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1.
Int J Med Sci ; 21(7): 1213-1226, 2024.
Article in English | MEDLINE | ID: mdl-38818465

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC), a gastrointestinal cancer, is associated with poor prognosis. Prognostic models predict the likelihood of disease progression and are important for the management of patients with ESCC. The objective of this study was to develop a prognostic model for ESCC using bioinformatics analysis. Methods: Two transcriptome microarray Gene Expression Omnibus ESCC datasets (GSE53624 and GSE53622) were analyzed using bioinformatics methods. Differentially expressed genes (DEGs) were identified using the R package limma, and genes associated with survival outcomes in both datasets were identified by Kaplan-Meier analysis. Genes with diagnostic or prognostic value were selected for further analysis, and hazard ratios and their relationship with pathological TNM (pTNM) staging were investigated using univariate and multivariate Cox analysis. After selecting the independent factors from pTNM staging, Cox analysis and nomogram plotting were performed. The ability of the model to stratify risk and predict survival was evaluated and compared with the pTNM staging system to determine its potential clinical value. Key genes were analyzed by immunohistochemistry and RT-PCR. Results: Four candidate genes (B3GNT3, MACC1, NELL2, and USH1G) with prognostic value were identified from the two transcriptome microarray datasets. Age, pTNM stage, and B3GNT3, MACC1, and NELL2 were identified as independent factors associated with survival in the multivariate Cox analysis and used to establish a prognostic model. The model demonstrated significantly higher accuracy in predicting 3-year survival than the pTNM staging system and was useful for further risk stratification in patients with ESCC. B3GNT3 was significantly downregulated in ESCC tumor tissues and negatively associated with lymph node metastasis. Bioinformatics analysis indicated that B3GNT3 may play a role in immune regulation by regulating M2 macrophages. Conclusion: This study developed a new prognostic model for ESCC and identified B3GNT3 as a potential biomarker negatively associated with lymph node metastasis, which warrants further validation.


Subject(s)
Biomarkers, Tumor , Computational Biology , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/mortality , Prognosis , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Male , Female , Middle Aged , Biomarkers, Tumor/genetics , Neoplasm Staging , Transcriptome/genetics , Kaplan-Meier Estimate , Aged , Nomograms
2.
PeerJ ; 12: e17272, 2024.
Article in English | MEDLINE | ID: mdl-38699187

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC) is highly prevalent and has a high mortality rate. Traditional diagnostic methods, such as imaging examinations and blood tumor marker tests, are not effective in accurately diagnosing ESCC due to their low sensitivity and specificity. Esophageal endoscopic biopsy, which is considered as the gold standard, is not suitable for screening due to its invasiveness and high cost. Therefore, this study aimed to develop a convenient and low-cost diagnostic method for ESCC using plasma-based lipidomics analysis combined with machine learning (ML) algorithms. Methods: Plasma samples from a total of 40 ESCC patients and 31 healthy controls were used for lipidomics study. Untargeted lipidomics analysis was conducted through liquid chromatography-mass spectrometry (LC-MS) analysis. Differentially expressed lipid features were filtered based on multivariate and univariate analysis, and lipid annotation was performed using MS-DIAL software. Results: A total of 99 differential lipids were identified, with 15 up-regulated lipids and 84 down-regulated lipids, suggesting their potential as diagnostic targets for ESCC. In the single-lipid plasma-based diagnostic model, nine specific lipids (FA 15:4, FA 27:1, FA 28:7, FA 28:0, FA 36:0, FA 39:0, FA 42:0, FA 44:0, and DG 37:7) exhibited excellent diagnostic performance, with an area under the curve (AUC) exceeding 0.99. Furthermore, multiple lipid-based ML models also demonstrated comparable diagnostic ability for ESCC. These findings indicate plasma lipids as a promising diagnostic approach for ESCC.


