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2.
Med Biol Eng Comput ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967693

RESUMEN

Lumbar disc herniation is one of the most prevalent orthopedic issues in clinical practice. The lumbar spine is a crucial joint for movement and weight-bearing, so back pain can significantly impact the everyday lives of patients and is prone to recurring. The pathogenesis of lumbar disc herniation is complex and diverse, making it difficult to identify and assess after it has occurred. Magnetic resonance imaging (MRI) is the most effective method for detecting injuries, requiring continuous examination by medical experts to determine the extent of the injury. However, the continuous examination process is time-consuming and susceptible to errors. This study proposes an enhanced model, BE-YOLOv5, for hierarchical detection of lumbar disc herniation from MRI images. To tailor the training of the model to the job requirements, a specialized dataset was created. The data was cleaned and improved before the final calibration. A final training set of 2083 data points and a test set of 100 data points were obtained. The YOLOv5 model was enhanced by integrating the attention mechanism module, ECAnet, with a 3 × 3 convolutional kernel size, substituting its feature extraction network with a BiFPN, and implementing structural system pruning. The model achieved an 89.7% mean average precision (mAP) and 48.7 frames per second (FPS) on the test set. In comparison to Faster R-CNN, original YOLOv5, and the latest YOLOv8, this model performs better in terms of both accuracy and speed for the detection and grading of lumbar disc herniation from MRI, validating the effectiveness of multiple enhancement methods. The proposed model is expected to be used for diagnosing lumbar disc herniation from MRI images and to demonstrate efficient and high-precision performance.

3.
Mol Neurobiol ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985257

RESUMEN

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

4.
Front Bioeng Biotechnol ; 12: 1405576, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988869

RESUMEN

Physical-based external compression medical modalities could provide sustainable interfacial pressure dosages for daily healthcare prophylaxis and clinic treatment of chronic venous disease (CVD). However, conventional ready-made compression therapeutic textiles (CTs) with improper morphologies and ill-fitting of pressure exertions frequently limit patient compliance in practical application. Therefore, the present study fabricated the personalized CTs for various subjects through the proposed comprehensive manufacturing system. The individual geometric dimensions and morphologic profiles of lower extremities were characterized according to three-dimensional (3D) body scanning and reverse engineering technologies. Through body anthropometric analysis and pressure optimization, the knitting yarn and machinery variables were determined as the digital design strategies for 3D seamless fabrication of CTs. Next, to visually simulate the generated pressure mappings of developed CTs, the subject-specific 3D finite element (FE) CT-leg modelings with high accuracy and acceptability (pressure prediction error ratio: 11.00% ± 7.78%) were established based on the constructed lower limb models and determined tissue stiffness. Moreover, through the actual in vivo trials, the prepared customized CTs efficiently (Sig. <0.05; ρ = 0.97) distributed the expected pressure requirements referring to the prescribed compression magnitudes (pressure error ratio: 10.08% ± 7.75%). Furthermore, the movement abilities and comfortable perceptions were evaluated subjectively for the ergonomic wearing comfort (EWC) assessments. Thus, this study promotes the precise pressure management and clinical efficacy for targeted users and leads an operable development approach for related medical biomaterials in compression therapy.

5.
Surg Endosc ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977502

RESUMEN

BACKGROUND: The safety and efficacy of robotic liver resection (RLR) for patients with hepatocellular carcinoma (HCC) have been reported worldwide. However, the exact role of RLR in HCC patients with liver cirrhosis is not sufficiently determined. METHODS: We conducted a retrospective study on consecutive patients with cirrhosis or non-cirrhosis who received RLR for HCC from 2018 to 2023. Data on patients' demographics and perioperative outcomes were collected and analyzed. Propensity score matching (PSM) analysis was performed. Multivariate logistic regression analysis was performed to determine the risk factors of prolonged postoperative length of stay (LOS) and morbidity. RESULTS: Of the 571 patients included, 364 (64%) had cirrhosis. Among the cirrhotic patients, 48 (13%) were classified as Child-Pugh B. After PSM, the cirrhosis and non-cirrhosis group (n = 183) had similar operative time, estimated blood loss, postoperative blood transfusion, LOS, overall morbidity (p > 0.05). In addition, the intraoperative and postoperative outcomes were similar between the two groups in the subgroup analyses of patients with tumor size ≥ 5 cm, major hepatectomy, and high/expert IWATE difficulty grade. However, patients with Child-Pugh B cirrhosis had longer LOS and more overall morbidity than that of Child-Pugh A. Child-Pugh B cirrhosis, ASA score > 2, longer operative time, and multiple tumors were risk factors of prolonged LOS or morbidity in patients with cirrhosis. CONCLUSION: The presence of Child-Pugh A cirrhosis didn't significantly influence the difficulty and perioperative outcomes of RLR for selected patients with HCC. However, even in high-volume center, Child-Pugh B cirrhosis was a risk factor for poor postoperative outcomes.

