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1.
Heliyon ; 8(8): e10410, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36090218

RESUMO

The dual tyrosine kinase (EGFR/HER2) inhibitor lapatinib is currently used to clinically treat HER2-positive breast cancer. However, a majority of patients do not respond to lapatinib therapy within 6 months. Therefore, potentiating the anti-tumor effect of lapatinib by combination treatment has a great potential to overcome the obstacle. Herein, we aim to investigate the anti-tumor activity of lapatinib in combination with brusatol and explore the potential mechanism involved in the combinatorial treatment. Our findings revealed that the Nrf2 inhibitor brusatol potently enhanced the anti-tumor effect of lapatinib against SK-BR-3, SK-OV-3 and AU565 cancer cells in a synergistic manner. Furthermore, we found that lapatinib plus brusatol more effectively decreased Nrf2 level and induced ROS generation in both SK-BR-3 and SK-OV-3 cells. Moreover, we also observed a significant reduction on the phosphorylation of HER2, EGFR, AKT and ERK1/2 in SK-BR-3 and SK-OV-3 cells when treated with lapatinib plus brusatol compared to either agent alone. More importantly, brusatol significantly augmented the anti-tumor effects of lapatinib in the SK-OV-3 xenograft model. In summary, these data provide a potential rationale for the combination of brusatol and lapatinib on the treatment of HER2-positive cancers.

2.
Front Surg ; 9: 929576, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090338

RESUMO

Aim: This study aims to construct a new staging system for colorectal cancer (CRC) based on the lymph node ratio (LNR) as a supplement to the American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system for predicting the prognosis of CRC patients with <12 lymph nodes. Methods: The data of 26,695 CRC patients with <12 lymph nodes were extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. A total of 635 CRC patients were also enrolled from Northern Jiangsu People's Hospital affiliated with Yangzhou University as an independent validation set. Classification and regression tree analysis was used to obtain the LNR cutoff value. Survival curves were estimated using the Kaplan-Meier method, and the log-rank test was used for comparisons of differences among the survival curves. The monotonic decreasing trend of the overall survival curve in the staging system was expressed by the linear correlation degree R. Results: The 5-year survival rates of patients in the training set based on the AJCC staging system from stage I to stage IV were 75.6% (95%CI: 74.4-76.8), 59.8% (95%CI: 58.6-61.0), 42.1% (95%CI: 34.5-49.7), 33.2% (95%CI: 24.6-41.8), 72.0% (95%CI: 69.1-74.9), 48.8% (95%CI: 47.4-50.2), 26.5% (95%CI: 23.0-30.0), and 11.3% (95%CI: 10.3-12.3). The 5-year survival rates of patients in the training set from stage I to stage IIIC were 80.4%, 72.9%, 59.8%, 48.4%, 32.5%, and 15.0%, according to the TNM + LNR (TNRM) staging system. According to the AJCC staging system, the 5-year survival rates of patients in the validation set from stage I to stage IIIC were 91.3%, 90.8%, 72.6%, 61.3%, 72.4%, 58.1%, and 32.8%. Based on the TNRM staging system, the 5-year survival rates of patients in the validation set from stage I to stage IIIC were 99.2%, 90.5%, 81.4%, 78.6%, 60.2%, and 35.8%. Conclusion: The TNRM staging system successfully eliminated "survival paradox" in the AJCC staging system, which might be superior to the AJCC staging system.

3.
Front Pharmacol ; 13: 967633, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091750

RESUMO

Breast cancer and gynecological tumors seriously endanger women's physical and mental health, fertility, and quality of life. Due to standardized surgical treatment, chemotherapy, and radiotherapy, the prognosis and overall survival of cancer patients have improved compared to earlier, but the management of advanced disease still faces great challenges. Recently, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been clinically approved for breast and gynecological cancer patients, significantly improving their quality of life, especially of patients with BRCA1/2 mutations. However, drug resistance faced by PARPi therapy has hindered its clinical promotion. Therefore, developing new drug strategies to resensitize cancers affecting women to PARPi therapy is the direction of our future research. Currently, the effects of PARPi in combination with other drugs to overcome drug resistance are being studied. In this article, we review the mechanisms of PARPi resistance and summarize the current combination of clinical trials that can improve its resistance, with a view to identify the best clinical treatment to save the lives of patients.

