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1.
World J Surg Oncol ; 22(1): 3, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38166925

ABSTRACT

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH). METHODS: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals. RESULTS: Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival. CONCLUSIONS: HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.


Subject(s)
Carcinoma, Hepatocellular , Hypertension, Portal , Laparoscopy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/complications , Liver Neoplasms/surgery , Hepatectomy/adverse effects , Treatment Outcome , Hypertension, Portal/complications , Hypertension, Portal/surgery , Laparoscopy/adverse effects , Length of Stay , Retrospective Studies
2.
Mikrochim Acta ; 191(8): 465, 2024 07 16.
Article in English | MEDLINE | ID: mdl-39012354

ABSTRACT

A novel Fe-MoOx nanozyme, engineered with enhanced peroxidase (POD)-like activity through strategic doping and the creation of oxygen vacancies, is introduced to catalyze the oxidation of TMB with high efficiency. Furthermore, Fe-MoOx is responsive to single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms related to antioxidants and can serve as a desirable nanozyme for total antioxidant capacity (TAC) determination. The TAC colorimetric platform can reach a low LOD of 0.512 µM in solution and 24.316 µM in the smartphone-mediated RGB hydrogel (AA as the standard). As proof of concept, the practical application in real samples was explored. The work paves a promising avenue to design diverse nanozymes for visual on-site inspection of food quality.


Subject(s)
Antioxidants , Colorimetry , Oxidation-Reduction , Antioxidants/chemistry , Antioxidants/analysis , Antioxidants/metabolism , Colorimetry/methods , Catalysis , Molybdenum/chemistry , Limit of Detection , Iron/chemistry , Benzidines/chemistry , Smartphone , Hydrogels/chemistry , Electron Transport , Biosensing Techniques/methods , Oxides/chemistry
3.
Acta Pharmacol Sin ; 44(4): 766-779, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36229601

ABSTRACT

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin (CAP), the main component of chili pepper. Despite studies in several neurological diseases, the role of TRPV1 in demyelinating diseases remains unknown. Herein, we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone (CPZ)-induced demyelination mouse model. TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice, whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination. TRPV1 was predominantly expressed in Iba1+ microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions. TRPV1 deficiency decreased microglial recruitment to the corpus callosum, with an associated increase in the accumulation of myelin debris. Conversely, the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance. Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment. In addition, the expression of the scavenger receptor CD36 was increased, and that of the glycolysis regulators Hif1a and Hk2 was decreased. We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.


Subject(s)
Demyelinating Diseases , Multiple Sclerosis , Animals , Humans , Mice , Cuprizone , Demyelinating Diseases/chemically induced , Demyelinating Diseases/drug therapy , Disease Models, Animal , Mice, Inbred C57BL , Microglia/metabolism , Multiple Sclerosis/drug therapy , Multiple Sclerosis/metabolism , Myelin Sheath/metabolism , TRPV Cation Channels , Capsaicin/pharmacology
4.
Nutr J ; 22(1): 50, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37798740

ABSTRACT

BACKGROUND: A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children. METHODS: Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight. RESULTS: Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity. CONCLUSIONS: This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.


Subject(s)
Chronotype , Overweight , Adult , Humans , Child , Overweight/epidemiology , Cross-Sectional Studies , Jet Lag Syndrome , Feeding Behavior/physiology , Sleep , Exercise , Surveys and Questionnaires , Schools
5.
Phytother Res ; 37(10): 4838-4850, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37458182

ABSTRACT

Diabetic encephalopathy is a common consequence of diabetes mellitus that causes cognitive dysfunction and neuropsychiatric disorders. Praeruptorin C (Pra-C) from the traditional Chinese medicinal herb Peucedanum praeruptorum Dunn. is a potential antioxidant and neuroprotective agent. This study was conducted to investigate the molecular mechanisms underlying the effect of Pra-C on diabetic cognitive impairment. A novel object recognition test and the Morris water maze test were performed to assess the behavioral performance of mice. Electrophysiological recordings were made to monitor synaptic plasticity in the hippocampus. A protein-protein interaction network of putative Pra-C targets was constructed, and molecular docking simulations were performed to predict the potential mechanisms of the action of Pra-C. Protein expression levels were detected by western blotting. Pra-C administration significantly lowered body weight and fasting blood glucose levels and alleviated learning and memory deficits in type 2 diabetic mice. Network pharmacology and molecular docking results suggested that Pra-C affects the PI3K/AKT/GSK3ß signaling pathway. Western blot analysis confirmed significant increases in phosphorylated PI3K, AKT, and GSK3ß levels in vivo and in vitro upon Pra-C administration. Pra-C alleviated cognitive impairment in type 2 diabetic mice by activating PI3K/AKT/GSK3ß pathway.

