Association of lipid levels with motor and cognitive function and decline in Parkinson's disease.

BACKGROUND: Most studies have focused on comparing blood lipid biomarkers between Parkinson's disease (PD) and normal controls (NC). However, further research is necessary to explore the impact of blood lipid levels on motor and cognitive function, as well as the progression of motor dysfunction and cognitive decline over time. Thus, the aim of this study is to investigate the relationship between blood lipid biomarkers and these indicators in individuals with PD. METHODS: The cohort study enrolled 157 PD patients and 146 NC from the Tianjin Huanhu Hospital from September 2017 to September 2019. Serum lipid fractions were detected in fasting serum samples. PD patients were followed up at 2 ± 0.6 years for clinical assessment. RESULTS: PD patients exhibited lower serum triglyceride (TG) levels as compared to NC (P = 0.008). PD male patients exhibited lower serum lipoprotein cholesterol(LDL-C) and total cholesterol (TC) levels than female patients (LDL-C: P = 0.034; TC: P = 0.019). Serum TG levels correlated significantly with Unified PD Rating Scale III, Hoehn and Yahr stage and Montreal Cognitive Assessment scores in PD patients. Additionally, serum TG levels were associated with follow-up motor function decline and cognitive decline in adjusted regression models in PD patients. CONCLUSIONS: To summarise, the study findings suggest that decreased serum TG levels are significantly associated with greater motor dysfunction, cognitive dysfunction and the greater deterioration of the two indicators.

Soluble TREM2 in body fluid in Alzheimer's disease and Parkinson's disease.

BACKGROUND: Previous studies showed conflicting results regarding soluble triggering receptor expressed on myeloid cells 2 (sTREM2) level alteration in body fluid in Alzheimer's disease (AD) and Parkinson's disease (PD). METHODS: We applied the STATA 12.0 software to compute standard mean difference (SMD) and 95% confidence interval (CI). RESULTS: The study showed elevated sTREM2 level in cerebrospinal fluid (CSF) in AD, mild cognitive impairment (MCI), and preclinical AD (pre-AD) patients, compared to healthy controls (HCs) with random effects models (AD: SMD 0.28, 95% CI 0.12 to 0.44, I2 = 77.6%, p < 0.001; MCI: SMD 0.29, 95% CI 0.09 to 0.48, I2 = 89.7%, p < 0.001; pre-AD: SMD 0.24, 95% CI 0.00 to 0.48, I2 = 80.8%, p < 0.001). The study showed no significant difference in sTREM2 level in plasma between AD patients and HCs with a random effects model (SMD 0.06, 95% CI - 0.16 to 0.28, I2 = 65.6%, p = 0.008). The study showed no significant difference in sTREM2 level in CSF or plasma between PD patients and HCs with random effects models (CSF: SMD 0.33, 95% CI - 0.02 to 0.67, I2 = 85.6%, p < 0.001; plasma: SMD 0.37, 95% CI - 0.17 to 0.92, I2 = 77.8%, p = 0.011). CONCLUSIONS: In conclusion, the study highlighted the CSF sTREM2 as a promising biomarker in the different clinical stages of AD. More studies were essential to explore the CSF and plasmatic concentrations of sTREM2 alteration in PD.

[Research progress on chemical constituents and pharmacological effects of Glechomae Herba and prediction of its Q-markers].

Glechomae Herba, the dried aerial part of Glechoma longituba(Labiatae), has the effects of promoting urination, draining dampness, and relieving stranguria. It has received wide attention in recent years owing to the satisfactory efficacy on lithiasis. Amid the in-depth chemical and pharmacological research, it has been found that Glechomae Herba has antibacterial, anti-inflammatory, antioxidant, antithrombotic, hepatoprotective, cholagogic, antitumor, hypoglycemic, and lipid-lowering effects. The main chemical constituents are volatile oils, flavonoids, terpenoids, phenylpropanoids, and organic acids. This paper summarized the chemical constituents and pharmacological effects of Glechomae Herba. Based on genetic relationship of plants, the characteristics, efficacy, and pharmacokinetics of the chemical constituents, and the potential of these constituents as quality markers(Q-markers), it was summed up that ursolic acid, caffeic acid, rosmarinic acid, luteolin-7-O-diglucuronide, apigenin, apigenin-7-O-diglucuronide, apigetrin, and glechone can be the candidate Q-markers of Glechomae Herba.

