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498 result(s) for "Cai, Xiaojun"
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Sonodynamic therapy‐assisted immunotherapy: A novel modality for cancer treatment
Sonodynamic therapy (SDT), which is based on photodynamic therapy (PDT), is a new cancer treatment modality. Unlike PDT, which has poor tissue penetration, ultrasound can penetrate deeply into tissues and largely target tumor tissue to mediate the cytotoxicity of sonosensitizers. We hypothesize that, similar to PDT, SDT may perform effectively as a cancer vaccine. Thus, we developed a therapeutic strategy to explore whether SDT can eliminate primary tumors, inhibit metastases, and prevent tumor relapse. In the present study, we found that HiPorfin (HPD)‐induced SDT killed tumor cells, promoted calreticulin expression on the cell surface and elicited immune responses. Meanwhile, we observed that SDT induced functional antitumor vaccination and abscopal effects in H22 tumor‐bearing mice. Furthermore, this strategy conferred an immunological memory, which could protect against tumor recurrence after the elimination of the initial tumor. These results showed important effects of SDT on immune responses. HiPorfin (HPD)‐induced SDT killed tumor cells, promoted calreticulin expression on the cell surface and provoked immune responses. Meanwhile, we observed functional antitumor vaccination and the abscopal effect as a result of SDT in H22 tumor‐bearing mice. Furthermore, this strategy conferred an immunological memory, which could protect against tumor recurrence after elimination of the initial tumor.
Nanozyme-mediated catalytic nanotherapy for inflammatory bowel disease
The overproduction of reactive oxygen species (ROS) is linked to inflammatory bowel disease (IBD) and causes oxidative damage to DNA, proteins, and lipids. These ROS promote the initiation and progression of ulcerative colitis (UC). This study proposes a unique concept of nanomaterials with intrinsic enzyme-like activity (nanozymes) to mediate catalytic nanotherapy for IBD. : We first synthesized manganese Prussian blue nanozymes (MPBZs) with multi-enzyme activity. A dextran sulfate sodium (DSS)-induced mouse model of colitis was built. The ROS scavenging capacity and anti-inflammatory effects of the MPBZs were investigated. : As a proof of concept, MPBZs with multi-enzyme activity were constructed of variable valence elements (Mn and Fe) via a facile and efficient strategy. Due to the increased intestinal permeability and positively charged surfaces of inflamed mucosa in murine colitis, the prepared MPBZs with nanoscale sizes and negative charges preferentially accumulated at inflamed sites after oral administration. Importantly, MPBZs mediated catalytic nanotherapy for IBD in mice via a primary effect on the toll-like receptor signaling pathway without adverse side effects. : MPBZs with multi-enzyme activity were constructed to treat IBD. This nanozyme-based approach is a promising strategy for catalytic nanotherapy in patients with colonic IBD.
Efficient solar water-splitting using a nanocrystalline CoO photocatalyst
The generation of hydrogen from water using sunlight could potentially form the basis of a clean and renewable source of energy. Various water-splitting methods have been investigated previously 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , but the use of photocatalysts to split water into stoichiometric amounts of H 2 and O 2 (overall water splitting) without the use of external bias or sacrificial reagents is of particular interest because of its simplicity and potential low cost of operation 1 , 2 , 3 , 4 . However, despite progress in the past decade, semiconductor water-splitting photocatalysts (such as (Ga 1− x Zn x )(N 1− x O x )) do not exhibit good activity beyond 440 nm (refs 1 , 2 , 9 ) and water-splitting devices that can harvest visible light typically have a low solar-to-hydrogen efficiency of around 0.1% 6 , 7 . Here we show that cobalt( II ) oxide (CoO) nanoparticles can carry out overall water splitting with a solar-to-hydrogen efficiency of around 5%. The photocatalysts were synthesized from non-active CoO micropowders using two distinct methods (femtosecond laser ablation and mechanical ball milling), and the CoO nanoparticles that result can decompose pure water under visible-light irradiation without any co-catalysts or sacrificial reagents. Using electrochemical impedance spectroscopy, we show that the high photocatalytic activity of the nanoparticles arises from a significant shift in the position of the band edge of the material. Cobalt oxide nanoparticles can carry out overall water splitting with a solar-to-hydrogen efficiency of around 5%.
Self-synergistic effect of Prussian blue nanoparticles for cancer therapy: driving photothermal therapy and reducing hyperthermia-induced side effects
Background Photothermal therapy (PTT), involving application of localized hyperthermia to kill cancer cells, has attracted wide attention in cancer therapy. The production of reactive oxygen species (ROS) during PTT may cause irreversible damage to healthy tissues around the tumor. Simultaneously, hyperthermia can stimulate inflammatory response, thus promoting tumor recurrence and metastasis. Therefore, it is of paramount importance to reduce the undesired side effects for further development of PTT. Results Using a hydrothermal method, spherical Prussian blue nanoparticles (PBs) with uniform size were prepared. The PBs exhibited good dispersion and stability in saline with an average hydrodynamic size of 110 nm. The prepared PBs had a high photothermal conversion efficiency and photothermal stability. The PBs showed intrinsic ROS scavenging properties in vitro. Antioxidant and anti-inflammatory effects of PBs were also observed in vivo. Assessment of toxicity and endoplasmic reticulum stress-inducing ability showed that PBs did not induce an inflammatory response. Tissues of major organs of mice stained with hematoxylin–eosin showed no significant damage, indicating good biocompatibility and safety of PBs. Conclusion The designed single-component PBs with intrinsic ROS scavenging and anti-inflammatory properties could avoid inflammatory response and heat stress-induced ROS during PTT. Thus, further research on PBs is worthwhile to achieve their clinical translation and promote the development of PTT.
