) in two separate electrolyte tanks. The system utilizes specially designed "cable-car" electrodes (CCE) that cycle between the HER and OER tanks, resulting in continuous hydrogen production with a purity of over 99.9% and Coulombic efficiency of 98% for prolonged periods. This membrane-free water splitting system offers promising prospects for scaled-up industrial-scale green hydrogen production, as it reduces the cost and complexity of the system, and allows for the use of renewable energy sources to power the electrolysis process, thus reducing the carbon footprint of hydrogen production.

16.
ACS Omega ; 8(21): 18472-18478, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37273579

RESUMO

Oily sludge (OS) was extracted with petroleum ether (PE), methanol, carbon disulfide (CDS), acetone, and isometric CDS/acetone mixture (IMCDSAM), respectively, to obtain soluble species (E1-E5) and extraction residues (R1-R5). The soluble species were analyzed by gas chromatography/mass spectrometry (GC/MS), and the extraction residues were characterized by Fourier transform infrared spectrometry (FTIR) and thermogravimetric analysis (TGA). Results showed that the extract yield of the soluble species from OS using CDS and IMCDSAM as the solvent was 61.0 and 67.3%, respectively. GC/MS results exhibited that the compounds detected in E1-E5 are mainly hydrocarbons and oxygen-containing compounds. E1-E5 are rich in alkanes, alkenes, ketones, alcohols, and other oxygen-containing compounds. Double-bond equivalence (DBE) and carbon numbers (CNs) of the compounds detected in E1, E2, and E4 are distributed in 0-4 (DBE) and 10-20 (CNs), respectively, while the DBE and CNs of the detected compounds in E3 and E5 are concentrated in 0-6 and 15-35, respectively. Thermogravimetry-differential thermogravimetry (TG-DTG) profiles presented that pyrolysis of OS occurred mainly in the temperature range of 150-750 °C, while pyrolysis of R1-R5 took place in the range of 350-750 °C. In the temperature range of 150-550 °C, the weight losses of OS and each extraction residue differ significantly, with OS having a much higher weight loss than the extraction residues. Meanwhile, the possible mechanism of oily sludge extraction was considered. Results revealed that selecting a low-polar or nonpolar solvent capable of selectively destroying hydrogen bonds and/or aromatic interactions is critical for improving the extract yield of OS.

17.
J Am Chem Soc ; 145(23): 12884-12893, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37249907

RESUMO

Lignin is the most abundant aromatic polymer from the natural and renewable lignocellulosic biomass resource. Developing highly efficient catalysts for lignin depolymerization to produce valuable monophenols with high yield and selectivity remains a desirable but challenging target in this field. Here, we design a synergistic catalyst combining atomically dispersed Mo centers and Al Lewis acid sites on a MgO substrate (Mo1Al/MgO) for the depolymerization of Eucalyptus lignin via the ß-aryl ether bond cleavage. A near-theoretical monophenol yield of 46% with an ultrahigh selectivity of 92% for coniferyl and sinapyl methyl ether, as well as good cycling durability, was achieved simultaneously by Mo1Al/MgO in an inert N2 atmosphere. First-principles calculations and control catalytic experiments confirmed the synergistic catalysis mechanism between Mo1-O5 single-atom centers and the neighboring Al Lewis acid sites with the participation of a methanol solvent. This study validates the feasibility of designing better-performing catalysts with synergistic multiactive sites for the efficient and selective disassembly of complex renewable biopolymers into highly value-added products with lower cost and greater security.