6.
Crit Rev Food Sci Nutr ; : 1-21, 2022 Sep 12.
Article in English | MEDLINE | ID: mdl-36094420

ABSTRACT

Food poisoning caused by eating contaminated food remains a threat to global public health. Making the situation even worse is the aggravated global environmental pollution, which poses a major threat to the safety of agricultural resources. Food adulteration has been rampant owing to negligent national food safety regulations. The speed at which contaminated food is detected and disposed of determines the extent to which consumers' lives are safeguarded and agricultural economic losses are prevented. Micro/nanomotors offer a high-speed mobile loading platform that substantially increases the chemical reaction rates and, accordingly, exhibit great potential as alternatives to conventional detection and degradation techniques. This review summarizes the propulsion modes applicable to micro/nanomotors in food systems and the advantages of using micro/nanomotors, highlighting examples of their potential use in recent years for the detection and removal of food contaminants. Micro/nanomotors are an emerging technology for food applications that is moving toward mass production, simple preparation, and important functions.

7.
Mol Pain ; 17: 1744806921990934, 2021.
Article in English | MEDLINE | ID: mdl-33590786

ABSTRACT

Chronic pain is highly prevalent worldwide and severely affects daily lives of patients and family members. Praeruptorin C (Pra-C) is a main active ingredient derived from Peucedanum praeruptorum Dunn, traditionally used as antibechic, anti-bronchitis and anti-hypertension drug. Here, we evaluated the effects of Pra-C in a chronic inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) injection. Pra-C (3 mg/kg) treatment for just 3 days after CFA challenge relieved CFA-induced mechanical allodynia and hindpaw edema in mice. In the anterior cingulate cortex (ACC), Pra-C treatment inhibited microglia activation and reduced levels of proinflammatory cytokines, TNF-α and IL-1ß, and suppressed upregulation of glutamate receptors caused by CFA injection. In addition, Pra-C attenuated neuronal hyperexcitability in ACC of CFA-injected mice. In vitro studies confirmed the analgesic effect of Pra-C was due to its inhibitory ability on microglial activation. In conclusion, Pra-C administration had a certain effect on relieving chronic pain by inhibiting microglial activation, attenuating proinflammatory cytokine releasing and regulating excitatory synaptic proteins in the ACC of the CFA-injected mice.


Subject(s)
Analgesics/pharmacology , Coumarins/pharmacology , Gyrus Cinguli/pathology , Microglia/pathology , Analgesics/therapeutic use , Animals , Cell Line , Chronic Pain/complications , Chronic Pain/drug therapy , Chronic Pain/physiopathology , Coumarins/chemistry , Coumarins/therapeutic use , Cytokines/metabolism , Disease Models, Animal , Edema/complications , Edema/pathology , Edema/physiopathology , Freund's Adjuvant , Hyperalgesia/complications , Hyperalgesia/pathology , Hyperalgesia/physiopathology , Inflammation/complications , Inflammation/drug therapy , Inflammation Mediators/metabolism , Male , Mice, Inbred C57BL , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Synapses/drug effects , Synapses/metabolism , Synaptic Transmission/drug effects , Up-Regulation/drug effects
8.
Health Qual Life Outcomes ; 18(1): 54, 2020 Mar 04.
Article in English | MEDLINE | ID: mdl-32131839