Subject(s)
Biomarkers, Tumor , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Lipidomics , Humans , Esophageal Squamous Cell Carcinoma/blood , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Neoplasms/blood , Esophageal Neoplasms/diagnosis , Male , Lipidomics/methods , Female , Biomarkers, Tumor/blood , Retrospective Studies , Middle Aged , Aged , Machine Learning , Lipids/blood , Chromatography, Liquid , Case-Control Studies
3.
Burns Trauma ; 12: tkae015, 2024.
Article in English | MEDLINE | ID: mdl-38752203

ABSTRACT

Background: Chronic skin wounds are a leading cause of hospital admissions and reduced life expectancy among older people and individuals with diabetes. Delayed wound healing is often attributed to a series of cellular abnormalities. Matrine, a well-studied component found in Sophora flavescens, is recognized for its anti-inflammatory effects. However, its impact on wound healing still remains uncertain. This study aims to explore the potential of matrine in promoting wound healing. Methods: In this study, we utilized gradient extrusion to produce fibroblast-derived exosome-mimetic vesicles as carriers for matrine (MHEM). MHEM were characterized using transmission electron microscopy and dynamic light scattering analysis. The therapeutic effect of MHEM in wound healing was explored in vitro and in vivo. Results: Both matrine and MHEM enhanced the cellular activity as well as the migration of fibroblasts and keratinocytes. The potent anti-inflammatory effect of matrine diluted the inflammatory response in the vicinity of wounds. Furthermore, MHEM worked together to promote angiogenesis and the expression of transforming growth factor ß and collagen I. MHEM contained growth factors of fibroblasts that regulated the functions of fibroblasts, keratinocytes and monocytes, which synergistically promoted wound healing with the anti-inflammatory effect of matrine. Conclusions: MHEM showed enhanced therapeutic efficacy in the inflammatory microenvironment, for new tissue formation and angiogenesis of wound healing.

4.
Physiol Plant ; 176(3): e14330, 2024.
Article in English | MEDLINE | ID: mdl-38698648

ABSTRACT

Wall-associated kinases (WAKs) have been determined to recognize pathogenic signals and initiate plant immune responses. However, the roles of the family members in host resistance against Valsa canker, a serious fungal disease of apples and pears, are largely unknown. Here, we identified MbWAK1 in Malus baccata, a resistant germplasm differentially expressed during infection by Valsa mali (Vm). Over-expression of MbWAK1 enhanced the Valsa canker resistance of apple and pear fruits and 'Duli-G03' (Pyrus betulifolia) suspension cells. A large number of phloem, cell wall, and lipid metabolic process-related genes were differentially expressed in overexpressed suspension cell lines in response to Valsa pyri (Vp) signals. Among these, the expression of xyloglucan endotransglucosylase/hydrolase (XTH) gene PbeXTH1 and sieve element occlusion B-like (SEOB) gene PbeSEOB1 were significantly inhibited. Transient expression of PbeXTH1 or PbeSEOB1 compromised the expressional induction of MbWAK1 and the resistance contributed by MbWAK1. In addition, PbeXTH1 and PbeSEOB1 suppressed the immune response induced by MbWAK1. Our results enriched the molecular mechanisms for MbWAK1 against Valsa canker and resistant breeding.


Subject(s)
Disease Resistance , Gene Expression Regulation, Plant , Malus , Plant Diseases , Plant Proteins , Pyrus , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Diseases/immunology , Disease Resistance/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Pyrus/genetics , Pyrus/microbiology , Malus/genetics , Malus/microbiology , Malus/immunology , Malus/enzymology , Cell Wall/metabolism
5.
ACS Appl Bio Mater ; 7(5): 2899-2910, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38607995

