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1.
Curr Med Chem ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39238390

ABSTRACT

INTRODUCTION: The high prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), a chronic progressive disease characterized by hepatic steatosis, poses a serious burden to human health. Depression and NAFLD share some common pathogenic mechanisms, and patients with depression are at an increased risk of NAFLD. The drug mirtazapine is commonly used in the treatment of depression, but it can also cause liver damage. However, whether mirtazapine induces or aggravates NAFLD remains uncertain. Thus, we evaluated the risk factors for NAFLD in patients with depression and the effects of mirtazapine on NAFLD in vitro. METHODS: Inpatients diagnosed with depression at the Second Xiangya Hospital of Central South University between 2019 and 2022 were included in this study, and NAFLD was determined using an abdominal ultrasound examination. The risk factors for the development of NAFLD in patients with depression were analyzed using logistic regression analysis. AML-12 and MIHA cell lines were used to observe the effects of mirtazapine on NAFLD using oil red O staining. RT-qPCR and western blotting were used to explore the molecular mechanism behind NAFLD development induced by mirtazapine. RESULTS: Logistic regression analysis showed that older age, use of mirtazapine or fluoxetine, longer duration of antidepressant use, and combined hyperlipidemia or T2DM were risk factors for NAFLD in patients with depression. in vitro experiments revealed a subsequent increase in the content of intracellular lipid droplets as mirtazapine concentration increased. Mechanistic studies showed that mirtazapine increased the expressions of TLR4, MyD88, IFN-γ, IL-1ß, IL-6, and TNF-α mRNA in hepatocytes. Moreover, the expressions of TLR4, MyD88, and p-NF-κB-p65 proteins increased in a dose-dependent manner. CONCLUSION: Age, antidepressant type, duration of antidepressant use, and comorbidities could be risk factors for NAFLD in patients with depression. Furthermore, mirtazapine can cause steatosis in both AML-12 and MIHA cell lines and may promote the development of NAFLD through the TLR4/MyD88/NF-κB signaling pathway. This study lays a solid foundation for further research on depression and NAFLD and can contribute to the prevention and treatment of these two diseases.

2.
BMC Anesthesiol ; 24(1): 269, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39097713

ABSTRACT

BACKGROUND: Different approach ultrasound-guided superior laryngeal nerve block was used to aid awake intubation, but little is known which approach was superior. We aimed to compare the parasagittal and transverse approaches for ultrasound-guided superior laryngeal nerve block in adult patients undergoing awake intubation. METHODS: Fifty patients with awake orotracheal intubation were randomized to receive either a parasagittal or transverse ultrasound-guided superior laryngeal nerve block. The primary outcome was patient's quality of airway anesthesia grade during insertion of the tube into the trachea. The patients' tube tolerance score after intubation, total procedure time, mean arterial pressure, heart rate, Ramsay sedation score at each time point, incidence of sore throat both 1 h and 24 h after extubation, and hoarseness before intubation, 1 h and 24 h after extubation were documented. RESULTS: Patients' quality of airway anesthesia was significantly better in the parasagittal group than in the transverse group (median grade[IQR], 0 [0-1] vs. 1 [0-1], P = 0.036). Patients in the parasagittal approach group had better tube tolerance scores (median score [IQR],1[1-1] vs. 1 [1-1.5], P = 0.042) and shorter total procedure time (median time [IQR], 113 s [98.5-125.5] vs. 188 s [149.5-260], P < 0.001) than those in the transverse approach group. The incidence of sore throat 24 h after extubation was lower in the parasagittal group (8% vs. 36%, P = 0.041). Hoarseness occurred in more than half of the patients in parasagittal group before intubation (72% vs. 40%, P = 0.023). CONCLUSIONS: Compared to the transverse approach, the ultrasound-guided parasagittal approach showed improved efficacy in terms of the quality of airway topical anesthesia and shorter total procedure time for superior laryngeal nerve block. TRIAL REGISTRATION: This prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20220425-014) and registered in the Chinese Clinical Trial Registry (19/6/2022, ChiCTR2200061287) prior to patient enrollment. Written informed consent was obtained from all participants in this trial.