7.
Curr Med Sci ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39039373

RESUMEN

OBJECTIVE: High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. METHODS: In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. RESULTS: After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. CONCLUSION: This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

8.
Cell ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38971151

RESUMEN

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

9.
Leuk Lymphoma ; : 1-10, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972063

RESUMEN

This retrospective analysis evaluated the use of anti-thymocyte globulin (ATG) with or without post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis in children with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT). The study included 57 children, with 35 in the ATG-PTCy group and 22 in the ATG group. While overall incidence of acute and chronic GvHD did not differ significantly between groups, the ATG-PTCy group had lower rates of grade II-IV acute GvHD (p = 0.013) and moderate-to-severe chronic GvHD (p = 0.001) compared to the ATG group. Importantly, ATG-PTCy significantly improved GvHD/relapse-free survival (GRFS) compared to ATG (65.71% vs. 36.63%; p = 0.003). There were no differences in engraftment, infection rates, immune reconstitution, overall survival, leukemia-free survival, relapse rate, or non-relapse mortality between the two groups. Combining ATG with PTCy may reduce moderate-to-severe GvHD and improve GRFS in children undergoing HSCT for acute leukemia.

10.
J Colloid Interface Sci ; 676: 283-297, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39029254

RESUMEN

Electrocatalytic carbon dioxide reduction (ECO2R) to formate is the most technically and economically feasible approach to achieve electrochemical CO2 value addition. Here, a few-layer graphene is prepared from vinegar residue. Then a series of heteroatom-doped vertical graphene electrodes (X-rGO, X=P/S/N/B/, NS/NP/NB, NSP/NSB/NPB/NSPB) are prepared. The NS-rGO has improved ECO2R to formate selectivity (Faraday Efficiency (FEHCOO-) = 78.7 %) thanks to the synergistic effect between N and S. Carbon quantum dots (CQDs) are introduced into the electrode, the doped heteroatoms are further removed by high-temperature to form the defects-rich electrode (NS-CQDs-rGO-1100), which has better catalytic performance (FEHCOO-=90 %, stability over 10 h) with electrochemical double layer capacitance of 12.5 mF cm-2. The intrinsic effect of heteroatom doping and defects on the ECO2R activity of the electrodes are explored by density functional theory calculation. This work broadens the field of preparation of graphene and opens the door to the development of cost-effective electrocatalysts for efficient ECO2R.

11.
Med Res Arch ; 12(1)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39026931

RESUMEN

Pediatric cancer consists of a diverse group of rare diseases. Due to limited patient populations, standard randomized and controlled trials are often infeasible. As a result, single-arm trials are common in pediatric oncology and the use of external controls is often desirable or necessary to help generate actionable evidence and contextualize trial results. In this paper, we illustrate unique features in pediatric oncology clinical trials and describe their impact on the use of external controls. Various types of relevant external control data sources are described in terms of their utility and drawbacks. Statistical methodologies and design implications with external control are discussed. Two recent case studies using external controls to support pediatric oncology drug development are described in detail.

12.
Infect Drug Resist ; 17: 2785-2791, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38984315

RESUMEN

We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient's blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.

13.
Eur J Med Res ; 29(1): 334, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38880878

RESUMEN

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.


Asunto(s)
Cognición , Genotipo , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Cognición/fisiología , Disfunción Cognitiva/genética , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Apolipoproteínas E/genética , Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteína E4/genética
15.
Ann Surg ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38939972

RESUMEN

OBJECTIVE: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. BACKGROUND: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. METHODS: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff. RESULTS: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. CONCLUSIONS: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.

16.
BMC Cardiovasc Disord ; 24(1): 328, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937716

RESUMEN

BACKGROUND: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology. METHODS: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline. RESULTS: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart. CONCLUSIONS: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.