ABSTRACT

Acne vulgaris is one of the most prevalent skin disorders; it affects up to 85% of adolescents and often persists into adulthood. Topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides an alternative treatment for acne; however, its efficacy is greatly undermined by the limited skin permeability of ALA. Herein, biocompatible ionic liquids (ILs) based on aliphatic acid/choline were employed to enhance the dermal delivery of ALA, thereby improving the efficacy of PDT. In addition to the one-step delivery of ALA by utilizing ILs as carriers, a two-step strategy of pretreating the skin with blank ILs, followed by the administration of free ALA, was employed to test the IL-facilitated dermal delivery of ALA in vitro. The cumulative permeation of ALA through the excised rat skin after IL pretreatment was significantly greater than that in the untreated group, the 20% dimethyl sulfoxide (DMSO) penetration enhancer group, and the one-step group. The penetration efficiency was influenced by formulation and treatment factors, including the type of IL, pretreatment duration, water content in the ILs, and concentration of ALA. In rats, IL pretreatment facilitated faster, greater, and deeper ALA-induced protoporphyrin IX (PpIX) accumulation. Moreover, the IL pretreatment regimen significantly improved the efficacy of ALA-based PDT against acne vulgaris in a rat ear model. The model IL choline citrate ([Ch]3[Cit]1) had a moderate effect on the skin barrier. Trans-epidermal water loss could be recovered 1 h after IL treatment, but no irritation to the rat skin was detected after 7 days of consecutive treatment. It was concluded that biocompatible IL pretreatment enhances the penetration of ALA and thus facilitates the transformation of PpIX and improves the efficacy of PDT against acne vulgaris.


Subject(s)
Acne Vulgaris , Aminolevulinic Acid , Ionic Liquids , Photochemotherapy , Photosensitizing Agents , Skin , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/chemistry , Animals , Ionic Liquids/chemistry , Ionic Liquids/pharmacology , Rats , Acne Vulgaris/drug therapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Skin/metabolism , Skin/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Materials Testing , Particle Size , Rats, Sprague-Dawley , Skin Absorption/drug effects , Male
6.
J Adv Res ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38460775

ABSTRACT

BACKGROUND: The promotion of epidermal barrier dysfunction is attributed to abnormalities in the lipid-microbiome positive feedback loop which significantly influences the imbalance of the epithelial immune microenvironment (EIME) in atopic dermatitis (AD). This imbalance encompasses impaired lamellar membrane integrity, heightened exposure to epidermal pathogens, and the regulation of innate and adaptive immunity. The lipid-microbiome loop is substantially influenced by intense adaptive immunity which is triggered by abnormal loop activity and affects the loop's integrity through the induction of atypical lipid composition and responses to dysregulated epidermal microbes. Immune responses participate in lipid abnormalities within the EIME by downregulating barrier gene expression and are further cascade-amplified by microbial dysregulation which is instigated by barrier impairment. AIM OF REVIEW: This review examines the relationship between abnormal lipid composition, microbiome disturbances, and immune responses in AD while progressively substantiating the crosstalk mechanism among these factors. Based on this analysis, the "lipid-microbiome" positive feedback loop, regulated by immune responses, is proposed. KEY SCIENTIFIC CONCEPTS OF REVIEW: The review delves into the impact of adaptive immune responses that regulate the EIME, driving AD, and investigates potential mechanisms by which lipid supplementation and probiotics may alleviate AD through the up-regulation of the epidermal barrier and modulation of immune signaling. This exploration offers support for targeting the EIME to attenuate AD.

7.
Int J Nanomedicine ; 19: 2057-2070, 2024.
Article in English | MEDLINE | ID: mdl-38482522

ABSTRACT

Purpose: Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). Methods: TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs). Results: Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. Conclusion: The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.


