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ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a disease involving the enteric canal which is characterised by chronisch inflammatory reaction. Coptisine (COP), the distinctive component of Coptis chinensis Franch., is famous for its anti-inflammation, antioxidation, anti-bacteria, and anti-cancer. Earlier researches certified that COP is a prospective remedy for colitis, but the mechanism of colitis and the therapeutical target of COP are deficiently elucidated. AIM OF THIS STUDY: In this follow-up study, we adopted dextran sulfate sodium (DSS)-elicited UC model to further elucidate the possible mechanism of COP on UC in mice. MATERIALS AND METHODS: COP and the positive drug sulfasalazine (SASP) were administered by oral gavage in DSS-induced colitis mouse model. Oxidative stress, inflammatory cytokines, intestinal barrier permeability, protein expression of the TXNIP/NLRP3 inflammasome pathway and intestinal microbiome structure were assessed. RESULTS: Among this investigation, our team discovered that COP could mitigate DSS-elicited UC in murines, with prominent amelioration in weight loss, disease activity index, intestinal permeability (serum diamine oxidase and D-lactate), contracted colonal length and histologic alterations. Furthermore, COP greatly lowered the generation of pro-inflammatory factors, malondialdehyde (MDA) activity and reactive oxygen species (ROS) level, while increased superoxide dismutase (SOD) activity in colonal tissues. Additionally, COP downmodulated the proteic expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, IL-1ß and IL-18. Enteric microbiome sequencing displayed that DSS and COP tremendously influenced the constitution and diversity of enteric microbes in DSS-elicited UC murines. Besides, COP elevated the abundance of probiotic bacteria Bacteroidota, Akkermansia_muciniphila and Bacteroides_acidifaciens, lowered the proportions of potential pathogenic bacteria, such as Lachnospiraceae, Acetatifactor_muris, Clostridium_XlVa, Alistipes and Oscillibacter, and reduced the ratio of Bacillota/Bacteroidota, which vastly helped to reverse the enteric microbiome to a balanceable condition. Alterations in these bacteria were strongly correlated with the colitis relative index. CONCLUSION: The mechanism of COP against UC is connected with the suppression of TXNIP/NLRP3 inflammasome signalling pathway and the adjustment of the enteric microbiome profiles. The proofs offer new understandings upon the anti-UC function of COP, which might be a prospective candidate against UC.
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OBJECTIVE: Mercury is one of the heavy metal pollutants causing serious harm to human health. Quercetin was observed to repair kidney damage through the TLR4/TRIM32 pathway, and the detoxification effect of quercetin on heavy metal poisoning was observed. METHODS: For the study, the researchers divided 40 male mice from the KM strain into five groups: control, HgCl2, QU30, HgCl2+QU15, and HgCl2+QU30. The biological effects of those mice in each group were detected by the biochemical experiment, histopathology experiment and protein expression experiment respectively. RESULTS: HgCl2 had effects in increasing the level of malondialdehyde (MDA) and decreasing the activity of antioxidant enzymes (P < 0.05). HgCl2 induced inflammation by increasing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and Toll Like Receptor 4 (TLR-4) (P < 0.05). The expression of creatinine (CRE) and urea nitrogen (BUN) showed that HgCl2 promoted kidney injury. HgCl2 altered renal tissue integrity and TRIM32 expression which resulted in the increased autophagy associated protein levels of LC3. In contrast, quercetin reduced oxidative stress, autophagy, inflammation and histopathological changes (P < 0.05). CONCLUSION: Quercetin has the renal protection effects of anti-inflammation, anti-oxidation and anti-autophagy.
