Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons.

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3ß expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3ß pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.

Multifractal characteristics of soil particle size distribution of abandoned homestead reclamation under different forest management modes.

In this study, fast-growing poplar reclaimed from abandoned homestead in Xixian New District, Xi'an City, Shaanxi Province, was used as the research object to explore the multi-fractal characteristics of soil particle size distribution under different management modes of abandoned land (control), irrigation, fertilizer irrigation and mixed fertilizer irrigation. The results showed that the mean values of soil clay, silt and sand in abandoned land were 14.58%, 81.21% and 4.22% respectively, 14.08%, 79.92% and 5.99% under irrigation, 15.17%, 81.19% and 3.64% under fertilizer irrigation, and 16.75%, 80.20% and 3.05% in mixed fertilizer treatment. From 40 cm, with increasing soil depth, soil clay particles increase under irrigation, fertilizer irrigation, and mixed fertilizer irrigation modes. The single fractal dimension of soil particle size distribution (D) in each treatment ranges from 2.721 to 2.808. At 60-100 cm, D shows fertilizer irrigation > mixed fertilizer irrigation > irrigation > abandoned land, indicating that fertilization and irrigation can increase the fine-grained matter of deep soil particles and reduce soil roughness. Compared with abandoned land, under irrigation, fertilizer irrigation and mixed fertilizer modes the capacity dimension (D0), entropy dimension (D1), correlation dimension(D2), shape characteristics of the multifractal spectrum (Δf) and overall inhomogeneity of the soil particle size distribution (D0-D10) indicate an uneven distribution of soil particle size; fractal structure characteristics of soil (D-10-D0) indicate a simplified soil structure, and degree of dispersion of soil particle size distribution (D1/D0) indicates that soil particle size is distributed in dense areas. Pearson correlation analysis showed that D was significantly correlated with clay, sand, D0-D10, soil organic matter (SOM) and soil available phosphorus (SAP) (P < 0.05). Stepwise regression analysis showed that clay was the main controlling factor of D and D0-D10 changes. The research results can provide some potential indicators for the quality evaluation of abandoned homestead reclamation.

Autoantigenic Peptide and Immunomodulator Codelivery System for Rheumatoid Arthritis Treatment by Reestablishing Immune Tolerance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by abnormal activation of CD4+ T cells and an imbalance of T helper 17 (Th17) and regulatory T (Treg) cells. Tolerogenic therapy via administration of self-antigens is a promising strategy for RA treatment, but delivery of autoantigens alone may exacerbate disease conditions. Current studies indicated that codelivery of autoantigens with immunomodulators can lead to a more tolerogenic immune response. Here, we constructed an autoantigen type II collagen peptide (CII250-270)- and immunomodulator leflunomide (LEF)-coloaded phosphatidylserine liposome vaccine (CII250-270-LEF-PSL) for RA treatment via induction of tolerant dendritic cells (tolDC) for further activation of Treg cells. The in vivo results showed that CII250-270-LEF-PSL can effectively induce tolDC, regulate the balance of Th1/Th2 and Th17/Treg, and reduce the secretion of pro-inflammatory cytokines (IFN-γ, IL-1ß, and IL-17A) and IgG antibodies to inhibit synovial inflammation and bone erosion. Furthermore, our study also suggested that LEF regulated Th1 cell differentiation by inhibiting the activation of the JAK1/STAT1 signaling pathway, further alleviating RA. Overall, this work proved that the combination of autoantigenic peptides and immunomodulators was a promising modality for RA treatment by reestablishing antigen-specific immune tolerance, which also inspired additional insights into the development of combination therapies for the tolerability of RA.

Integrated analysis of ceRNA-miRNA changes in paraquat-induced pulmonary epithelial-mesenchymal transition via high-throughput sequencing.