4.
Transl Cancer Res ; 11(8): 2767-2782, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36093520

RESUMO

Background: Therapy-induced senescence plays an important role in the clinical treatment of tumors, which is positively correlated with the treatment response. However, senescent cells reshape tumor microenvironment and increase the risk of cancer recurrence. Regarded as hormones to regulate cell-to-cell communication, microRNA (miRNA) is highly sensitive to environmental stress. To understand the response of tumor cells to chemotherapeutic drugs, miRNAs in chemotherapy-induced senescent cells and their secreted extracellular vehicles (EVs) were detected and the miRNA profiles were analyzed, hoping to provide some thoughts for the evaluation of chemotherapy effect in clinical tumor treatment. Methods: Neuroblastoma cell line IMR32 was treated with low concentration of aurora kinase A (AURKA) inhibitor MLN8237 to establish a cell senescence model. RNAs were extracted from senescent cells and extracellular vesicles, and miRNA spectrum was investigated by small RNA deep sequencing. Results: Thirteen miRNAs including miR-378b and miR-206 were significantly increased, whereas 32 miRNAs including miR-205-5p, miR-378d, and miR-378f were significantly decreased in the senescence cell group. In senescent cells secreted extracellular vesicles, there were 48 of up-regulated miRNAs including miR-205-5p and 9 of down-regulated miRNAs. Bioinformatics analysis revealed that these differentially expressed miRNAs in senescent cells may potentially regulate many common target genes which belong to the metabolic signaling pathway and transcriptional misregulation in cancer. Conclusions: The expression profiles of miRNA in senescent neuroblastoma cells and extracellular vesicles were altered, and the differentially expressed miRNAs were mostly involved in cellular metabolic pathways. The information decryption can provide reference for clinical interpretation of the phenomenon of therapy-induced senescence.

5.
J Colloid Interface Sci ; 629(Pt A): 487-495, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36088694

RESUMO

Bismuth vanadate (BVO) possesses great potential in photoelectrochemical water splitting application, but still suffers from low charge transfer efficiency as well as poor chemical stability. Herein, we have fabricated a thin NiFe-bimetal-organic framework (NiFe-MOF) layer grafting surface oxygen vacancies enriched BVO photoanode (NiFe-Ovac-BVO), which improves the charge separation and transfer efficiency during oxygen evolution process. Meanwhile, the NiFe-MOFs thin layer can not only protect the surface Ovac of BVO, but also efficiently inhibits the photocorrosion. As a result, the resultant NiFe-Ovac-BVO exhibits good chemical stability and achieves an outstanding photocurrent density of 4.42 ± 0.1 mA·cm-2 at 1.23 V vs reversible hydrogen electrode (RHE), which is 3.7-time higher than that of BVO photoanode. This work supplies an efficient avenue to design photoanode with enhanced photocurrent and stability by using a thin NiFe-MOF layer grafting Ovac-BVO.

6.
Biomed Pharmacother ; : 113541, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36127221

RESUMO

Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that are essential in mediating the body's natural and adaptive immune responses. The body can regulate the function of DCs in various ways to enhance their antitumor effects. In the tumour microenvironment (TME), antigen-specific T cell responses are initiated through DC processing and delivery of tumour-associated antigens (TAAs); conversely, tumour cells inhibit DC recruitment by releasing metabolites, cytokines and other regulatory TME and function. Different subpopulations of DCs exist in tumour tissues, and their functions vary. Insight into DC subgroups in TME allows assessment of the effectiveness of tumour immunotherapy. Astragalus polysaccharide (APS) is the main component of the Chinese herb Astragalus membranaceus. The study found that the antitumor effects of APS are closely related to DCs. APS can promote the expression of surface molecules CD80 and CD86, promote the maturation of DCs, and activate CTL to exert antitumor effects. We reviewed the application of DCs in tumor immunotherapy and the mechanism of modulation of DCs by Astragalus polysaccharide to provide new directions and strategies for tumor therapy and new drug development.

