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1.
AME Case Rep ; 8: 78, 2024.
Article in English | MEDLINE | ID: mdl-39091549

ABSTRACT

Background: Reasonable nutritional intervention is very important to promote wound healing and rehabilitation in patients with radical esophagectomy for esophageal cancer. This report aims to summarize the experience of nutritional and continuous nursing intervention in a patient who underwent radical resection of esophageal cancer after liver transplantation, by testing a comprehensive approach to optimize nursing plans in similar clinical practice. We hope that the implementation of home enteral nutrition can improve the nutrition status and quality of life of postoperative patients. Case Description: A patient with liver transplantation was admitted to The Fourth Hospital of Hebei Medical University for postoperative care. The nursing intervention were subsequently summarized and analyzed. In July 2023, the patient successfully underwent radical resection for esophageal cancer. Following the operation, the patient received regular medication and on-site nutritional intervention with the consent of her family. At discharge, the prealbumin, albumin, total protein and hemoglobin values of the patient were low, and body weight was 91 kg. The patient's nutritional risk screening (NRS2022) score was 5 points, and the Patient-Generated Subjective Global Assessment (PG-SGA) score was 4 points. After discharge, the patient continued to receive family enteral nutrition treatment, dietary guidance and psychological nursing. A follow-up review conducted 4 weeks after discharge showed improvements in the patient's NRS2022, albumin, total protein, hemoglobin, and body weight. Conclusions: Strengthening postoperative nutritional intervention are vital for promoting rehabilitation in patients who undergo radical resection of esophageal cancer after liver transplantation.

2.
Article in English | MEDLINE | ID: mdl-39028609

ABSTRACT

Motor imagery (MI) based brain computer interface (BCI) has been extensively studied to improve motor recovery for stroke patients by inducing neuroplasticity. However, due to the lower spatial resolution and signal-to-noise ratio (SNR) of electroencephalograph (EEG), MI based BCI system that involves decoding hand movements within the same limb remains lower classification accuracy and poorer practicality. To overcome the limitations, an adaptive hybrid BCI system combining MI and steady-state visually evoked potential (SSVEP) is developed to improve decoding accuracy while enhancing neural engagement. On the one hand, the SSVEP evoked by visual stimuli based on action-state flickering coding approach significantly improves the recognition accuracy compared to the pure MI based BCI. On the other hand, to reduce the impact of SSVEP on MI due to the dual-task interference effect, the event-related desynchronization (ERD) based neural engagement is monitored and employed for feedback in real-time to ensure the effective execution of MI tasks. Eight healthy subjects and six post-stroke patients were recruited to verify the effectiveness of the system. The results showed that the four-class gesture recognition accuracies of healthy individuals and patients could be improved to 94.37 ± 4.77% and 79.38 ± 6.26%, respectively. Moreover, the designed hybrid BCI could maintain the same degree of neural engagement as observed when subjects solely performed MI tasks. These phenomena demonstrated the interactivity and clinical utility of the developed system for the rehabilitation of hand function in stroke patients.

3.
World Neurosurg ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39032631

ABSTRACT

OBJECTIVE: Comparison of predictive performance for pedicel screw loosening (PSL) between CT-based Hounsfield units (HU) and MRI-based vertebral bone quality score (VBQ) following lumbar surgery METHODS: A retrospective study was conducted on patients who received transforaminal lumbar interbody fusion (TLIF) continuously at our institution from May 2018 to September 2020. Based on 12 months follow-up lumbar X-ray, screw loosening was defined as a clear zone of minimal thickness of ≥ 1 mm around the pedicle screw on radiography. VBQ score and HU value were measured using preoperative MRI and CT, respectively. Then, we evaluated the predictive performance of these two parameters by comparing the receiver operating characteristic (ROC) curve. RESULTS: In all patients, area under the curve (AUC) of the VBQ score (AUC = 0.752; 95% confidence interval (CI): 0.663-0.841; P < 0.001) was larger than those of the CT HU value (AUC = 0.652; 95% CI: 0.558-0.746; P = 0.005), but there was no significant difference between them (PAUC = 0.076). In patients with lumbar spinal stenosis (LSS), AUC of VBQ score (AUC = 0.863; 95% CI: 0.764-0.961; P < 0.001) was larger than those of the CT HU value (AUC = 0.673; 95% CI: 0.513-0.833; P = 0.043), with significant difference (PAUC = 0.003). CONCLUSION: MRI-based VBQ score, and CT-based HU value have similar performance in predicting PSL after lumbar surgery. Furthermore, in patients with LSS, VBQ score demonstrated better predictive ability than HU value.