Imminent cognitive decline in normal elderly individuals is associated with hippocampal hyperconnectivity in the variant neural correlates of episodic memory.

The secondary prevention trials of Alzheimer's disease (AD) require an enrichment strategy to recruit individuals with imminent cognitive decline at the preclinical stage. Previously, we demonstrated a variant neural correlates of episodic memory (EM) function in apolipoprotein E (APOE) ε4 carriers. Herein, we investigated whether this variation was associated with longitudinal EM performance. This 3-year longitudinal study included 88 normal elderly subjects with EM assessment and resting-state functional MRI data at baseline; 48 subjects (27 ε3 homozygotes and 21 ε4 carriers) underwent follow-up EM assessment. In the identified EM neural correlates, multivariable regression models examined the association between hippocampal functional connectivity (HFC) and longitudinal EM change. Independent validation was performed using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. At baseline, the EM neural correlates were characterized in the Papez circuit regions in the ε3 homozygotes, but in the sensorimotor cortex and cuneus in the ε4 carriers. Longitudinally, the ε4 carriers exhibited a negative association of the baseline HFC strength in the EM neural correlates with annual rate of EM change (R2 = 0.25, p = 0.05). This association also showed a trend in the ADNI dataset (R2 = 0.42, p = 0.06). These results indicate that hippocampal hyperconnectivity in the variant EM neural correlates is associated with imminent EM decline in ε4 carriers, which may serve as a promising enrichment strategy for secondary prevention trials of AD.

Effect of cognitive reserve on cognitive function in Parkinson's disease.

BACKGROUND: Previous studies showed inconsistent results for the correlation between cognitive reserve (CR) and cognitive function in Parkinson's disease (PD). Additionally, conflicting results were obtained for the association between CR and risk of longitudinal cognitive decline, longitudinal progression to mild cognitive impairment (MCI), and longitudinal progression to dementia in PD patients. OBJECTIVES: Thus, a meta-analysis is essential to summary these inconsistent results. METHODS: Articles published before November 2021 were searched in databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed Fisher's z score and standard error (SE) of each transformation value of correlation coefficient for the correlation between educational level and cognitive function. Additionally, odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed as effect sizes for the correlation between educational level and risk of longitudinal progression to MCI. RESULTS: The present study showed that higher educational levels were related to better general cognitive function, executive function, memory, and information processing speed in PD patients, whereas no significant association was showed between educational levels and visuospatial function, language in PD patients. Additionally, included studies reported a negative association between educational level and risk of longitudinal progression to MCI in PD patients. CONCLUSIONS: In conclusion, the study demonstrated that higher CR might be correlated with better cognitive function and lower risk of longitudinal progression to MCI in PD. In addition, large-scale prospective studies are necessary to explore the effect of CR on cognitive function in PD.

Functional brain changes in Parkinson's disease: a whole brain ALE study.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) was widely used as an effective tool in the diagnosis of neurodegenerative diseases. However, prior rs-fMRI studies reported inconsistent results for comparison between Parkinson's disease (PD) and healthy controls (HC). METHODS: We searched studies published before December 2021 in databases (PubMed, Web of Science, and Google Scholar). An activation likelihood estimation (ALE) meta-analysis was made for functional changes in PD. RESULTS: The study finally included 25 studies (including 973 PD patients and 766 HC). PD patients showed reduced amplitude of low frequency fluctuations (ALFF) in the left superior temporal gyrus (STG), the left superior frontal gyrus (SFG), the left medial frontal gyrus (MFG), the left precuneus (PCUN), and the right lentiform nucleus, compared to HC. PD patients showed increased ALFF in the right SFG, the left superior parietal lobule (SPL), the left STG, the right fusiform gyrus, the left inferior temporal gyrus (ITG), and the right parahippocampal gyrus (PHG), compared to HC. PD patients showed reduced regional homogeneity (ReHo) in the right declive, the right MFG, the left culmen, and the left thalamus, compared to HC. PD patients showed increased ReHo in the right SFG, compared to HC. Additionally, PD patients showed reduced functional connectivity (FC) in the right posterior cingulate (PCG), compared to HC. CONCLUSIONS: The present ALE analysis has confirmed functional deficits in motor-, emotion-, and cognition-related regions in PD. Deficits in these regions in rs-fMRI studies could play a role in early diagnosis of PD.