Subject(s)
Carcinoma, Squamous Cell , Nanoparticles , Organometallic Compounds , Phenanthrolines , Photochemotherapy , Skin Neoplasms , Humans , Carcinoma, Squamous Cell/drug therapy , Skin Neoplasms/drug therapy , Tirapazamine/pharmacology , Hypoxia/drug therapy , Cell Line, Tumor , Photosensitizing Agents , Tumor Microenvironment
8.
J Control Release ; 368: 372-396, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38408567

ABSTRACT

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) is a highly specific anti-tumor immunotherapy that has shown promise in the treatment of hematological malignancies. However, there has been a slow progress toward the treatment of solid tumors owing to the complex tumor microenvironment that affects the localization and killing ability of the CAR cells. Solid tumors with a strong immunosuppressive microenvironment and complex vascular system are unaffected by CAR cell infiltration and attack. To improve their efficacy toward solid tumors, CAR cells have been modified and upgraded by "decorating" and "pruning". This review focuses on the structure and function of CARs, the immune cells that can be engineered by CARs and the transformation strategies to overcome solid tumors, with a view to broadening ideas for the better application of CAR cell therapy for the treatment of solid tumors.


Subject(s)
Neoplasms , Receptors, Chimeric Antigen , Humans , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , T-Lymphocytes , Neoplasms/pathology , Cell- and Tissue-Based Therapy , Tumor Microenvironment
9.
Biofilm ; 7: 100175, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38298832

ABSTRACT

Staphylococcus aureus can readily form biofilm which enhances the drug-resistance, resulting in life-threatening infections involving different organs. Biofilm formation occurs due to a series of developmental events including bacterial adhesion, aggregation, biofilm maturation, and dispersion, which are controlled by multiple regulatory systems. Rapidly increasing research and development outcomes on natural products targeting S. aureus biofilm formation and/or regulation led to an emergent application of active phytochemicals and combinations. This review aimed at providing an in-depth understanding of biofilm formation and regulation mechanisms for S. aureus, outlining the most important antibiofilm strategies and potential targets of natural products, and summarizing the latest progress in combating S. aureus biofilm with plant-derived natural products. These findings provided further evidence for novel antibiofilm drugs research and clinical therapies.

10.
J Adv Res ; 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38242529

ABSTRACT

BACKGROUND: The incidence of skin cancer is currently increasing, and conventional treatment options inadequately address the demands of disease management. Fortunately, the recent rapid advancement of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has ushered in a new era for numerous cancer patients. However, the efficacy of immunotherapy remains suboptimal due to the impact of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs), a major component of the TME, play crucial roles in tumor invasion, metastasis, angiogenesis, and immune evasion, significantly impacting tumor development. Consequently, TAMs have gained considerable attention in recent years, and their roles have been extensively studied in various tumors. However, the specific roles of TAMs and their regulatory mechanisms in skin cancer remain unclear. AIM OF REVIEW: This paper aims to elucidate the origin and classification of TAMs, investigate the interactions between TAMs and various immune cells, comprehensively understand the precise mechanisms by which TAMs contribute to the pathogenesis of different types of skin cancer, and finally discuss current strategies for targeting TAMs in the treatment of skin cancer. KEY SCIENTIFIC CONCEPTS OF OVERVIEW: With a specific emphasis on the interrelationship between TAMs and skin cancer, this paper posits that therapeutic modalities centered on TAMs hold promise in augmenting and harmonizing with prevailing clinical interventions for skin cancer, thereby charting a novel trajectory for advancing the landscape of immunotherapeutic approaches for skin cancer.

11.
Biomed Pharmacother ; 171: 116167, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38262152

ABSTRACT

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The Janus kinase (JAK) has been identified as a target in AD, as it regulates specific inflammatory genes and adaptive immune responses. However, the efficacy of topically applied JAK inhibitors in AD is limited due to the unique structure of skin. We synthesized JAK1/JAK2 degraders (JAPT) based on protein degradation targeting chimeras (PROTACs) and prepared them into topical preparations. JAPT exploited the E3 ligase to mediate ubiquitination and degradation of JAK1/JAK2, offering a promising AD therapeutic approach with low frequency and dosage. In vitro investigations demonstrated that JAPT effectively inhibited the release of pro-inflammatory cytokines and reduced inflammation by promoting the degradation of JAK. In vivo studies further confirmed the efficacy of JAPT in degrading JAK1/JAK2, leading to a significant suppression of type I, II, and III adaptive immunity. Additionally, JAPT demonstrated a remarkable reduction in AD severity, as evidenced by improved skin lesion clearance and AD severity scores (SCORAD). Our study revealed the therapeutic potential of JAPT, surpassing conventional JAK inhibitors in the treatment of AD, which suggested that JAPT could be a promising topically applied anti-AD drug targeting the JAK-STAT signaling pathway.


