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Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain's physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field. [ABSTRACT FROM AUTHOR]

Aim of the Study. This study is aimed at exploring the effects and pharmacological mechanisms of the extracts from the Heritiera littoralis fruit (EFH) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) in mice. Materials and Methods. The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results. LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions. EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) causes multiple organ dysfunction. Here, we identify a possible mechanism that can drive brain vessel injury after AKI. We induced 30-minute bilateral renal ischemia-reperfusion injury in C57Bl/6 mice and isolated brain microvessels and macrovessels 24 hours or 1 week later to test their responses to vasoconstrictors and found that after AKI brain vessels were sensitized to Ang II (angiotensin II). Upregulation of FGF2 (fibroblast growth factor 2) and FGFBP1 (FGF binding protein 1) expression in both serum and kidney tissue after AKI suggested a potential contribution to the vascular sensitization. Administration of FGF2 and FGFBP1 proteins to isolated healthy brain vessels mimicked the sensitization to Ang II after AKI. Brain vessels in Fgfbp1-/- AKI mice failed to induce Ang II sensitization. Complementary to this, systemic treatment with the clinically used FGF receptor kinase inhibitor BGJ398 (Infigratinib) reversed the AKI-induced brain vascular sensitization to Ang II. All these findings lead to the conclusion that FGFBP1 is especially necessary for AKI-mediated brain vascular sensitization to Ang II and inhibitors of FGFR pathway may be beneficial in preventing AKI-induced brain vessel injury. [ABSTRACT FROM AUTHOR]

Three undescribed seco -iridoid glycosides, one undescribed flavonoid glycoside, and three known glycosides were isolated and identified from Gentiana olivieri Griseb. The structures of these compounds were determined through spectroscopic analysis and ECD calculations. Olivierisecosides N P (1 – 3) were identified as aromatic conjugated seco -iridoid glucosides, among them olivierisecoside N was representing a particularly rare subtype known as the morroniside seco -iridoids. The compounds 2 , 3 , 5 , and 6 exhibited significant inhibition of COX-2 expression, particularly compound 5 which demonstrated the most pronounced inhibitory activity with IC 50 value of 23.33 ± 0.51 μM. This study provides evidence for the potential development and utilization of G. olivieri as a source of anti-inflammatory components. Four seco -iridoid glucosides were isolated from Gentiana olivieri Griseb, all compounds screened for their anti-inflammatory effects and compound 5 had the most significant inhibitory activity against COX-2. [Display omitted] • Four undescribed glucosides were isolated from the Gentiana olivieri Griseb. • Structures were elucidated by NMR, MS, and absolute configurations were established by ECD. • All the isolates screened for the anti-inflammatory activity by inhibition COX-2. [ABSTRACT FROM AUTHOR]