7.
Arch Insect Biochem Physiol ; : e21967, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36111353

RESUMO

Carboxylesterases (COEs) have various functions in wide taxons of organisms. In insects, COEs are important enzymes involved in the hydrolysis of a variety of ester-containing xenobiotics, neural signal transmission, pheromone degradation, and reproductive development. Understanding the diversity of COEs is basic to illustrate their functions. In this study, we identified 53, 105, 37, and 39 COEs from the genomes of Tenebrio molitor, Asbolus verucosus, Hycleus cichorii, and H. phaleratus in the superfamily of Tenebrionidea, respectively. Phylogenetic analysis showed that 234 COEs from these four species and those reported in Tribolium castaneum (63) could be divided into 12 clades and three major classes. The α-esterases significantly expanded in T. molitor, A. verucosus, and T. castaneum compared to dipteran and hymenopteran insects. In T. molitor, most COEs showed tissue and stage-specific but not a sex-biased expression. Our results provide insights into the diversity and evolutionary characteristics of COEs in tenebrionids, and lay a foundation for the functional characterization of COEs in the yellow mealworm.

8.
Front Immunol ; 13: 914612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072600

RESUMO

Yutao Wang, China Medical University, ChinaThe tumor microenvironment (TME) has been shown to impact the prognosis of tumors in patients including cutaneous melanoma (CM); however, not all components of TME are important. Given the aforementioned situation, the functional immune cell contents correlated with CM patient prognosis are needed to optimize present predictive models and reflect the overall situation of TME. We developed a novel risk score named core tumor-infiltrating immune cell score (cTICscore), which showed certain advantages over existing biomarkers or TME-related signatures in predicting the prognosis of CM patients. Furthermore, we explored a new gene signature named cTILscore-related module gene score (cTMGs), based on four identified TME-associated genes (GCH1, GZMA, PSMB8, and PLAAT4) showing a close correlation with the cTICscore, which was generated by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis to facilitate clinical application. Patients with low cTMGs had significantly better overall survival (OS, P = 0.002,< 0.001, = 0.002, and = 0.03, respectively) in the training and validating CM datasets. In addition, the area under the curve values used to predict the immune response in four CM cohorts were 0.723, 0.723, 0.754, and 0.792, respectively, and that in one gastric cohort was 0.764. Therefore, the four-gene signature, based on cTICscore, might improve prognostic information, serving as a predictive tool for CM patients receiving immunotherapy.cutaneous melanoma, tumor microenvironment, prognosis, immunotherapy, cTICscore.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Imunoterapia , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Microambiente Tumoral/genética
9.
Front Pharmacol ; 13: 918071, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052142

RESUMO

Solanum nigrum Linn., is a common edible medicinal herb of the Solanaceae family which is native to Southeast Asia and is now widely distributed in temperate to tropical regions of Europe, Asia, and America. Traditionally, it has been used to treat various cancers, acute nephritis, urethritis, leucorrhea, sore throat, toothache, dermatitis, eczema, carbuncles, and furuncles. Up to now, 188 chemical constituents have been identified from S. nigrum. Among them, steroidal saponins, alkaloids, phenols, and polysaccharides are the major bioactive constituents. Investigations of pharmacological activities of S. nigrum revealed that this edible medicinal herb exhibits a wide range of therapeutic potential, including antitumor, anti-inflammatory, antioxidant, antibacterial, and neuroprotective activities both in vivo and in vitro. This article presents a comprehensive and systematic overview of the botanical, traditional uses, phytochemical compositions, pharmacological properties, clinical trials, and toxicity of S. nigrum to provide the latest information for further exploitation and applications of S. nigrum in functional foods and medicines.

10.
Aging Cell ; : e13704, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056774

RESUMO

With the aging world population, the prevalence of aging-related disorders is on the rise. Diseases such as Alzheimer's, type 2 diabetes mellitus (T2DM), Parkinson's, atherosclerosis, hypertension, and osteoarthritis are age-related, and most of these diseases are comorbidities or risk factors for AD; however, our understandings of molecular events that regulate the occurrence of these diseases are still not fully understood. Brain and muscle Arnt-like protein-1 (Bmal1) is an irreplaceable clock gene that governs multiple important physiological processes. Continuous research of Bmal1 in AD and associated aging-related diseases is ongoing, and this review picks relevant studies on a detailed account of its role and mechanisms in these diseases. Oxidative stress and inflammation turned out to be common mechanisms by which Bmal1 deficiency promotes AD and associated aging-related diseases, and other Bmal1-dependent mechanisms remain to be identified. Promising therapeutic strategies involved in the regulation of Bmal1 are provided, including melatonin, natural compounds, metformin, d-Ser2-oxyntomodulin, and other interventions, such as exercise, time-restricted feeding, and adiponectin. The establishment of the signaling pathway network for Bmal1 in aging-related diseases will lead to advances in the comprehension of the molecular and cellular mechanisms, shedding light on novel treatments for aging-related diseases and promoting aging-associated brain health.

