Melendezkilic7211

In vitro studies demonstrated the damage in intracellular DNA double strands and the inhibition of cell proliferation in 4T1 breast cancer cells treated with ROS-induced sensitized RT. A substantial reduction in cell viability was also observed owing to the effects of the combination of photo-mediated treatments with sensitized RT compared to the effects of RT administration alone. Complete eradication of the primary tumor and the inhibition of lung metastasis was observed in five of six orthotopic 4T1 breast cancer-bearing mice subjected to combined PDT/PTT in nanophototherapeutics with ROS-induced sensitized RT at a low dosage (6 Gy), leading to the prominent survival fraction of ca. 83% over 60 days.Multifunctional nanoplatforms combined with photodynamic therapy (PDT) and anticancer drugs have shown great promising in cancer therapy. However, their efficacy is limited by the low specificity, low oxygen levels, and a tolerant tumor immune microenvironment. Herein, we developed a biocompatible theranostic nanoplatform (FM@VP) based on co-assembly of a nanocomplex formed by a functional polysaccharide fucoidan and a bioreducible polyamidoamine (PAMAM) dendrimer, a photosensitizer verteporfin (VP), and MnO2 nanoparticles (a tumor microenvironment responsive oxygen evolving nanomaterial) into a multifunctional nanoparticle cluster. The dendrimer-fucoidan polyionic nanocomplex (DFPN) specifically targeted P-selectin-overexpressed triple-negative breast cancer (TNBC) and the tumor-associated vasculature, and was sensitive to glutathione (GSH) in tumor. More importantly, this FM@VP nanocomplex simultaneously overcame tumor hypoxia, suppressed oncogenic signaling, and attenuated tumor-mediated immunosuppression, resulting in improving therapeutic efficacy of PDT while enhancing antitumor immunity and anti-metastasis. This discovery provides a powerful strategy for synergetic cancer targeting/photodynamic/immunotherapy and could serve as a safe clinical translational approach.

Tumors with seizures as primary mode of presentation are collectively called Long-term epilepsy associated tumors (LEATs or Epileptomas). The overall survival is good so 'seizure outcome' becomes the primary goal rather than neuro-oncological outcome.

A retrospective analysis of our surgical database (2015-19) was done to find operated patients of intra-axial brain tumors with age less than 25-years and who had presented with seizures.

The mean age at presentation was 16.44 years (SD + 6.82 years). Complex partial seizures/focal unaware seizures were the most common type of seizures encountered (n = 22) with mean duration of seizures was 49.50 months (SD + 31.04 months). The most common pathology was glioneuronal tumors (GNTs) (n = 17). Gross total resection (GTR) group had a significantly better seizure outcome as compared with the Subtotal resection (STR) group (p = 0.006). Presence of focal or partial seizure was a significant factor pointing towards a better seizure control (p = 0.005).

The shorter duration of symptoms, partial/focal seizures and gross total excision were predictors of a good seizure-outcome. Age of the patient and the histopathology of the tumor does not affect seizure-outcome on comparing GNTs with non GNTs.