For numerous years, the Xiehuo Xiaoying decoction (XHXY), a traditional Chinese medicine formula, has demonstrated substantial promise in treating Graves' disease (GD) in clinical settings, showcasing significant potential. However, the therapeutic mechanism and efficacy material basis of XHXY remains obscure. This work aims to investigate the underlying mechanisms and to study the efficacy material basis of XHXY in anti-GD effect using a combination of TMT quantitative proteomics and molecular docking method. GD model was initiated by administering Ad-TSH289. Subsequently, the mice underwent a four-week regimen that included oral gavage of XHXY at doses of 17 g/kg·d and 34 g/kg·d, along with intraperitoneal injections of Gentiopicroside (GPS). Utilizing the principles of pharmacological chemistry in traditional Chinese medicine, we employed high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS) to discern prescribed prototype composition of XHXY in serum samples from mouse. TMT proteomics research provided evidence of XHXY's putative targets and important pathways in vivo. The binding activity of probable action targets and prototype composition was detected by molecular docking. Finally, Immunohistochemistry (IHC) and TUNEL staining were used to verify the mechanism of XHXY and GPS in anti-GD. XHXY and GPS alleviated GD by ameliorating the pathological changes and reducing thyroxine and TRAb levels. In mouse serum, a total of 31 prototypical XHXY ingredients were detected, and the majority of these components were from monarch and minister medicine. Proteomics study results indicated that the XHXY may mainly regulate targets including FAS-associated death domain protein (FADD), Apolipoprotein C-III, etc. and main pathways are Apoptosis, Cholesterol metabolism, TNF signalling pathway, etc. Strong binding activity of the prototypical active ingredient and GPS towards FADD, Caspase 8, and Caspase 3 was demonstrated by molecular docking. XHXY and its primary component, GPS, elevated the expression of FADD, Caspase 8, and Caspase 3, and enhance apoptosis in thyroid cells, as lastly validated by TUNEL and IHC staining. XHXY exhibits a favorable therapeutic effect in treating GD by promoting apoptosis in thyroid cells through the upregulation of FADD, Caspase 8, and Caspase 3 expression. And GPS is the main efficacy material basis for its therapeutic effect in anti-GD. [Display omitted] • FAS-associated death domain protein (FADD) was identified as the central target for XHXY in GD treatment through TMT-based proteomics, showing strong binding interactions with prototype components of XHXY and Gentiopicroside. • XHXY relieved GD through enhances apoptosis in thyroid cells by upregulating levels of FADD, Caspase 8, Caspase 3. • Gentiopicroside is the main pharmacodynamic material basis for its therapeutic effect in anti-GD. [ABSTRACT FROM AUTHOR]

Attenuated inflammatory response is a property of embryonic stem cells (ESCs). However, the underlying mechanisms are unclear. Moreover, whether the attenuated inflammatory status is involved in ESC differentiation is also unknown. Here, we found that autophagy-related protein ATG5 is essential for both attenuated inflammatory response and differentiation of mouse ESCs and that attenuation of inflammatory signaling is required for mouse ESC differentiation. Mechanistically, ATG5 recruits FBXW7 to promote ubiquitination and proteasome-mediated degradation of β-TrCP1, resulting in the inhibition of nuclear factor κB (NF-κB) signaling and inflammatory response. Moreover, differentiation defects observed in ATG5-depleted mouse ESCs are due to β-TrCP1 accumulation and hyperactivation of NF-κB signaling, as loss of β-TrCP1 and inhibition of NF-κB signaling rescued the differentiation defects. Therefore, this study reveals a previously uncharacterized mechanism maintaining the attenuated inflammatory response in mouse ESCs and further expands the understanding of the biological roles of ATG5. [Display omitted] • ATG5 attenuates inflammation of mESCs through NF-κB signaling independent of autophagy • Attenuated inflammatory signaling is required for mESC differentiation • FBXW7 is an E3 ubiquitin ligase for β-TrCP1 and employed by ATG5 to regulate β-TrCP1 Li et al. demonstrate that autophagy-related protein ATG5 recruits FBXW7 to regulate β-TrCP1 ubiquitination and degradation and further affect NF-κB signaling. The ATG5-β-TrCP1- NF-κB axis is essential for attenuated inflammatory response and differentiation of mESCs and early embryo development. [ABSTRACT FROM AUTHOR]

Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun , has been used to treat gastrointestinal diseases for nearly 1800 years. To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H–C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H–C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC. Image 1 [ABSTRACT FROM AUTHOR]

Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun , is safe and effective for treatment of ulcerative colitis (UC). To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway. Huangqin decoction (HQD) ameliorated dextran sulfate sodium (DSS)-induced ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway. [Display omitted] • HQD alleviated DSS-induced colitis by restructuring gut microbiota and improving intestinal long-chain fatty acids. • HQD regulated fatty acid metabolism to mediate M2 macrophage polarization by activating FFAR1/FFAR4-AMPK-PPARα pathway. • FFAR4 was more central than FFAR1 in M2 macrophage polarization and FFAR1/FFAR4-AMPK-PPARα pathway. [ABSTRACT FROM AUTHOR]