N200 and P300 component changes in Parkinson's disease: a meta-analysis.

BACKGROUND: Cognitive impairment can seriously affect the quality of life of Parkinson's disease (PD) patients. Although numerous studies showed that N200, P300 latency and amplitude are correlated with cognitive functions, there is a sufficient amount of controversial results. Therefore, it is necessary to conduct a meta-analysis of N200, P300 latency and amplitude data of event-related potential (ERP) in PD. METHODS: We systematically searched on PubMed and Web of Science for PD-related ERP studies published before December 2021. Standard mean difference (SMD) and 95% confidence interval (CI) estimates of N200 and P300 components were compared among PD patients, PD dementia (PDD) patients, PD non-dementia (PDND) patient, and healthy control (HC). RESULTS: Our meta-analysis showed prolonged N200 latency at the Fz, Cz electrode sites, prolonged P300 latency at the Fz sites in PD patients, compared to HC; prolonged N200 latency at the Cz, Pz electrode sites in PDND patients, compared to HC; prolonged P300 latency at the Cz site in PDD patients, compared to PDND patients; and reduced P300 amplitude at the Fz electrode site in PDND patients, compared to HC. CONCLUSIONS: N200 and P300 component may be potential electrophysiological biomarkers of early cognitive impairment in PD patients. Future studies are needed to confirm this conclusion. Estimates of N200 and P300 component can be a valuable support for clinicians in diagnosis of early cognitive impairment in PD patients due to the simplicity and non-invasiveness of the procedure.

Noninvasive Brain Stimulation for Poststroke Dysphagia: A Meta-Analysis for Randomized Controlled Trials.

BACKGROUND: Past research has indicated that repetitive transcranial magnetic stimulation (rTMS) on the pharyngeal motor cortex may be beneficial to poststroke dysphagic patients. In addition, some studies have supported that transcranial direct current stimulation (tDCS) over the pharyngeal motor cortex can improve swallowing function in poststroke dysphagia. However, some studies showed that rTMS and tDCS show no effect on poststroke dysphagia. This study aims to make a meta-analysis to investigate the therapy effect of rTMS and tDCS on poststroke dysphagia in randomized controlled trials (RCTs). METHODS: We searched for studies published before March 2021 in databases (PubMed, Web of Science, MEDLINE, EMBASE, and Google Scholar). Meta-analysis was made to compute the results of included studies using STATA 12.0 software. RESULTS: The present study shows a significant increase in the swallowing function in poststroke dysphagia given rTMS compared to those given sham rTMS (standardized mean difference [SMD] = 1.08, 95% confidence interval [CI] = 0.37-1.80, I2 = 81.2%, p < 0.001). In addition, the study shows a significant increase in the swallowing function in poststroke dysphagia given tDCS (combined or not combined with conventional swallowing therapy), compared to those given sham tDCS (combined or not combined with conventional swallowing therapy) (SMD = 1.43, 95% CI = 0.73-2.13, I2 = 77.6%, p < 0.001). CONCLUSIONS: The study demonstrates that rTMS and tDCS over the pharyngeal motor cortex show therapy effects on poststroke dysphagia. Many more large-scale, blinded RCTs are essential to investigate the effect of rTMS and tDCS on poststroke dysphagia.

Association between migraine and cognitive impairment.