ABSTRACT

BACKGROUNDS: Social Health Scale for the Elderly short version (SHSE-S) is a psychometrically sound instrument that comprehensively assesses the social health status of older adults in China. The aim of the present study was to establish continuous normative data of SHSE-S. METHODS: We conducted a multicenter cross-sectional study among 31 communities in eastern China. Older adults aged 60 years and above were invited to participate in the study. Each participant was interviewed in-person to finish a structured questionnaire. The SHES-S score was calculated and standardized for each participant. We split the sample into generation and validation datasets and compared the distribution of SHSE-S score between two datasets. Multivariable linear regression was used to assess the SHSE-S score and demographic variables. Regression-based norms were built using a four-step process. RESULTS: A total of 6089 participants (51.2% females) aged 60 years old and above (mean age = 71.3, SD = 8.0) were enrolled as the normative sample. No significant difference was found between the distribution of SHSE-S standardized score in the generation (N = 2392) and validation (N = 3697) datasets. Multivariable linear regression showed that females, higher education levels were positive indicators while aging, living alone, divorced or never married, multimorbidity were negative factors. The regression-based norm which taking demographic factors into account was established and a user-friendly worksheet was also provided to facilitate the scoring and norming of the SHSE-S. CONCLUSIONS: The population-based regression norm of SHSE-S can be a useful tool for assessing the social health status of the Chinese elderly population.


Subject(s)
Quality of Life/psychology , Social Determinants of Health/statistics & numerical data , Surveys and Questionnaires/standards , Aged , Aged, 80 and over , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Psychometrics , Social Adjustment , Social Support
9.
Angew Chem Int Ed Engl ; 59(42): 18556-18562, 2020 10 12.
Article in English | MEDLINE | ID: mdl-32557982

ABSTRACT

Hypoxia and the acidic microenvironment play a vital role in tumor metastasis and angiogenesis, generally compromising the chemotherapeutic efficacy. This provides a tantalizing angle for the design of platinum(IV) prodrugs for the effective and selective killing of solid tumors. Herein, two carbonic anhydrase IX (CAIX)-targeting platinum(IV) prodrugs have been developed, named as CAIXplatins. Based on their strong affinity for and inhibition of CAIX, CAIXplatins can not only overcome hypoxia and the acidic microenvironment, but also inhibit metabolic pathways of hypoxic cancer cells, resulting in a significantly enhanced therapeutic effect on hypoxic MDA-MB-231 tumors both in vitro and in vivo compared with cisplatin/oxaliplatin, accompanied with excellent anti-metastasis and anti-angiogenesis activities. Furthermore, the cancer selectivity indexes of CAIXplatins are 70-90 times higher than those of cisplatin/oxaliplatin with effectively alleviated side-effects.


Subject(s)
Carbonic Anhydrase IX/antagonists & inhibitors , Cell Hypoxia , Coordination Complexes/chemistry , Platinum/chemistry , Prodrugs/chemistry , Animals , Carbonic Anhydrase IX/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cisplatin/pharmacology , Cluster Analysis , Coordination Complexes/metabolism , Coordination Complexes/pharmacology , Coordination Complexes/therapeutic use , Drug Screening Assays, Antitumor , Humans , Larva/drug effects , Larva/metabolism , Mice , Mice, Nude , Neoplasms/drug therapy , Neoplasms/pathology , Prodrugs/metabolism , Prodrugs/pharmacology , Prodrugs/therapeutic use , Proteome/analysis , Proteome/drug effects , Proteomics , Zebrafish/growth & development
10.
Bioorg Med Chem Lett ; 26(2): 677-683, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26652482

ABSTRACT

A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13µM to 128.06µM in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26µM/0.51µM, respectively, comparable to the positive control erlotinib (IC50=0.41µM for HER-2 and IC50=0.20µM for EGFR) and lapatinib (IC50=0.54µM for HER-2 and IC50=0.28µM for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity of the proposed compounds and activity relationship (SAR) of these pyrazole-nitroimidazole derivatives.


Subject(s)
ErbB Receptors/antagonists & inhibitors , Nitroimidazoles/chemistry , Nitroimidazoles/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Design , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Neoplasms/drug therapy , Neoplasms/metabolism , Pyrazoles/chemistry , Pyrazoles/pharmacology , Receptor, ErbB-2/metabolism
11.
Bioorg Med Chem ; 22(11): 2947-54, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24792811

ABSTRACT

A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a-3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC50 value of 3.11 µM and Hela with IC50 value of 2.54 µM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50=0.45 µM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Dioxanes/chemistry , Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors , Molecular Docking Simulation , Nitroimidazoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Focal Adhesion Protein-Tyrosine Kinases/metabolism , HeLa Cells , Humans , Molecular Structure , Nitroimidazoles/chemical synthesis , Nitroimidazoles/chemistry , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship
12.
Int J Surg Case Rep ; 120: 109836, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38824740

