Danielsenkang8445
Most intravenously administered drug-loaded nanoparticles are taken up by liver Kupffer cells, and only a small portion can accumulate at the tumor, resulting in an unsatisfactory therapeutic efficacy and side effects for chemotherapeutic agents. Tumor-targeted drug delivery proves to be the best way to solve this problem; however, the complex synthesis, or surface modification process, together with the astonishing high cost make its clinical translation nearly impossible.
Referring to Ouyang's work and over-threshold dosing theory in general, blank PEGylated liposomes (PEG-Lipo) were prepared and used as tumor delivery enhancers to determine whether they could significantly enhance the tumor accumulation and in vivo antitumor efficacy of co-injected liposomal ACGs (PEG-ACGs-Lipo), a naturally resourced chemotherapeutic. Here, the phospholipid dose was used as an indicator of the number of liposomes particles with similar particle sizes, and the liposomes was labelled with DiR, a near-red fluorescent prof liposomal ACGs (the same dose of ACGs at 50mg/kg of equivalent phospholipids) achieved a similar tumor inhibition rate (TIR) to that of co-injection. In the U87 MG tumor-bearing mouse model, co-injection of the enhancer also significantly promoted the TIR (83.32% vs. 66.80%, P < 0.05) and survival time of PEG-ACGs-Lipo.
An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs.
An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs.
The present study was conducted to determine if using α
-adrenergic agonists results in decreased stress levels (lower cortisol levels) in goats used for laparoscopic embryo [somatic cell nuclear transfer (SCNT)] transfer; and there is an effect on pregnancy rate when stress levels are lessened. Sixty healthy does aged 24 ± 4 months and weighing 30 ± 3 kg were used in experimental, prospective, randomized and blinded study. In this study, embryos were obtained by the Somatic Cell Nuclear Transfer (SCNT) method. Animals were randomly assigned to five groups control (normal saline); xylazine (100 μg kg
); detomidine (50 μg kg
); medetomidine (20 μg kg
); and dexmedetomidine (5 μg kg
). Embryo transfer (through laparoscopic technique) began at 15 min and continued till 45 min post-treatment. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), and ruminal motility were performed before (baseline) and after drug administration. Pregnancy detection was performed 38 days after embryo transfer.
sing the pregnancy rate of recipient goats receiving cloned embryos. No significant differences were detected among different α2-adrenergic agonists.Two-dimensional (2D) transition metal dichalcogenide (TMD) nanosheets (e.g., MoS2) with metallic phase (1T or 1T´ phase) have been proven to exhibit superior performances in various applications as compared to their semiconducting 2H-phase counterparts. However, it remains unclear how the crystal phase of 2D TMD nanosheets affects their sonodynamic property. In this work, we report the preparation of MoS2 nanosheets with different phases (metallic 1T/1T´ or semiconducting 2H) and exploration of its crystal-phase effect on photothermal-enhanced sonodynamic antibacterial therapy. Interestingly, the defective 2D MoS2 nanosheets with high-percentage metallic 1T/1T´ phase (denoted as M-MoS2) present much higher activity towards the ultrasound-induced generation of reactive oxygen species (ROS) as compared to the semiconducting 2H-phase MoS2 nanosheets. More interestingly, owing to its metallic phase-enabled strong absorption in the near-infrared-II (NIR-II) regime, the ultrasound-induced ROS generation performance of the M-MoS2 nanosheets can be further enhanced by the photothermal effect under a 1064 nm laser irradiation. Thus, after modifying with polyvinylpyrrolidone, the M-MoS2 nanosheets can be used as an efficient sonosensitizer for photothermal-enhanced sonodynamic bacterial elimination under ultrasound treatment combining with NIR-II laser irradiation. This study demonstrates that metallic MoS2 nanosheets can be used as a promising sonosensitizer for antibacterial therapy, which might be also promising for cancer therapies.
Ovarian cancer (OC) is an invasive gynaecologic cancer with a high cancer-related death rate. The purpose of this study was to establish an invasion-related multigene signature to predict the prognostic risk of OC.
We extracted 97 invasion-related genes from The Cancer Genome Atlas (TCGA) database. Then, the ConsensusClusterPlus and limma packages were used to calculate differentially expressed genes (DEGs). To calculate the immune scores of the molecular subtypes, we used ESTIMATE to evaluate the stromal score, immune score and ESTIMATE score. MCP-counter and the GSVA package ssgsea were used to evaluate the types of infiltrating immune cells. Survival and nomogram analyses were performed to explore the prognostic value of the signature. Finally, qPCR, immunohistochemistry staining and functional assays were used to evaluate the expression and biological abilities of the signature genes in OC.