BACKGROUND: Previous studies revealed inconsistent results regarding association between migraine and cognitive impairment. In addition, previous studies found inconsistent results regarding the association between migraine and risk of dementia. Thus, the study aimed to make a meta-analysis exploring comparison result in different types of cognitive function between migraine patients and non-migraine subjects. In addition, meta-analysis was made to explore the association between migraine and risk of dementia. METHODS: Articles published before June 2022 were searched in the following databases: PubMed, Web of Science, SCOPUS, EMBASE, EBSCO, PROQUEST, ScienceDirect and Cochrane Database of Systematic Reviews. Results were computed using STATA 12.0 software. RESULTS: Meta-analysis showed lower general cognitive function and language function in migraine group, compared to no migraine group (general cognitive function: standard mean difference (SMD) = - 0.40, 95% CI = - 0.66 to - 0.15; language: SMD = - 0.14, 95% confidence interval (CI) = - 0.27 to - 0.00), whereas the study showed no significant difference in visuospatial function, attention, executive function and memory between migraine group and no migraine group (visuospatial function: SMD = - 0.23, 95% CI = - 0.53 to 0.08; attention: SMD = - 0.01, 95% CI = - 0.10 to 0.08; executive function: SMD = - 0.05, 95% CI = - 0.16 to 0.05; memory: SMD = - 0.14, 95% CI = - 0.30 to 0.03). In addition, the meta-analysis showed a significant association between migraine and risk of dementia (odds ratio (OR)/relative risk (RR) = 1.30, 95% CI = 1.11 to 1.52). CONCLUSIONS: In conclusion, the meta-analysis demonstrated lower general cognitive function and language function in migraine. In addition, migraine is associated with an increased risk of all-cause dementia, VaD and AD. These results suggest a significant association between migraine and cognitive impairment. Because of the association between migraine and cognitive impairment, neurological physician should be vigilant and effectively intervene in migraineurs with high risk factors of cognitive impairment to prevent the development of cognitive impairment.

The reduced left hippocampal volume related to the delayed P300 latency in amnestic mild cognitive impairment.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is characterized by delayed P300 latency and reduced grey matter (GM) volume, respectively. The relationship between the features in aMCI is unclear. This study was to investigate the relationship between the altered P300 latency and the GM volume in aMCI. METHODS: Thirty-four aMCI and 34 well-matched normal controls (NC) were studied using electroencephalogram during a visual oddball task and scanned with MRI. Both tests were finished in the same day. RESULTS: As compared with the NC group, the aMCI group exhibited delayed P300 latency in parietal cortex and reduced GM volumes in bilateral temporal pole and left hippocampus/parahippocampal gyrus. A remarkable negative correlation was found between delayed P300 latency and reduced left hippocampal volume only in the aMCI group. Interestingly, the mediating analysis found P300 latency significantly mediated the association between right supramarginal gyrus volume and information processing speed indicated by Stroop Color and Word Test A scores. CONCLUSIONS: The association between delayed P300 latency and reduced left hippocampal volume in aMCI subjects suggests that reduced left hippocampal volume may be the potential structural basis of delayed P300 latency.

New chlorophenolic glycoside from Curculigo orchioides and their activities on 5α-reductase.

Two new chlorophenolic glucosides curculigines P (1) and Q (2), together with seven known compounds (3-9), were isolated from the dried rhizomes of Curculigo orchioides. Their structures were determined by spectroscopic methods including 1 D, 2 D NMR and MS. All the isolated compounds were evaluated on 5α-reductase activity by a HaCaT-based bioassay. Compounds 1-9 showed varying degrees of inhibiting activity against 5α-reductase, while compound 1 indicated the most potent inhibitory effect.[Formula: see text].

Electrophysiological Processes on Motor Imagery Mediate the Association Between Increased Gray Matter Volume and Cognition in Amnestic Mild Cognitive Impairment.