11.
Rev Port Cardiol ; 41(3): 197-205, 2022 Mar.
Artigo em Inglês, Português | MEDLINE | ID: mdl-36062652

RESUMO

OBJECTIVES: Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhiza extract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms. METHODS: A myocardial IRI model was established in Wistar rats via surgical ligation of the left anterior descending coronary artery followed by loosening of the occlusion. The rats were divided into four groups: saline, sham, alprostadil, and S. miltiorrhiza. Rats in the saline and sham groups were injected with normal saline by tail vein once daily for 10 consecutive days. Rats in the S. miltiorrhiza and alprostadil groups were injected with S. miltiorrhiza extract (20 µg/kg) or alprostadil. Histological differences in myocardial tissues between rats in the sham group and in the myocardial IRI model were observed by hematoxylin and eosin staining. India ink perfusion was used to quantify the number of capillary microvessels. Real-time quantitative reverse transcription polymerase chain reaction was used to determine serum expression levels of soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), CD11b and CD18. RESULTS: The alprostadil and S. miltiorrhiza groups had significantly higher numbers of microvessels than the saline group. Serum sICAM and sVCAM expression was significantly reduced in the alprostadil and S. miltiorrhiza groups. Meanwhile, sICAM and sVCAM in the alprostadil group were markedly lower than in the S. miltiorrhiza group. Moreover, the alprostadil group had markedly lower mRNA expression of CD11b and CD18, which were clearly lower than in the S. miltiorrhiza group. CONCLUSION: Alprostadil may have cardioprotective effects for myocardial IRI, with down-regulated expression of sICAM, sVCAM, CD11b, and CD18.

12.
JAMA Netw Open ; 5(9): e2230359, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069982

RESUMO

Importance: The potential effects of long-term occupational exposure to formaldehyde (FA) on human semen quality is not clear. Objective: To assess whether long-term occupational exposure to FA is associated with semen quality. Design, Setting, and Participants: This population-based cohort study was conducted from June 1 to June 30, 2021, in Xi'an, China. Participants were adults aged 23 to 40 years who had lived in the study area for 24 months or longer. Data analysis was performed from September 1 to October 1, 2021. Exposures: Long-term occupational exposure to FA was measured using a formaldehyde detector, and the FA exposure index (FEI) was calculated as follows: FEI = final concentration of FA (mg/m3) × work time during a workday (hour) × cumulative workdays (year). Main Outcomes and Measures: Semen samples were collected by masturbation after 3 to 7 days of abstinence and were then assessed by the computer-automated semen analysis system, Baso-Papanicolaou staining, and sperm-chromatin structure assay. Results: A total of 205 men (mean [SD] age, 29.49 [3.64] years), with 124 individuals in the FA exposure group (mean [SD] FEI, 73.72 [54.86]) and 81 age-matched controls, were included in the final analysis. Long-term personal occupational exposure to FA was significantly associated with poor semen quality. Specifically, a 1-unit increase in FEI was associated with a change of -0.99% (95% CI, -1.00% to -0.98%) in total sperm motility, -0.99% (95% CI, -0.99% to -0.97%) in progressive sperm motility, -0.05% (95% CI, -0.08% to -0.02%) in curvilinear velocity, -0.07% (95% CI, -0.10% to -0.04%) in straight line velocity, -0.07% (95% CI, -0.10% to -0.04%) in time-average velocity, -0.98% (95% CI, -0.99% to -0.93%) in normal sperm morphology, -0.24% (95% CI, -0.35% to -0.11%) in seminal neutral glucosidase, -0.61% (95% CI, -0.66% to -0.56%) in seminal plasma zinc, 0.52% (95% CI, 0.15% to 1.02%) in beat cross frequency, and 0.10% (95% CI, 0.06% to 0.14%) in the DNA fragmentation index. These associations remained significant after adjusting for confounding factors. Furthermore, subgroup analysis found that high levels of oxidative stress might promote the associations between FA exposure and semen quality. Conclusions and Relevance: This study found an association between long-term occupational exposure to FA and semen quality. This deterioration was dose and time dependent and might be induced by oxidative stress.


