Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy.

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

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.

Do not stumble over the same "stone" twice: a case series of endogenous endophthalmitis secondary to severe systemic diseases.

BACKGROUND: Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. CASE PRESENTATION: This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. CONCLUSIONS: Our observation suggest that prompt identification and treatment could save patients' vision from EE.

Functionalized MoS2-nanosheets with NIR-Triggered nitric oxide delivery and photothermal activities for synergistic antibacterial and regeneration-promoting therapy.

Bacterial infection in skin and soft tissue has emerged as a critical concern. Overreliance on antibiotic therapy has led to numerous challenges, including the emergence of multidrug-resistant bacteria and adverse drug reactions. It is imperative to develop non-antibiotic treatment strategies that not only exhibit potent antibacterial properties but also promote rapid wound healing and demonstrate biocompatibility. Herein, a novel multimodal synergistic antibacterial system (SNO-CS@MoS2) was developed. This system employs easily surface-modified thin-layer MoS2 as photothermal agents and loaded with S-nitrosothiol-modified chitosan (SNO-CS) via electrostatic interactions, thus realizing the combination of NO gas therapy and photothermal therapy (PTT). Furthermore, this surface modification renders SNO-CS@MoS2 highly stable and capable of binding with bacteria. Through PTT's thermal energy, SNO-CS@MoS2 rapidly generates massive NO, collaborating with PTT to achieve antibacterial effects. This synergistic therapy can swiftly disrupt the bacterial membrane, causing protein leakage and ATP synthesis function damage, ultimately eliminating bacteria. Notably, after effectively eliminating all bacteria, the residual SNO-CS@MoS2 can create trace NO to promote fibroblast migration, proliferation, and vascular regeneration, thereby accelerating wound healing. This study concluded that SNO-CS@MoS2, a novel multifunctional nanomaterial with outstanding antibacterial characteristics and potential to promote wound healing, has promising applications in infected soft tissue wound treatment.

Biodegradable Hollow-Structured Nanozymes Modulate Phenotypic Polarization of Macrophages and Relieve Hypoxia for Treatment of Osteoarthritis.

Nanozymes are widely applied for treating various major diseases, including neurological diseases and tumors. However, the biodegradability of nanozymes remains a great challenge, which hinders their further clinical translation. Based on the microenvironment of osteoarthritis (OA), a representative pH-responsive biodegradable hollow-structured manganese Prussian blue nanozyme (HMPBzyme) is designed and applied for treatment of OA. HMPBzyme with good pH-responsive biodegradability, biocompatibility, and multi-enzyme activities is constructed by bovine serum albumin bubbles as a template-mediated biomineralization strategy. HMPBzyme suppresses hypoxia-inducible factor-1α (HIF-1α) expression and decreases reactive oxygen species (ROS) level in the in vitro experiment. Furthermore, HMPBzyme markedly suppresses the expression of ROS and alleviates the degeneration of cartilage in OA rat models. The results indicate that the biodegradable HMPBzyme inhibits oxidative damage and relieves hypoxia synergistically to suppress inflammation and promote the anabolism of cartilage extracellular matrix by protecting mitochondrial function and down-regulating the expression of HIF-1α, which modulates the phenotypic conversion of macrophages from pro-inflammatory M1 subtype to anti-inflammatory M2 subtype for OA treatment. This research lays a solid foundation for the design, construction, and biomedical application of biodegradable nanozymes and promotes the application of nanozymes in biomedicine.

Circ_0008673 regulates breast cancer malignancy by miR-153-3p/CFL2 axis.

BACKGROUND: Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway. METHODS: The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo. RESULTS: Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo. CONCLUSION: Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.

Elevated Preoperative NMPR Predicts an Unfavorable Chance of Survival in Resectable Esophageal Squamous Cell Carcinoma.

Background and objectives: Combined peripheral neutrophil−platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil−platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil−meanplateletvolume−platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy.

Weighted gene co-expression network-based approach to identify key genes associated with anthracycline-induced cardiotoxicity and construction of miRNA-transcription factor-gene regulatory network.