Motor imagery is considered as an ideal window to observe neural processes of action representations. Behavioral evidence has indicated an alteration of motor imagery in amnestic mild cognitive impairment (aMCI). However, it still remains unclear on the altered neurophysiological processing mechanism of motor imagery and whether this mechanism links the abnormal biological basis of motor imagery with impaired cognition in aMCI. This study was to investigate the altered neurophysiological processing mechanism of motor imagery and to examine the relationships between this knowledge and the altered structural basis of motor imagery with impaired cognition in aMCI. A hand mental rotation paradigm was used to manipulate the processing of motor imagery while event-related brain potentials (ERPs) were recorded and gray matter (GM) voxel-based morphometry was performed in 20 aMCI and 29 healthy controls. Compared with controls, aMCI exhibited lower ERP amplitudes in parietal cortex and higher ERP amplitudes in frontal cortex during motor imagery. In addition, aMCI showed reduced GM volumes in cerebellum posterior lobe, insula and hippocampus/parahippocampal gyrus, and increased GM volumes in middle cingulate gyrus and superior frontal gyrus. Most importantly, increased ERP amplitude significantly mediated the association between increased GM and cognition. This study provided a novel evidence for the relationships between the electrophysiological processing mechanism and structural basis of motor imagery with impaired cognition in aMCI. It suggests that improving neural activity by stimulating the frontal lobe can potentially contribute to acquire motor imagery skills for neurological rehabilitation in aMCI subjects.

Hypoxia-inducible factor-prolyl hydroxylase inhibitor ameliorates myopathy in a mouse model of chronic kidney disease.

Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Therefore, proangiogenesis therapy is considered a potentially effective strategy for limiting CKD-associated myopathy. Hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia; however, little evidence was available from CKD models. Here, we assessed whether pharmacological activation of HIF by MK-8617 (MK), a novel orally active HIF-PHI, improves CKD-associated myopathy. Mice were divided into sham or CKD groups, and CKD mice were subdivided into CKD + vehicle or MK treatment groups (1.5, 5, or 12.5 mg/kg for 12 wk). In CKD mice, skeletal muscle mass, mitochondrial amount, and exercise capacity decreased compared with sham mice. Compared with the CKD + vehicle group, low (1.5 mg/kg) and medium (5 mg/kg) doses of MK, but not the high dose (12.5 mg/kg), significantly restored these changes and was accompanied by incremental increases in HIF-1α. Furthermore, increased capillary density and area were observed in a MK dose-dependent manner, which is likely related to an improved VEGF response in the skeletal muscle of CKD mice. In addition, macrophage and proinflammatory cytokines, including monocyte chemoattractant protein 1, TNF-α, and IL-6, significantly increased in the high-dose MK group. These results indicate that HIF-PHI provides a potential therapeutic strategy to improve CKD-associated myopathy.

Preparation and purification of canthinone and ß-carboline alkaloids from Picrasma quassioides based on bioautography and mass-spectrometry-directed autopurification system.

Picrasma quassioides (D. Don) Benn. is a widely used traditional Chinese medicine for anti-inflammation and antibiosis. Canthinone and ß-carboline alkaloids are the main characteristic constituents that possess diverse pharmacological effects, such as anti-inflammatory and anti-infectious properties. In this study, bioautography in thin-layer chromatography indicated that the antiradical activity compound may be alkaloids. Then, a simple, fast, and efficient method was established for the separation and purification of two types of alkaloids from P. quassioides by mass-spectrometry-directed autopurification system. Eight alkaloids were isolated and purified in this one-step methodology. Among them, five compounds (3, 95.1%, 58.8 mg; 4, 98.4%, 71.7 mg; 6, 97.8%, 365.4 mg; 7, 97.7%, 172.7 mg; 8, 98.2%, 180.3 mg) were obtained in large amounts with extremely high purities. Then, the antiradical activities of the isolates showed that 4-methoxy-5-hydroxycanthin-6-one (6) exhibited obvious 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging activity with an IC50 value of 84.037 µM. This study offers a new method for the preparation of targeted bioactive alkaloids in P. quassioides. This work also provides a reference for the separation of other targeted chemical components with potential activities from traditional Chinese herbal medicines.

Seventeen steroids from the pith of Tetrapanax papyriferus.

Two new steroidal ketones (1, 2), together with 10 known steroids (3-12) and five known steroidal saponins (13-17), have been obtained from the pitch of Tetrapanax papyrierus. The structures of 1 and 2 were elucidated as 3ß-hydroxystigmast-8, 22-diene-7,11-dione and 3ß-hydroxystigmast-8-ene-7,11-dione by IR, HR-ESI-MS, 1D and 2D NMR techniques. Except for 4, 14, 15, 16, 13 compounds reported in this paper were isolated from Tetrapanax papyriferus for the first time.