The shorter duration of symptoms, partial/focal seizures and gross total excision were predictors of a good seizure-outcome. Age of the patient and the histopathology of the tumor does not affect seizure-outcome on comparing GNTs with non GNTs.Nanoparticle-based CRISPR/Cas9 delivery systems hold great promise for specific and precise treatment of genetic disorder diseases. Herein, we developed a DNA nanoflower-based platform for microRNA-responsive cytosolic delivery of Cas9/sgRNA complex into tumor cells. The biocompatible DNA nano-vehicles can efficiently load Cas9/sgRNA by sequence hybridization. Importantly, this hybridization can be replaced by a tumor specific miRNA through toehold-mediated strand displacement process and achieve cell-type-specific release of Cas9/sgRNA from the DNA nanoflowers. 3-TYP We have verified that this miRNA-responsive releasing process can significantly improve the genome editing efficiency comparing with non-responsive control. This strategy suggests a versatile way for designing more specific and efficient CRISPR-based genome therapy system by incorporating stimuli-responsive Cas9/sgRNA release process.The clustered regularly interspaced short palindromic repeat (CRISPR) systems have a wide variety of applications besides precise genome editing. In particular, the CRISPR/dCas9 system can be used to control specific gene expression by CRISPR activation (CRISPRa) or interference (CRISPRi). However, the safety concerns associated with viral vectors and the possible off-target issues of systemic administration remain huge concerns to be safe delivery methods for CRISPR/Cas9 systems. In this study, a layer-by-layer (LbL) self-assembling peptide (SAP) coating on nanofibers is developed to mediate localized delivery of CRISPR/dCas9 systems. Specifically, an amphiphilic negatively charged SAP- is first coated onto PCL nanofibers through strong hydrophobic interactions, and the pDNA complexes and positively charged SAP+-RGD are then absorbed via electrostatic interactions. The SAPcoated scaffolds facilitate efficient loading and sustained release of the pDNA complexes, while enhancing cell adhesion and proliferation. As a proof of concept, the scaffolds are used to activate GDNF expression in mammalian cells, and the secreted GDNF subsequently promotes neurite outgrowth of rat neurons. These promising results suggest that the LbL self-assembling peptide coated nanofibers can be a new route to establish a bioactive interface, which provides a simple and efficient platform for the delivery of CRISPR/dCas9 systems for regenerative medicine.An overview of applications of fiber-optic biochemical sensor in microfluidic chips was carried out with a specific focus on different fiber-optic sensors used on chip, detection methods and biochemical application. First, the structure and sensing mechanism of different fiber-optic sensors used on chip was introduced. Second, optical detection methods in microfluidic chips combined with optical fibers and the advantages and disadvantages of each method were introduced and analyzed in detail. Then, applications of fiber-optic biochemical sensors in microfluidic sensor chips in detecting nucleic acids, proteins, cells, chemicals and microfluidic flow rate were classified and introduced, and different fiber-optic biochemical sensors in microfluidic chip were compared. Finally, a prospect of future development of fiber-optic biochemical sensor combined with microfluidic chip was addressed.Cancer-derived exosomes have recently emerged as potent candidates for diagnosis and prognosis of breast cancer. As an example, programmed death ligand-1 positive (PD-L1+) exosomes are found to be correlated with the progression and immunotherapy response of breast cancer, and therefore show great potential in liquid biopsy. Herein, we propose an electrochemical biosensing method for accurate identification of PD-L1+ exosomes by using DNA amplification-responsive metal-organic frameworks, PVP@HRP@ZIF-8. Specially, PD-L1+ exosomes are captured by anti-CD63 functionalized magnetic beads and bound with anti-PD-L1-linked capture probe. Then, in situ hyperbranched rolling circle amplification, a typical DNA amplification reaction, is conducted using the surface-attached capture probes as primers, which lows environmental pH. As a result, disassembly of PVP@HRP@ZIF-8 takes place, leading to the release of enzymes, which can arouse amplified electrochemical responses for the identification of target exosomes. Experimental results reveal that the biosensing method displays a linear range for PD-L1+ exosomes identification from 1 × 103 to 1 × 1010 particles/mL and the detection limit reaches 334 particles/mL. What is more, by using the method, elevated level of circulating PD-L1+ exosomes is found in the undiluted serum samples from patients with breast cancer, particularly for metastatic breast cancer, revealing a positive correlation of the PD-L1+ exosome level with the tumor staging and disease progression of breast cancer. Therefore, the biosensing method may be valuable for not only exosome identification but also providing reference information for diagnosis and real-time monitoring of breast cancer in the future.Aortic dissection (AD) is a condition of the main artery of the human body, resulting in the formation of a new flow channel, or false lumen. The disease is usually diagnosed with a computed tomography angiography scan during the acute phase. A better understanding of the causes of AD requires knowledge of the aortic geometry (segmentation), including the true and false lumina, which is very time-consuming to reconstruct when performed manually on a slice-by-slice basis. Hence, different automatic and semi-automatic medical image analysis approaches have been proposed for this task over the last years. In this review, we present and discuss these computing techniques used to segment dissected aortas, also in regard to the detection and visualization of clinically relevant information and features from dissected aortas for customized patient-specific treatments.Several studies have shown an association between asthma and opiate abuse. This retrospective study aims to analyse the demographic, toxicological, and seasonal differences in asthmatic and non-asthmatic subjects who died of opiates. In addition, the relationship between toxicological levels of opiates and histologic grade of lung inflammation is examined. Deaths from 2013 to 2018 involving opiates as the primary cause of death in Cook County, Illinois (USA) were reviewed. Twenty-six cases of opiate deaths of individuals with a history of asthma and lung histology slides available were identified. In comparison, 40 cases of deaths due to opiates only were analysed. A check-list system for the evaluation of the grade of microscopic inflammation in asthma was developed. We found statistically significant differences between the asthmatics and the non-asthmatics regarding demography (age and race) and toxicology (6-MAM presence). In particular, the "opiate and asthma group" was mainly composed of African-American subjects, in contrast with the "opiate group", consisting mostly of Caucasian. The mean age was significantly higher in the "opiate and asthma group" compared with the "opiate group". A greater presence of 6-MAM was detected in the "opiate group" compared with the "opiate and asthma group". While we expected to find that low opiate levels would lead to deaths in asthmatics and, in particular, that lower opiate concentrations would cause deaths in subjects with higher grades of histologic inflammation, our study suggests that the quantity of drug and the level of inflammation are not statistically significant in the determination of death. We, therefore, recommend histologic examination of the lungs to evaluate for asthma, particularly in suspected low-level opiate-related deaths, to help further clarify any relationship between asthma and opiate use.