Subject(s)
Intubation, Intratracheal , Laryngeal Nerves , Nerve Block , Ultrasonography, Interventional , Humans , Female , Male , Ultrasonography, Interventional/methods , Middle Aged , Intubation, Intratracheal/methods , Nerve Block/methods , Adult , Prospective Studies , Hoarseness/prevention & control , Hoarseness/etiology , Aged
3.
Heliyon ; 10(13): e33740, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39055804

ABSTRACT

Background & aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, for which there is currently no effective treatment. ACY-1215 is a selective inhibitor of histone deacetylation 6, which has shown therapeutic potential in many tumors, as well as acute liver injury. However, no research about ACY-1215 on NAFLD has been published. Therefore, our study aims to explore the role and mechanism of ACY-1215 in the experimental model of NAFLD, to propose a new treatment strategy for NAFLD. Methods: We established cell and animal models of NAFLD and verified the effect of ACY-1215 on NAFLD. The mechanism of ACY-1215 on NAFLD was preliminarily explored through TMT relative quantitative proteomics, and then we verify the mechanism discovered in the experimental model of NAFLD. Results: ACY-1215 can reduce lipid aggregation, IL-1ß, and TNF α mRNA levels in liver cells in vitro. ACY-1215 can reduce the weight gain and steatosis in the liver of the NAFLD mouse model, alleviate the deterioration of liver function, and reduce IL-1ßs and TNF α mRNA levels in hepatocytes. TMT relative quantitative proteomics found that ACY-1215 decreased the expression of CD14 in hepatocytes. It was found that ACY-1215 can inhibit the activation level of CD14/TLR4/MyD88/MAPK/NFκB pathway in the NAFLD experimental model. Conclusions: ACY-1215 has a protective effect on the cellular model of NAFLD induced by fatty acids and lipopolysaccharide, as well as the C57BL/6J mouse model induced by a high-fat diet. ACY-1215 may play a protective role by inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

4.
Aesthetic Plast Surg ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977452

ABSTRACT

BACKGROUND: Facial aging is a complex process influenced by environmental factors, genetics, and lifestyle. The contribution of the skin microbiota to this process remains poorly understood. METHODS: This two-sample Mendelian randomization (MR) study was performed using genome-wide genotype data from the UK Biobank and previously published studies on skin microbiota. The primary approach for MR analyses included inverse-variance weighting (IVW), MR-Egger regression, simple mode, weighted median, and weighted mode methods. Sensitivity analyses were performed to assess heterogeneity and pleiotropy, and reverse-direction MR analyses were performed to evaluate potential reverse causation. RESULTS: The MR analysis identified ten skin microbiotas with potential causal relationships with facial aging. Protective skin microbiotas included Genus Finegoldia, ASV011 [Staphylococcus (unc.)], ASV008 [Staphylococcus (unc.)], phylum Firmicutes, Family Rhodobacteraceae, and ASV021 [Micrococcus (unc.)], which were negatively associated with facial aging. Conversely, Order Pseudomonadales, Family Moraxellaceae, ASV039 [Acinetobacter (unc.)], and phylum Bacteroidetes were positively associated with facial aging, indicating a risk factor for accelerated aging. Sensitivity analyses confirmed the robustness of these findings, and reverse-direction MR analyses did not suggest any reverse causation. CONCLUSION: This study identified specific skin microbial that may influence facial aging and offered new insights into the rejuvenation strategies. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

5.
J Exp Clin Cancer Res ; 43(1): 133, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38698462

ABSTRACT

BACKGROUND: Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. METHODS: Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. RESULTS: Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor ß (IR-ß) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-ß phosphorylation, ultimately resulting in IR-ß inactivation. This inactivation of IR-ß suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. CONCLUSIONS: These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , Animals , Female , Humans , Male , Mice , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Disease Models, Animal , Down-Regulation , Fatty Acids, Monounsaturated/metabolism , Fatty Acids, Monounsaturated/pharmacology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Xenograft Model Antitumor Assays
6.
Surg Endosc ; 38(4): 2041-2049, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38429572

ABSTRACT

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.


Subject(s)
Endoscopic Mucosal Resection , Gastrointestinal Neoplasms , Neuroendocrine Tumors , Rectal Neoplasms , Humans , Margins of Excision , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/pathology , Treatment Outcome , Gastrointestinal Neoplasms/surgery , Gastrointestinal Neoplasms/pathology , Endoscopic Mucosal Resection/methods , Risk Factors , Retrospective Studies , Intestinal Mucosa/surgery , Rectal Neoplasms/surgery
7.
Polymers (Basel) ; 16(6)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38543396