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Autofagia , Inflamación , Cloruro de Mercurio , Quercetina , Receptor Toll-Like 4 , Animales , Cloruro de Mercurio/toxicidad , Receptor Toll-Like 4/metabolismo , Quercetina/farmacología , Ratones , Masculino , Autofagia/efectos de los fármacos , Inflamación/inducido químicamente , Riñón/efectos de los fármacos , Riñón/patología , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Factores de Transcripción/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Antioxidantes/farmacologíaRESUMEN
Hydroformylation is one of the most important homogeneous reactions in industrial production. Herein, a density functional theory (DFT) method was employed to investigate two proposed reaction mechanisms of hydroformylation catalyzed by cationic cobalt(II) complexes, the carbonyl dissociative mechanism and the associative mechanism. The calculated results showed that the heterolytic H2 activation is the rate-determining step for both the dissociative mechanism and the associative mechanism, with energy barriers of 26.8 kcal mol-1 and 40.5 kcal mol-1, respectively. Meanwhile, the regioselectivity, the spin multiplicity of the catalyst and the substituent effects on the reaction were also investigated. The most stable cobalt(II) catalyst has a doublet state and the linear aldehyde is the dominant product. In addition, it was found that the energy barrier of the reaction decreased when the electron density of the Co center of the catalyst was increased by changing the ligand. The catalytic activity of the catalyst was proposed to be the best when the PEt2 group of the ligand is replaced by the P(tBu)2 group. This study might not only provide new insights for hydroformylation catalyzed by cobalt but also facilitate theory-guided design of novel transition metal catalysts for hydroformylation.
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Social norms are pivotal in guiding social interactions. The current study investigated the potential contribution of the posterior cerebellum, a critical region involved in perceiving and comprehending the sequential dynamics of social actions, in detecting actions that either conform to or deviate from social norms. Participants engaged in a goal-directed task in which they observed others navigating towards a goal. The trajectories demonstrated either norm-violating (trespassing forbidden zones) or norm-following behaviors (avoiding forbidden zones). Results revealed that observing social norm-violating behaviors engaged the bilateral posterior cerebellar Crus 2 and the right temporoparietal junction (TPJ) from the mentalizing network, and the parahippocampal gyrus (PHG) to a greater extent than observing norm-following behaviors. These mentalizing regions were also activated when comparing social sequences against non-social and non-sequential control conditions. Reproducing norm-violating social trajectories observed earlier, activated the left cerebellar Crus 2 and the right PHG compared to reproducing norm-following trajectories. These findings illuminate the neural mechanisms in the cerebellum associated with detecting norm transgressions during social navigation, emphasizing the role of the posterior cerebellum in detecting and signaling deviations from anticipated sequences.
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Mapeo Encefálico , Cerebelo , Imagen por Resonancia Magnética , Humanos , Cerebelo/fisiología , Cerebelo/diagnóstico por imagen , Masculino , Femenino , Adulto Joven , Adulto , Imagen por Resonancia Magnética/métodos , Normas Sociales , Percepción Social , Conducta Social , Mentalización/fisiologíaRESUMEN
The development of homogeneous metal catalysts for the efficient hydrogenation of carbon dioxide (CO2) into methanol (CH3OH) remains a significant challenge. In this study, a new cyclopentadienone diphosphine ligand (CPDDP ligand) was designed, which could coordinate with ruthenium to form a Ru-CPDDP complex to efficiently catalyze the CO2-to-methanol process using dihydrogen (H2) as the hydrogen resource based on density functional theory (DFT) mechanistic investigation. This process consists of three catalytic cycles, stage I (the hydrogenation of CO2 to HCOOH), stage II (the hydrogenation of HCOOH to HCHO), and stage III (the hydrogenation of HCHO to CH3OH). The calculated free energy barriers for the hydrogen transfer (HT) steps of stage I, stage II, and stage III are 7.5, 14.5, and 3.5 kcal/mol, respectively. The most favorable pathway of the dihydrogen activation (DA) steps of three stages to regenerate catalytic species is proposed to be the formate-assisted DA step with a free energy barrier of 10.4 kcal/mol. The calculated results indicate that the designed Ru-CPDDP and Ru-CPDDPEt complexes could catalyze hydrogenation of CO2 to CH3OH (HCM) under mild conditions and that the transition-metal owning designed CPDDP ligand framework be one kind of promising potential efficient catalysts for HCM.
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BACKGROUND: Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis. METHODS: Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms. RESULTS: Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3ß/ß-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells. CONCLUSIONS: The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3ß/ß-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.
