Fiber optic-based integrated system for in vivo multiscale pharmacokinetic monitoring.

This paper presents the development of a fiber-optic-based fluorescence detection system for multi-scale monitoring of drug distribution in living animals. The integrated system utilized dual laser sources at the wavelengths of 488 nm and 650 nm and three photomultiplier channels for multi-color fluorescence detection. The emission spectra of fluorescent substances were tracked using the time-resolved fluorescence spectroscopy module to continuously monitor their blood kinetics. The fiber bundle, consisting of 30,000 optic filaments, was designed for wide-field mesoscopic imaging of the drug's interactions within organs. The inclusion of a gradient refractive index (GRIN) lens within the setup enabled fluorescence confocal laser scanning microscopy to visualize the drug distribution at the cellular level. The system performance was verified by imaging hepatic and renal tissues in mice using cadmium telluride quantum dots (CdTe QDs) and R3. By acquiring multi-level images and real-time data, our integrated system underscores its potential as a potent tool for drug assessment, specifically within the realms of pharmacokinetic and pharmacodynamic investigations.

Objectivization study of acupuncture Deqi and brain modulation mechanisms: a review.

Deqi is an important prerequisite for acupuncture to achieve optimal efficacy. Chinese medicine has long been concerned with the relationship between Deqi and the clinical efficacy of acupuncture. However, the underlying mechanisms of Deqi are complex and there is a lack of systematic summaries of objective quantitative studies of Deqi. Acupuncture Deqi can achieve the purpose of treating diseases by regulating the interaction of local and neighboring acupoints, brain centers, and target organs. At local and neighboring acupoints, Deqi can change their tissue structure, temperature, blood perfusion, energy metabolism, and electrophysiological indicators. At the central brain level, Deqi can activate the brain regions of the thalamus, parahippocampal gyrus, postcentral gyrus, insular, middle temporal gyrus, cingulate gyrus, etc. It also has extensive effects on the limbic-paralimbic-neocortical-network and default mode network. The brain mechanisms of Deqi vary depending on the acupuncture techniques and points chosen. In addition, Deqi 's mechanism of action involves correcting abnormalities in target organs. The mechanisms of acupuncture Deqi are multi-targeted and multi-layered. The biological mechanisms of Deqi are closely related to brain centers. This study will help to explore the mechanism of Deqi from a local-central-target-organ perspective and provide information for future clinical decision-making.

Metabolomics of Mice with Type 2 Diabetes and Nonalcoholic Fatty Liver Treated by Acupuncture.

Introduction: To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods: Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results: After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion: Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism.

Transthoracic single-port-assisted laparoscopic gastrectomy versus laparoscopic transhiatal approach for Siewert type II adenocarcinoma of the esophagogastric junction: a single-center retrospective study.

BACKGROUND: The surgical approach for patients with Siewert type II AEG remains controversial. Several studies have described a new laparoscopic radical resection approach of Siewert type II AEG through the left diaphragm. However, the technical safety and feasibility of the new surgical approach compared with the transhiatal approach have not yet been tested. STUDY DESIGN: We retrospectively reviewed patients with AEG who underwent TSLG and LTH operations in the Guangdong Provincial Hospital of Chinese Medicine between January 2017 and April 2021. Histologically confirmed AEG and D2 lymphadenectomy with curative R0 patients were included, and patients with Siewert I/III AEG or distant metastasis were excluded. Blood loss, the amount of harvested lymph node, and complications related to surgery were evaluated. RESULTS: A total of 99 patients with Siewert type II AEG were analyzed, 44 in the TSLG group and 55 in the LTH group. There was no difference in clinicopathological features between the two groups. The more harvested lymph node (23.33 ± 11.41 vs. 32.18 ± 12.85, p < 0.01), lower mediastinal lymph node (1.07 ± 2.08 vs. 3.25 ± 3.31, p < 0.01), and longer proximal margin length (3.08 ± 1.19 vs. 4.47 ± 0.95 cm, p < 0.01) were observed in the TSLG group. The rate of cure (R0 gastrectomy) in the TSLG group was higher than that in the LTH group (100% vs. 89.09%, p = 0.03). CONCLUSION: The TSLG approach is associated with improved surgical views, simplified lymphatic dissection in the inferior mediastinum, and more reliable margins. TSLG surgery may be an effective addition to LTH surgery, particularly when lower mediastinal lymph node metastases are suspected.

