T-cell subsets and cytokines are indicative of neoadjuvant chemoimmunotherapy responses in NSCLC.

PURPOSE: Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. METHODS: Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry. Cytokine profiles and function-related gene expression of CD8 + T cells and Tregs were analyzed through flow cytometry and mRNA-seq. Infiltrating T-cell subsets in resected tissues from patients with different pathological responses were analyzed through multiplex immunofluorescence. RESULTS: Forty-two NSCLC patients receiving neoadjuvant chemoimmunotherapy were enrolled and then underwent surgical resection and pathological evaluation. Nineteen patients had pCR (45%), 7 patients had MPR (17%), and 16 patients had non-MPR (38%). In patients with pCR, the frequencies of CD137 + CD8 + T cells (P = 0.0475), PD-1 + Ki-67 + CD8 + T cells (P = 0.0261) and Tregs (P = 0.0317) were significantly different from those of non-pCR patients before treatment. pCR patients usually had low frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs, and their AUCs were higher than that of tissue PD-L1 expression. Neoadjuvant chemoimmunotherapy markedly improved CD8 + T-cell proliferation and activation, especially in pCR patients, as the frequencies of CD137 + CD8 + (P = 0.0136) and Ki-67 + CD8 + (P = 0.0391) T cells were significantly increased. The blood levels of cytokines such as IL-2 (P = 0.0391) and CXCL10 (P = 0.0195) were also significantly increased in the pCR group, which is consistent with the high density of activated cytotoxic T cells at the tumor site (P < 0.0001). CONCLUSION: Neoadjuvant chemoimmunotherapy drives CD8 + T cells toward a proliferative and active profile. The frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs at baseline might predict the response to neoadjuvant chemoimmunotherapy in NSCLC patients. The increase in IL-2 and CXCL10 might reflect the chemotaxis and enrichment of cytotoxic T cells at the tumor site and a better response to neoadjuvant chemoimmunotherapy.

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria.

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

[Application and development of electronic sensing technologies represented by electronic nose in modern traditional Chinese medicine preparations].

Odor is one of the important indicators evaluating the quality of traditional Chinese medicines. Research data has shown that there are increasing methods available for evaluating the odors of traditional Chinese medicines. Compared with conventional odor sensing techniques, electronic noses stand out for their convenience, high speed, and objectivity. The progress in the pharmaceutical technology of traditional Chinese medicines has provided new formulas and dosage forms for the innovative development in this field. The electronic nose with versatility can be customized to be equipped with a variety of cross-sensors, which can well satisfy the needs of the traditional Chinese medicine preparation technology. This study summarizes the characteristics, application status, and representative products of the current electronic nose, and analyzes the application and feasibility of electronic nose in the production of traditional Chinese medicine preparations based on the current status of odor evaluation. This review is expected to provide new methods, techno-logies, and ideas for electronic nose to play its unique role in the whole-process quality control and pharmaceutical process of traditional Chinese medicine preparations.

Soft interface confined DNA walker for sensitive and specific detection of SARS-CoV-2 variants.

Nucleic acid detection is conducive to preventing the spread of COVID-19 pandemic. In this work, we successfully designed a soft interface confined DNA walker by anchoring hairpin reporter probes on cell membranes for the detection of SARS-CoV-2 variants. In the presence of target RNA, the cyclic self-assembly reaction occurred between hairpin probes H1 and H2, and the continuous walking of target RNA on cell membranes led to the gradual amplification of fluorescence signal. The enrichment of H1 on membranes and the unique fluidity of membranes promoted the collision efficiency between DNA strands in the reaction process, endowing this method with high sensitivity. In addition, the double-blind test of synthetic RNA in 5% normal human serum demonstrated the good stability and anti-interference in complex environment of this method, which exhibited great potential in clinical diagnostics.

Sijunzi decoction, a classical Chinese herbal formula, improves fatigue symptoms with changes in gut microbiota in chronic fatigue syndrome: A randomized, double-blind, placebo-controlled, multi-center clinical trial.

BACKGROUD: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. PURPOSE: To evaluate the efficacy and safety of SJZD for CFS. STUDY DESIGN: A multi-center, double-blinded, randomized controlled trial. METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect. RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study. CONCLUSION: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD's application. CLINICAL TRIAL REGISTRATION: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).

Recent understanding of the mechanisms of the biological activities of hesperidin and hesperetin and their therapeutic effects on diseases.