4.
J Immunol Res ; 2024: 2899154, 2024.
Article in English | MEDLINE | ID: mdl-39021433

ABSTRACT

As another receptor for complement activation product C5a, C5aR2 has been paid much attention these years. Although controversial and complex, its specific signals or roles in modulating the classic receptor C5aR1 have been investigated and gradually revealed. The hypothesis of the heterodimer of C5aR1 and C5aR2 has also been suggested and observed under extremely high C5a concentrations. In this article, we tried to investigate whether C5aR2 would affect C5aR1 expression under normal or inflammatory conditions in WT and C5ar2 -/- mice of C57BL/6 background. We focused on the innate immune cells-neutrophils and macrophages. The mRNA levels of C5ar1 in normal kidney, liver, and the mRNA or protein levels of naïve-bone marrow and peripheral blood leukocytes and peritoneal Mφs were comparable between WT and C5ar2 -/- mice, indicating the technique of C5aR2 knockout did not affect the transcription of its neighboring gene C5aR1. However, the mean fluorescence intensity of surface C5aR1 on naïve circulating C5ar2 -/- neutrophils detected by FACS was reduced, which might be due to the reduced internalization of C5aR1 on C5ar2 -/- neutrophils. In the peritonitis model induced by i.p. injection of thioglycollate, more neutrophils were raised after 10 hr in C5ar2 -/- peritoneal cavity, indicating the antagonism of C5aR2 on C5aR1 signal in neutrophil chemotaxis. After 3 days of thioglycollate injection, the mainly infiltrating macrophages were comparable between WT and C5ar2 -/- mice, but the C5ar1 mRNA and surface or total C5aR1 protein expression were both reduced in C5ar2 -/- macrophages, combined with our previous study of reduced chemokines and cytokines expression in C5ar2 -/- peritoneal macrophages, indicating that C5aR2 in macrophages may cooperate with C5aR1 inflammatory signals. Our article found C5aR2 deficiency lessened C5aR1 distribution and expression in neutrophils and macrophages with different functions, indicating C5aR2 might function differently in different cells.


Subject(s)
Macrophages , Neutrophils , Peritonitis , Receptor, Anaphylatoxin C5a , Animals , Mice , Complement C5a/metabolism , Complement C5a/immunology , Disease Models, Animal , Immunity, Innate , Macrophages/immunology , Macrophages/metabolism , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/immunology , Neutrophils/metabolism , Peritonitis/immunology , Receptor, Anaphylatoxin C5a/metabolism , Receptor, Anaphylatoxin C5a/genetics
5.
ACS Biomater Sci Eng ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39056337

ABSTRACT

Itaconic acid and its derivative 4-octyl itaconate (OI) represent a novel anti-inflammatory medication that has demonstrated efficacy in multiple inflammation models because of its minimal side effects. Recently, natural polymers conjugated with small molecule drugs, known as polymer-drug conjugates (PDCs), have emerged as a promising approach to sustained drug release. In this work, we reported an approach to prepare a PDC containing an OI and make it into an injectable hydrogel. Chitosan (CS) was selected for PDC synthesis because of its abundant free amino groups that can be conjugated with molecules containing carboxyl groups by carbodiimide chemistry. We used an ethanol/water cosolvent system to synthesize a CS-OI conjugate via EDC/NHS catalysis. The CS-OI conjugate had improved water solubility and unique anti-inflammatory activity and did not show compromised antibacterial activity compared with unmodified CS. Beta-glycerophosphate (ß-GP) cross-linked CS-OI hydrogel exhibited good injectability with sustainable OI release and effectively modulated inflammatory response in a rat model. Therefore, this study provides valuable insights into the design of PDC hydrogels with inflammatory modulatory properties.

