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1.
Int Immunopharmacol ; 133: 112093, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38669947

RESUMO

BACKGROUND: IFI30 is a lysosomal thiol reductase involved in antigen presentation and immune regulation in various cancers, including breast cancer. Despite its known involvement, the precise mechanism, function, and relationship with the PD-L1 axis and immune response remain unclear. METHODS: We conducted an extensive investigation into IFI30 mRNA expression in breast cancer utilizing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Furthermore, we characterized IFI30 mRNA expression across various cell types using publicly available single-cell RNA sequencing datasets, and assessed protein expression through immunohistochemistry using an in-house breast cancer tissue microarray. Functional experiments were performed to elucidate the effects of IFI30 overexpression on PD-L1 expression and inhibitory efficacy in both macrophages and breast tumor cells. RESULTS: Our study unveiled a marked upregulation of IFI30 expression in breast cancer tissues compared to their normal counterparts, with notable associations identified with tumor stage and prognosis. Additionally, IFI30 expression demonstrated significant correlations with various immune-related signaling pathways, encompassing peptide antigen binding, cytokine binding, and MHC class II presentation. Notably, breast cancer samples exhibiting high IFI30 expression in tumor cells displayed high PD-L1 expression on corresponding cells, alongside a diminished ratio of CD8 + T cell infiltration within the tumor microenvironment. Furthermore, ectopic knockdown of IFI30 in both tumor cells and macrophages resulted in a reduction of PD-L1 expression, while conversely, overexpression of IFI30 led to an increase in PD-L1 expression. CONCLUSIONS: This study offers new insights into the involvement of IFI30 in breast cancer, elucidating its interplay with the PD-L1 axis and immune response dynamics. Our findings suggest that modulation of the IFI30-PD-L1 axis could serve as a promising strategy for regulating T cells infiltration in breast cancer thus treating breast cancer.


Assuntos
Antígeno B7-H1 , Neoplasias da Mama , Imunoterapia , Humanos , Neoplasias da Mama/imunologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Feminino , Prognóstico , Imunoterapia/métodos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Linfócitos T CD8-Positivos/imunologia
2.
J Pharm Pharmacol ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600792

RESUMO

OBJECTIVES: Achyranthes bidentata Blume (A. bidentata) is a plant of Amaranthaceae family, and its root is the main medicinal part, named "Huai-Niu-Xi." It is used to expel blood stasis through menstruation, tonify liver and kidney, strengthen muscles and bones, and induce diuresis. This review aimed to provide a systematic summary of botany, traditional uses, phytochemistry, pharmacology, and toxicology of A. bidentata. METHODS: The present review covers the literature survey. The data have been collected from various journals, books, and some of the electronic search via Internet-based information such as Web of Science, PubMed, Google Scholar, Google patents, CNKI, SpringerLink, online electronic journals, and ScienceDirect. KEY FINDINGS: So far, more than 270 metabolites have been isolated from A. bidentata, including terpenoids, steroids, alkaloids, flavonoids, and so on. Among them, terpenoids and steroids are the main metabolites. The extract and metabolites exert multiple pharmacological activities such as alleviating osteoarthritis effect, antiosteoporosis activity, neuroprotective effect, antidiabetic activity-associated complications, immunoregulatory activity, and so on. SUMMARY: Some traditional uses of A. bidentata need further in-depth studies to confirm. Similarly, the separation and screening of active compounds, as well as the corresponding molecular mechanisms of action of compounds, are also needed to be studied.

3.
J Pharm Pharmacol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687135

RESUMO

OBJECTIVES: Oxytropis DC is a perennial plant of Fabaceae family, which is widely distributed in the northern temperate zone. It is known as "locoweed" because of its toxic component swainsonine. However, it is widely used in Tibetan medicine and Mongolian medicine, mainly for the treatment of heat-clearing and detoxifying, pain-relieving, anti-inflammatory, hemostasis, and other diseases. To provide a basis for the further development and utilization of Oxytropis DC, the pieces of literature about the application, phytochemistry, pharmacological action, and toxicity of Oxytropis DC were reviewed and analyzed. KEY FINDINGS: A total of 373 chemical constituents were found from Oxytropis DC, including flavonoids, alkaloids, steroids, terpenoids, and others. Pharmacological actions mainly include antitumor, antioxidation, anti-inflammatory, analgesic, antibacterial, antifibrosis, and other pharmacological actions, among them, the antitumor effect is particularly prominent. SUMMARY: At present, studies on its pharmacological effects are mainly concentrated on the extracts, some flavonoids, and alkaloids. In the follow-up studies, research on the pharmacological activities of the other chemical constituents in Oxytropis should be strengthened. It has the potential to pave the way for research and development of novel Oxytropis medicines.