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in lemon, sweet orange, bitter orange, clementine. Hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory, antioxidant, antitumor and antibacterial potential. Preclinical studies and clinical trials demonstrated therapeutical effects of hesperidin and its aglycone hesperetin in various diseases, such as bone diseases, cardiovascular diseases, neurological diseases, respiratory diseases, digestive diseases, urinary tract diseases. This review provides a comprehensive overview of the biological activities of hesperidin and hesperetin, their therapeutic potential in various diseases and their associated molecular mechanisms. This article also discusses future considerations for the clinical applications of hesperidin and hesperetin.

A Novel Fault Diagnosis Method for a Power Transformer Based on Multi-Scale Approximate Entropy and Optimized Convolutional Networks.

Dissolved gas analysis (DGA) in transformer oil, which analyzes its gas content, is valuable for promptly detecting potential faults in oil-immersed transformers. Given the limitations of traditional transformer fault diagnostic methods, such as insufficient gas characteristic components and a high misjudgment rate for transformer faults, this study proposes a transformer fault diagnosis model based on multi-scale approximate entropy and optimized convolutional neural networks (CNNs). This study introduces an improved sparrow search algorithm (ISSA) for optimizing CNN parameters, establishing the ISSA-CNN transformer fault diagnosis model. The dissolved gas components in the transformer oil are analyzed, and the multi-scale approximate entropy of the gas content under different fault modes is calculated. The computed entropy values are then used as feature parameters for the ISSA-CNN model to derive diagnostic results. Experimental data analysis demonstrates that multi-scale approximate entropy effectively characterizes the dissolved gas components in the transformer oil, significantly improving the diagnostic efficiency. Comparative analysis with BPNN, ELM, and CNNs validates the effectiveness and superiority of the proposed ISSA-CNN diagnostic model across various evaluation metrics.

Pan-cancer analysis predicts CANT1 as a potential prognostic, immunologic biomarker.

BACKGROUND: CANT1, calcium-activated nucleotidase 1, was reported to be upregulated in certain tumors. However, the function mechanism of CANT1 in pan-cancer is still unclear. METHODS: We utilized the Cancer Genome Atlas Program (TCGA) and UALCAN databases to analyze CANT1 expression at the level of mRNA, protein, and promoter methylation in pan-cancer, and the cBioportal database to study the frequency of gene changes for CANT1. Wilcoxon test was applied to discuss the correlation between CANT1 and clinicopathological features in different tumor types. The prognosis of CANT1 in pan-cancer was discussed by Cox regression. Spearman analysis was applied to discuss the relationship of CANT1 with tumor mutation burden(TMB), microsatellite instability(MSI), immune cell infiltration, and immune checkpoints. The association between CANT1 expression and drug sensitivity for pan-cancer was investigated by the GSCALite database. In addition, we collected 40 cases of lung adenocarcinoma (LUAD) and adjacent normal tissues for immunohistochemical staining and investigated the relationship between CANT1 and clinicopathology and prognosis in LUAD. Finally, the molecular pathways involved in CANT1-related genes in LUAD were analyzed by gene set enrichment analysis(GSEA). RESULTS: The CANT1 mRNA level was significant higher in 14 tumors, and CANT1 protein level was significant higher in 7 tumors compared with normal tissues. CANT1 expression was linked with the T stage, N stage, and pathological stage in some tumors, and overexpression CANT1 was associated with adverse overall survival(OS) and disease-specific survival(DSS) in kidney renal papillary cell carcinoma(KIRP), brain lower grade glioma(LGG), and LUAD. By Spearman correlation analysis, the results showed that CANT1 had a positive correlation with TMB and MSI in bladder urothelial carcinoma(BLCA), breast invasive carcinoma(BRCA), esophageal carcinoma(ESCA), LGG, and sarcoma(SARC). Furthermore, CANT1 was related to immune cell infiltration and immune checkpoints in several cancers. Drug sensitivity analysis suggested that CANT1 was inversely linked with three drugs. Immunohistochemical staining analysis showed that CANT1 expression was higher in LUAD than in normal tissues, and was related to N stage and pathological stage. Survival curves showed that CANT1 overexpression had poor OS and DSS. Time-dependent ROC curves revealed that the 1-year, 5-year, and 10-year OS and DSS in LUAD were above 0.5. CANT1-related genes in LUAD mainly participated in the pathway of dorso ventral axis formation, small cell lung cancer, DNA replication, O-glycan biosynthesis, and cell cycle. CONCLUSION: CANT1 is considered a potential marker for prognosis in several tumors, and a promising target for tumor immunological treatment.