Electron transfer and microbial mechanism of synergistic degradation of lignocellulose by hydrochar and aerobic fermentation.

In response to the problem of asynchronous fermentation between lignocellulose and perishable materials in compost, the combined technology of low-temperature hydrochar and compost has been studied. Hydrochar was prepared through low-temperature hydrothermal reactions and applied to aerobic fermentation. The response relationship between lignocellulose content, electron transfer capability, and microbes was explored. The results showed that a pore structure with oxygen-containing functional groups was formed in hydrochar, promoting electron transfer during composting. With the rapid increase in composting temperature, the lignocellulose content decreased by 64.36 mg/g. Oceanobacillus, Cerasibacillus, Marinimicrobium, and Gracilibacillus promoted the degradation of lignocellulose and the carbon/nitrogen cycle during aerobic fermentation, and there was a significant response relationship between electron transfer capability and functional microbes. The combined application of hydrochar and aerobic fermentation accelerated the degradation of lignocellulose. This study provides technical support for the treatment of heterogeneous organic waste.

Aucubin Alleviates Intervertebral Disc Degeneration by Repressing NF-κB-NLRP3 Inflammasome Activation in Endplate Chondrocytes.

Background: Intervertebral disc degeneration (IDD) is a prevalent degenerative disease and often recognized as the primary cause of lower back pain (LBP). Aucubin (Au) is a natural compound with anti-inflammatory properties in various diseases. The present study aimed to confirm the therapeutic effect of Au on IDD and explore its potential mechanism in vivo and in vitro. Methods: The process of IDD was simulated using the lumbar spine instability (LSI) model. In vivo, the therapeutic effect of Au on LSI-induced mice was evaluated by micro-CT and histomorphometry. Additionally, immunohistochemistry was applied to detect the cartilage metabolism and inflammasome activation in endplate. In vitro, the cytotoxicity of Au on ATDC5 cells was detected by Cell Counting Kit-8 (CCK-8), and the biological effects of Au were evaluated by Quantitative Real-time PCR (qRT-PCR) and Western blotting. Results: Micro-CT analysis showed that Au administration significantly alleviated LSI-induced disc volume narrowing and endplate cartilage degeneration, which was further supported by Alcian Blue Hematoxylin/Orange G (ABH/OG) staining. Immunohistochemistry results verified that Au could increase the expression of Col2α1 and Aggrecan, reduce the expression of Mmp-13, and attenuate the degradation of the endplate extracellular matrix (ECM). Mechanistically, we found that Au treatment, both in vivo and in vitro, significantly inhibited NF-κB-NLRP3 inflammasome activation in chondrocytes as determined by the decreased expression of p-P65, NLRP3, and Caspase-1. Discussion: Taken together, our findings have demonstrated for the first time that Au treatment ameliorated the degeneration of cartilage endplates in IDD may by inhibiting NF-κB-NLRP3 inflammasome activation in chondrocytes and provided a potential candidate for the treatment of IDD.

Application of image overlapping in percutaneous nephrolithotomy.