Recent studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in paraquat (PQ)-induced tissue fibrosis, which is the main cause of death in patients with PQ poisoning. However, no effective treatment for pulmonary interstitial fibrosis caused by PQ poisoning exists. It is of great significance for us to find new therapeutic targets through bioinformatics in PQ-induced EMT. We conducted transcriptome sequencing to determine the expression profiles of 1210 messenger RNAs (mRNAs), 558 long noncoding RNAs, 28 microRNAs (miRNAs), including 18 known-miRNAs, 10 novel-miRNAs and 154 circular RNAs in the PQ-exposed EMT group mice. Using gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses, we identified the pathways associated with signal transduction, cancers, endocrine systems and immune systems were involved in PQ-induced EMT. Furthermore, we constructed long noncoding RNA-miRNA-mRNA interrelated networks and found that upregulated genes included Il22ra2, Mdm4, Slc35e2 and Angptl4, and downregulated genes included RGS2, Gabpb2, Acvr1, Prkd3, Sp100, Tlr12, Syt15 and Camk2d. Thirteen new potential competitive endogenous RNA targets were also identified for further treatment of PQ-induced pulmonary tissue fibrosis. Through further study of the pathway and networks, we may identify new molecular targets in PQ-induced pulmonary EMT.

M-MDSCs mediated trans-BBB drug delivery for suppression of glioblastoma recurrence post-standard treatment.

We found that immunosuppressive monocytic-myeloid-derived suppressor cells (M-MDSCs) were more likely to be recruited by glioblastoma (GBM) through adhesion molecules on GBM-associated endothelial cells upregulated post-chemoradiotherapy. These cells are continuously generated during tumor progression, entering tumors and expressing PD-L1 at a high level, allowing GBM to exhaust T cells and evade attack from the immune system, thereby facilitating GBM relapse. αLy-6C-LAMP is composed of (i) drug cores with slightly negative charges condensed by cationic protamine and plasmids encoding PD-L1 trap protein, (ii) pre-formulated cationic liposomes targeted to Ly-6C for encapsulating the drug cores, and (iii) a layer of red blood cell membrane on the surface for effectuating long-circulation. αLy-6C-LAMP persistently targets peripheral, especially splenic, M-MDSCs and delivers secretory PD-L1 trap plasmids, leveraging M-MDSCs to transport the plasmids crossing the blood-brain barrier (BBB), thus expressing PD-L1 trap protein in tumors to inhibit PD-1/PD-L1 pathway. Our proposed drug delivery strategy involving intermediaries presents an efficient cross-BBB drug delivery concept that incorporates live-cell targeting and long-circulating nanotechnology to address GBM recurrence.

The potential application of complement inhibitors-loaded nanosystem for autoimmune diseases via regulation immune balance.

The complement is an important arm of the innate immune system, once activated, the complement system rapidly generates large quantities of protein fragments that are potent mediators of inflammation. Recent studies have shown that over-activated complement is the main proinflammatory system of autoimmune diseases (ADs). In addition, activated complements interact with autoantibodies, immune cells exacerbate inflammation, further worsening ADs. With the increasing threat of ADs to human health, complement-based immunotherapy has attracted wide attention. Nevertheless, efficient and targeted delivery of complement inhibitors remains a significant challenge owing to their inherent poor targeting, degradability, and low bioavailability. Nanosystems offer innovative solutions to surmount these obstacles and amplify the potency of complement inhibitors. This prime aim to present the current knowledge of complement in ADs, analyse the function of complement in the pathogenesis and treatment of ADs, we underscore the current situation of nanosystems assisting complement inhibitors in the treatment of ADs. Considering technological, physiological, and clinical validation challenges, we critically appraise the challenges for successfully translating the findings of preclinical studies of these nanosystem assisted-complement inhibitors into the clinic, and future perspectives were also summarised. (The graphical abstract is by BioRender.).

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Adaptive Internal Model Control for a Flexible Wing With Unsteady Aerodynamic Loads.

This article proposes adaptive internal model controls for the collocated output regulation of a flexible wing, where distributed disturbances, boundary disturbances, and references are from an exactly unknown exosystem. Observer-based tracking error feedback controls are first designed to address the robust output regulation in case of a known exosystem matrix. If the exosystem has an unknown matrix, an adaptive observer is further proposed with the observer error system converging to zero exponentially. Then, we can obtain adaptive observer-based controls by combining adaptive observers and observer-based controls, which are able to regulate the tracking errors toward zero in case of the exactly unknown disturbances and references. The corresponding closed-loop system is proved to be internally asymptotically stable. A simulation example is further provided for adaptive internal model control of the wing system.