3D Morphological Scanning and Environmental Correlates of Bufo gargarizans in the Yellow River Basin.

Morphology plays a crucial role in understanding the intricacies of biological forms. Traditional morphometric methods, focusing on one- or two-dimensional geometric levels, often fall short of accurately capturing the three-dimensional (3D) structure of organisms. The advent of 3D scanning techniques has revolutionized the study of organismal morphology, enabling comprehensive and accurate measurements. This study employs a 3D structured light scanning system to analyze the morphological variations in the Chinese toad (Bufo gargarizans Cantor, 1842) along the Yellow River Basin. The 3D digital model obtained from the scan was used to calculate various morphological parameters including body surface area, volume, fractal dimensions, and limb size. The research explores geographic variability patterns and identifies environmental drivers affecting the 3D phenotypic variation of B. gargarizans. Results reveal a bimodal pattern of variation in the toad population, with higher elevations exhibiting smaller body sizes, greater appendage proportions, and more complex body structures. Linear regression analyses highlight the influence of elevation and annual mean temperature on the morphological variation of B. gargarizans, with elevation playing a significant role. This study underscores the significance of 3D morphometric analysis in unraveling the intricacies of organismal morphology and understanding the adaptive strategies of species in diverse environments.

Easily applicable predictive score for MPR based on parameters before neoadjuvant chemoimmunotherapy in operable NSCLC: a single-center, ambispective, observational study.

BACKGROUND: Neoadjuvant chemoimmunotherapy (NACI) is promising for resectable non-small cell lung cancer (NSCLC), but predictive biomarkers are still lacking. We aimed to develop a model based on pretreatment parameters to predict major pathological response (MPR) for such an approach. METHODS: We enrolled operable NSCLC treated with NACI between March 2020 and May 2023 and then collected baseline clinical-pathology data and routine laboratory examinations before treatment. The efficacy and safety data of this cohort was reported and variables were screened by Logistic and Lasso regression and nomogram was developed. In addition, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess its power. Finally, internal cross-validation and external validation was performed to assess the power of the model. RESULTS: In total, 206 eligible patients were recruited in this study and 53.4% (110/206) patients achieved MPR. Using multivariate analysis, the predictive model was constructed by seven variables, prothrombin time (PT), neutrophil percentage (NEUT%), large platelet ratio (P-LCR), eosinophil percentage (EOS%), smoking, pathological type, and programmed death ligand-1 (PD-L1) expression finally. The model had good discrimination, with area under the ROC curve (AUC) of 0.775, 0.746 and 0.835 for all datasets, cross-validation and external validation, respectively. The calibration curves showed good consistency, and DCAs indicated its potential value in clinical practice. CONCLUSION: This real world study revealed favourable efficacy in operable NSCLC treated with NACI. The proposed model based on multiple clinically accessible parameters could effectively predict MPR probability and could be a powerful tool in personalized medication.

Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis.

OBJECTIVES: The negative effects of smoking on numerous cardiovascular and metabolic diseases have been widely acknowledged. However, the potential effect of smoking cessation is relatively unelucidated. The objective of this study is to explore whether the prevalence of non-alcoholic fatty liver disease (NAFLD) in former smokers differs from the prevalence in current smokers. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Four databases, that is, PubMed, Web of Science, Journal@Ovid and Scopus were searched from inception to 31 January 2023. ELIGIBILITY CRITERIA: Population-based cross-sectional studies, including the baseline data of cohort studies with identified NAFLD diagnostic methods, and smoking status (current smoker or former smoker) of participants were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the data including cigarette smoking status, country/region of studies, NAFLD diagnostic methods, sex, the average age and body mass index (BMI) of NAFLD participants and assessed the risk of bias with Agency for Healthcare Research and Quality (AHRQ) methodology checklist. Risk ratio (RR) of NAFLD prevalence in former smokers was pooled using the random-effects model. RESULTS: 28 studies involving 4 465 862 participants were included. Compared with current smokers, the RR of overall NAFLD prevalence in former smokers was 1.13 (95% CI: 1.08 to 1.19, prediction interval: 0.92-1.39). This result persisted after adjustment for diagnostic methods, country/region, sex, age and BMI. Sensitivity analysis and risk of bias assessment indicated a stable conclusion. CONCLUSIONS: NAFLD prevalence in former smokers was at least not lower than that in current smokers and was partially related to increased BMI after smoking cessation, indicating that smoking cessation was possibly not a protective factor against NAFLD. Although the meta-analysis based on cross-sectional studies cannot conclude the causal relationships between smoking cessation and NAFLD onset, the potential onset of NAFLD associated with smoking cessation should be highlighted. PROSPERO REGISTRATION NUMBER: CRD42023394944.