OBJECTIVE: To investigate the application of ultrasound and CT image overlap in percutaneous nephrolithotomy (PCNL). METHODS: A total of 140 patients with complicated kidney stones requiring PCNL were prospectively enrolled, from January 2020 to December 2022. These patients were randomly divided into 2 groups, with 70 patients each in the research group and the control group. All participants underwent dual-source, non-contrast CT scan of both kidneys and pelvis before surgery. Preoperative three-dimensional CT reconstruction and simulated puncture were performed in patients from the research group. The best puncture path was determined through ultrasound and CT image overlap. Puncture guided by regular CT and ultrasound was conducted in patients from the control group. Differences in the surgical outcomes between the two groups were compared. RESULTS: Compared to the control group, the research group had higher stone clearance rate in stage I PCNL, success rate of one-time puncture, less percutaneous channels, less reduction of hemoglobin and shorter procedure time. Complications in stage I PCNL were comparable in the two groups, and there was no significant change in the final stone clearance rates between the two groups. CONCLUSION: An optimal puncture channel can be chosen using ultrasound and CT image overlap. PCNL can be achieved with precise puncturing, thus achieving coincidence between imaging and anatomy and reducing the amount of blood loss during stage I of PCNL. It also shortens the procedure time and improves stone clearance rate of PCNL.

Polyethylene microplastics impede the innate immune response by disrupting the extracellular matrix and signaling transduction.

Microplastics (MPs) can accumulate in animal organs. Numerous studies have linked MPs with immune system. However, the impact of MPs on immune response remains unclear. This study examined the innate immune response of mice exposed to 5 µm MPs. In the lipopolysaccharide challenge, mice treated with MPs exhibited lower levels of serum immune factors and activated immune cells. MPs disrupted immune-related receptors and cause dysfunction in cell signal transduction within the liver and spleen. Proteomic analysis revealed that MPs impede the activation of serum immune-related signals. In addition, the tissue section imaging exhibited a significant enrichment of MPs in the extracellular matrix (ECM), consistent with the ECM dysfunction and immune receptor suppression. Therefore, our data suggest excessive MPs accumulation in ECM inhibits cell signaling pathways, thereby suppressing the activation of immune responses. We propose the biotoxicity of MPs is partly through the MP disruption of ECM (MPDEM).

Research methods and efficacy of acupuncture in the treatment of Parkinson's disease: a scoping review of systematic reviews and meta-analyses.

Introduction: Research on acupuncture for Parkinson's Disease is growing rapidly. A scoping review examines emerging evidence and is important to guide policy and practice. The purpose of this scoping review was to examine the breadth and methodological quality of systematic reviews and meta-analyses, and to map the quality of evidence of these studies to evaluate the efficacy of acupuncture for treatment of PD. Methods: Seven literature databases were searched. Two researchers independently screened the literature and extracted relevant information (such as general characteristics, inclusion criteria, study results, and report quality).The inclusion criteria include publicly published systematic reviews/meta-analyses/systematic reviews of acupuncture treatment for Parkinson's disease. The research subjects are any patients who meet the diagnostic criteria for Parkinson's disease, and intervention measures include acupuncture treatment including electro acupuncture, scalp acupuncture, or combination with other treatment methods. The outcome indicators are all types of results related to PD and the effective measurement tools used. Results: A total of 23 systematic reviews and/or meta-analyses of studies were included. Most of the articles were published between 2019 and 2023 (47.8%). A total of 14 articles (60.9%) were evaluated and classified, and 89 (36.8.1%) of the 242 included articles were of medium and high quality. Discussion: This study comprehensively evaluates the quality and research methods of incorporating SRs/MAs, and concludes that acupuncture treatment for Parkinson's disease may be significant. Considering the shortcomings in research design and methodology, it is not possible to draw conclusions on the evidence of acupuncture treatment for PD at this stage, but it does not mean that acupuncture treatment is ineffective. We hope to focus on improving research design and methods in the study of acupuncture treatment for Parkinson's disease, an increase the credibility of research results.

Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH.