Glutathione Consumptive Dual-Sensitive Lipid-Composite Nanoparticles Induce Immunogenic Cell Death for Enhanced Breast Tumor Therapy.

Although chemotherapy remains the standard therapy for tumor treatment, serious side effects can occur because of nontargeted distribution and damage to healthy tissues. Hollow mesoporous silica nanoparticles (HMSNs) modified with lipids offer potential as delivery systems to improve therapeutic outcomes and reduce adverse effects. Herein, we synthesized HMSNs with integrated disulfide bonds (HMSN) for loading with the chemotherapeutic agent oxaliplatin (OXP) which were then covered with the synthesized hypoxia-sensitive lipid (Lip) on the surface to prepare the dual-sensitive lipid-composite nanoparticles (HMSN-OXP-Lip). The empty lipid-composite nanoparticles (HMSN-Lip) would consume glutathione (GSH) in cells because of the reduction of disulfide bonds in HMSN and would also inhibit GSH production because of NADPH depletion driven by Lip cleavage. These actions contribute to increased levels of ROS that induce the immunogenic cell death (ICD) effect. Simultaneously, HMSN-Lip would disintegrate in the presence of high concentrations of GSH. The lipid in HMSN-OXP-Lip could evade payload leakage during blood circulation and accelerate the release of the OXP in the tumor region in the hypoxic microenvironment, which could significantly induce the ICD effect to activate an immune response for an enhanced therapeutic effect. The tumor inhibitory rate of HMSN-OXP-Lip was almost twice that of free OXP, and no apparent side effects were observed. This design provides a dual-sensitive and efficient strategy for tumor therapy by using lipid-composite nanoparticles that can undergo sensitive drug release and biodegradation.

Combining Multifunctional Delivery System with Blood-Brain Barrier Reversible Opening Strategy for the Enhanced Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative illness characterized by intracellular tau-phosphorylation, ß-amyloid (Aß) plaques accumulation, neuroinflammation, and impaired behavioral ability. Owing to the lack of effective brain delivery approaches and the presence of the blood-brain barrier (BBB), current AD therapeutic endeavors are severely limited. Herein, a multifunctional delivery system (RVG-DDQ/PDP@siBACE1) is elaborately combined with a protein kinase B (AKT) agonist (SC79) for facilitating RVG-DDQ/PDP@siBACE1 to target and penetrate BBB, enter brain parenchyma, and further accumulate in AD brain lesion. Moreover, compared with the unitary dose of RVG-DDQ/PDP@siBACE1, this collaborative therapy strategy exhibits a distinctive synergistic function including scavenging reactive oxygen species (ROS), decreasing of Aß production, alleviating neuroinflammation by promoting the polarized microglia into the anti-inflammatory M2-like phenotype and significantly enhancing the cognitive functions of AD mice. More strikingly, according to these results, an innovative signaling pathway "lncRNA MALAT1/miR-181c/BCL2L11" is found that can mediate the neuronal apoptosis of AD. Taken together, combining the brain targeted delivery system with noninvasive BBB opening can provide a promising strategy and platform for targeting treatment of AD and other neurodegenerative diseases.

Atmospheric chemistry of 2-nitrobenzaldehyde: Initiated by photo-excitation, OH-oxidation, and small TiO2 clusters adsorption catalysis.