Alpha-synuclein in peripheral body fluid as a biomarker for Parkinson's disease.

OBJECTIVE: Whether alpha-synuclein in peripheral body fluids can be used for the diagnosis of Parkinson's disease (PD) remains in controversy. This study evaluates diagnostic potential of alpha-synuclein for PD in various peripheral body fluids using a meta-analysis approach. METHODS: Studies published before October 2022 were searched in Web of Science and PubMed databases. The results were computed using the STATA 12.0 statistical software. RESULTS: In plasma, PD patients exhibited elevated alpha-synuclein levels relative to healthy controls (HCs) [standard mean difference (SMD) = 0.78, 95% confidence interval (CI) = 0.42 to 1.15] with a sensitivity of 0.79 (95% CI: 0.64-0.89) and a specificity of 0.95 (95% CI: 0.90-0.98). Higher plasma alpha-synuclein levels were correlated with longer disease durations, higher Unified Parkinson's Disease Rating Scale motor scores, and higher Hoehn and Yahr stages in PD patients. Plasma neural-derived exosomal alpha-synuclein levels (SMD = 1.82, 95% CI = 0.30 to 3.35), ratio of plasma neural-derived exosomal alpha-synuclein to total alpha-synuclein (SMD = 1.26, 95% CI = 0.19 to 2.33), and erythrocytic alpha-synuclein levels were also increased in PD patients (SMD = 6.57, 95% CI = 3.55 to 9.58). In serum, there was no significant difference in alpha-synuclein levels between PD patients and HCs (SMD = 0.54, 95% CI = - 0.27 to 1.34). In saliva, reduced alpha-synuclein levels were observed in PD patients (SMD = - 0.85, 95% CI = - 1.67 to - 0.04). CONCLUSIONS: Alpha-synuclein levels in plasma, plasma neural-derived exosome, erythrocyte, and saliva may serve as potential biomarkers for the diagnosis of PD.

FDSR: An Interpretable Frequency Division Stepwise Process Based Single-Image Super-Resolution Network.

Deep learning has excelled in single-image super-resolution (SISR) applications, yet the lack of interpretability in most deep learning-based SR networks hinders their applicability, especially in fields like medical imaging that require transparent computation. To address these problems, we present an interpretable frequency division SR network that operates in the image frequency domain. It comprises a frequency division module and a step-wise reconstruction method, which divides the image into different frequencies and performs reconstruction accordingly. We develop a frequency division loss function to ensure that each reconstruction module (ReM) operates solely at one image frequency. These methods establish an interpretable framework for SR networks, visualizing the image reconstruction process and reducing the black box nature of SR networks. Additionally, we revisited the subpixel layer upsampling process by deriving its inverse process and designing a displacement generation module. This interpretable upsampling process incorporates subpixel information and is similar to pre-upsampling frameworks. Furthermore, we develop a new ReM based on interpretable Hessian attention to enhance network performance. Extensive experiments demonstrate that our network, without the frequency division loss, outperforms state-of-the-art methods qualitatively and quantitatively. The inclusion of the frequency division loss enhances the network's interpretability and robustness, and only slightly decreases the PSNR and SSIM metrics by an average of 0.48 dB and 0.0049, respectively.

Glechomenes A-G, diterpenoids with anti-inflammatory activities from the aerial part of Glechoma longituba.

Ten diterpenoids including six unreported abietane-type diterpenoids Glecholmenes A-F (1-6) and an undescribed labdane-type diterpenoid Glecholmene G (9), together with three known diterpenoids (7,8,10), were firstly isolated from the aerial part of G. longituba. Their structures were established mainly by nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) methods. Electronic circular dichroism (ECD) calculations and X-ray crystallographic analyses were used for the determination of their absolute configurations. The anti-inflammatory activity of all compounds was evaluated using the classical LPS-induced NO release model in RAW264.7 cells. Compound 2 displayed significant anti-inflammatory activities with IC50 values of 29.08 ± 1.40 µM (Aminoguanidine hydrochloride as the positive control, IC50 = 21.84 ± 0.48 µM).