Smart Responsive and Controlled-Release Hydrogels for Chronic Wound Treatment.

Chronic wounds are a major health challenge that require new treatment strategies. Hydrogels are promising drug delivery systems for chronic wound healing because of their biocompatibility, hydration, and flexibility. However, conventional hydrogels cannot adapt to the dynamic and complex wound environment, which involves low pH, high levels of reactive oxygen species, and specific enzyme expression. Therefore, smart responsive hydrogels that can sense and respond to these stimuli are needed. Crucially, smart responsive hydrogels can modulate drug release and eliminate pathological factors by changing their properties or structures in response to internal or external stimuli, such as pH, enzymes, light, and electricity. These stimuli can also be used to trigger antibacterial responses, angiogenesis, and cell proliferation to enhance wound healing. In this review, we introduce the synthesis and principles of smart responsive hydrogels, describe their design and applications for chronic wound healing, and discuss their future development directions. We hope that this review will inspire the development of smart responsive hydrogels for chronic wound healing.

Unusual Case of Primary Hepatic Squamous Carcinoma on 18F-FDG PET/CT.

ABSTRACT: Primary hepatic squamous carcinoma is an extremely rare liver tumor type with high malignancy and poor prognosis. We present 18F-FDG PET/CT findings of primary squamous carcinoma of the liver in a 65-year-old man, who was admitted to the hospital with subxiphoid pain in the epigastric region radiating to the left lower back for 2 months. 18F-FDG PET/CT demonstrated a large heterogeneous mild enhancing mass in the left lobe of the liver, with intense circumferential 18F-FDG activity.

Machine-learning-based classification of diffuse large B-cell lymphoma patients by a 7-mRNA signature enriched with immune infiltration and cell cycle.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) exhibits remarkable heterogeneity but still remains undiagnosed in identifying the subpopulation of DLBCL to predict the prognosis and guide clinical treatment. METHODS: Molecular subgroups were identified in gene expression data from GSE10846 by a consensus clustering algorithm. And gene set enrichment analysis, immune infiltration, and the proposed cell cycle algorithm were applied to explore the biological functions of different subtypes. Meanwhile, univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of DLBCL. Finally, the prognostic model, including some key genes screened by Lasso regression, Random Forest algorithm, and point-biserial correlation, was constructed by an optimal classifier from seven machine learning algorithms and validated by another three external datasets (GSE34171, GSE87371, GSE31312). RESULTS: Comprehensive genomic analysis of 1,143 DLBCL samples identify 2 molecularly, prognostically relevant subtypes: immune-enriched (IME) and cell-cycle-enriched (CCE). Then a new predictive model including seven key genes (SERPING1, TIMP2, NME1, DCTPP1, RFC4, POLE2, and SNRPD1) was developed with high prediction accuracy (88.6%) and strong predictive power (AUC = 0.973) based on the Support Vector Machine (SVM) algorithm in 414 patients from GSE10846. The predictive power was similar in another three testing sets (HR > 1.400, p < 0.05). CONCLUSION: This model could evaluate survival independently with strong predictive power compared with other clinical risk factors. Our study constructed a reliable model to predict two new subtypes of DLBCL patients, which could guide the implementation of individualized treatment.

Head-to-head comparison of 18F-FAPI and 18F-FDG PET/CT in staging and therapeutic management of hepatocellular carcinoma.