BACKGROUND: This study aimed to investigate the pathogenic factors of glucocorticoids (GCs)-induced osteonecrosis of the femoral head (GONFH) and its underlying pathogenesis in vivo and in vitro. METHODS: Radiographical (µCT) scanning, histopathological, immunohistochemical, reactive oxygen species (ROS) and tunel staining were conducted on GONFH patients and rats. ROS, tunel, flow cytometry, alkaline phosphatase, Oil red O staining, reverse transcription­quantitative PCR and western blotting were applied to elucidate the exact pathogenesis mechanism. RESULTS: Clinical and animal studies demonstrated increased levels of ROS, aggravated oxidative stress (OS) microenvironment, augmented apoptosis and imbalance in osteogenic/lipogenic in the GONFH group compared to the control group. The fate of mesenchymal stem cells (MSCs) directed by GCs is a crucial factor in determining GONFH. In vitro studies further revealed that GCs promote excessive ROS production through the expression of NOX family proteins, leading to a deterioration of the OS microenvironment in MSCs, ultimately resulting in apoptosis and imbalance in osteogenic/lipogenic differentiation. Furthermore, our results confirmed that the NOX inhibitor-diphenyleneiodonium chloride and the NF-κB inhibitor-BAY 11-7082 ameliorated apoptosis and osteogenic/lipogenic differentiation imbalance of MSCs induced by an excess of GCs. CONCLUSION: We demonstrated for the first time that the aggravation of the OS microenvironment in MSCs caused by high doses of GCs leading to apoptosis and differentiation imbalance is a crucial factor in the pathogenesis of GONFH, mediated through activating the NOX/ROS/NF-κB signaling pathway.

Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration.

BACKGROUND: Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion. METHODS: AOM/DSS model in Il11-/- and Apcmin/+/Il11-/- mice were used to detect tumor growth and CD8+ T infiltration. STAT1/3 phosphorylation and MHC-I, CXCL9, H2-K1 and H2-D1 expression were detected in MC38 cells and intestine organoids treated with/without recombinant IL11 to explore effect of IL11/STAT3 signaling, with IL11 mutein used to competitively inhibit IL11 and rescue inhibited STAT1 activation. Correlation between IL11 and CD8+ T infiltration was analyzed using TIMER2.0 website. IL11 expression and survival prognosis was analyzed in clinical data of patient cohort from Nanfang Hospital. RESULTS: IL11 is highly expressed in CRC and indicates unfavorable prognosis. IL11 knockout increased CD8+ T cell infiltration and reduced intestinal and colon formation. Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. CONCLUSIONS: This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.

"Adjust Zang and arouse spirit" electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice.

Introduction: Diabetic cognitive impairment (DCI) is a chronic complication of the central nervous system (CNS) caused by diabetes that affects learning and memory capacities over time. Recently, acupuncture has been shown to improve cognitive impairment in streptozotocin-induced diabetic rats. However, the effects of electroacupuncture on DCI and its underlying mechanism have not yet been elucidated in detail. Methods: In this study, we used db/db mice as DCI animal models which showed low cognitive, learning and memory functions. Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. The db/db mice with cognitive impairment were randomly divided into a model group (Mod) and an electroacupuncture treatment group (Acup), while db/m mice were used as a normal control group (Con). First, the mice were subjected to behavioural tests using the Morris water maze (MWM), and body weight, blood glucose, insulin, triglycerides (TG) and total cholesterol (TC) were observed; HE, Nissl, and TUNEL staining were used to observe the morphological changes and neuronal apoptosis in the mice hippocampus; Finally, Western blot and rt-PCR were applied to detect the essential proteins and mRNA of ERS and insulin signalling pathway, as well as the expression levels of Tau and Aß. Results: Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. Moreover, electroacupuncture attenuated diabetes-induced morphological structure change, neuronal apoptosis in the hippocampus of db/db mice. Our results revealed that electroacupuncture could regulate the expression levels of Tau and Aß by improving hippocampal ERS levels in db/db mice, inhibiting JNK activation, attenuating IRS1 serine phosphorylation, and restoring normal transduction of the insulin signaling pathway. Discussion: In summary, ERS and insulin signaling pathway paly causal roles in DCI development. Electroacupuncture can significantly alleviate the pathogenesis of DCI, improve mice's learning and memory ability, and improve cognitive dysfunction. This study adds to our understanding of the effect of acupuncture on DCI and opens the door to further research on DCI.