Asunto(s)
Valor Predictivo de las Pruebas , Traumatismos por Radiación , Sístole , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Función Ventricular Izquierda/efectos de la radiación , Traumatismos por Radiación/etiología , Traumatismos por Radiación/fisiopatología , Traumatismos por Radiación/diagnóstico por imagen , Medición de Riesgo , Cardiotoxicidad , Factores de Riesgo , Adulto , Factores de Tiempo , Neoplasias Torácicas/radioterapia , Neoplasias Torácicas/diagnóstico por imagen , Radioterapia/efectos adversos , Función Ventricular Derecha , Ecocardiografía , Factores de Riesgo de Enfermedad Cardiaca , Volumen Sistólico
17.
Int J Biol Sci ; 20(8): 3046-3060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904018

RESUMEN

Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. As a first-line treatment for advanced HCC, Lenvatinib has been applicated in clinic since 2018. Resistance to Lenvatinib, however, has severely restricted the clinical benefits of this drug. Therefore, it is urgent to explore the potential resistance mechanisms of Lenvatinib and identify appropriate methods to reduce resistance for the treatment of HCC. We identified SAHA, a HDAC inhibitor, to have effective anti-tumor activity against Lenvatinib-resistant HCC organoids by screening a customized drug library. Mechanism analysis revealed that SAHA upregulates PTEN expression and suppresses AKT signaling, which contributes to reversing Lenvatinib resistance in liver cancer cells. Furthermore, combinational application of Lenvatinib and HDAC inhibitor or AKT inhibitor synergistically inhibits HCC cell proliferation and induces cell apoptosis. Finally, we confirmed the synergistic effects of Lenvatinib and SAHA, or AZD5363 in primary liver cancer patient derived organoids. Collectively, these findings may enable the development of Lenvatinib combination therapies for HCC.


Asunto(s)
Carcinoma Hepatocelular , Inhibidores de Histona Desacetilasas , Neoplasias Hepáticas , Compuestos de Fenilurea , Proteínas Proto-Oncogénicas c-akt , Quinolinas , Quinolinas/farmacología , Compuestos de Fenilurea/farmacología , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Inhibidores de Histona Desacetilasas/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Animales , Vorinostat/farmacología , Sinergismo Farmacológico , Ratones , Resistencia a Antineoplásicos/efectos de los fármacos
18.
Ann Surg Oncol ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879668

RESUMEN

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

19.
Phytomedicine ; 132: 155329, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38853123

RESUMEN

BACKGROUND: Currently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet ß cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota. PURPOSE: To explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the "intestinal flora bile acid TGR5'' axis. METHODS: The T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co-localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum. RESULTS: The modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/PKA/CREB signal pathway, and stimulate GLP-1 secretion. CONCLUSION: GQD can regulate the "intestinal flora-bile acid-TGR5" axis and has a therapeutic effect on T2DM in mice.

20.
Int J Biol Macromol ; 275(Pt 2): 133190, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897503

RESUMEN

Codonopsis pilosula polysaccharides (CPP), the main active ingredient of Codonopsis pilosula, has gained significant attention as a liver-protective agent. Previous studies have demonstrated that CPP could alleviate gut microbiota dysbiosis in colitis or obese mice. However, the effects of CPP on mycotoxin-induced liver injury and gut microbiota dysbiosis are still poorly understood. In this study, we aimed to investigate the protective effects of CPP on sterigmatocystin (STC)-induced liver injury, as well as its regulatory effects on gut microbiota. Our results revealed that CPP intervention significantly alleviated STC-induced liver injury, as evidenced by decreased liver index, reduced liver histopathological changes, and modulation of related molecular markers. Additionally, we found that CPP could alleviate liver injury by reducing liver inflammation and oxidative stress, inhibiting hepatocyte apoptosis, and regulating lipid metabolism. Notably, we also observed that CPP could alleviate STC-induced gut microbiota dysbiosis by modulating the diversity and richness of gut microbiota, suggesting that gut microbiota modulation may also serve as a mechanism for CPP-mediated remission of liver injury. In summary, our study not only provided a new theoretical basis for understanding the hepatotoxicity of STC and the protective effects of CPP against STC-induced liver injury, but also provided new perspectives for the application of CPP in the fields of food, healthcare products, and medicine.

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