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Insuficiencia Renal Crónica , beta Catenina , Masculino , Ratones , Animales , beta Catenina/metabolismo , Ácido Succínico/metabolismo , Liposomas/metabolismo , Ácido Clodrónico/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Insuficiencia Renal Crónica/metabolismo , Fibrosis , Macrófagos/metabolismoRESUMEN
Objective: To assess prevalence, clinical characteristics, and risk factors associated with low flow state (LFS) in a multiethnic population with normal left ventricular ejection fraction (LVEF). Patients and Methods: The study included 4398 asymptomatic participants undergoing cardiac magnetic resonance from July 17, 2000, to August 29, 2002. Left ventricular (LV) mass, volume, and myocardial contraction fraction were assessed. Low flow state was defined as stroke volume index (SVi of <35 mL/m2). Clinical characteristics, cardiac risk factors, and cardiac magnetic resonance findings were compared between LFS and normal flow state (NFS) groups (NFS: SVi of ≥35 mL/m2). Results: There were significant differences in the prevalence of LFS in different ethnic groups. Individuals with LFS were older (66±9.6 vs 61±10 years; P<.0001). The prevalence of LFS was 19% in the group aged older than 70 years. The logistic multivariable regression analysis found that age was independently associated with LFS. The LFS group had significantly higher prevalence of diabetes (30% vs 24%; P=.001), LV mass-volume ratio (1.13±0.22 vs 0.91±0.15; P<.0001), inflammatory markers, a lower LV mass index (59±10 vs 65±11 kg/m2; P<.001), lower myocardial contraction fraction (58.1±10.6% vs 75.7±13%; P<.001), and a lower left atrial size index (32.2±4.6 vs 36.7±5.9 mm/m2; P<.0001) than NFS. Conclusion: Low flow state may be considered an under-recognized clinical entity associated with increasing age, multiple risk factors, increased inflammatory markers, a lower LV mass index, and suboptimal myocardial performance despite the presence of normal LVEF and absence of valvular disease.
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Herein, a new series of bowl-shaped quadridentate ligands with a Si-N-Si-C-Si-C six-membered ring core and their manganese catalysts were designed using the density functional theory (DFT) method for the hydrogenation of unsaturated CîX (XîN, O) bonds. The frameworks of these ligands named by LYG (LYG = P(R1)2CH2Si(CH2)(CH3)NSi(CH3)(CH2Si(CH3)CH2P(R3)2)CH2P(R2)2) have a Si-N-Si-C-Si-C six-membered ring core at the bottom of the bowl structure and each Si atom links with one phosphorus arm (-CH2PR2). The Mn catalyst Mn(CO)-LYG was constructed to catalyze the hydrogenation of CîO/CîN bonds. The calculated results indicate that due to the bowl-shaped structure of LYG quadridentate ligands, these Mn catalysts could be advantageous not only in the tuneup of catalytic activity and stereoselectivity by modifying three phosphorus arms but also in the homogeneous catalyst immobilization by linking with the Si-N-Si-C-Si-C six-membered ring core using different supports. This work might provide theoretical insights to design new framework transition-metal catalysts for the hydrogenation of CîX bonds.
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Although the human cerebellum has a surface that is about 80% of that of the cerebral cortex and has about four times as many neurons, its functional organization is still very much uncharted. Despite recent attempts to provide resting-state and task-based parcellations of the cerebellum, these two approaches lead to large discrepancies. This article describes a comprehensive task-based functional parcellation of the human cerebellum based on a large-scale functional database, NeuroSynth, involving an unprecedented diversity of tasks, which were reliably associated with ontological key terms referring to psychological functions. Involving over 44,500 participants from this database, we present a parcellation that exhibits replicability with earlier resting-state parcellations across cerebellar and neocortical structures. The functional parcellation of the cerebellum confirms the major networks revealed in prior work, including sensorimotor, directed (dorsal) attention, divided (ventral) attention, executive control, mentalizing (default mode) networks, tiny patches of a limbic network, and also a unilateral language network (but not the visual network), and the association of these networks with underlying ontological key terms confirms their major functionality. The networks are revealed at locations that are roughly similar to prior resting-state cerebellar parcellations, although they are less symmetric and more fragmented across the two hemispheres. This functional parcellation of the human cerebellum and associated key terms can provide a useful guide in designing studies to test specific functional hypotheses and provide a reference for interpreting the results.