4.
Small ; : e2308574, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429234

RESUMO

Age is a significant contributor to the onset of AD. Senolysis has been recently demonstrated to ameliorate aging-associated diseases that showing a great potential in AD therapy. However, due to the presence of BBB, the anti-AD activity of senolytics are significantly diminished. SSK1 is a prodrug that can be activated by ß-gal, a lysosomal enzyme commonly upregulated in senescent cells, and thus selectively eliminates senescent cells. Furthermore, the level of ß-gal is significantly correlated with conventional AD genes from clinical sequencing data. SSK1-loaded neurotransmitter -derived lipid nanoparticles are herein developed (SSK1-NPs) that revealing good BBB penetration and bioavailability of in the body. At the brain lesion, SSK1-NP treatment significantly reduces the expression of genes associated with senescence, induced senescent cells elimination, decreased amyloid-beta accumulation, and eventually improve cognitive function of aged AD mice. SSK1-NPs, a novel nanomedicine displaying potent anti-AD activity and excellent safety profile, provides a promising strategy for AD therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38423197

RESUMO

2-ethylhexyl-4-methoxycinnamate (EHMC) is a commonly used UV filter, and is receiving increasing concerns due to its ubiquitous occurrence in a variety of environmental media and potential adverse effects. This study was aimed to assess the ecotoxicological potentials of EHMC on the marine polychaete Perinereis aibuhitensis. To this end, ragworms were exposed to 2, 20, 200 µg/L EHMC for 14 days and multiple toxicological endpoints were investigated. The results showed that EHMC significantly reduced burrowing rate, but did not affect AChE activity. Exposure to EHMC significantly elevated the activities of SOD and CAT and decreased the levels of lipid peroxidation. Besides, the induction of AKP activity indicated a stimulated immune response in the ragworms when exposed to high concentration of EHMC. Furthermore, the upregulated expression of caspase-8 suggested that EHMC might induce apoptosis in ragworms via the death receptor-mediated extrinsic pathway. Our findings highlight the potential environmental risks of EHMC to marine ecosystems.


Assuntos
Ecossistema , Poliquetos , Animais , Cinamatos , Poliquetos/metabolismo
6.
Arch Toxicol ; 98(3): 865-881, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38212449

RESUMO

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1-1000 nM) had potent and highly selective toxic effects on HER2+ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2+ breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Neoplasias , Pró-Fármacos , Humanos , Animais , Camundongos , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico , Lapatinib/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral
7.
Nat Prod Res ; : 1-7, 2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38143317

RESUMO

Three undescribed compounds, 1-(4-hydroxyphenyl)-3-((4-hydroxyphenyl)thio) -2-propanone (I), 4'-hydroxybenzyl 4-(4''- hydroxybenzyloxy) benzyl thioether (II) and 3-(4'-hydroxybenzyl)-6-hydroxy-quinazolinone (III) were isolated from the seeds of Sinapis alba L. The structures of all compounds were elucidated based on NMR and MS analysis, along with the comparison with published data. The potential targets of compounds I-III were identified by virtual screening. The potential inhibitory effects of these compounds on protein kinase C theta type were compared by molecular docking. The docking score of compound III was the highest.