Shengmai San formula alleviates high-fat diet-induced obesity in mice through gut microbiota-derived bile acid promotion of M2 macrophage polarization and thermogenesis.

BACKGROUND: Shengmai San Formula (SMS) is a traditional Chinese medicine (TCM) that has been used to treat wasting-thirst regarded as diabetes mellitus, which occurs disproportionately in obese patients. Therefore, we investigated whether SMS could be used to treat obesity, and explored possible mechanisms by which it might improve glucose and fat metabolism. METHODS: To investigate the effects of SMS on a high-fat diet (HFD)-induced obesity (DIO) model, we studied glucose metabolism via glucose tolerance testing (GTT) and insulin tolerance testing (ITT). Browning of white adipose tissue (WAT) was evaluated using H&E staining, along with browning-related gene and protein expression. Changes in bile acid (BA) levels in serum, liver, ileum, and inguinal white adipose tissue were detected by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, antimicrobial mixture (ABX) and fecal microbial transplantation (FMT) experiments were used to verify the role of gut flora in the effects produced by SMS on HFD-induced obesity model. RESULTS: SMS ameliorated diet-induced dyslipidemia in a dose-dependent manner and reduced glucose intolerance and insulin resistance in DIO mice, helping to restore energy metabolism homeostasis. SMS significantly altered the structure of intestinal microbiome composition, decreasing the abundance of Lactobacillus carrying bile salt hydrolase (BSH) enzymes and thereby increasing the level of conjugated BAs in the blood, ileum, and iWAT. Increased TCA content promoted the secretion of Slit3 from M2 macrophages in iWAT, which activates the protein kinase A/calmodulin-dependent protein kinase II (PKA/CaMKII) signaling pathway in sympathetic neurons via the roundabouts receptor 1(ROBO1). This pathway promotes the synthesis and release of norepinephrine (NE), inducing cyclic adenosine monophosphate (cAMP) release in adipose tissue that activates the cyclic adenosine monophosphate/protein kinase A/phosphorylated hormone-sensitive lipase (cAMP/PKA/pHSL) pathway and enhances WAT browning. ABX treatment eliminated SMS effects on glucose and lipid metabolism in DIO mice, whereas glucose and lipid metabolism in obese mice improved following SMS-FMT and increased the level of serum bile acids. CONCLUSION: SMS affects intestinal flora and bile acid composition in vivo and increased TCA promotes M2 macrophage polarization and Slit3 release in adipose tissue. This induces NE release and increases WAT browning in obese mice, which may be a mechanism by which SMS could be used to treat obesity.

Functional brain alterations in migraine patients: an activation likelihood estimation study.

BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies reported inconsistent results for comparison in brain activation between migraine patients and healthy controls (HC). Thus, activation likelihood estimation (ALE) method, a powerful voxel-based technique, was used to explore the concordant functional brain changes in migraine patients. METHODS: Studies published before October 2022 were searched in the following databases (PubMed, Web of Science and Google Scholar). RESULTS: Migraine without aura (MWoA) patients showed reduced amplitude of low-frequency fluctuations (ALFF) in right lingual gyrus, the left posterior cingulate and the right precuneus (PCUN), compared to HC. Migraine patients showed increased ALFF in the right claustrum, the left caudate, the left insula and the right parahippocampal gyrus, compared to HC. MWoA patients showed reduced regional homogeneity (ReHo) in the right culmen, compared to HC. In addition, migraine patients showed increased ReHo in the bilateral thalamus, compared to HC. MWoA patients showed reduced whole-brain functional connectivity (FC) in the left middle occipital gyrus and the right superior parietal lobule, compared to HC. In addition, migraine patients showed increased whole-brain FC in the left middle temporal gyrus (MTG), the right inferior frontal gyrus, the right superior temporal gyrus (STG) and the left inferior temporal gyrus, compared to HC. CONCLUSIONS: ALE analysis identified consistent functional changes in widespread regions, especially in cingulate gyrus, basal ganglia region and frontal cortex in migraine. These regions involve in pain processing, cognitive dysfunction and emotional problems. These results may provide important clues for clarifying the pathophysiology of migraine.