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In this work, high-performance two-dimensional (2D) graphene-based single-atom electrocatalysts (ZZ/ZA-MNxCy) for the oxygen reduction reaction (ORR) were screened out using machine learning (ML). A model was built for the fast prediction of electrocatalysts and two descriptors valence electron correction (VEc) and degree of construction differences (DC) were proposed to improve the accuracy of the model prediction. Two evaluation criteria, high-performance catalyst retention rate rR and high-performance catalyst occupancy rate rO, were proposed to evaluate the accuracy of ML models in high-performance catalyst screening. The addition of VEc and DC in the model could change the mean absolute error (MAEtest) of the test set, the coefficient of determination (R2test) of the test set, rO, and rR from 0.334 V, 0.683, 0.222, and 0.360 to 0.271 V, 0.774, 0.421, and 0.671, respectively. The partially screened potential high-performance ORR electrocatalysts such as ZZ-CoN4 and ZZ-CoN3C1 were also further investigated using a Density Functional Theory (DFT) method, which confirmed the accuracy of the ML model (MAE = 0.157 V, R2 = 0.821).
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The synthesis of 1,1-diborylalkanes from readily available alkenes is an appealing method. The density functional theory (DFT) method was employed to investigate the reaction mechanism of 1,1-diborylalkanes, which was synthesized from alkenes and a borane, and the reaction was catalyzed by a zirconium complex Cp2ZrCl2. The entire reaction is divided into two cycles: dehydrogenative boration to form vinyl boronate esters (VBEs) and hydroboration of VBEs. This article focuses on the hydroboration cycle and elaborates on the role of the reducing reagents in the equilibrium of self-contradictory reactivity (dehydrogenative boration and hydroboration). The H2 and HBpin pathways were investigated as the reducing reagents in the hydroboration process. The calculated results showed that it is more advantageous to use H2 as a reducing agent (path A). Furthermore, the σ-bond metathesis is the rate-determining step (RDS) with an energetic span of 21.4 kcal/mol. This is consistent with the self-contradictory reactivity balance proposed in the experiment. The reaction modes of the hydroboration process were also discussed. These analyses revealed the origin of selectivity in this boration reaction, in which the σ-bond metathesis of HBpin needs to overcome the strong interaction between HBpin and the Zr metal. Meanwhile, the origin of the selectivity of different positions of H2 is the interaction between the σ(H1-H2) â σ*(Zr1-C1) overlap and these findings have implications for catalyst design and application.
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The synthesis of amides is of great significance in academia and industrial fields. Herein, density functional theory (DFT) studies were employed to investigate the mechanism of the formation of amides via aryl epoxides and amines catalyzed by ruthenium pincer complexes. The entire reaction mainly comprises three processes: isomerization of epoxides to aldehydes, aldimine condensation, and amide formation. Calculated results showed that bipyridine-based Ru-PNN A1 (PNN = 2-(di-tert-butylphosphinomethyl)bipyridine) pincer complexes could be potential highly catalytic species for the synthesis of amides and that the rate-determining step is the amine-assisted hydrogen elimination with a free energy barrier of 28.0 kcal mol-1. This study might not only provide new insights into the future of the formation of amides by transition-metal complexes but also facilitate the theoretical guidance needed to design novel transition-metal catalysts.