Subject(s)
Dermatitis, Atopic , Janus Kinase Inhibitors , Skin Diseases , Humans , Dermatitis, Atopic/drug therapy , Janus Kinase Inhibitors/therapeutic use , Skin , Inflammation/drug therapy , Janus Kinases/metabolism , Skin Diseases/metabolism , Janus Kinase 1/metabolism , Janus Kinase 2/metabolism
12.
J Control Release ; 365: 818-832, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38070601

ABSTRACT

Psoriasis is a chronic inflammatory skin disease characterised by the abnormal proliferation of keratinocytes and dysregulation of immune cells. The upregulation of fibroblast growth factor-inducible molecule 14 (Fn14) in psoriatic lesions has been linked to the development of psoriasis. Transdermal delivery of siRNAs for Fn14 inhibition is challenging. In this study, we developed a composite ionic liquid (CIL) for the transdermal delivery of Fn14 siRNA (siFn14) into keratinocytes, with the aim of modulating the inflammatory response associated with psoriasis. The results showed that CIL-siFn14 effectively suppressed Fn14 expression, resulting in a reduction in both the Psoriasis Area and Severity Index (PASI) score and skin thickness. Furthermore, CIL-siFn14 effectively inhibited the abnormal proliferation of keratinocytes, decreased the production of inflammatory factors associated with psoriasis, prevented the over-activation of CD4+ and CD8+ T cells, and restored the balance of Type 1 T helper (Th1), Th2, Th17 and Treg cells. In conclusion, our findings unveiled the critical role of Fn14 in the pathogenesis of psoriasis and demonstrated the potential of CIL-siFn14 as a novel and effective topical treatment for its management.


Subject(s)
Ionic Liquids , Psoriasis , Skin Diseases , Humans , RNA, Small Interfering/metabolism , CD8-Positive T-Lymphocytes/pathology , Psoriasis/drug therapy , Psoriasis/genetics , Skin Diseases/metabolism , Skin/metabolism , Keratinocytes/metabolism
13.
J Sep Sci ; 47(1): e2300577, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38109069

ABSTRACT

Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids from the crude extract of Corydalis decumbens. The experiment was performed with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (5:5:3:7, v/v/v/v) where triethylamine (10 mM) was added to the stationary phase and hydrochloric acid (10 mM) to the mobile phase. From 1.6 g of the crude extract, 43 mg protopine, 189 mg (+)-egenine, and 158 mg tetrahydropalmatine were obtained with a purity of 98.2%, 94.6%, and 96.7%, respectively. Tetrahydropalmatine showed an interesting anticomplement effect with CH50 0.11 and AP50 0.25 mg/mL, respectively. In a mechanistic study, tetrahydropalmatine interacted with C1, C3, C4, and C5 components in the complement activation cascade.


Subject(s)
Alkaloids , Complement Inactivator Proteins , Corydalis , Corydalis/chemistry , Countercurrent Distribution/methods , Alkaloids/pharmacology , Alkaloids/chemistry , Solvents/chemistry , Hydrogen-Ion Concentration , Complex Mixtures , Chromatography, High Pressure Liquid
14.
Anal Chem ; 96(1): 401-408, 2024 01 09.
Article in English | MEDLINE | ID: mdl-38134291