6.
Phytomedicine ; 132: 155886, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39059092

ABSTRACT

BACKGROUND: Shugan Lidan Xiaoshi Granules (SLXG) is a traditional Chinese medicine (TCM) formulation frequently employed to prevent and treat cholesterol gallstones. SLXG is formulated based on the Chaihu Shugan Formula found in an ancient Chinese medical book, a traditional remedy in China for centuries, and has demonstrated successful treatment of numerous patients with gallbladder stones. PURPOSE: This research sought to clarify the therapeutic impact and molecular mechanisms of SLXG and its active components in the treatment of cholesterol gallbladder stones. METHODS: The study employed network pharmacology, UPLC-HRMS transcriptome sequencing, animal model experiments, molecular docking, and Surface Plasmon Resonance (SPR) to explore the molecular mechanisms of SLXG and its relationship with Traditional Chinese Medicines (TCMs) and potential targets. Furthermore, PPI network analysis, along with GO and KEGG enrichment analyses, were performed to explore the potential mechanisms through which SLXG and its active ingredient, naringenin, prevent and treat cholesterol gallstones. The mechanism of action was further elucidated using an animal model for gallbladder stone formation. RESULTS: The study employed a network pharmacology and UPLC-HRMS to investigate the active compounds of SLXG for the treatment of cholesterol gallbladder stones, and subsequently constructed a network of therapeutic targets of SLXG. The results from gene enrichment analyses indicated that SLXG targets the metabolic pathway of bile secretion and the cholesterol metabolism pathway in addressing cholesterol gallbladder stones. The molecular docking results confirmed the interaction between the genes enriched in the pathways and the active ingredients in SLXG. Transcriptome sequencing results demonstrated that SLXG exerts its therapeutic effect on gallstones by regulating cholesterol and bile acid synthesis and metabolism. Furthermore, animal model experiments and SPR provided evidence that SLXG and its active ingredient, naringenin, exert therapeutic effects on cholesterol gallbladder stones by targeting the genes HMGCR, SOAT2, and UGT1A1, and influencing substances associated with cholesterol synthesis and metabolism. CONCLUSIONS: Using systematic network pharmacology methods combined with in vivo validation experiments, we uncovered the fundamental pharmacological effects and potential mechanisms of SLXG and its active ingredient, naringenin, in the treatment of cholesterol gallstones. This research underscores the valuable role that traditional remedies can play in addressing medical challenges and suggests a promising direction for further exploration of natural treatments for the disease.

7.
Perioper Med (Lond) ; 13(1): 81, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39049003

ABSTRACT

OBJECTIVE: Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients. METHOD: This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models. RESULTS: Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843-0.954) and good calibration. CONCLUSION: Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.

8.
Obes Facts ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39047689

ABSTRACT

Introduction The purpose of this study is to investigate the association of central lean mass distribution with the risk of mortality. Methods This cohort study included 40283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual energy X-ray absorptiometry, with the risk of mortality. Results The median age of the participants was 65 years and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer, and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95%CI, 1.23 - 1.94), 1.69 (95%CI, 1.26 - 2.26), and 1.14 (95%CI, 0.72 - 1.80) for all-cause, cancer and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI, 3.3%-40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. Conclusion Trunk-to-leg lean mass ratio, assessed by dual energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging, and poor diet quality to further increase the risk of death.

9.
J Neural Eng ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39074506

ABSTRACT

OBJECTIVE: In recent years, the robot assisted (RA) rehabilitation training has been widely used to counteract defects of the manual one provided by physiotherapists. However, since the proprioception feedback provided by the robotic assistance or the manual methods is relatively weak for the paralyzed patients, their rehabilitation efficiency is still limited. In this study, a dynamic electrical stimulation (DES) based proprioception enhancement and the associated quantitative analysis methods have been proposed to overcome the limitation mentioned above. APPROACH: Firstly, the DES based proprioception enhancement method was proposed for the RA neural rehabilitation. In the method, the relationship between the surface electromyogram (sEMG) envelope of the specified muscle and the associated joint angles was constructed, and the electrical stimulation (ES) pulses for the certain joint angles were designed by consideration of the corresponding sEMG envelope, based on which the ES can be dynamically regulated during the rehabilitation training. Secondly, power spectral density, source estimation, and event-related desynchronization of electroencephalogram, were combinedly used to quantitatively analyze the proprioception from multiple perspectives, based on which more comprehensive and reliable analysis results can be obtained. Thirdly, four modes of rehabilitation training tasks, namely active, RA, DES-RA, and ES-only training, were designed for the comparison experiment and validation of the proposed DES based proprioception enhancement method. MAIN RESULTS: The results indicated that the activation of the sensorimotor cortex was significantly enhanced when the DES was added, and the cortex activation for the DES-RA training was similar to that for the active training. Meanwhile, relatively consistent results from the multiple perspectives were obtained, which validates the effectiveness and robustness of the proposed proprioception analysis method. SIGNIFICANCE: The proposed methods have the potential to be applied in the practical rehabilitation training to improve the rehabilitation efficiency.

10.
Adv Sci (Weinh) ; : e2402114, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896802

ABSTRACT

Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1-EVs substantially improved motor function in spinal cord-injured mice. Rg1-EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1-EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1-EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1-EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2-phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1-EVs in neuronal protection and functional recovery following SCI through MYCBP2-mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1-EVs.