8.
J Ethnopharmacol ; 314: 116636, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37182673

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Angiogenesis is particularly important in ischemic cardiovascular diseases such as coronary heart disease (CHD). Xinkeshu tablets (XKS) are a commonly used Chinese patent medicine for CHD with a defined clinical effect. However, the proangiogenic effect of XKS remains unknown. AIM OF THE STUDY: We attempted to investigate the chemical composition and proangiogenic effect of XKS, as well as its underlying mechanisms. MATERIALS AND METHODS: The chemical composition of a XKS methanol extract was analyzed using a UPLC-Q-Orbitrap-MS system. The compound's proangiogenic effects were evaluated in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). Furthermore, the underlying mechanisms were investigated using transcriptome assays and real-time quantitative PCR validation. RESULTS: We identified 116 chemical constituents of XKS. XKS significantly stimulated subintestinal vessel plexus (SIVs) growth and rescued tyrosine kinase inhibitor (PTK787)-induced intersegmental vessels (ISVs) injury in zebrafish in a concentration-dependent manner. XKS significantly rescued the proliferation, migration capacity and tube formation of Recombinant VEGFR tyrosine kinase inhibitor II (VRI)-injured HUVECs. XKS promoted angiogenesis through multiple signaling pathways, including metabolic pathways, the PPAR signaling pathway, the AGE-RAGE signaling pathway, the NOD-like receptor signaling pathway, the VEGF signaling pathway, and the PI3K/Akt signaling pathway. CONCLUSION: Herein, we identified 116 chemical constituents of XKS for the first time and demonstrated that XKS may regulate angiogenesis through multiple signaling pathways to treat CHD.


Assuntos
Fosfatidilinositol 3-Quinases , Peixe-Zebra , Animais , Humanos , Células Endoteliais da Veia Umbilical Humana , Fosfatidilinositol 3-Quinases/metabolismo , Neovascularização Fisiológica , Transdução de Sinais , Movimento Celular , Proliferação de Células
9.
Nat Commun ; 14(1): 2263, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081012

RESUMO

As rubber-like elastomers have led to scientific breakthroughs in soft, stretchable characteristics-based wearable, implantable electronic devices or relevant research fields, developments of degradable elastomers with comparable mechanical properties could bring similar technological innovations in transient, bioresorbable electronics or expansion into unexplored areas. Here, we introduce ultra-stretchable, biodegradable elastomers capable of stretching up to ~1600% with outstanding properties in toughness, tear-tolerance, and storage stability, all of which are validated by comprehensive mechanical and biochemical studies. The facile formation of thin films enables the integration of almost any type of electronic device with tunable, suitable adhesive strengths. Conductive elastomers tolerant/sensitive to mechanical deformations highlight possibilities for versatile monitoring/sensing components, particularly the strain-tolerant composites retain high levels of conductivities even under tensile strains of ~550%. Demonstrations of soft electronic grippers and transient, suture-free cardiac jackets could be the cornerstone for sophisticated, multifunctional biodegradable electronics in the fields of soft robots and biomedical implants.


Assuntos
Robótica , Dispositivos Eletrônicos Vestíveis , Elastômeros/química , Eletrônica , Próteses e Implantes
10.
J Vet Sci ; 24(2): e20, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37012029

RESUMO

BACKGROUND: As Actinobacillus pleuropneumonniae (APP) infection causes considerable losses in the pig industry, there is a growing need to develop effective therapeutic interventions that leverage host immune defense mechanisms to combat these pathogens. OBJECTIVES: To demonstrate the role of microRNA (miR)-127 in controlling bacterial infection against APP. Moreover, to investigate a signaling pathway in macrophages that controls the production of anti-microbial peptides. METHODS: Firstly, we evaluated the effect of miR-127 on APP-infected pigs by cell count/enzyme-linked immunosorbent assay (ELISA). Then the impact of miR-127 on immune cells was detected. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The expression of cytokines (anti-microbial peptides [AMPs]) was assessed using quantitative polymerase chain reaction. The expression level of IL-6, TNF-α and p-P65 were analyzed by western blot. The expression of p65 in the immune cells was investigated by immunofluorescence. RESULTS: miR-127 showed a protective effect on APP-infected macrophage. Moreover, the protective effect might depend on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17 and AMPs by targeting sphingosine-1-phosphate receptor3 (SIPR3), the element involved in the Toll-like receptor (TLR) cascades. CONCLUSIONS: Together, we identify that miR-127 is a regulator of S1PR3 and then regulates TLR/nuclear factor-κB signaling in macrophages with anti-bacterial acticity, and it might be a potential target for treating inflammatory diseases caused by APP.