Polystyrene microplastics trigger adiposity in mice by remodeling gut microbiota and boosting fatty acid synthesis.

Microplastic (MP) pollution has become a global environmental problem, with particular concerns for its harmful effects on human health. Several studies have demonstrated that MP can penetrate animals and humans resulting in tissue dysfunction, but their influences on metabolism remain poorly understood. In this study, we investigated the impact of MP exposure on metabolism and the results showed that different treatment doses produce a bidirectional modulatory effects on mice. When exposed to high concentrations of MP, mice lost significant weight, while those in the lowest concentration treatment group showed little change, but those treated at relatively low concentrations became overweight. There was excessive lipid accumulation in these heavier mice, with a better appetite and lower activity level. Transcriptome sequencing revealed that MPs increased fatty acid synthesis in the liver. In addition, the gut microbiota composition of the MPs-induced obese mice was remodeled, which would enhance the nutrient absorption capacity of the intestine. Our results uncovered an MP dose-dependent lipid metabolism in mice and a non-unidirectional model of the physiological responses to different MP concentrations was proposed. These results provided new insights into the seemingly contradictory effects of MP on metabolism in the previous study.

Repetitive transcranial magnetic stimulation for post-stroke depression: An overview of systematic reviews.

Objective: There is conflicting published research about the clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the treatment of post-stroke depression (PSD). In order to provide trustworthy information for upcoming therapeutic treatments, this review attempts to compile and assess the data from pertinent systematic reviews and meta-analyses. Methods: The systematic evaluation of repetitive transcranial magnetic stimulation for post-stroke depression was collected by searching CNKI, VIP, Wanfang Database, CBM, PubMed, EMBASE, Web of Science, and Cochrane Library. The retrieval time is from database construction to September 2022. After selection, the included literature was evaluated for methodological quality, reporting quality, and evidence quality using AMSTAR2, PRISMA statements, and the GRADE system. Results: There were a total of 13 studies included, with three having generally comprehensive reporting according to the PRISMA statement, eight having some reporting issues, two having pretty substantial information issues, and 13 having extremely poor methodological quality according to the AMSTAR2. The GRADE was used to grade the quality of the evidence, and the included literature had 0 high-level evidence, eight medium-level evidence, 12 low-level evidence, and 22 very low-level evidence. Limitations: The results of this study are from researchers' subjective evaluation and only qualitative analysis, not quantitative evaluation. Although repeated cross-evaluation of researchers is carried out, the results will be personal. The interventions included in the study were complex, and it was impossible to analyze their effect values quantitatively. Conclusion: Patients with post-stroke depression may benefit from repetitive transcranial magnetic stimulation. However, in terms of the quality of the reports, the methodology, and the quality of the evidence, published systematic evaluations/meta-analyses are of low quality. We list the drawbacks of the current clinical trials of repetitive transcranial magnetic stimulation for post-stroke depression as well as potential therapeutic mechanisms. This information may serve as a guide for future clinical trials aiming to establish a solid foundation for the clinical efficacy of repetitive transcranial magnetic stimulation in the treatment of post-stroke depression.

Effect of acupuncture on the modulation of functional brain regions in migraine: A meta-analysis of fMRI studies.