Assuntos
Exposição Ocupacional , Análise do Sêmen , Adulto , China/epidemiologia , Estudos de Coortes , Formaldeído/efeitos adversos , Formaldeído/toxicidade , Humanos , Masculino , Exposição Ocupacional/efeitos adversos , Hipersensibilidade Respiratória , Sêmen , Motilidade Espermática
13.
Molecules ; 27(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36080490

RESUMO

The Systematic Evolution of Ligands by EXponential enrichment (SELEX) is conventionally an effective method to identify aptamers, which are oligonucleotide sequences with desired properties to recognize targets specifically and sensitively. However, there are some inherent limitations, e.g., the loss of potential high-affinity sequences during biased iterative PCR enrichment processes and the limited structural diversity of the initial library, which seriously restrict their real-world applications. To overcome these limitations, the in silico base mutagenesis post-SELEX strategy based on the low Gibbs free energy (ΔG) and genetic algorithm was developed for the optimization of the interferon-gamma aptamer (B1-4). In the process of evolution, new sequences were created and the aptamer candidates with low ΔG values and advanced structures were produced. After five rounds of selection, systematic studies revealed that the affinity of the newly developed evolutionary aptamer (M5-5) was roughly 10-fold higher than that of the parent aptamer (B1-4), and an aptasensor detection system with a limit-of-detection (LOD) value of 3.17 nM was established based on the evolutionary aptamer. The proposed approach provided an efficient strategy to improve the aptamer with low energy and a high binding ability, and the good analytical utility thereof.


Assuntos
Aptâmeros de Nucleotídeos , Técnica de Seleção de Aptâmeros , Aptâmeros de Nucleotídeos/química , Interferon gama/genética , Ligantes , Mutagênese , Técnica de Seleção de Aptâmeros/métodos
14.
Opt Lett ; 47(17): 4379-4382, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048658

RESUMO

In this Letter, we introduce a multiplexing encoding method with a bandwidth constraint strategy to realize a color dynamic holographic display based on complex amplitude modulation (CAM). The method first uses the angular spectrum method (ASM) with a bandwidth constraint strategy to calculate the diffracted wavefronts of red, green, and blue channels. Then the diffracted wavefronts of three channels are synthesized into a color-multiplexed hologram (CMH) based on the double-phase method after they interfere with off-axis reference lights. The color 3D objects can be reconstructed when the combination of red, green, and blue lights is used to illuminate the double-phase CMH, and a 4f system with a slit filter is introduced to extract the desired spectrums. Numerical simulations and optical experiments are performed to verify the effectiveness of the proposed method and the results show that it can achieve a color holographic display with high quality. Our proposal is simple and fast, and the display system is compact. It is expected that our proposed method could in future be widely used in the holographic field.

15.
Contrast Media Mol Imaging ; 2022: 2820851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051920

RESUMO

This study was to explore the effect of traditional Chinese medicine (TCM) nursing intervention based on intracoronary ultrasound imaging on patients with coronary heart disease (CHD) and phlegm and blood stasis syndrome (PBSS). 100 hospitalized patients with CHD with Qi deficiency and blood stasis syndrome (QDBSS) were rolled into the experimental (Exp) group (routine nursing intervention) and control (Ctrl) group (TCM nursing intervention, syndrome differentiation nursing), with 50 patients in each group. They underwent the intracoronary ultrasound imaging scanning. The results showed that after intervention, the plaque load (45.08 ± 6.02%), plaque eccentricity index (0.47 ± 0.08%), vascular remodeling index (0.53 ± 0.11%), and vascular external elastic membrane area (8.67 ± 3.06 mm2) of the Exp group were notably inferior to those of the Ctrl group (60.22 ± 5.82%, 0.59 ± 0.08%, 0.71 ± 0.09%, and 10.56 ± 2.31 mm2). The total effective rate in the Exp group (88%) was greatly superior to that of the Ctrl group (68%). In terms of TCM symptom scores, the TCM symptom scores of chest pain, chest tightness, and shortness of breath in the Exp group after intervention (1.07 ± 0.21 points, 0.75 ± 0.27 points, and 0.58 ± 0.12 points) were notably inferior to those in the Ctrl group (1.62 ± 0.28 points, 1.03 ± 0.21 points, and 0.79 ± 0.14 points). In the Exp group, after intervention, the degree of physical activity limitation (67.05 ± 5.08 points), the stable state of angina pectoris (65.28 ± 3.76 points), the frequency of angina pectoris attack (85.92 ± 2.97 points), the degree of treatment satisfaction (75.39 ± 5.94 points), the cognition score of disease (63.56 ± 5.84 points), the levels of triglyceride (1.27 ± 0.41 mmol/L), and total cholesterol (2.24 ± 0.41 mmol/L) were remarkably inferior to the Ctrl group (52.97 ± 4.31 points, 50.77 ± 4.69 points, 71.36 ± 3.77 points, 64.08 ± 5.64 points, 51.77 ± 6.33 points, 2.09 ± 0.57 mmol/L, and 3.06 ± 0.84 mmol/L) (P < 0.05). It suggested that intracoronary ultrasound imaging can clearly display the coronary plaques of patients and accurately evaluate the clinical efficacy of patients with CHD. The TCM nursing program can greatly improve the angina symptoms and quality of life of patients with CHD and PBSS, reduce blood lipid levels, and effectively improve the clinical efficacy of patients.