Assuntos
Macrófagos Alveolares , MicroRNAs , Animais , Suínos , Macrófagos Alveolares/metabolismo , Transdução de Sinais , Macrófagos , Citocinas/genética , Citocinas/metabolismo , NF-kappa B/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
11.
Pharmaceuticals (Basel) ; 16(3)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36986561

RESUMO

Fucoidan and deep-sea water (DSW) are attractive marine resources for treating type 2 diabetes (T2DM). In this study, the regulation and mechanism associated with the co-administration of the two were first studied using T2DM rats, induced by a high fat diet (HFD) and streptozocin (STZ) injection. Results demonstrate that, compared to those with DSW or FPS alone, the orally administered combination of DSW and FPS (CDF), especially the high dose (H-CDF), could preferably inhibit weight loss, decrease levels of fasting blood glucose (FBG) and lipids, and improve hepatopancreatic pathology and the abnormal Akt/GSK-3ß signaling pathway. The fecal metabolomics data show that H-CDF could regulate the abnormal levels of metabolites mainly through the regulation of linoleic acid (LA) metabolism, bile acid (BA) metabolism, and other related pathways. Moreover, H-CDF could adjust the diversity and richness of bacterial flora and enrich bacterial groups, such as Lactobacillaceae and Ruminococcaceae UCG-014. In addition, Spearman correlation analysis illustrated that the interaction between the gut microbiota and BAs plays an essential role in the action of H-CDF. In the ileum, H-CDF was verified to inhibit activation of the farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) pathway, which is regulated by the microbiota-BA-axis. In conclusion, H-CDF enriched Lactobacillaceae and Ruminococcaceae UCG-014, thereby changing BA metabolism, linoleic acid metabolism, and other related pathways, as well as enhancing insulin sensitivity and improving glucose and lipid metabolism.

12.
Front Genet ; 14: 1077126, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923798

RESUMO

Objective: BOLA2B is a recently discovered protein-coding gene. Here, pan-cancer analysis was conducted to determine the expression patterns of BOLA2B and its impact on immune response, gene mutation, and possible molecular biological mechanisms in different tumors, together with investigating its potential usefulness for cancer prognosis. Methods: Data on BOLA2B expression and mutations were downloaded from TCGA and GTEx databases. Clinical survival data from TCGA were used to analyze the prognostic value of BOLA2B. TIMER and ESTIMATE algorithms were used to assess correlations between BOLA2B and tumor-infiltrating immune cells, immune cytokines, and immune scores. Results: BOLA2B was found to be highly expressed at both mRNA and protein levels in multiple tumors, where it was associated with worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in all cancers apart from ovarian cancer. BOLA2B was also found to be positively correlated with copy number variation (CNV), and mutations in TP53, TTN, and MUC16 were found to influence BOLA2B expression. Post-transcriptional modifications, including m5C, m1A, and m6A, were observed to regulate BOLA2B expression in all cancers. Functional analysis showed that BOLA2B was enriched in pathways associated with iron-sulfur cluster formation, mTOR-mediated autophagy, and cell cycle inhibition. Decreased BOLA2B expression induced the proliferation of breast cancer cells and G2/M cell cycle arrest. Conclusion: BOLA2B was found to be highly expressed in malignant tumors and could be used as a biomarker of poor prognosis in multiple cancers. Further investigation into BOLA2B's role and molecular functions in cancer would provide new insights for cancer diagnosis and treatment.

13.
Front Pharmacol ; 14: 1096379, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817117

RESUMO

Dendrophthoe falcata (L.f.) Ettingsh. (DF) and Dendrophthoe pentandra (L.) Miq. (DP) have been traditionally used for the treatment of various ailments, such as cancer, ulcers, asthma, paralysis, skin diseases, tuberculosis, and menstrual troubles, in the ethnomedicinal systems of India and Indonesia. Currently, the chemical structures of 46 compounds have been elucidated from DF and DP, including flavonoids, triterpenes, tannins, steroids, open-chain aliphatics, benzyl derivates, and cyclic chain derivatives. In vitro assays have revealed their anti-tumor and anti-microbial activities. In vivo studies have unraveled their pharmacological properties against tumors, depression, fertility disorders, inflammatory responses, and so on. Additionally, their weak toxicity to rats and brine shrimp, as well as their promising applications for pharmaceutical preparations and combined medication, were also revealed. Herein, we not only recapitulated traditional medical uses, phytochemistry, pharmacology, toxicity, and applications of DF and DP but also discussed current research limitations and future perspectives, which are instructive for those interested in them and are committed to advancing parasitic plants to the Frontier of phytomedicine. We highlighted that DF and DP will become promising medical plants rather than being discarded as notorious pests, provided that more and deeper research is undertaken.