11.
Neuroscience ; 552: 47-53, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-38880241

ABSTRACT

Cerebral small vessel disease (CSVD) impairs visuospatial function, and this is one of the most obvious areas of cognitive impairment in CSVD. So, recognizing, monitoring, and treating visuospatial dysfunction are all important to the prognosis of CSVD. This review discussed the anatomical and pathological mechanisms, clinical recognition (scales, imaging, and biomarkers), and treatment of cognitive impairment especially visuospatial dysfunction in CSVD.


Subject(s)
Cerebral Small Vessel Diseases , Humans , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/physiopathology , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/etiology , Space Perception/physiology , Perceptual Disorders/physiopathology , Perceptual Disorders/etiology , Visual Perception/physiology
12.
Biomacromolecules ; 25(7): 4358-4373, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38924782

ABSTRACT

Chitosan (CS)-based photo-cross-linkable hydrogels have gained increasing attention in biomedical applications. In this study, we grafted CS with gallic acid (GA) by carbodiimide chemistry to prepare the GA-CS conjugate, which was subsequently modified with methacrylic anhydride (MA) modification to obtain the methacrylated GA-CS conjugate (GA-CS-MA). Our results demonstrated that the GA-CS-MA hydrogel not only exhibited improved physicochemical properties but also showed antibacterial, antioxidative, and anti-inflammatory capacity. It showed moderate antibacterial activity and especially showed a more powerful inhibitory effect against Gram-positive bacteria. It modulated macrophage polarization, downregulated pro-inflammatory gene expression, upregulated anti-inflammatory gene expression, and significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) production under lipopolysaccharide (LPS) stimulation. Subcutaneously implanted GA-CS-MA hydrogels induced significantly lower inflammatory responses, as evidenced by less inflammatory cell infiltration, thinner fibrous capsule, and predominately promoted M2 polarization. This study provides a feasible strategy to prepare CS-based photo-cross-linkable hydrogels with improved physicochemical properties for biomedical applications.


Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Antioxidants , Chitosan , Gallic Acid , Hydrogels , Methacrylates , Chitosan/chemistry , Gallic Acid/chemistry , Gallic Acid/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Mice , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/chemical synthesis , Methacrylates/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , RAW 264.7 Cells , Cross-Linking Reagents/chemistry , Macrophages/drug effects , Macrophages/metabolism , Nitric Oxide/metabolism
13.
Orthop Surg ; 16(8): 1929-1938, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38859720

ABSTRACT

OBJECTIVE: Retention or sacrifice of the posterior cruciate ligament (PCL) is one of the most controversial issues while performing total knee arthroplasty (TKA). This study aimed to evaluate the impact of PCL resection on flexion-extension gaps, femoral component rotation, and bone resection amounts during robot-assisted TKA. METHODS: This prospective study included 40 patients with knee osteoarthritis who underwent robot-assisted posterior-stabilized (PS) TKA between September 2021 and February 2022. Of the patients, 75% were women (30/40) with a mean age and BMI of 72.6 years and 27.4 kg/m2, respectively. The guidance module and camera stand assembly were used to capture gaps before and after PCL resection. Measurements of femoral component rotation and bone resection amounts were made in cruciate-retaining (CR) TKA mode and PS-TKA mode. RESULTS: After PCL resection, the mean change in the medial and lateral compartments of flexion gaps increased by 2.0 and 0.6 mm, respectively (p < 0.001). Compared with the CR-TKA mode group, the bone resection amounts of the medial posterior condyle and the lateral posterior condyle in the PS-TKA mode group decreased by 2.0 ± 1.1 and 1.1 ± 1.1 mm, respectively, and the external rotation of the femoral prosthesis relative to the posterior condylar axis and trans-epicondylar line was reduced by 1.0° ± 1.3° and 1.2° ± 1.6°, respectively (p < 0.001). CONCLUSION: The release of the PCL did not affect the extension gap, but significantly increased the flexion gap. Moreover, the increases in the medial flexion gap were greater than those of the lateral flexion gap. After PCL resection, less external rotation of the femoral prosthesis and fewer bone cuts of the posterior femur were needed in PS-TKA.


Subject(s)
Arthroplasty, Replacement, Knee , Posterior Cruciate Ligament , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Knee/methods , Female , Posterior Cruciate Ligament/surgery , Male , Aged , Prospective Studies , Robotic Surgical Procedures/methods , Middle Aged , Osteoarthritis, Knee/surgery , Aged, 80 and over , Range of Motion, Articular
14.
Langmuir ; 40(21): 11251-11262, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38748644

ABSTRACT

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

15.
Nat Metab ; 6(6): 1161-1177, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38698281

ABSTRACT

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.