ABSTRACT

A comparative experimental and numerical study of the impact behaviour of carbon-fiber-reinforced thermoplastic (TP) and thermoset (TS) composites has been carried out. On the one hand, low velocity impact (LVI) tests were performed on TP and TS composites with different lay-up sequences at different energy levels, and the damage modes and microscopic damage mechanisms after impact were investigated using macroscale inspection, C-scan inspection, and X-ray-computed tomography. The comparative results show that the initial damage valve force under LVI depends not only on the material, but also on the layup sequence. The initial valve force of the P2 soft layer with lower stiffness is about 11% lower than that of the P1 quasi-isotropic layer under the same material, while the initial valve force of thermoplastic composites is about 28% lower than that of thermoset composites under the same stacking order. Under the same stacking order and impact energy level, the damage area and depth of TP composites are smaller than those of TS composites; while under the same material and impact energy level, the indentation depth of P2 plies is greater than that of P1 plies, and the damage area of P2 plies is smaller than that of P1 plies, but the change of thermoplastic composites is not as obvious as that of thermoset composites. This indicates that TP composites have a higher initial damage threshold energy and impact resistance at the same lay-up order, while increasing the lay-up ratio of the same material by 45° improves the impact resistance of the structure. In addition, a damage model based on continuum damage mechanics (CDM) was developed to predict different damage modes of thermoplastic composites during low velocity impact, and the analytical results were compared with the experimental results. At an impact energy of 4.45 J/mm, the error of the initial damage valve force is 5.26% and the error of the maximum impact force is 4.36%. The simulated impact energy and impact velocity curves agree with the experimental results, indicating that the finite element model has good reliability.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1030922

ABSTRACT

Objective To conduct a network meta-analysis on the effectiveness of first-line immunotherapy on patients with brain metastases from advanced non-small cell lung cancer (NSCLC). Methods Two investigators conducted a computerized search of Pubmed, Embase, Cochrane, and other databases to screen the literature, extract the information, and assess the risk of bias of the included studies. The included clinical trials were statistically analyzed using R (4.1.3) software. For the study outcome indicators OS and PFS, the risk ratios (HRs), and the 95% confidence intervals (CIs) were extracted from the included studies and logarithmically transformed into effect analysis statistics. Results Six randomized controlled trials were finally included, including 327 patients with non-excludable NSCLC brain metastases. Network meta-analysis suggested that PD-1 inhibitor + CTLA-4 was more advantageous than the conventional chemotherapy for enhancing patients’ OS (HR: 0.13, 95%CI: 0.03-0.71), followed by PD-L1 inhibitor (HR: 0.17, 95%CI: 0.04-0.74) and PD-1 inhibitor + chemotherapy (HR: 0.36, 95%CI: 0.2-0.63). PD-1 inhibitor + CTLA-4 was also more advantageous (HR: 0.37, 95%CI: 0.15-0.93) than the conventional chemotherapy for boosting patients’ PFS, followed by PD-L1 inhibitor + chemotherapy (HR: 0.44, 95%CI: 0.29-0.66) and PD-1 inhibitor (HR: 0.48, 95%CI: 0.27-0.86). Conclusion Immune checkpoint inhibitor therapy improves the survival of patients with brain metastases from advanced NSCLC. In particular, the combination of PD-1 inhibitor and CTLA-4 inhibitor show excellent survival benefit.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1039102

ABSTRACT

Oligonucleotide drugs have experienced accelerated development in the past 10 years, and some of them have been used in clinical treatment. Because of its convenient design, flexible sequence, and high specificity, it is expected to solve the “undruggable” challenge of many targets which are difficult in drug development. Moreover, its clinical transformation period and cost are relatively low, which makes oligonucleotide drug become the frontier of emerging biotechnology drug discovery. Brain diseases include a series of incurable diseases, such as neurodegenerative diseases, glioma, and motor neuron diseases. Many of them are age-related and regarded as aging-associated brain diseases. Due to the complex etiology, many targets are difficult to be drugged. At the same time, the existence of the barrier system “blood-brain barrier” in the brain makes most drugs unable to achieve effective accumulation at brain lesions, and many small molecule drugs have failed in clinical transformation. The specificity and sequence flexibility of oligonucleotide acid drugs provide new possibilities for drug development, but they also face the challenge of brain delivery. Although a variety of oligonucleotide drugs have been used in the medical market, brain-targeted oligonucleotide drugs are still extremely rare. This article reviewed recent advances and discussed key topics and clinical transformation challenges in this field, such as clinical approval cases, bottlenecks of brain-targeted delivery and current strategies, as well as potential targets for aging-related brain diseases.