BACKGROUND: Cardiotoxicity is a common complication following anthracycline chemotherapy and represents one of the serious adverse reactions affecting life, which severely limits the effective use of anthracyclines in cancer therapy. Although some genes have been investigated by individual studies, the comprehensive analysis of key genes and molecular regulatory network in anthracyclines-induced cardiotoxicity (AIC) is lacking but urgently needed. METHODS: The present study integrating several transcription profiling datasets aimed to identify key genes associated with AIC by weighted correlation network analysis (WGCNA) and differentially expressed analysis (DEA) and also constructed miRNA-transcription factor-gene regulatory network. A total of three transcription profiling datasets involving 47 samples comprising 41 rat heart tissues and 6 human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) samples were enrolled. RESULTS: The WGCNA and DEA with E-MTAB-1168 identified 14 common genes affected by doxorubicin administrated by 4 weeks or 6 weeks. Functional and signal enrichment analyses revealed that these genes were mainly enriched in the regulation of heart contraction, muscle contraction, heart process, and oxytocin signaling pathway. Ten (Ryr2, Casq1, Fcgr2b, Postn, Tceal5, Ccn2, Tnfrsf12a, Mybpc2, Ankrd23, Scn3b) of the 14 genes were verified by another gene expression profile GSE154603. Importantly, three key genes (Ryr2, Tnfrsf12a, Scn3b) were further validated in a hiPSCMs-based in-vitro model. Additionally, the miRNA-transcription factor-gene regulatory revealed several top-ranked transcription factors including Tcf12, Ctcf, Spdef, Ebf1, Sp1, Rcor1 and miRNAs including miR-124-3p, miR-195-5p, miR-146a-5p, miR-17-5p, miR-15b-5p, miR-424-5p which may be involved in the regulation of genes associated with AIC. CONCLUSIONS: Collectively, the current study suggested the important role of the key genes, oxytocin signaling pathway, and the miRNA-transcription factor-gene regulatory network in elucidating the molecular mechanism of AIC.

L-Arg-Rich Amphiphilic Dendritic Peptide as a Versatile NO Donor for NO/Photodynamic Synergistic Treatment of Bacterial Infections and Promoting Wound Healing.

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H2 O2 generated during PDT to oxidize Arg-ADP to NO and l-citrulline, without affecting singlet oxygen (1 O2 ) production. The combination of 1 O2 and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.

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.

Biodegradable reduce expenditure bioreactor for augmented sonodynamic therapy via regulating tumor hypoxia and inducing pro-death autophagy.

BACKGROUNDS: Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor strategy is challenged by the rapid depletion of oxygen, as well as the hypoxic tumor microenvironment. Instead of the presently available coping strategies that amplify the endogenous O2 level, we have proposed a biodegradable O2 economizer to reduce expenditure for augmenting SDT efficacy in the present study. RESULTS: We successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) via conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (hematoporphyrin monomethyl ether; HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia conditions. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induced excessive activation of autophagy for promoting the therapeutic efficacy. As a result, when accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP could achieve the remarkable antitumor activity, which was systematically validated both in vivo and in vitro assays. CONCLUSIONS: This work not only provides a reduce expenditure means for enduring SDT, but also represents an inquisitive strategy for tumor treatments by inducing pro-death autophagy.

Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation.

BACKGROUND: The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake. RESULTS: Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106 cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy. CONCLUSIONS: This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies.

Chemical constituents of radix Actinidia chinensis planch by UPLC-QTOF-MS.