ABSTRACT

INTRODUCTION: Midgut volvulus in adults based on congenital malrotation, which required emergency surgery, may occur under the stimulation of adverse factors and is rare and easy to be misdiagnosed. PRESENTATION OF CASE: A young male was taken to the emergency room of a local hospital after six hours abdominal pain. Computed tomography (CT) shows intestinal volvulus and exploratory laparotomy was performed. Postoperative CT revealed remission of small intestinal torsion and congenital malrotation of the midgut. The patient vomited frequently within 48 h after the surgery, and was transferred to our hospital for conservative treatment. After 4 days of conservative treatment, the vomiting symptoms were relieved at first, but worsened again after a liquid diet. CT showed complete duodenal obstruction and exploratory laparotomy was performed again. Congenital malrotation was found, which resulted in midgut volvulus and duodenal obstruction due to anomalous fixation of the mesentery. The bowel was placed in normal anatomical position, and the mesentery was sutured to the posterior abdominal wall. The patient was followed up for 24 months with no complaints. DISCUSSION: Due to the rare incidence and atypical pain clinical manifestations, it is difficult for the congenital malrotation in adults to be diagnosed. Midgut volvulus in adults with malrotation is even rarer and requires emergency operation, and may be misdiagnosed. CONCLUSION: Midgut volvulus with midgut malrotation is very rare in adults. Exploratory laparotomy must be careful to reduce misdiagnosis and recurrence of volvulus.

13.
Front Oncol ; 14: 1396726, 2024.
Article in English | MEDLINE | ID: mdl-39055563

ABSTRACT

Background: Prognostic assessment for colorectal cancer (CRC) displays substantial heterogeneity, as reliance solely on traditional TNM staging falls short of achieving precise individualized predictions. The integration of diverse biological information sources holds the potential to enhance prognostic accuracy. Objective: To establish a comprehensive multi-tiered precision prognostic evaluation system for CRC by amalgamating gene expression profiles, clinical characteristics, and tumor microsatellite instability (MSI) status in CRC patients. Methods: We integrated genomic data, clinical information, and survival follow-up data from 483 CRC patients obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. MSI-related gene modules were identified using differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Three prognostic models were constructed: MSI-Related Gene Prognostic Model (Model I), Clinical Prognostic Model (Model II), and Integrated Multi-Layered Prognostic Model (Model III) by combining clinical features. Model performance was assessed and compared using Receiver Operating Characteristic (ROC) curves, Kaplan-Meier analysis, and other methods. Results: Six MSI-related genes were selected for constructing Model I (AUC = 0.724); Model II used two clinical features (AUC = 0.684). Compared to individual models, the integrated Model III exhibited superior performance (AUC = 0.825) and demonstrated good stability in an independent dataset (AUC = 0.767). Conclusion: This study successfully developed and validated a comprehensive multi-tiered precision prognostic assessment model for CRC, providing an effective tool for personalized medical management of CRC.

14.
PLoS One ; 19(7): e0306463, 2024.
Article in English | MEDLINE | ID: mdl-39058673

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication. METHODS: PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures. RESULTS: A total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84-12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89-22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63-9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93-14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60-11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26-20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09-1.58), P = 0.004] [OR = 1.85, 95% CI (1.54-2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41-1.29), P = 0.28] [OR = 0.69, 95% CI (0.39-1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39-1.11), P = 0.12] [OR = 0.85, 95% CI (0.52-1.38), P = 0.50]} compared to placebo. CONCLUSION: This meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose.