Based on the consistent clustering of invasion-related genes, cases in the OC datasets were divided into two sients.
We developed a 6-gene prognostic stratification system (FOXJ1, MXRA5, KIF26B, VSIG4, CXCL9 and COL6A6) that is independent of clinical features. These results suggest that the signature could potentially be used to evaluate the prognostic risk of OC patients.
The increasing use of cerium dioxide nanoparticles (CeO
NPs) in biomedical field has attracted substantial attention about their potential risks to human health. Recent studies have shown that nanoparticles can induce placental dysfunction and even fetal abortion, but a more detailed mechanism of nanoparticles affecting placental development remains elusive.
Here, we constructed a mouse exposure model with different doses of CeO
NPs (2.5, 4, 5, 7.5, and 10mg kg
day
, average particle size 3-5nm), finding that intravenous exposure to pregnant mice with CeO
NPs could cause abnormal placental development. Deposited nanoparticles were able to be observed in the placental trophoblast at doses of 5 and 7.5mg kg
day
. Diving into molecular mechanisms indicated that CeO
NPs exposure could lead to autophagy activation in placental trophoblast. At the cellular level, exposure to CeO
NPs inhibited the migration and invasion of HTR-8/SVneo and activated the autophagy through mammalian target of rapamycin coduced by rare-earth nanoparticles exposure.Extracellular vesicles (EVs) are a group of secretory vesicles with cell-derived membrane and contents. Due to the cargo delivery capability, EVs can be designed as drug delivery platforms for cancer therapy. Biocompatibility and immune compatibility endow EVs with unique advantages compared with other nanocarriers. With the development of this field, multiple ingenious modification methods have been developed to obtain engineered EVs with desired performance. Application of engineered EVs in cancer therapy has gradually shifted from monotherapy to combinational therapy to fight against heterogeneous cancer cells and complex tumor microenvironment. In addition, the strong plasticity and load capacity of engineered EV make it potential to achieve various combinations of cancer treatment methods. In this review, we summarize the existing schemes of cancer combination therapy realized by engineered EVs, highlight the mechanisms and representative examples of these schemes and provide guidance for the future application of engineered EVs to design more effective cancer combination treatment plans.
The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing transmission and guide response activities.
At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS).
Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text.
We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as 'somewhat' or 'very accepting'. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS pelivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.
Patient-reported outcome measures (PROMs) assess patient-relevant effects of medical treatments. We aimed to evaluate the implementation of the International Consortium for Health Outcomes Measurement Standard Set for Stroke (ICHOM-SSS) into routine inpatient care of a stroke unit.
The ICHOM-SSS was administered in a certified stroke unit during and after inpatient care. Semi-structured interviews with medical staff (n= 5) and patients or their proxies (n= 19) about their experience were audio-recorded and analysed using thematic analyses. Implementation outcomes were chosen in advance and adhered to current standards of implementation science.
Patients perceived the ICHOM-SSS to be relevant and feasible. They reported limited understanding of why the assessment was introduced. The overall acceptance of using PROMs was high. While medical staff, too, perceived the assessment to be appropriate and relevant, their appraisal of feasibility, sustainability, and their acceptance of the implementation were low.
For a sustainable implementation of PROMs in clinical practice, IT resources need to be adapted, medical care needs to be reorganized, and additional clinical resources are required. Lirafugratinib chemical structure Future research should investigate benefits of the ICHOM-SSS and a simpler, automated implementation in stroke care.
ClinicalTrials.gov Identifier NCT03795948 ,retrospectively registered on 8 January 2019.
ClinicalTrials.gov Identifier NCT03795948 , retrospectively registered on 8 January 2019.
Human rights are best protected, promoted and guaranteed when they can compel binding and enforceability duty. One prominent criticism of category of human rights which includes the human right to health is that it is difficult, to assign the duties that correspond to these rights, because of stark disparity in how the main duty bearers approach their duties.
This paper adopts a doctrinal approach to examine and evaluate the duties to the right to health. The method in this study entails a detailed literature search to systematically evaluate the legal implications, regulations, arguments and policy regarding the nature of the obligation to the right to health. This study also engages with normative and philosophical aspects of human rights.
This paper posits that human rights protect against common, serious, and remediable threats and risks, and ensure that there are remedies from governments and third parties. However, it is difficult to compel duties especially in regard to the right to health. First it is not easy to achieve a uniform standard for duty bearers implied by the words 'highest attainable physical and mental health.