Radix Actinidia decoction and its prescriptions are used to treat tumors and other diseases. Although some chemical components have been isolated from Radix Actinidia, systematic analysis of its chemical components has not been reported, which hinders the basic research on its effective substances and its quality control. In this work, a UPLC-QTOF-MS method was employed to profile and characterize the chemical constituents of water extracts from Radix Actinidia Chinensis Planch (RACP). We unambiguously or tentatively identified 295 chemical components from RACP, including 46 pentacyclic triterpenes, 72 flavonoids, 53 phenolic acids, 24 coumarins, three anthraquinones and other compounds. Most of the chemical components have not been described so far in Actinidia. More than 180 phytochemicals are reported in Actinidia for the first time. 2α,3α,24-trihydroxyurs-12-en-28-oic acid, asiatic acid, syringic acid, fraxin, esculetin, 5,7-dihydroxychromone, esculin, (+)-catechin, (-)-epi-catechin, vanillic acid, ferulic acid, protocatechuic acid and rutin were unambiguously identified by comparison with the reference standards. Catechin derivatives, coumarin derivatives and phenolic acid derivatives were the main water-soluble components in RACP. This study broadened the chemical profiles of RACP, and laid the foundation for subsequent research on the effective components and their mechanism of action. This work also provides an important reference for the quality control and evaluation of RACP.

miR-124a enhances therapeutic effects of bone marrow stromal cells transplant on diabetic nephropathy-related epithelial-to-mesenchymal transition and fibrosis.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has been gradually considered as one of the major pathways that causes the production of interstitial myofibroblasts in diseased kidneys. MATERIALS AND METHODS: The study was done to investigate the effect of a bone marrow stromal cell (BMSCs) transplant on rat podocytes and diabetic nephropathy (DN) rats in high-glucose concentration, and to explore the effect of miR-124a on BMSC therapy. High glucose-injured podocytes and streptozotocin-induced DN rats have been respectively used as injury models in in vitro and in vivo studies. Podocyte viability was measured using the Cell Counting Kit-8 assay. Renal pathological examination was observed by HE staining and Masson staining. The messenger RNA and protein levels were determined via real-time polymerase chain reaction and Western blotting, respectively. RESULTS: By mediating the activation of caveolin-1 (cav-1) and ß-catenin and affecting the expression levels of EMT biomarkers including p-cadherin, synaptopodin, fibroblast-specific protein-1, α-smooth muscle actin and snail, our in vitro study confirmed that miR-124a played a significant role in the treatment of high glucose-induced podocyte injury by BMSCs. The therapeutic effects of the BMSC transplant on DN rats were also proved to be further enhanced by miR-124a overexpression in BMSCs, and such a phenomenon was accompanied by the improvement of renal fibrosis and mitigation of DN-related kidney impairment. Regulation of fibronectin, collagen1, and EMT-related proteins was closely implicated with the mechanism, and the activation of cav-1 and ß-catenin was also possibly involved. CONCLUSION: The study demonstrated the pivotal effect of miR-124a on BMSC therapy for DN rats via mitigating EMT and fibrosis. Our results provide a novel insight into how therapeutic effects of BMSCs can be improved at the posttranscriptional level.

Protosappanin-A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT-mTOR signaling.

Protosappanin-A (PrA) and oleanolic acid (OA), which are important effective ingredients isolated from Caesalpinia sappan L., exhibit therapeutic potential in multiple diseases. This study focused on exploring the mechanisms of PrA and OA function in podocyte injury. An in vitro model of podocyte injury was induced by the sC5b-9 complex and assays such as cell viability, apoptosis, immunofluorescence, quantitative real-time polymerase chain reaction, and western blot were performed to further investigate the effects and mechanisms of PrA and OA in podocyte injury. The models of podocyte injury were verified to be successful as seen through significantly decreased levels of nephrin, podocin, and CD2AP and increased level of desmin. The sC5b-9-induced podocyte apoptosis was inhibited in injured podocytes treated with PrA and OA, accompanied by increased protein levels of nephrin, podocin, CD2AP, and Bcl2 and decreased levels of desmin and Bax. The p-AKT/p-mTOR levels were also reduced by treatment of PrA and OA while AKT/mTOR was unaltered. Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K-AKT inhibitor). PrA and OA were also seen to inhibit podocyte apoptosis and p-AKT/p-mTOR levels induced by IGF-1 (a PI3K-AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT-mTOR signaling.

Hollow Prussian Blue Nanozymes Drive Neuroprotection against Ischemic Stroke via Attenuating Oxidative Stress, Counteracting Inflammation, and Suppressing Cell Apoptosis.