Subject(s)
Dermatitis, Atopic , Heterocyclic Compounds, 3-Ring , Humans , Dermatitis, Atopic/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Treatment Outcome , Severity of Illness Index , Randomized Controlled Trials as Topic
15.
Int Immunopharmacol ; 127: 111408, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38128309

ABSTRACT

Microglia aggregate in regions of active inflammation and demyelination in the CNS of multiple sclerosis (MS) patients and are considered pivotal in the disease process. Targeting microglia is a promising therapeutic approach for myelin repair. Previously, we identified two candidates for microglial modulation and remyelination using a Connectivity Map (CMAP)-based screening strategy. Interestingly, with results that overlapped, sanguinarine (SAN) emerged as a potential drug candidate to modulate microglial polarization and promote remyelination. In the current study, we demonstrate the efficacy of SAN in mitigating the MS-like experimental autoimmune encephalomyelitis (EAE) in a dose-dependent manner. Meanwhile, prophylactic administration of a medium dose (2.5 mg/kg) significantly reduces disease incidence and ameliorates clinical signs in EAE mice. At the cellular level, SAN reduces the accumulation of microglia in the spinal cord. Morphological analyses and immunophenotyping reveal a less activated state of microglia following SAN administration, supported by decreased inflammatory cytokine production in the spinal cord. Mechanistically, SAN skews primary microglia towards an immunoregulatory state and mitigates proinflammatory response through PPARγ activation. This creates a favorable milieu for the differentiation of oligodendrocyte progenitor cells (OPCs) when OPCs are incubated with conditioned medium from SAN-treated microglia. We further extend our investigation into the cuprizone-induced demyelinating model, confirming that SAN treatment upregulates oligodendrocyte lineage genes and increases myelin content, further suggesting its pro-myelination effect. In conclusion, our data propose SAN as a promising candidate adding to the preclinical therapeutic arsenal for regulating microglial function and promoting myelin repair in CNS demyelinating diseases such as MS.


Subject(s)
Benzophenanthridines , Encephalomyelitis, Autoimmune, Experimental , Isoquinolines , Multiple Sclerosis , Humans , Mice , Animals , Microglia , PPAR gamma , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Myelin Sheath/physiology , Multiple Sclerosis/drug therapy , Mice, Inbred C57BL , Disease Models, Animal
16.
Mol Plant ; 17(1): 158-177, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37950440

ABSTRACT

The Lamiaceae family is renowned for its terpenoid-based medicinal components, but Leonurus, which has traditional medicinal uses, stands out for its alkaloid-rich composition. Leonurine, the principal active compound found in Leonurus, has demonstrated promising effects in reducing blood lipids and treating strokes. However, the biosynthetic pathway of leonurine remains largely unexplored. Here, we present the chromosome-level genome sequence assemblies of Leonurus japonicus, known for its high leonurine production, and Leonurus sibiricus, characterized by very limited leonurine production. By integrating genomics, RNA sequencing, metabolomics, and enzyme activity assay data, we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase (ADC), uridine diphosphate glucosyltransferase (UGT), and serine carboxypeptidase-like (SCPL) acyltransferase enzymes that catalyze key reactions in this pathway. Further analyses revealed that the UGT-SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L. japonicus, which contributed to the accumulation of leonurine specifically in L. japonicus. Collectively, our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.


Subject(s)
Lamiaceae , Leonurus , Leonurus/genetics , Multiomics , Plant Extracts
17.
Zhonghua Yi Xue Za Zhi ; 93(29): 2309-11, 2013 Aug 06.
Article in Zh | MEDLINE | ID: mdl-24300152

ABSTRACT

OBJECTIVE: To explore the effects of statins upon bone mineral density (BMD) and bone metabolic markers in postmenopausal women with hypercholesterolemia. METHODS: A prospective study was conducted for 100 women receiving treatment from January 2011 to August 2012 and meeting the inclusion criteria of osteopenia or osteoporosis with hypercholesterolemia postmenopausal. They were randomly divided into treatment group on atorvastatin 10 mg once daily and control group. The parameters of lumbar BMD, bone resorption markers of type I collagen cross-linked C-telopeptide (CTX) , bone synthesis markers procollagen type I N-terminal peptide (PINP) were compared between two groups after half a year and one year. RESULTS: There was an upward trend of lumbar spine BMD and PINP in the treatment group at half a year and one year compared with the control group. And two groups had significant difference (P < 0.05). Although two groups had no significant difference in all parameters at half a year, the values of lumbar spine BMD and PINP were higher in the treatment group at one year than the control group. Two groups had significant difference (P < 0.05). CONCLUSIONS: Statins can help maintain or increase bone mass of hypercholesterolemic menopausal women through promoting bone synthesis.