Background: Acupuncture, a traditional Chinese medicine therapy, is an effective migraine treatment, especially in improving pain. In recent years, many acupuncture brain imaging studies have found significant changes in brain function following acupuncture treatment of migraine, providing a new perspective to elucidate the mechanism of action of acupuncture. Objective: To analyse and summarize the effects of acupuncture on the modulation of specific patterns of brain region activity changes in migraine patients, thus providing a mechanism for treating migraine by acupuncture. Methods: Chinese and English articles published up to May 2022 were searched in three English databases (PubMed, Embase and Cochrane) and four Chinese databases (China national knowledge infrastructure, CNKI; Chinese Biomedical Literature database, CBM; the Chongqing VIP database, VIP; and the Wanfang database, WF). A neuroimaging meta-analysis on ALFF, ReHo was performed on the included studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software. Subgroup analyses were used to compare differences in brain regions between acupuncture and other groups. Meta-regression was used to explore the effect of demographic information and migraine alterations on brain imaging outcomes. Linear models were drawn using MATLAB 2018a, and visual graphs for quality evaluation were produced using R and RStudio software. Results: A total of 7 studies comprising 236 patients in the treatment group and 173 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps to improve pain symptoms in patients with migraine. The left angular gyrus is hyperactivation, and the left superior frontal gyrus and the right superior frontal gyrus are hypoactivated. The migraine group showed hyperactivation in the corpus callosum compared to healthy controls. Conclusion: Acupuncture can significantly regulate changes in brain regions in migraine patients. However, due to the experimental design of neuroimaging standards are not uniform, the results also have some bias. Therefore, to better understand the potential mechanism of acupuncture on migraine, a large sample, multicenter controlled trial is needed for further study. In addition, the application of machine learning methods in neuroimaging studies could help predict the efficacy of acupuncture and screen migraine patients suitable for acupuncture treatment.

Enhancing the Chemical Stability of MXene Through Synergy of Hydrogen Bond and Coordination Bond in Aqueous Solution.

MXenes with unique physicochemical properties have shown substantial potential in electromagnetic interference (EMI) shielding. However, the chemical instability and mechanical fragility of MXenes has become a major hurdle for their application. Abundant strategies have been dedicated to improving the oxidation stability of colloidal solution or mechanical properties of films, which always come at the expense of electrical conductivity and chemical compatibility. Here, hydrogen bond (H-bond) and coordination bond are employed to achieve chemical and colloidal stability of MXenes (0.1 mg mL-1 ) by occupying the reaction sites of Ti3 C2 Tx attacking of water and oxygen molecules. Compared to the Ti3 C2 Tx , the Ti3 C2 Tx modified with alanine via H-bond shows significantly improved oxidation stability (at room temperature over 35 days), while the Ti3 C2 Tx modified with cysteine by synergy of H-bond and coordination bond can be maintained even after 120 days. Simulation and experimental results verify the formation of H-bond and Ti-S bond by a Lewis acid-base interaction between Ti3 C2 Tx and cysteine. Furthermore, the synergy strategy significantly improves the mechanical strength of the assembled film (up to 78.1 ± 7.9 MPa), corresponding the increment of 203% compared to untreated one, almost without compromising the electrical conductivity and EMI shielding performance.

FXR1 facilitates axitinib resistance in clear cell renal cell carcinoma via regulating KEAP1/Nrf2 signaling pathway.

Axitinib is emerging as a first-line combination treatment drug for metastatic renal cell carcinoma, but the acquired resistance significantly bothers the treatment efficacy. This article is to investigate the impact of fragile X mental retardation autosomal homolog 1 (FXR1) and its mechanistic involvement with Kelch-like epoxy chloropropan-associated protein 1 (KEAP1)/NF-E2-related factor 2 (Nrf2) pathway on cell resistance to axitinib in clear cell renal cell carcinoma (ccRCC). Establishment of axitinib resistance cells (786-O, Caki-1, 786-O/axitinib, or Caki-1/axitinib) was made, and the cells were then transfected with sh-FXR1, or co-transfected with sh-FXR1 and sh-KEAP1. The quantitative real-time PCR (qRT-PCR) and western blotting assays were employed to measure the expression of FXR1, KEAP1, Nrf2, LC3 II/I, Beclin 1, p62, MDR-1, and MRP-1. In addition, the binding between FXR1 and KEAP1 was verified by RNA-immunoprecipitation and RNA pull-down assays, and FXR1-dependent KEAP1 mRNA degradation was determined. Herein, FXR1 was demonstrated to be overexpressed in ccRCC cells, and showed higher expression in 786-O/axitinib and Caki-1/axitinib cells. Mechanistically, FXR1 enriched KEAP1 mRNA, and pulled downed by biotinylated KEAP1 probes. Results of RNA stability assay reveled that KEAP mRNA stability was suppressed by FXR1. Furthermore, knockdown of FXR1 promoted cell apoptosis and showed a restrained feature on cell resistance to axitinib. Of note, KEAP1 knockdown suppressed cell autophagy, oxidative stress, resistance to axitinib, and promoted apoptosis, despite FXR1 was downregulated in ccRCC cells. In conclusion, FXR1 played an encouraging role in ccRCC cell resistance to axitinib by modulating KEAP/Nrf2 pathway.