Photodynamic and nitric oxide therapy-based synergistic antimicrobial nanoplatform: an advanced root canal irrigation system for endodontic bacterial infections
Background The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. Results This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. Conclusions This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.
Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice
Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure. Clinical applications of therapeutic agents for long-term management of heart failure have been hindered by the poor delivery efficiency. Here, the authors propose a myocardium-targeted strategy based on inhalable cardiac-targeting peptide-modified nanomedicine for the pharmacological treatment of heart failure.
Engineered nanodrug targeting oxidative stress for treatment of acute kidney injury
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function, and is associated with a high risk of death. Many pathological changes happen in the process of AKI, including crucial alterations to oxidative stress levels. Numerous efforts have thus been made to develop effective medicines to scavenge excess reactive oxygen species (ROS). However, researchers have encountered several significant challenges, including unspecific biodistribution, high biotoxicity, and in vivo instability. To address these problems, engineered nanoparticles have been developed to target oxidative stress and treat AKI. This review thoroughly discusses the methods that empower nanodrugs to specifically target the glomerular filtration barrier and presents the latest achievements in engineering novel ROS‐scavenging nanodrugs in clustered sections. The analysis of each study's breakthroughs and imperfections visualizes the progress made in developing effective nanodrugs with specific biodistribution and oxidative stress‐targeting capabilities. This review fills the blank of a comprehensive outline over current progress in applying nanotechnology to treat AKI, providing potential insights for further research. Engineered nanoparticles targeting oxidative stress have shown promising perspectives in treating acute kidney injury (AKI). By examining the challenges, advancements, and limitations of different studies in this field, this review fills a significant knowledge gap. In addition, it offers valuable insights for future research on engineering nanoparticles to address AKI.
Pharmacokinetics of Anthraquinones from Medicinal Plants
Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
Meta-analytical insight on probiotic metabolites and inflammatory markers in diabetes
Systemic inflammation is a hallmark of diabetes mellitus and contributes to insulin resistance and disease progression. Emerging evidence suggests that gut microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), play a crucial role in modulating immune responses. Probiotics and synbiotics are increasingly explored for their potential to mitigate inflammation via microbiota-targeted mechanisms. This study aims to evaluate the effects of probiotic and synbiotic supplementation on inflammatory markers and microbial metabolites in individuals with type 1 and type 2 diabetes through meta-analytical techniques. A total of 46 randomized controlled trials (RCTs) comprising 3,580 diabetic patients were included following PRISMA guidelines. Meta-analyses were performed using random-effects models to assess changes in inflammatory markers (CRP, IL-6, TNF-α, IL-10) and SCFA levels (butyrate, propionate, acetate). Subgroup analyses and meta-regressions were conducted to identify effect modifiers such as intervention duration, formulation type (probiotic vs. synbiotic), and SCFA concentrations. Probiotic/synbiotic interventions led to significant reductions in CRP (SMD = -0.54), IL-6 (SMD = -0.41), and TNF-α (SMD = -0.48), along with an increase in IL-10 (SMD = +0.38). SCFA levels rose significantly, with butyrate showing the strongest effect (SMD = +0.46). Meta-regression revealed that butyrate levels, synbiotic use, and intervention duration ≥8 weeks were strong predictors of anti-inflammatory efficacy. Multi-strain and synbiotic interventions were more effective than single-strain or probiotic-only formulations. Sensitivity analyses confirmed the robustness of findings, and publication bias was minimal. These findings support the adjunctive use of targeted, SCFA-oriented probiotic formulations (e.g., with inulin/FOS, ≥10^9-10^10 CFU/day) to mitigate metabolic inflammation alongside standard care. Strain- and dose-standardized RCTs should confirm impacts on glycemic and cardiometabolic outcomes.
H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation
Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first‐line treatments for IBD have limited efficacy and significant side effects. An innovative H2S‐releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO‐1, PI3K‐AKT, and RAS/MAPK/AP‐1, and inhibiting the p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management. An H2S‐releasing montmorillonite nanoformulation (DPs@MMT) is developed by adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels onto the MMT surface. DPs@MMT can remodel intestinal mucosal immune homeostasis by activating Nrf2/HO‐1 and PI3K‐AKT pathways, inhibiting p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways along with HIF‐1‐induced glycolysis; repair mucosal barrier by activating RAS/MAPK/AP‐1 pathway; and modulate gut microbiota by eliminating pathogens and increasing probiotics.