The fate of 2-nitrobenzaldehyde (2-NBA) is of interest in atmospheric chemistry as it is a semi-volatile organic compound with high photosensitivity. This study presents a quantum chemical study of the gas-phase reactions of 2-NBA photo-excitation and OH-oxidation in the absence and presence of small TiO2 clusters. To further understand the unknown photolysis mechanism, the photo-reaction pathways of ground singlet state and the lying excited triplet state of 2-NBA were investigated including the initial and subsequent reactions of proton transfer, direct CO, NO2, and HCO elimination routes in the presence of O2 and NO. Meanwhile, the OH-mediated degradation of 2-NBA proceeded via five H-extraction and six OH-addition channels by indirect mechanism, which follows a succession of reaction steps initiated by the formation of weakly stable intermediate complexes. The H-extraction from the -CHO group was the dominant pathway with a negative activation energy of -1.22 kcal/mol. The calculated rate coefficients at 200-600 K were close to the experimental data in literature within 308-352 K, and the kinetic negative temperature independence was found in both experimental literature and computational results. Interestingly, 2-NBA was favored to be captured onto small TiO2 clusters via six adsorption configurations formed via various combination of three types of bonds of Ti···O, Ti···C, and O···H between the molecularly adsorbed 2-NBA and TiO2 clusters. Comparison indicted that the chemisorptions of aldehyde oxygen have largest energies. The results suggested adsorption conformations have a respectable impact on the catalysis barrier. This study is significant for understanding the atmospheric chemistry of 2-nitrobenzaldehyde.

Nanocarriers transport across the gastrointestinal barriers: The contribution to oral bioavailability via blood circulation and lymphatic pathway.

Oral administration is the preferred route of drug delivery in clinical practice due to its noninvasiveness, safety, convenience, and high patient compliance. The gastrointestinal tract (GIT) plays a crucial role in facilitating the targeted delivery of oral drugs. However, the GIT presents multiple barriers that impede drug absorption, including the gastric barrier in the stomach and the mucus and epithelial barriers in the intestine. In recent decades, nanotechnology has emerged as a promising approach for overcoming these challenges by utilizing nanocarrier-based drug delivery systems such as liposomes, micelles, polymeric nanoparticles, solid lipid nanoparticles, and inorganic nanoparticles. Encapsulating drugs within nanocarriers not only protects them from degradation but also enhances their transport and absorption across the GIT, ultimately improving oral bioavailability. The aim of this review is to elucidate the mechanisms underlying nanocarrier-mediated transportation across the GIT into systemic circulation via both the blood circulation and lymphatic pathway.

SGK1 is involved in doxorubicin-induced chronic cardiotoxicity and dysfunction through activation of the NFκB pathway.

Breast cancer is the predominant cancer among women worldwide, and chemotherapeutic agents, such as doxorubicin (DOX), have the potential to significantly prolong survival, albeit at the cost of inducing severe cardiovascular toxicity. Inflammation has emerged as a crucial biological process contributing to the remodeling of cardiovascular toxicity. The role of serum glucocorticoid kinase 1 (SGK1) in various inflammatory diseases has been extensively investigated. Here, we studied the molecular mechanisms underlying the function of SGK1 in DOX-induced cardiotoxicity in HL-1 cardiomyocyte cell lines and in a tumor-bearing mouse model. SGK1 was upregulated in the DOX-induced cardiotoxicity model, accompanied by increased levels of inflammatory factors. Furthermore, inhibition of SGK1 suppresses the phosphorylation of nuclear factor-kappa B (NFκB) in cardiomyocytes, which inhibits the production of inflammatory factors and apoptosis of cardiomyocytes, and has cardioprotective effects. Simultaneously, small interfering RNA targeting SGK1 inhibited the proliferation of breast cancer cells. Conversely, overexpression of SGK1 increases the phosphorylation of NFκB and aggravates myocardial injury. In conclusion, our study demonstrates that SGK1 promotes DOX-induced cardiac inflammation and apoptosis by promoting NFκB activity. Our results indicate that inhibiting SGK1 might be an effective treatment strategy that can provide both tumor-killing and cardioprotective functions. Further in vivo research is needed to fully elucidate the effects and mechanisms of combination therapy with SGK1 inhibitors and DOX in breast cancer treatment.

Eicosapentaenoic acid enhances the sensitivity of osteosarcoma to cisplatin by inducing ferroptosis through the DNA-PKcs/AKT/NRF2 pathway and reducing PD-L1 expression to attenuate immune evasion.