14.
Neoplasma ; 70(1): 71-81, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36620876

RESUMO

Breast cancer is one of the leading cancer deaths around the world. Targeted drugs have greatly increased the survival rate of breast cancer patients in recent years. But in some patients, the current regimen is still ineffective. Therefore, more therapeutic targets for treating breast cancer are demanding. The core heterochromatin-related genes of breast cancer were identified by utilizing prognostic survival analysis and multivariate Cox hazard proportional regression analysis. Both breast cancer and adjacent normal tissue were collected and analyzed with western blot and immunohistochemistry. Colony formation assay, CCK-8 assay, and EdU assay were used to measure the effect of CBX3 on breast cancer cell growth, wound-healing assay and Transwell assay were used to analyze the effect of CBX3 on breast cancer cell migration and invasion. Flow cytometry assay and western blot were used to study the molecular mechanism of CBX3 in breast cancer. High expression of heterochromatin-related proteins CBX3, H2AFY, and SULF1 showed a poor prognosis in patients in both TCGA dataset and GEO datasets. Western blot demonstrated that the expression level of CBX3 was significantly higher in breast cancer than that in adjacent normal tissues. Colony formation assay, CCK-8 assay, and EdU assay showed that the knockdown of CBX3 could significantly inhibit breast cancer cell growth, and the overexpression of CBX3 could promote the growth of breast cancer cells. Transwell assay and wound healing assay showed that knockdown of CBX3 inhibited breast cancer cell migration and invasion, and the overexpression of CBX3 promoted breast cancer cell migration and invasion. Western blot showed that CBX3 might promote breast cancer cell proliferation, invasion, and migration in breast cancer by modulating the ERK1/2 signaling pathway and epithelial-mesenchymal transition (EMT)-related genes. CBX3 was a biomarker of poor prognosis in breast cancer patients. CBX3 promoted the proliferation of breast cancer cells through the ERK signaling pathway, and migration and invasion of breast cancer cells through EMT-related genes. The CBX3/p-ERK1/2 signaling axis might provide a new therapeutic method against breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Heterocromatina , Linhagem Celular Tumoral , Movimento Celular/genética , Prognóstico , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Cromossômicas não Histona/genética
15.
J Pharm Pharmacol ; 75(3): 328-362, 2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36632823

RESUMO

OBJECTIVES: Solanum lyratum Thunb (SLT) is a perennial plant of the Solanaceae family, and is extensively used in the clinical practice of traditional Chinese medicine. Malaria, oedema, gonorrhoea, cancer, wind and fever, jaundiced hepatitis, cholecystitis and rheumatoid arthritis are among the diseases that it is used to treat. To offer a foundation for further development and usage of SLT, the pieces of literature about the chemical composition and pharmacological action of SLT were reviewed and analysed. KEY FINDINGS: The chemical constituents of SLT mainly included steroids, alkaloids, flavonoids, terpenoids, anthraquinones, phenylpropanoids and others. Pharmacological action mainly contains anti-tumour, antibacterial, anti-inflammatory, anti-oxidation and other pharmacological actions, among them, the anti-tumour effect is particularly outstanding. SUMMARY: At present, studies on the pharmacological effects of SLT mainly focus on alkaloids and steroidal saponins. In the follow-up studies, studies on the pharmacological activities of other chemical components in SLT, such as flavonoids and terpenoids, should be strengthened. It has the potential to pave the way for more research and development of novel SLT medicines.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias , Solanum , Humanos , Solanum/química , Extratos Vegetais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias/tratamento farmacológico , Flavonoides/uso terapêutico , Terpenos/uso terapêutico
16.
Bioact Mater ; 19: 360-375, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35574051

RESUMO

The high demand for rapid wound healing has spurred the development of multifunctional and smart bioadhesives with strong bioadhesion, antibacterial effect, real-time sensing, wireless communication, and on-demand treatment capabilities. Bioadhesives with bio-inspired structures and chemicals have shown unprecedented adhesion strengths, as well as tunable optical, electrical, and bio-dissolvable properties. Accelerated wound healing has been achieved via directly released antibacterial and growth factors, material or drug-induced host immune responses, and delivery of curative cells. Most recently, the integration of biosensing and treatment modules with wireless units in a closed-loop system yielded smart bioadhesives, allowing real-time sensing of the physiological conditions (e.g., pH, temperature, uric acid, glucose, and cytokine) with iterative feedback for drastically enhanced, stage-specific wound healing by triggering drug delivery and treatment to avoid infection or prolonged inflammation. Despite rapid advances in the burgeoning field, challenges still exist in the design and fabrication of integrated systems, particularly for chronic wounds, presenting significant opportunities for the future development of next-generation smart materials and systems.