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Pt/CeO2 catalysts exhibit excellent catalytic performance for the methanol dehydrogenation (MD) reaction. In this work, MD reactions on three systems of Pt1/CeO2(110)), Pt7/CeO2(110), and Pt1/Ce1-xO2(110) are investigated via density functional theory (DFT) calculations. The CH3OH adsorption, electronic structure of the catalyst, and mechanism of methanol decomposition (MD) are systematically calculated. The results reveal that the d-band center of the Pt atom moves away from the Fermi level in the order of Pt1/CeO2(110) < Pt7/CeO2(110) < Pt1/Ce1-xO2(110), and the order of the activity of the MD reaction is Pt1/CeO2(110) < Pt7/CeO2(110) < Pt1/Ce1-xO2(110). The results of the microkinetic dynamics simulation verify that only Pt1/Ce1-xO2(110) is conducive to the decomposition of methanol at low temperatures (373 K), and the products CO and H2 are easily dissociated from the catalyst surface. This work uncovers that both the small size and the Ce vacancy substituted sites of Pt favor the performance of the Pt/CeO2 catalyst, and provides theoretical guidance for the construction and design of efficient metal-support catalysts for the MD reaction.
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The assembly of various azo dyes and pigments with inorganic layered materials could develop new types of intercalation materials. The electronic structures and photothermal properties of composite materials (AbS--LDH) constituted by azobenzene sulfonate anions (AbS-) and Mg-Al layered double hydroxide (LDH) lamella were theoretically studied at the M06-2X/def2-TZVP//M06-2X/6-31G(d,p) level using density functional theory and time-dependent density functional theory. Meanwhile, the influences of LDH lamella on the AbS- in AbS--LDH materials were investigated. The calculated results showed that the addition of LDH lamella could lower the isomerization energy barrier of CAbS- anions (CAbS- stands for cis AbS-). The thermal isomerization mechanisms of AbS--LDH and AbS were related to the conformational change of the azo group, out-of-plane rotation and in-plane inversion. The LDH lamella could reduce the energy gap of the n â π* and π â π* electronic transition and lead to a red-shift in the absorption spectra. When a polar solvent DMSO was applied, the excitation energy of the AbS--LDHs was increased, making its photostability stronger than in nonpolar solvent and solvent-free.
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In this paper the density functional theory (DFT) method was employed to investigate the cross-coupling of methanol with benzyl alcohol to afford methyl benzoate, catalysed by Mn-PNN pincer complex. The whole reaction process mainly includes three stages: the dehydrogenation of benzyl alcohol to benzaldehyde, the coupling of benzaldehyde with methanol to hemiacetal and the dehydrogenation of hemiacetal to methyl benzoate. The calculated results indicated that two dehydrogenation processes are influenced by two competitive mechanisms of inner and outer spheres. Dehydrogenation of benzyl alcohol to benzaldehyde is the rate-determining step of the whole reaction, with the energy barrier of 22.1â kcal/mol. In addition, the regeneration of catalyst is also extremely important. Compared with direct dehydrogenation, the dehydrogenation mode assisted by formic acid is more advantageous. This work might provide theoretical insights and shed light on the design of cheap transition-metal catalysts for the dehydrogenation reaction.
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Manganeso , Metanol , Alcohol Bencilo , BenzaldehídosRESUMEN
Accumulating evidence shows that the posterior cerebellum is involved in mentalizing inferences of social events by detecting sequence information in these events, and building and updating internal models of these sequences. By applying anodal and sham cerebellar transcranial direct current stimulation (tDCS) on the posteromedial cerebellum of healthy participants, and using a serial reaction time (SRT) task paradigm, the current study examined the causal involvement of the cerebellum in implicitly learning sequences of social beliefs of others (Belief SRT) and non-social colored shapes (Cognitive SRT). Apart from the social or cognitive domain differences, both tasks were structurally identical. Results of anodal stimulation (i.e., 2 mA for 20 min) during the social Belief SRT task, did not show significant improvement in reaction times, however it did reveal generally faster responses for the Cognitive SRT task. This improved performance could also be observed after the cessation of stimulation after 30 min, and up to one week later. Our findings suggest a general positive effect of anodal cerebellar tDCS on implicit non-social Cognitive sequence learning, supporting a causal role of the cerebellum in this learning process. We speculate that the lack of tDCS modulation of the social Belief SRT task is due to the familiar and overlearned nature of attributing social beliefs, suggesting that easy and automatized tasks leave little room for improvement through tDCS. (AU)