ABSTRACT

Fluorescent lateral flow immunoassay (LFA) systems are versatile tools for sensitive and quantitative detection of disease markers at the point of care. However, traditional fluorescent nanoparticle-based lateral flow immunoassays are not visible under room light, necessitate an additional fluorescent reader, and lack flexibility for different application scenarios. Herein, we report a dual-readout LFA system for the rapid and sensitive detection of C-reactive protein (CRP) in clinical samples. The system relied on the aggregation-induced emission nanobeads (AIENBs) encapsulated with red AIE luminogen, which possesses both highly fluorescent and colorimetric properties. The AIENB-based LFA in the naked-eye mode was able to qualitatively detect CRP levels as low as 8.0 mg/L, while in the fluorescent mode, it was able to quantitatively measure high-sensitivity CRP (hs-CRP) with a limit of detection of 0.16 mg/L. The AIENB-based LFA system also showed a good correlation with the clinically used immunoturbidimetric method for CRP and hs-CRP detection in human plasma. This dual-modal AIENB-based LFA system offers the convenience of colorimetric testing and highly sensitive and quantitative detection of disease biomarkers and medical diagnostics in various scenarios.


Subject(s)
C-Reactive Protein , Nanoparticles , Humans , Point-of-Care Systems , Immunoassay/methods , Limit of Detection , Coloring Agents
15.
Int J Nanomedicine ; 18: 7149-7172, 2023.
Article in English | MEDLINE | ID: mdl-38059000

ABSTRACT

Melanoma, a highly aggressive skin tumor, exhibits notable features including heterogeneity, a high mutational load, and innate immune escape. Despite advancements in melanoma treatment, current immunotherapies fail to fully exploit the immune system's maximum potential. Activating immunogenic cell death (ICD) holds promise in enhancing tumor cell immunogenicity, stimulating immune amplification response, improving drug sensitivity, and eliminating tumors. Nanotechnology-enabled ICD has emerged as a compelling therapeutic strategy for augmenting cancer immunotherapy. Nanoparticles possess versatile attributes, such as prolonged blood circulation, stability, and tumor-targeting capabilities, rendering them ideal for drug delivery. In this review, we elucidate the mechanisms underlying ICD induction and associated therapeutic strategies. Additionally, we provide a concise overview of the immune stress response associated with ICD and explore the potential synergistic benefits of combining ICD induction methods with the utilization of nanocarriers.


Subject(s)
Melanoma , Neoplasms , Skin Neoplasms , Humans , Melanoma/therapy , Melanoma/pathology , Immunogenic Cell Death , Neoplasms/pathology , Immunotherapy , Cell Death , Skin Neoplasms/therapy , Tumor Microenvironment
16.
Acta Pharm Sin B ; 13(11): 4391-4416, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37969727

ABSTRACT

Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment, nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, and controlling various diseases and are attracting an unfathomable amount of input of research resources. Against the backdrop of an exponentially growing number of publications, it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines. Herein, this review elaborates on the development trends of nanomedicines, emerging nanocarriers, in vivo fate and safety of nanomedicines, and their extensive applications. Moreover, the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed. The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.

17.
Int J Pharm ; 648: 123623, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37989402

ABSTRACT

The prognosis of pancreatic cancer (PCa) is extremely poor because of its resistance to conventional therapies. Many previous studies have demonstrated that triptolide (TPL) has a potent tumoricidal activity on PCa. However, the clinical application of TPL in tumor therapy has been greatly limited by its poor aqueous solubility, short half-time, high toxicity and inefficient delivery. Here, through the engineering of prodrug technology combined with the nanodrug-delivery system (NDDS) strategy, we modified the main active site of TPL C14-OH by esterification reaction to obtain a highly lipophilic prodrug, and then encapsulated the drug in a phospholipid bilayer in liposomal vehicles through the thin-film hydration method for efficient delivery. A delivery system based on TPL lignocerate liposomes (TPL-LA-lip) for drug loading for targeted therapy against PCa was established. Our results showed that TPL-LA demonstrates exceptional compatibility with the phospholipid layer of liposomes, thereby enhancing drug retention in liposomal vehicle and improving tumor targeting and cellular uptake. Moreover, The system of TPL-LA-lip exhibited a sustained drug release profile in vitro, and intravenous administration significantly impedes tumor progression while reducing the toxicity of TPL in the PCa mouse model. These results demonstrated that the prodrug-loaded liposomes could significantly reduce the toxicity of TPL and enhance the biosafety. Overall, this prodrug approach is a simple and effective method to transform the highly toxic TPL into a safe and efficacious nanomedicine with excellent in vivo tolerability for PCa treatment.