Subject(s)
Diabetic Cardiomyopathies , Fatty Acids , Receptors, G-Protein-Coupled , Animals , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Diabetic Cardiomyopathies/metabolism , Mice , Male , Female , Fatty Acids/metabolism , Humans , Mice, Knockout , Bile Acids and Salts/metabolism , Diet, High-Fat , CD36 Antigens/metabolism , CD36 Antigens/genetics , Myocardium/metabolism , Lipid Metabolism , Myocytes, Cardiac/metabolism , Diabetes Mellitus, Experimental/metabolism
16.
World Neurosurg ; 187: e1097-e1105, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38762028

ABSTRACT

OBJECTIVES: To compare magnetic resonance (MR) short T1 inversion recovery (STIR) sequence with MR T2-weighted (T2W) sequence for detecting increased signal intensity (ISI) and assessing outcomes of ISI in cervical spondylotic myelopathy (CSM). METHODS: Data of patients with CSM who showed ISI on MR imaging and had undergone cervical spine surgery were retrospectively reviewed. STIR and T2W images were examined to assess signal intensity ratio (SIR), length and grading of the ISI, maximal spinal cord compression, canal narrowing ratio, and ligamentum flavum hypertrophy. The patients were divided into good and poor groups based on their outcomes. χ2 tests and variance analysis were used to assess intergroup differences. Univariate and multivariate logistic regression analyses were performed to identify risk factors for poor outcomes, and receiver operating characteristic curves were plotted to detect prognostic effects. RESULTS: SIR and ISI lengths were significantly different between the STIR and T2 images. In the univariate logistic regression analysis, age, diabetes, SIRT2, SIRSTIR, and ISISTIR grading were significant factors. Accordingly, in the multivariate logistic regression analysis, age, diabetes, SIRT2, and SIRSTIR were included in the model. Among patients with diabetes, we observed a significant difference between SIRT2 and SIRSTIR. CONCLUSIONS: The STIR sequence demonstrated superior capability to the T2W sequence in detecting ISI; however, there was no obvious difference in predicted outcomes. STIR sequence has a better prognostic value than T2W sequence in patients with diabetes who have CSM. ISI grading based on the STIR sequence may be a clinically valuable indicator.


Subject(s)
Cervical Vertebrae , Magnetic Resonance Imaging , Spondylosis , Humans , Male , Female , Middle Aged , Spondylosis/surgery , Spondylosis/diagnostic imaging , Magnetic Resonance Imaging/methods , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Aged , Retrospective Studies , Spinal Cord Compression/surgery , Spinal Cord Compression/diagnostic imaging , Spinal Cord Compression/etiology , Adult , Spinal Cord Diseases/surgery , Spinal Cord Diseases/diagnostic imaging
17.
Sci Rep ; 14(1): 10096, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698014

ABSTRACT

Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON-OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2-/- mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.


Subject(s)
Dyslexia , Glaucoma , Myopia , Retinal Ganglion Cells , Animals , Humans , Mice , Disease Models, Animal , Dyslexia/genetics , Dyslexia/metabolism , Dyslexia/pathology , Glaucoma/pathology , Glaucoma/metabolism , Glaucoma/genetics , Intraocular Pressure , Mice, Inbred DBA , Mice, Knockout , Myopia/pathology , Myopia/metabolism , Myopia/genetics , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/metabolism , Risk Factors
18.
IBRO Neurosci Rep ; 16: 560-566, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38764541

ABSTRACT

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

19.
Article in English | MEDLINE | ID: mdl-38788061

ABSTRACT

OBJECTIVE: To investigate the role of Pink1/Parkin-mediated mitochondrial autophagy in exertional heat stroke-induced acute lung injury in rats. METHODS: Sixty SD rats were divided into four groups: normal group (CON group), normal Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. RESULTS: Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly reduced. The levels of inflammatory factors IL-6, IL-1ß, TNF- α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Impairment of Pink1/Parkin-mediated mitochondrial autophagy function is one of the mechanisms of exertional heat stroke-induced acute lung injury in rats. Activation of the Pink1/Parkin pathway can alleviate acute lung injury caused by exertional heat stroke.

20.
J Nat Prod ; 87(6): 1501-1512, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38603577

ABSTRACT

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.


Subject(s)
Cannabidiol , Carcinoma, Ovarian Epithelial , Gastrointestinal Microbiome , Ovarian Neoplasms , Cannabidiol/pharmacology , Cannabidiol/chemistry , Gastrointestinal Microbiome/drug effects , Female , Humans , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Animals , Mice , ErbB Receptors/metabolism , Cell Line, Tumor , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Molecular Structure
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