BACKGROUND: Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has limitations in staging hepatocellular carcinoma (HCC). The recently introduced 18F-labeled fibroblast-activation protein inhibitor (FAPI) has shown promising prospects in detection of HCC lesions. This study aimed to investigate the initial staging and restaging performance of 18F-FAPI PET/CT compared to 18F-FDG PET/CT in HCC. METHODS: This prospective study enrolled histologically confirmed HCC patients from March 2021 to September 2022. All patients were examined with 18F-FDG PET/CT and 18F-FAPI PET/CT within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. RESULTS: A total of 67 patients (57 men; median age, 57 [range, 32-83] years old) were included. 18F-FAPI PET showed higher SUVmax and TBR values than 18F-FDG PET in the intrahepatic lesions (SUVmax: 6.7 vs. 4.3, P < 0.0001; TBR: 3.9 vs. 1.7, P < 0.0001). In diagnostic performance, 18F-FAPI PET/CT had higher detection rate than 18F-FDG PET/CT in intrahepatic lesions [92.2% (238/258) vs 41.1% (106/258), P < 0.0001] and lymph node metastases [97.9% (126/129) vs 89.1% (115/129), P = 0.01], comparable in distant metastases [63.6% (42/66) vs 69.7% (46/66), P > 0.05]. 18F-FAPI PET/CT detected primary tumors in 16 patients with negative 18F-FDG, upgraded T-stages in 12 patients and identified 4 true positive findings for local recurrence than 18F-FDG PET, leading to planning therapy changes in 47.8% (32/67) of patients. CONCLUSIONS: 18F-FAPI PET/CT identified more primary lesions, lymph node metastases than 18F-FDG PET/CT in HCC, which is helpful to improve the clinical management of HCC patients. TRIAL REGISTRATION: Clinical Trials, NCT05485792 . Registered 1 August 2022, Retrospectively registered.

The sigma-1 receptor-TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis.

BACKGROUND: Therapy in the latent period is favorable for retarding the process of epileptogenesis. Recently, we have discovered that the activated sigma-1 receptor (Sig-1R) attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis. But the molecular mechanism needs further investigation. METHODS: PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice. After the treatment of PRE-084, the pro-inflammatory cytokines, neuropathological traits, and the level of mitochondrial translocator assembly and maintenance 41 homolog (TAMM41) in the hippocampus were examined. The mode in which the Sig-1R interacts with TAMM41 was explored. The role of TAMM41 in the protecting effect of PRE-084 was established. RESULTS: PRE-084 inhibited the growth of pro-inflammatory cytokines, reduced the formation of gliosis, alleviated neuronal damage in the hippocampus, and attenuated memory impairment in the latent period of epileptogenesis. The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice. The Sig-1R bound with TAMM41 directly, maintaining the stability of TAMM41. Knockdown of TAMM41 reversed the protective effect of PRE-084, and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084. CONCLUSION: We presented the concept of the "sigma-1 receptor-TAMM41 axis" and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.

Application of hyaluronic acid-based nanoparticles for cancer combination therapy.

Cancer is a significant public health problem in the world. The treatment methods include surgery, chemotherapy, phototherapy, and immunotherapy. Due to their respective limitations, the treatment effect is often unsatisfactory, laying hidden dangers for metastasis and recurrence. Since their exceptional biocompatibility and excellent targeting capabilities, hyaluronic acid-based biomaterials have generated great interest as drug delivery methods for tumor therapy. Moreover, modified HA can self-assemble into hydrogels or nanoparticles (NPs) for precise drug administration. This article summarizes the application of HA-based NPs in combination therapy. Ultimately, it is anticipated that this research will offer guidance for creating various HA-based NPs utilized in numerous cancer therapies.

Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer.

Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.

Targeting macrophage M1 polarization suppression through PCAF inhibition alleviates autoimmune arthritis via synergistic NF-κB and H3K9Ac blockade.

Sustained inflammatory invasion leads to joint damage and progressive disability in several autoimmune rheumatic diseases. In recent decades, targeting M1 macrophage polarization has been suggested as a promising therapeutic strategy for autoimmune arthritis. P300/CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) that exhibits a strong positive relationship with the proinflammatory microenvironment. However, whether PCAF mediates M1 macrophage polarization remains poorly studied, and whether targeting PCAF can protect against autoimmune arthritis in vivo remains unclear. Commonly used drugs can cause serious side effects in patients because of their extensive and nonspecific distribution in the human body. One strategy for overcoming this challenge is to develop drug nanocarriers that target the drug to desirable regions and reduce the fraction of drug that reaches undesirable targets. In this study, we demonstrated that PCAF inhibition could effectively inhibit M1 polarization and alleviate arthritis in mice with collagen-induced arthritis (CIA) via synergistic NF-κB and H3K9Ac blockade. We further designed dextran sulfate (DS)-based nanoparticles (DSNPs) carrying garcinol (a PCAF inhibitor) to specifically target M1 macrophages in inflamed joints of the CIA mouse model via SR-A-SR-A ligand interactions. Compared to free garcinol, garcinol-loaded DSNPs selectively targeted M1 macrophages in inflamed joints and significantly improved therapeutic efficacy in vivo. In summary, our study indicates that targeted PCAF inhibition with nanoparticles might be a promising strategy for treating autoimmune arthritis via M1 macrophage polarization inhibition.