17.
Front Oncol ; 12: 1030571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457503

RESUMO

Breast cancer patients' outcomes have improved dramatically in recent years, but relapses and poor prognosis remain common due to its aggressiveness and heterogeneity. The development of reliable biomarkers is still needed for predicting prognosis and treatment effectiveness. Recently, a growing body of research suggests that pseudouridine synthases contribute to the development of many cancers, but their contribution to breast cancer remains largely unknown. Using an integrative analysis, we selected pseudouridine synthase1(PUS1) as the candidate biomarker. A tissue microarray of 131 breast cancer patients was then utilized to determine the clinical significance and prognostic value of PUS1. RNA sequencing analysis was conducted to identify downstream genes that differ between control and PUS1 knockdown cells. The effect of PUS1 on phenotypes of cells was assessed using cell proliferation, colony formation, and transwell invasion assays. We found that breast tumors overexpressed PUS1 compared with paired normal tissues. PUS1 expression was positively correlated with triple-negative breast cancer (TNBC) status (P= 0.020) and tumor grade (P <0.0001), but not with age (P= 0.736), tumor size (P= 0.608), lymph node (P= 0.742), oestrogen receptor (ER) (P= 0.162), progesterone receptor (PR) (P= 0.901), human epidermal growth factor receptor 2 (HER2) (P= 0.608) or tumor stage (P= 0.411). Comparatively, patients with high PUS1 levels had shorter overall survival time (P=0.0001) and relapse-free survival time (P = 0.0093). A univariate and multivariate survival analysis suggested that the overall survival of patients was independently influenced by the PUS1 score (Univariate Cox P <0.0001, HR=5.176, 95% CI =2.420-11.07; Multivariate Cox P = 0.001, HR = 5.291, 95% CI =1.893-14.78). RNA sequencing data revealed the PUS1 knockdown significantly affects a series of cancer related biological process such as regulation of cell proliferation and cell migration, as well as KEGG pathways including Mitophagy and PI3K-Akt signaling. In vitro, knockdown of PUS1 significantly suppressed the proliferation and colony formation abilities of MDA-MB-231 cells and BT-549 cells. Additionally, the ability of tumor cells to invade was remarkably attenuated in low PUS1 expression groups compared with the corresponding control groups. Our results suggested that PUS1 is a novel biomarker that predicts poor outcomes in patients with breast cancer and may prove to be a promising treatment target.

18.
Comput Math Methods Med ; 2022: 9841070, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439954

RESUMO

[This corrects the article DOI: 10.1155/2022/8660752.].

19.
Mar Pollut Bull ; 184: 114195, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36208552

RESUMO

Horseshoe crabs (HSCs) are a group of ancient chelicerates with great ecological and biomedical importance. Food poisonings caused by the consumption of Asian HSCs have significant impacts on public health and safety. This study measured tetrodotoxin (TTX) concentrations in two HSC species across various life stages in May 2020 from the northern Beibu Gulf, their most important spawning and nursery habitats in China. The average TTX contents in both Carcinoscorpius rotundicauda and Tachypleus tridentatus ranged 6.2-8.0 µg/kg and 3.8-8.4 µg/kg, respectively. While sampling location, growth and molt stages have little influence on TTX distribution in both species, significantly higher levels of TTX were detected in hemolymph, but lower in pooled tissues of early-instar juvenile T. tridentatus. These results provide a regional view of TTX occurrence and distribution in HSCs during their spawning season, which are critical for future studies to enhance understanding of TTX dynamics and formation in HSCs.


Assuntos
Hemolinfa , Caranguejos Ferradura , Animais , Tetrodotoxina , China , Ecossistema
20.
Nat Prod Res ; : 1-9, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36255124

RESUMO

A phytochemical investigation of Bidens procera L.C.Xu ex X.W.Zheng afforded two novel polyacetylenes, tridecane-2E-monoene-4,6,8-triyntylen-1,13-diol-12-O-ß-glucoside (1) and tetradecane-2E,8E-diene-4,6-diyne-1,14-diol-13-O-ß-glucoside (2), together with ten known compounds (3 - 12). Their chemical structures were elucidated by NMR and MS spectrums as well as the comparison of the published data. Furthermore, the chemotaxonomy of the yielded compounds was also discussed.

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