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Estimulación Transcraneal de Corriente Directa , Cerebelo , Cognición , Estimulación Encefálica Profunda , Tiempo de ReacciónRESUMEN
Humans read the minds of others to predict their actions and efficiently navigate social environments, a capacity called mentalizing. Accumulating evidence suggests that the cerebellum, especially Crus 1 and 2, and lobule IX are involved in identifying the sequence of others' actions. In the current study, we investigated the neural correlates that underly predicting others' intentions and how this plays out in the sequence of their actions. We developed a novel intention prediction task, which required participants to put protagonists' behaviors in the correct chronological order based on the protagonists' honest or deceitful intentions (i.e., inducing true or false beliefs in others). We found robust activation of cerebellar lobule IX and key mentalizing areas in the neocortex when participants ordered protagonists' intentional behaviors compared with not ordering behaviors or to ordering object scenarios. Unlike a previous task that involved prediction based on personality traits that recruited cerebellar Crus 1 and 2, and lobule IX (Haihambo et al., 2021), the present task recruited only the cerebellar lobule IX. These results suggest that cerebellar lobule IX may be generally involved in social action sequence prediction, and that different areas of the cerebellum are specialized for distinct mentalizing functions.
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Mentalización , Neocórtex , Humanos , Intención , Cerebelo/fisiología , Mentalización/fisiología , Imagen por Resonancia MagnéticaAsunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Valor Predictivo de las Pruebas , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Resultado del TratamientoRESUMEN
Succinate has long been known to be only an intermediate product of the tricarboxylic acid cycle until identified as a natural ligand for SUCNR1 in 2004. SUCNR1 is widely expressed throughout the body, especially in the kidney. Abnormally elevated succinate is associated with many diseases, including obesity, type 2 diabetes, nonalcoholic fatty liver disease, and ischemia injury, but it is not known whether succinate can cause kidney damage. This study showed that succinate induced apparent renal injury after treatment for 12 wk, characterized by a reduction in 24 h urine and the significant detachment of the brush border of proximal tubular epithelial cells, tubular dilation, cast formation, and vacuolar degeneration of tubular cells in succinate-treated mice. Besides, succinate caused tubular epithelial cell apoptosis in kidneys and HK-2 cells. Mechanistically, succinate triggered cell apoptosis via SUCNR1 activation. In addition, succinate upregulated ERK by binding to SUCNR1, and inhibition of ERK using PD98059 abolished the proapoptotic effects of succinate in HK-2 cells. In summary, our study provides the first evidence that succinate acts as a risk factor and contributes to renal injury, and further research is required to discern the pathological effects of succinate on renal functions.
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Diabetes Mellitus Tipo 2 , Ácido Succínico , Animales , Ratones , Apoptosis , Diabetes Mellitus Tipo 2/patología , Células Epiteliales/metabolismo , Riñón/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Succinatos , Ácido Succínico/metabolismoRESUMEN
Prior studies suggest that the cerebellum contributes to the prediction of action sequences as well as the detection of social violations. In this dynamic causal modeling study, we explored the effective connectivity of the cerebellum with the cerebrum in processing social action sequences. A first model aimed to explore functional cerebello-cerebral connectivity when learning trait/stereotype-implying action sequences. We found many significant bidirectional connectivities between mentalizing areas of the cerebellum and the cerebrum including the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC). Within the cerebrum, we found significant connectivity between the right TPJ and the mPFC, and between the TPJ bilaterally. A second model aimed to investigate cerebello-cerebral connectivity when conflicting information arises. We found many significant closed loops between the cerebellum and cerebral mentalizing (e.g. dorsal mPFC) and executive control areas (e.g. medial and lateral prefrontal cortices). Additional closed loops were found within the cerebral mentalizing and executive networks. The current results confirm prior research on effective connectivity linking the cerebellum with mentalizing areas in the cerebrum for predicting social sequences, and extend it to cerebral executive areas for social violations. Overall, this study emphasizes the critical role of cerebello-cerebral connectivity in understanding social sequences.