Effect of acupuncture on brain regions modulation of mild cognitive impairment: A meta-analysis of functional magnetic resonance imaging studies.

Background: As a non-pharmacological therapy, acupuncture has significant efficacy in treating Mild Cognitive Impairment (MCI) compared to pharmacological therapies. In recent years, advances in neuroimaging techniques have provided new perspectives to elucidate the central mechanisms of acupuncture for MCI. Many acupuncture brain imaging studies have found significant improvements in brain function after acupuncture treatment of MCI, but the underlying mechanisms of brain regions modulation are unclear. Objective: A meta-analysis of functional magnetic resonance imaging studies of MCI patients treated with acupuncture was conducted to summarize the effects of acupuncture on the modulation of MCI brain regions from a neuroimaging perspective. Methods: Using acupuncture, neuroimaging, magnetic resonance, and Mild Cognitive Impairment as search terms, PubMed, EMBASE, Web of Science, Cochrane Library, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects (DARE), Google Scholar, China National Knowledge Infrastructure (CNKI), China Biology Medicine disk (CBM disk), Wanfang and Chinese Scientific Journal Database (VIP) for brain imaging studies on acupuncture on MCI published up to April 2022. Voxel-based neuroimaging meta-analysis of fMRI data was performed using voxel-based d Mapping with Permutation of Subject Images (SDM-PSI), allowing for Family-Wise Error Rate (FWER) correction correction for correction multiple comparisons of results. Subgroup analysis was used to compare the differences in brain regions between the acupuncture treatment group and other control groups. Meta-regression was used to explore demographic information and altered cognitive function effects on brain imaging outcomes. Linear models were drawn using MATLAB 2017a, and visual graphs for quality evaluation were produced using R software and RStudio software. Results: A total of seven studies met the inclusion criteria, with 94 patients in the treatment group and 112 patients in the control group. All studies were analyzed using the regional homogeneity (ReHo) method. The experimental design of fMRI included six task state studies and one resting-state study. The meta-analysis showed that MCI patients had enhanced activity in the right insula, left anterior cingulate/paracingulate gyri, right thalamus, right middle frontal gyrus, right median cingulate/paracingulate gyri, and right middle temporal gyrus brain regions after acupuncture treatment. Further analysis of RCT and longitudinal studies showed that Reho values were significantly elevated in two brain regions, the left anterior cingulate/paracingulate gyrus and the right insula, after acupuncture. The MCI group showed stronger activity in the right supramarginal gyrus after acupuncture treatment compared to healthy controls. Meta-regression analysis showed that the right anterior thalamic projection ReHo index was significantly correlated with the MMSE score after acupuncture treatment in all MCI patients. Conclusions: Acupuncture therapy has a modulating effect on the brain regions of MCI patients. However, due to the inadequate experimental design of neuroimaging studies, multi-center neuroimaging studies with large samples are needed better to understand the potential neuroimaging mechanisms of acupuncture for MCI. In addition, machine learning algorithm-based predictive models for evaluating the efficacy of acupuncture for MCI may become a focus of future research. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022287826, identifier: CRD 42022287826.