Subject(s)
Bone Density/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypercholesterolemia/metabolism , Postmenopause , Female , Humans , Middle Aged , Osteoporosis, Postmenopausal/prevention & control , Peptide Fragments/metabolism , Procollagen/metabolism , Prospective Studies
18.
Food Res Int ; 163: 112211, 2023 01.
Article in English | MEDLINE | ID: mdl-36596142

ABSTRACT

Natural superoxide dismutase (SOD), consisting of proteins and metal cofactors, is widely used in food preservation because of its good antioxidant activity. However, due to the poor stability of SOD enzyme, its activity was reduced in the process of moving into the film, resulting in limited application. Based on the structure of the active site of the natural enzyme, Cu2+ was used to functionalize the melanin nanoparticles (NMPs) in ink of cuttlefish, and an SOD-like nanozyme (Cu-NMPs) with high stability, high activity and strong free radical scavenging capacity was constructed. In order to apply the constructed simulated enzyme to food preservation, the simulated enzyme was embedded into carrageenan (Carr) films to prepare the composite film for food packaging. The results showed that when the concentration of Cu-NMPs was 10 µg/mL, the ·O2- rate could reach more than 80 %, the activity exceeded that of 60 U/mL natural SOD. In addition, the fresh-keeping test of cherry tomatoes showed that Carr/Cu-NMPs composite film extended the storage time of cherry tomatoes by more 3 days. Therefore, the present work showed that nanozymes with advanced catalytic capabilities can be constructed by metal ions and NMPs, thus successfully combined with food packaging for food preservation.


Subject(s)
Melanins , Nanoparticles , Ink , Superoxide Dismutase/metabolism , Food Preservation , Metals
19.
Food Chem ; 401: 134117, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36096001

ABSTRACT

Although nanocomposite films had shown excellent potential in antibacterial food packaging, their potential harmful impact limits their further application in reality. Therefore, exploring a Generally Recognized As Safe (GRAS) nanomaterial that has antibacterial ability is the pioneer for the fabrication of a real edible nanocomposite-based antibacterial packaging film. Herein, for the first time by using the natural nanostructure extracted from cuttlefish ink, an edible antibacterial food packaging with high safety were constructed. The natural melanin nanoparticles (NMPs) in cuttlefish ink have good photothermal conversion ability. As such, by incorporating with natural pectin (PC) film and with near infrared (NIR) irradiation triggering, the results show that PC/NMPs films perform high-efficiency and short-term bactericidal activity against foodborne pathogenic bacteria, including thermotolerant Listeria monocytogenes. The sterilization rate could reach more than 90 % within only 5 min. Also, this nanocomposite film showed better mechanical properties, thermal stability and barrier properties than the neat pectin film. Antibacterial test on food sample also proved the good antibacterial ability of the PC/NMPs films. Therefore, exploring GRAS natural functional nanocomposite film is expected to be the effective way to promote edible nano-antibacterial packaging.


Subject(s)
Edible Films , Nanoparticles , Food Packaging/methods , Melanins , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Pectins/pharmacology , Pectins/chemistry
20.
Food Chem ; 412: 135539, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-36731236

ABSTRACT

Given the enormous burden pathogens pose on human health, rapid capture and removal of bacteria for sterilization or further bacterial detection is essential. Herein, tannic acid-functionalized virus-like Fe3O4 (vFe3O4-TA) was established for bacterial enrichment. We investigated the ability of vFe3O4-TA to capture Gram-negative bacteria (E. coli, S. flex and S. typhi) and Gram-positive bacteria (S. aureus, MRSA and LM), respectively. Compared to the capture efficiency of <15 % for Gram-negative bacteria, vFe3O4-TA showed excellent selectivity and efficiency in isolating Gram-positive bacteria with >87 % removal efficiency. GFN-xTB semiempirical quantum chemical calculations revealed that the selective recognition originates from the high affinity between TA and peptidoglycan. Without impacting ingredients, the TA-mediated trapper also shows excellent ability to distinguish Gram-positive bacteria in juice samples. These results are expected to reveal the interaction of TA with bacteria, and inaugurate a potential natural safe tool for food safety control, medical treatment and environmental remediation.


Subject(s)
Malus , Humans , Escherichia coli , Staphylococcus aureus , Bacteria , Tannins , Gram-Positive Bacteria , Gram-Negative Bacteria , Salmonella typhi , Anti-Bacterial Agents/pharmacology
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