10.
Acta Pharmaceutica Sinica B ; (6): 602-622, 2024.
Article in English | WPRIM (Western Pacific) | ID: wpr-1011272

ABSTRACT

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca2+-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca2+ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013600

ABSTRACT

Chronic obstructive pulmonary disease ( COPD ) major chronic disease threatening public health with complex pathological mechanisms. The change of the cell microenvironment of the lung is an important part of the pathophysiology of COPD. Cell culture technology is an important method to investigate the pathological mechanism of COPD and evaluate the pharmacological effect of medicine. Here we introduce the composition of the cell microenvironment of the lung, the change of the cell microenvironment in the pathological process of COPD, and summarize the application of in vitro model mimics cell microenvironment of COPD in the study of mechanism. In addition, we aim to put forward the ideas of the in vitro model establishment of cell microenvironment of COPD.

12.
J Colloid Interface Sci ; 659: 119-126, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38159488

ABSTRACT

We report zinc cobalt-layered double hydroxides (ZnCo-LDH) as the active cathode materials for the development of high-performance Zn-ZnCo batteries. Electrochemical investigations show the battery's capacity increases linearly with increasing the ZnCo-LDH loading (up to 60 mg cm-2). The resulting Zn-ZnCo battery exhibits excellent rate performance and cycle stability, retaining 86% of its capacity even after 5000 cycles of testing. By incorporating ZnCo-LDH with a Pt/C-coated gas diffusion layer to form an integrated multifunctional air-cathode, we demonstrate a hybrid Zn battery, which combines the merits of Zn-ZnCo and Zn-air batteries to show a characteristic two-stage charge-discharge voltage profile. The current work demonstrates the linear relationship between the battery capacity and the active material loading. The results also highlight that a greater battery capacity requires further increasing of loading though very challenging.

14.
Polymers (Basel) ; 15(22)2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38006192

ABSTRACT

In this paper, the damage initiation/propagation mechanisms and failure modes of open-hole carbon fiber-reinforced thermoplastic composites and thermosetting composites with tension, compression, and bearing loads are investigated, respectively, by experiments and finite element simulations. The experimental evaluations are performed on the specimens using the Combined Loading Compression (CLC) test method, the tensile test method, and the single-shear test method. The differences in macroscopic damage initiation, evolution mode, and damage characteristics between thermoplastic composite materials and thermosetting composite material open-hole structures are obtained and analyzed under compressive load. Based on scanning electron microscope SEM images, a comparative analysis is conducted on the micro-failure modes of fibers, matrices, and fiber/matrix interfaces in the open-hole structures of thermoplastic and thermosetting composites under compressive load. The differences between thermoplastic and thermosetting composites were analyzed from the micro-failure mechanism. Finally, based on continuum damage mechanics (CDM), a damage model is also developed for predicting the initiation and propagation of damage in thermoplastic composites. The model, which can capture fiber breakage and matrix crack, as well as the nonlinear response, is used to conduct virtual compression tests, tensile test, and single-shear test, respectively. Numerical simulation results are compared with the extracted experimental results. The displacement-load curve and failure modes match the experimental result, which indicates that the finite element model has good reliability.

15.
BMC Anesthesiol ; 23(1): 284, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37608257

ABSTRACT

BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P < 0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P < 0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P < 0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%. CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.


Subject(s)
Aging , Cognitive Dysfunction , Aged , Humans , Retrospective Studies , Leukocytes , Telomere
16.
Nutr Metab (Lond) ; 20(1): 30, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37415199

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that is becoming increasingly prevalent, and it ranges from simple steatosis to cirrhosis. However, there is still a lack of pharmacotherapeutic strategies approved by the Food and Drug Administration, which results in a higher risk of death related to carcinoma and cardiovascular complications. Of note, it is well established that the pathogenesis of NAFLD is tightly associated with whole metabolic dysfunction. Thus, targeting interconnected metabolic conditions could present promising benefits to NAFLD, according to a number of clinical studies. Here, we summarize the metabolic characteristics of the development of NAFLD, including glucose metabolism, lipid metabolism and intestinal metabolism, and provide insight into pharmacological targets. In addition, we present updates on the progresses in the development of pharmacotherapeutic strategies based on metabolic intervention globally, which could lead to new opportunities for NAFLD drug development.