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen and nitrogen species (RONS) following ischemic insult is known as a key factor in exacerbating brain damage. Thus, RONS scavengers that can block excessive production of RONS have great therapeutic potential. Herein, we propose an efficient treatment strategy in which an artificial nanozyme with multienzyme activity drives neuroprotection against ischemic stroke primarily by scavenging RONS. Specifically, through a facile, Bi3+-assisted, template-free synthetic strategy, we developed hollow Prussian blue nanozymes (HPBZs) with multienzyme activity to scavenge RONS in a rat model of ischemic stroke. The comprehensive characteristics of HPBZs against RONS were explored. Apart from attenuating oxidative stress, HPBZs also suppressed apoptosis and counteracted inflammation both in vitro and in vivo, thereby contributing to increased brain tolerance of ischemic injury with minimal side effects. This study provides a proof of concept for a novel class of neuroprotective nanoagents that might be beneficial for treatment of ischemic stroke and other RONS-related disorders.

Influence of remote ischemic conditioning on radial artery occlusion.

This study aimed to explore the influence of remote ischemic conditioning (RIC) on radial artery occlusion (RAO) and distinguish the risk factors for RAO. A total of 640 consecutive patients who prospectively underwent transradial artery coronary angiography (TRACA) (322 patients received RIC before TRACA) were enrolled. RIC was not performed in 318 patients. RAO was estimated using Doppler ultrasonography after the procedure. Patients were divided into two groups according to the protocol of RIC: RIC and non-RIC. The rate of RAO was significantly lower in the RIC group than in the non-RIC group. Patients were divided into two groups according to the patency of radial artery: radial artery patency (RAP) and RAO. The radial artery diameter was significantly narrower in the RAO group (2.31 ± 0.53) than in the RAP group (2.59 ± 0.47). The rate of applying ß-blocker was significantly higher in the RAP group (69%) than in the RAO group (41%). The rate of applying trimetazidine was significantly higher in the RAP group (49.1%) than in the RAO group (17.6%). The multiple logistic regression analysis using radial artery diameter, RIC, ß-blocker, and trimetazidine treatments revealed that small radial artery diameter, lack of ß-blockers, and RIC were independent predictors of RAO. RIC might help in improving the rate of RAO. The multiple logistic regression analysis showed that the lack of ß-blockers, RIC, and small radial artery diameter were independent predictors of RAO.

A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study.

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer's agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of m/z 531.2 → 383.1 and m/z 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL (R² = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2-86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D.

Efficacy of different drugs in the treatment of minimal hepatic encephalopathy: A network meta-analysis involving 826 patients based on 10 randomized controlled trials.

Minimal hepatic encephalopathy (MHE), a complex neuropsychological complication of cirrhosis, is characterized by delayed reaction time and the inhibition of abnormal response. This network meta-analysis (NMA) was adopted to compare the efficacy of five drugs including lactulose, probiotics, rifaximin, acetyl-L-carnitine (ALC), and L-Ornithine L-aspartate (LOLA) in the treatment of MHE. The Cochrane Library, PubMed, and Embase databases were searched for any existing entail on these five drugs from the inception to February 2018, including Randomized controlled trials (RCTs). The NMA of the five drugs, accounting for both direct and indirect comparisons to assess WMD (weighted mean difference) and SUCRA (surface under the cumulative ranking curves) was conducted. In total, 10 RTCS with 826 MHE patients met the inclusion criteria and were included in the NMA. The meta-analysis revealed that compared with placebo, lactulose, and probiotics had better efficacy in reducing ammonia serum levels and total SIP (Sickness Impact Profil) score; ALC had better efficacy in lowering serum level of ammonia and increasing the serum level of albumin; rifaximin and LOLA had better efficacy in reducing total SIP score. The results from SUCRA revealed that in terms of ammonia and albumin serums, ALC presented with the highest rankings when it comes to efficacy (serum ammonia: 87.2%; serum albumin: 92.25%). Hence, the key findings from the present study highly suggested that ALC had the best efficacy in the treatment of MHE patients.

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.