Subject(s)
Pancreatic Neoplasms , Prodrugs , Mice , Animals , Liposomes/chemistry , Prodrugs/chemistry , Cell Line, Tumor , Pancreatic Neoplasms/drug therapy , Phospholipids , Pancreatic Neoplasms
18.
Acta Pharm Sin B ; 13(10): 4105-4126, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37799378

ABSTRACT

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

19.
J Adv Res ; 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37743016

ABSTRACT

BACKGROUND: There has been widespread concern about the high cancer mortality rate and the shortcomings of conventional cancer treatments. Immunotherapy is a novel oncology therapy with high efficiency and low side effects, which is a revolutionary direction for clinical oncology treatment. However, its clinical effectiveness is uneven. Based on the redefinition and reclassification of programmed cell death (PCD) (divided into necroptosis, ferroptosis, pyroptosis, and autophagy), the role of nanomedicine-induced PCD in cancer therapy has also received significant attention. Clinical and preclinical studies have begun to combine PCD with immunotherapy. AIM OF REVIEW: In this article, we present recent research in tumor immunotherapy, provide an overview of how nanomedicine-induced PCD is involved in tumor therapy, and review how nanomedicine-induced PCD can improve the limitations of immunotherapy to enhance tumor immunotherapy. The future development of nanomedicine-mediated PCD tumor therapy and tumor immunotherapy is also proposed Key scientific concepts of overview Nanomedicine-induced PCD is a prospective method of tumor immunotherapy. Nanomedicines increase tumor site penetration and targeting ability, and nanomedicine-mediated PCD activation can stimulate powerful anti-tumor immune effects, which has a good contribution to immunotherapy of tumors.

20.
PeerJ ; 11: e15895, 2023.
Article in English | MEDLINE | ID: mdl-37667750

ABSTRACT

Background: The challenges in cancer diagnosis underline the need for continued research and development of new diagnostic tools and methods. This study aims to explore an effective, noninvasive, and convenient diagnostic tool using urine based near-infrared spectroscopy (NIRS) analysis combined with machine learning algorithm. Methods: Urine samples were collected from a total of 327 participants, including 181 cancer cases and 146 healthy controls. These participants were randomly spit into train set (n = 218) and test set (n = 109). NIRS analysis (4,000 ∼10,000 cm-1) was performed for each sample in both train and test sets. Five pretreatment methods, including Savitzky-Golay (SG) smoothing, multiplicative scatter correction (MSC), baseline removal (BSL) with fitting polynomials to be used as baselines, the first derivative (DERIV1), and the second derivative (DERIV2), and combination with "scaling" and "center", were investigated. Then partial least-squares (PLS) and linear support-vector machine (SVM) classification models were established, and prediction performance was evaluated in test set. Results: NIRS had greatly overlapping in peaks, and PCA analysis failed in separation between cancers and healthy controls. In modeling with urine based NIRS data, PLS model showed its highest prediction accuracy of 0.780, with DERIV2, "scaling" and "center" pretreatment, while linear SVM displayed its best prediction accuracy of 0.844, with raw NIRS. With optimization in SVM, the prediction accuracy could improve to 0.862, when the top 262 features were involved as variables. Discussion: This pilot study combining urine based NIRS analysis and machine learning is effective and convenient that might facilitate in cancer diagnosis, encouraging further evaluation with a large-size multi-center study.


Subject(s)
Body Fluids , Neoplasms , Humans , Algorithms , Neoplasms/diagnosis , Pilot Projects , Spectroscopy, Near-Infrared
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