17.
Fundam Clin Pharmacol ; 37(6): 1129-1138, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37350460

ABSTRACT

BACKGROUND: Ginsenoside RT4 (RT4) is a new biologically active compound extracted from ginseng that possesses numerous medicinal and pharmacological properties. However, its potential therapeutic effect of ginsenoside RT4 on ulcerative colitis remains unknown. METHODS AND RESULTS: In this study, we investigated the anti-inflammatory effects of ginsenoside RT4 and its underlying molecular mechanism in the treatment of ulcerative colitis mice induced with dextran sulfate sodium (DSS). Our results demonstrate that ginsenoside RT4 effectively reduced weight, shortening of colonic tract length, colonic bowel damage, and disease activity index (DAI) scores in DSS-induced colitis mice. Additionally, ginsenoside RT4 regulates miR-144-3p expression in DSS-induced colitis mice, and we further confirmed that the solute carrier family 7 member 11 (SLC7A11) was the target gene of miR-144-3p by database analysis. Finally, ginsenoside RT4 inhibits the activation of the miR-144-3p/SLC7A11 signaling pathway, which alleviates colitis. Ginsenoside RT4 significantly decreased the expression of pro-inflammatory cytokines TNF-α and IL-1ß and increased the anti-inflammatory cytokine IL-10. CONCLUSIONS: These findings suggest that ginsenoside RT4 may have therapeutic potential for treating ulcerative colitis by downregulating levels of miR-144-3p/SLC7A11 signaling pathway, which are expected to be useful in treating clinical ulcerative colitis.


Subject(s)
Colitis, Ulcerative , Colitis , Ginsenosides , MicroRNAs , Animals , Mice , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Ginsenosides/pharmacology , Ginsenosides/metabolism , Ginsenosides/therapeutic use , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colon , Signal Transduction , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , MicroRNAs/metabolism , Mice, Inbred C57BL , Disease Models, Animal
18.
Front Pharmacol ; 14: 1184774, 2023.
Article in English | MEDLINE | ID: mdl-37251340

ABSTRACT

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported. Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis. Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity. Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.

19.
Environ Res ; 228: 115822, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37028542

ABSTRACT

Al-KBC was produced through the simple pyrolysis of Al-modified kapok fibres at high temperatures. Using the N2 adsorption Brunauer Emmett Teller (BET) process, Fourier transforms infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), the energy-dispersive X-ray spectroscopy (EDS) spectroscopy, and X-ray photoelectron spectroscopy (XPS), the sorbent changes and characteristics were analysed. As a result of Al's addition to the fibre's surface, Al-KBC exhibited superior As(V) adsorption performance compared to KBC due to better pore structures. Experiments on the kinetics of As(V) adsorption revealed that the adsorption followed the pseudo-second-order model and that intradiffusion was not the only factor governing the adsorption. Experiments with isotherms indicated that the adsorption mechanism corresponded to the Langmuir model, and the adsorption capacity Qm of Al-KBC at 25 °C was 483 µg/g. The thermodynamic experiments suggested that the adsorption reactions were spontaneous endothermic with a random approach at the adsorption interface. 25 mg/L of coexisting ions such as sulphate and phosphate reduced the sorbent As(V) removal ability to 65% and 39%. After seven cycles of adsorption/desorption, Al-KBC demonstrated satisfactory performance in terms of reusability, adsorbing 53% of 100 µg/L As(V) from the water. This novel BC can probably be used as a filter to purify groundwater with high As(V) concentration in the rural zone.


Subject(s)
Arsenates , Water Pollutants, Chemical , Adsorption , Spectroscopy, Fourier Transform Infrared , Water Pollutants, Chemical/chemistry , Kinetics , Water , Hydrogen-Ion Concentration
20.
Mar Pollut Bull ; 187: 114608, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36652864

ABSTRACT

Total of 172 total suspended particulate (TSP) samples and its chemical compositions were collected and analyzed from January to December 2010 in Pengjia Yu Island, an open region in East China Sea (ECS). Despite the predominance of sea-salt major ions (Na+, Cl-), the presence of non-sea-salt SO42- (nss-SO42-) and NO3- as well as combustion-derived trace metals clearly establishes the impact of anthropogenic sources over ECS. The annual contributions of coal, heavy-fuel oil and traffic to the measured chemical species were 21.0 %, 15.0 % and 15.5 %, respectively. Especially in spring, the contributions of crustal minerals to measured chemical species during dust period (33.6 %) were higher than that (13.2 %) during non-dust period. The calculated annual average dry deposition fluxes for trace metals and total inorganic nitrogen were 246.1 ± 345.8 µg/m2/d and 2950.4 ± 2245.0 µg/m2/d, suggesting that atmospheric deposition is an important source of nutrient elements for the south of ECS.


Subject(s)
Air Pollutants , Particulate Matter , Particulate Matter/analysis , Air Pollutants/analysis , Seasons , Dust/analysis , China , Ions/analysis , Minerals , Coal/analysis , Environmental Monitoring , Aerosols/analysis
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