Assuntos
Doença das Coronárias , Medicina Tradicional Chinesa , Angina Pectoris/tratamento farmacológico , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/terapia , Humanos , Medicina Tradicional Chinesa/métodos , Qualidade de Vida , Ultrassonografia
16.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4358-4364, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046862

RESUMO

Epimedii Folium possesses many pharmacological activities including immunomodulation, anti-oxidation, and anti-tumor. Polysaccharides are the main components of Epimedii Folium, and their activities are closely related to the structure. The present study isolated a neutral polysaccharide(EPS-1-1) and an acidic polysaccharide(EPS-2-1) from the aqueous extract of Epimedii Folium through DEAE-52 cellulose anion-exchange chromatography and Sephadex G-100. The structures were characterized by chemical composition analysis, high-performance gel permeation chromatography(HPGPC), Fourier-transform infrared spectrometry(FT-IR), 1-phenyl-3-methyl-5-pyrazolone(PMP) derivatization, scanning electron microscopy(SEM), Congo red test, etc. The immunomodulatory activity of polysaccharides in vitro was determined by investigating the effects on the maturation of bone marrow-derived dendritic cells(BMDCs) and the release of inflammatory cytokines. According to the structural characterization analysis, EPS-1-1 was composed of fructose(Fuc), mannose(Man), ribose(Rib), rhamnose(Rha), glucose(Glc), galactose(Gal), xylose(Xyl), and arabinose(Ara) at 1.90∶0.67∶0.05∶0.08∶3.29∶1.51∶0.05∶0.37(molar ratio), while EPS-2-1 was mainly composed of Fuc, Man, Rha, glucuronic acid(GlcA), galacturonic acid(GalA), Glc, Gal, Xyl, and Ara at 5.25∶0.18∶0.32∶0.13∶1.14∶0.16∶0.55∶0.08∶0.2. EPS-1-1 and EPS-2-1 could promote the maturation and function of BMDCs through up-regulating the expression of MHC-Ⅱ, CD86, CD80, and CD40, and increasing the levels of inflammatory cytokines(IL-6, IL-12, and TNF-α) in vitro experiments, which suggested that EPS-1-1 and EPS-2-1 possessed good immunomodulatory activity.


Assuntos
Citocinas , Polissacarídeos , Citocinas/metabolismo , Medicamentos de Ervas Chinesas , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunomodulação , Polissacarídeos/química , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4446-4453, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046874