Acquired drug resistance poses a significant challenge in osteosarcoma therapy. Therefore, it is necessary for us to discover and develop an alternative anti-cancer strategy. Previous studies have shown that eicosapentaenoic acid (EPA) significantly increases chemosensitivity in cancer cells. In this study, we discovered that EPA enhances the sensitivity of osteosarcoma to cisplatin (DDP). Interestingly, in addition to inhibiting growth and inducing apoptosis, EPA also enhances DDP-induced ferroptosis. Western blot analysis confirmed that EPA treatment significantly decreases the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), p-AKT, nuclear factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) in cells. Knockdown of DNA-PKcs by siRNA further enhances the level of ferroptosis induced by EPA. Importantly, EPA can reverse the high expression level of programmed death ligand 1 (PD-L1) induced by DDP. ELISA and western blotting analysis revealed that EPA treatment decreases the levels of IL-6 and p-STAT3, which are increased by DDP treatment. Furthermore, a co-immunoprecipitation (co-IP) assay confirmed the interaction between DNA-PKcs and PD-L1, and knockdown of DNA-PKcs further reduces the expression of PD-L1. This data provides the first evidence that EPA suppresses the DNA-PKcs/AKT/NRF2/GPX4 pathway to enhance ferroptosis, and inhibits IL-6/STAT3 and DNA-PKcs to decrease PD-L1 expression, thereby sensitizing osteosarcoma to DDP. The combination of EPA and DDP presents an encouraging and promising anti-tumor strategy.

Tamoxifen induced cardiac damage via the IL-6/p-STAT3/PGC-1α pathway.

Tamoxifen (TAM) is an effective anticancer drug for breast and ovarian cancer. However, increased risk of cardiotoxicity is a long-term clinical problem associated with TAM, while the underlying mechanisms remain unclear. Here, we performed experiments in cardiomyocytes and tumor-bearing or nontumor-bearing mice, and demonstrated that TAM induced cardiac injury via the IL-6/p-STAT3/PGC-1α/IL-6 feedback loop, which is responsible for reactive oxygen species (ROS) accumulation. Compared with non-tumor bearing mice, tumor-bearing mice showed stronger cardiac toxicity after TAM injection, although there was no significant difference. In vitro experiments demonstrated STAT3 phosphorylation inhibitor can increase PGC-1α expression and protect cardiomyocyte via decreasing ROS. Since tumor has higher STAT3 phosphorylation and IL-6 expression level, our research results indicated combining TAM and STAT3 inhibitor might be an effective treatment strategy which can provide both tumor killing and cardioprotective function. Further in vivo research is needed to fully elucidate the effect and mechanisms of the combination therapy of TAM and STAT3 inhibitor.

Evaluation of peripapillary retinal nerve fiber layer thickness in intracranial atherosclerotic stenosis.

PURPOSE: To evaluate the peripapillary retinal nerve fiber layer thickness (pRNFL) in patients with intracranial atherosclerotic stenosis (ICAS). METHODS: A cross-sectional study was performed in a general hospital. The intracranial atherosclerotic stenosis was evaluated by digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA). High-definition optical coherence tomography (HD-OCT) was used to evaluate the peripapillary retinal nerve fiber layer thickness. RESULTS: A total of 102 patients, including 59(57.8%) patients with ICAS and 43(42.2%) patients without ICAS, were finally analysed in the study. The peripapillary retinal nerve fiber layer thickness (pRNFL) was reduced significantly in the average, the superior and the inferior quadrants of the ipsilateral eyes and in the superior quadrant of the contralateral eyes in patients with ICAS compared with patients without ICAS. After multivariate analysis, only the superior pRNFL thickness in the ipsilateral eyes was significantly associated with ICAS (OR,0.968; 95% CI,0.946-0.991; p = 0.006). The area under receiver operator curve was 0.679 (95% CI,0.576-0.782) for it to identify the presence of ICAS. The cut-off value of the superior pRNFL was 109.5 µm, and the sensitivity and specificity were 50.8% and 83.7%, respectively. CONCLUSION: The superior pRNFL in the ipsilateral eye was significantly associated with ICAS in this study. Larger studies are needed to explore the relation between pRNFL and ICAS further.

A narrative review of retinal vascular parameters and the applications (Part II): Diagnosis in stroke.