18.
Microbiol Spectr ; 11(3): e0030223, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37212669

RESUMO

Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota. However, the role and mechanism of the gut microbiota in cognitive impairment after METH exposure are still largely unknown. Here, we investigated the impact of the gut microbiota on the phenotype status of microglia (microglial phenotypes M1 and microglial M2) and their secreting factors, the subsequent hippocampal neural processes, and the resulting influence on spatial learning and memory of chronically METH-exposed mice. We determined that gut microbiota perturbation triggered the transformation of microglial M2 to M1 and a subsequent change of pro-brain-derived neurotrophic factor (proBDNF)-p75NTR-mature BDNF (mBDNF)-TrkB signaling, which caused reduction of hippocampal neurogenesis and synaptic plasticity-related proteins (SYN, PSD95, and MAP2) and, consequently, deteriorated spatial learning and memory. More specifically, we found that Clostridia, Bacteroides, Lactobacillus, and Muribaculaceae might dramatically affect the homeostasis of microglial M1/M2 phenotypes and eventually contribute to spatial learning and memory decline after chronic METH exposure. Finally, we found that fecal microbial transplantation could protect against spatial learning and memory decline by restoring the microglial M1/M2 phenotype status and the subsequent proBDNF-p75NTR/mBDNF-TrkB signaling in the hippocampi of chronically METH-exposed mice. IMPORTANCE Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated "specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment" pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.


Assuntos
Microbioma Gastrointestinal , Metanfetamina , Camundongos , Animais , Metanfetamina/toxicidade , Metanfetamina/metabolismo , Aprendizagem Espacial , Microglia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Fenótipo
19.
Microbiol Spectr ; : e0471522, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36942972

RESUMO

Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury (ALI) in Western countries. Many studies have shown that the gut microbiota plays an important role in liver injury. Currently, the only approved treatment for APAP-induced ALI is N-acetylcysteine; therefore, it is essential to develop new therapeutic agents and explore the underlying mechanisms. We developed a novel monoclonal anti-Toll-like receptor 4 (TLR4) antibody (ATAB) and hypothesized that it has therapeutic effects on APAP-induced ALI and that the gut microbiota may be involved in the underlying mechanism of ATAB treatment. Male C57BL/6 mice were treated with APAP and ATAB, which produced a therapeutic effect on ALI and altered the members of the gut microbiota and their metabolic pathways, such as Roseburia, Lactobacillus, Akkermansia, and the fatty acid pathway, etc. Furthermore, we verified that purified short-chain fatty acids (SCFAs) could alleviate ALI. Moreover, a separate group of mice that received feces from the ATAB group showed less severe liver injury than mice that received feces from the APAP group. ATAB therapy also improved gut barrier functions in mice and reduced the expression of the protein zonulin. Our results revealed that the gut microbiota plays an important role in the therapeutic effect of ATAB on APAP-induced ALI. IMPORTANCE In this study, we found that a monoclonal anti-Toll-like receptor 4 antibody can alleviate APAP-induced acute liver injury through changes in the gut microbiota, metabolic pathways, and gut barrier function. This work suggested that the gut microbiota can be a therapeutic target of APAP-induced acute liver injury, and we performed foundation for further research.

20.
Sci Adv ; 9(13): eadg1746, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36989361

RESUMO

Magnetocardiography (MCG), which uses high-sensitivity magnetometers to record magnetic field signals generated by electrical activity in the heart, is a noninvasive method for evaluating heart diseases such as arrhythmia and ischemia. The MCG measurements usually require the participant keeping still in a magnetically shielded room due to the immovable sensor and noisy external environments. These requirements limit MCG applications, such as exercise MCG tests and long-term MCG observations, which are useful for early detections of heart diseases. Here, we introduce a movable MCG system that can clearly record MCG signals of freely behaving participants in an unshielded environment. On the basis of optically pumped magnetometers with a sensitivity of 140 fT/Hz1/2, we successfully demonstrated the resting MCG and the exercise MCG tests. Our method is promising to realize a practical movable multichannel unshielded MCG system that nearly sets no limits to participants and brings another kind of insight into the medical diagnosis of heart disease.


Assuntos
Cardiopatias , Magnetocardiografia , Humanos , Magnetocardiografia/métodos , Arritmias Cardíacas/diagnóstico , Teste de Esforço , Coração
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