RESUMO

In this study, the secondary osteoporosis model was induced by oral administration of retinoic acid for two weeks in SD male rats. The efficacy and mechanism of LG on secondary osteoporosis in rats were explored through the bone morphogenetic protein 2(BMP-2)/Runt-related transcription factor 2(Runx2)/Osterix signaling pathway. With Xianling Gubao Capsules(XLGB) as the positive control, three dose groups of low glycoside from Epimedii Folium flavonoids(LG), i.e., low-dose group(LG-L), medium-dose group(LG-M), and high-dose group(LG-H), were set up. After modeling, the rats in each group were treated correspondingly by gavage for eight weeks. The action target of LG in the treatment of secondary osteoporosis in rats was analyzed by measuring the body weight and the organ indexes of rats including heart index and testis index. The efficacy of LG was characterized by the pathological changes of the femur, the microstructural parameters of the trabecular bone, and the biomechanical properties of femoral tissues in rats. The mechanism of LG was explored by measuring the relevant biochemical indexes and the changes in BMP-2, Runx2, and Osterix content in rats with secondary osteoporosis. The results showed that the action target of LG in the treatment of secondary osteoporosis in rats was the testis. LG can improve the bone loss of the femur, increase the number and thickness of the trabecular bone, reduce the porosity and separation of the trabecular bone, potentiate the resistance of bone to deformation and destruction, up-regulate the serum content of Ca, P, aminoterminal propeptide of type Ⅰ procollagen(PINP), and osteocalcin(OC), promote bone matrix calcification and the expression of BMP-2, Runx2, and Osterix proteins, and accelerate bone formation, thereby reducing the risk of fractures, and ultimately exerting anti-secondary osteoporosis efficacy.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , Osteoporose , Animais , Densidade Óssea , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medicamentos de Ervas Chinesas , Flavonoides/uso terapêutico , Glicosídeos/uso terapêutico , Masculino , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Ratos , Ratos Sprague-Dawley , Tretinoína/efeitos adversos
18.
Sci Adv ; 8(38): eabq1799, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36129988

RESUMO

Pancreatic ß cell failure is a hallmark of diabetes. However, the causes of ß cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue-enriched secretory molecule, as a negative regulator of insulin secretion in ß cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet-fed mice. Mechanistically, TN binds with high selectivity to ß cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte-ß cell cross-talk that contributes to ß cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Adipócitos/metabolismo , Animais , Glucose/metabolismo , Insulina/metabolismo , Secreção de Insulina , Lectinas Tipo C , Camundongos , Tiorredoxinas , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Colloids Surf B Biointerfaces ; 219: 112837, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36137334

RESUMO

Cholestasis of the indwelling biliary stents usually leads to stone recurrence after endoscopic retrograde cholangio pancreatoraphy (ERCP). Biliary stents, including metallic and none-degradable plastic stents are widely used in clinical settings due to their many excellent properties. However, conventional biliary stents still suffer from poor antibacterial activity and anti-bile-adhesion, which lead to injured, local fibroblasts proliferating. Currently, various coatings for biliary stents have been prepared to meet the clinical demands. In this review, we start by summarizing and discussing classifications of biliary stents and antibacterial/antibiofilm mechanism. Then, the latest advances about developing antibacterial and antibiofilm coatings for improving the properties of biliary stents are reviewed and discussed in detail. Lastly, we list several possible directions for future development of biliary stents coatings and biliary stent, such as anti-bile-adhesion coating, multifunctional coating, drug-eluting biodegradable biliary stents and 3D printed biliary stents.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36141437

RESUMO

The potential application of biochar in water treatment is attracting interest due to its sustainability and low production cost. In the present study, H3PO4-modified porous biochar (H-PBC), ethylenediaminetetraacetic acid-modified porous biochar (E-PBC), and NaOH-modified porous biochar (O-PBC) were prepared for Ni(II) and Pb(II) adsorption in an aqueous solution. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Brunauer-Emmett-Teller analysis (BET), and Fourier-transform infrared (FT-IR) spectroscopy were employed to characterize the as-obtained samples, and their capacities for Ni(II) and Pb(II) adsorption were determined. SEM showed that H-PBC retained the hierarchical porous structure of pristine biochar. FT-IR showed that H-PBC possessed abundant oxygen-containing and phosphorus-containing functional groups on the surface. BET analysis demonstrated that the surface areas of H-PBC (344.17 m2/g) was higher than O-PBC (3.66 m2/g), and E-PBC (1.64 m2/g), respectively. H-PBC, E-PBC, and O-PBC all exhibited excellent performance at Ni(II) and Pb(II) adsorption with maximum adsorption capacity of 64.94 mg/g, 47.17 mg/g, and 60.24 mg/g, and 243.90 mg/g, 156.25 mg/g, and 192.31 mg/g, respectively, which were significantly higher than the adsorption capacity (19.80 mg/g and 38.31 mg/g) of porous biochar (PBC). Pseudo-second order models suggested that the adsorption process was controlled by chemical adsorption. After three regeneration cycles, the Ni(II) and Pb(II) removal efficiency with H-PBC were still 49.8% and 56.3%. The results obtained in this study suggest that H-PBC is a promising adsorbent for the removal of heavy metals from aqueous solutions.

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