The retina, as an external extension of the diencephalon, can be directly, noninvasively observed by ocular fundus photography. Therefore, it offers a convenient and feasible mode to study nervous system diseases. Caliber, tortuosity, and fractal dimension, as three commonly used retinal vascular parameters, are not only the reflection of structural changes in the retinal microcirculation but also capture the branching pattern or density changes of the retinal microvascular network. Therefore, it contributes to better reflecting the subclinical pathological changes (e.g., lacunar stroke and small cerebral vascular disease) and predicting the risk of incident stroke and recurrent stroke.

A narrative review of retinal vascular parameters and the applications (Part I): Measuring methods.

The retina is often used to evaluate the vascular health status of eyes and the whole body directly and noninvasively in vivo. Retinal vascular parameters included caliber, tortuosity and fractal dimension. These variables represent the density or geometric characteristics of the vascular network apart from reflecting structural changes in the retinal vessel system. Currently, these parameters are often used as indicators of retinal disease, cardiovascular and cerebrovascular disease. Advanced digital fundus photography apparatus and computer-assisted analysis techniques combined with artificial intelligence, make the quantitative calculation of these parameters easier, objective, and labor-saving.

Association of Chronic Kidney Disease with Cardiovascular Disease in Cancer Patients: A Cross-Sectional Study.

INTRODUCTION: Due to the cardiotoxicity of cancer treatment and traditional risk factors for cardiovascular disease (CVD) such as obesity, diabetes, dyslipidemia, and hypertension, cancer patients are at higher risk of developing CVD. However, limited research exists on the correlation between chronic kidney disease (CKD) and CVD risk in cancer patients. METHODS: This cross-sectional study selected cancer patients aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) conducted from 2015 to 2020. Multivariable logistic regression was used to assess the association between CKD and CVD in cancer patients. Additionally, subgroup analyses were conducted to investigate the association among different groups of cancer patients. RESULTS: We included 1,700 adult cancer patients (52.53% were females). After multivariable adjustment for covariates including traditional CVD factors, CKD was significantly associated with CVD, with an odds ratio (95% confidence interval) and p value of 1.61 (1.18, 2.19) and 0.004. Subgroup analyses after multivariable adjustment showed a significant correlation between CKD and increased CVD risk in the following cancer patients: age ≥60 years, males, white ethnicity, and individuals with or without traditional CVD factors (obesity, diabetes, dyslipidemia, and hypertension). CONCLUSIONS: CKD remains a significant factor in the higher risk of CVD among adult cancer patients in the United States, even after adjustment for traditional CVD risk factors. Therefore, to reduce the risk of CVD in cancer patients, it is important to treat CKD as a non-traditional risk factor for CVD and actively manage it.

"Targeted plus controlled" - Composite nano delivery system opens the tumor vascular and microenvironment normalization window for anti-tumor therapy.

The bottleneck of traditional anti-tumor therapy is mainly limited by the abnormal microenvironment of tumors. Leaky vessels are difficult for drugs or immune cells to penetrate deep into tumors, but tumor cells can easily escape through which and metastasize to other organs. Reprogramming the tumor microenvironment is one of the main directions for anti-cancer research, among which, tumor vascular normalization has received increasing attention. However, how to control the dose and time of anti-angiogenic drugs for stable vascular normalizing effect limits it for further research. We developed a composite nano delivery system, P-V@MG, with double delivery function of pH-responsibility and sustained drug release. The PHMEMA shell improves amphiphilicity of nano delivery system and prolongs in vivo retention, and releases V@MG in the weakly acidic tumor microenvironment, which slowly release anti-angiogenic drugs, Vandetanib. We found that P-V@MG not only prolonged the normalization window of tumor vascular but also reprogram tumor microenvironment with increased perfusion, immune cells infiltration and relieved hypoxia, which further opened the pathway for other anti-cancer therapeutics. This synergy was proved by the improving anti-tumor efficiency by combination of P-V@MG with the doxorubicin hydrochloride in 4 T1 breast cancer model suggesting the desirable value of pro-vascular normalization nano delivery systems in the field of anti-tumor combination therapy.