A carrier-free nanovaccine combined with cancer immunotherapy overcomes gemcitabine resistance.

Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.

A comprehensive evaluation and meta-analysis of the perioperative and oncological outcomes of robotic radical prostatectomy using the DaVinci vs the Hugo RAS surgical platforms.

Because of the increasing popularity of Hugo RAS as a surgical platform, a comparison examination of intraoperative and oncological outcomes across DaVinci and Hugo RAS robotic surgery platforms is urgently needed. We carried out a comprehensive review and meta-analysis of the literature of current research, comprehensively searching PubMed, Cochrane and Embase for eligible studies comparing the results between the DaVinci and Hugo RAS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were followed in the conduct of this study, with language restricted to English and a final search date of June 2024. We excluded articles composed solely of conference abstracts and irrelevant content. Composite outcomes were assessed using weighted mean differences (WMD) and odds ratios (ORs). The risk of bias in individual research was assessed using the Newcastle-Ottawa Scale (NOS), and heterogeneity and bias risk were controlled for using a sensitivity analysis. Six studies in all were considered, comprising 1025 patients, including 626 DaVinci patients and 399 Hugo RAS patients. Review Manager V5.4.1 software (Cochrane Collaboration, Oxford, UK) was utilized to conduct the meta-analysis, including 6 trials, which demonstrated that compared to Hugo RAS, DaVinci was associated with statistically significant differences in several outcomes: a reduction in operative time (OT) (WMD - 8.46, 95% CI - 13.56 to 3.36; p = 0.001), an increase in estimated blood loss (EBL) (WMD 41.68, 95% CI 23.59 to 59.77; p < 0.00001), and an increased pelvic lymphadenectomy ratio (OR 1.5, 95% CI 1.05-2.05; p = 0.01). On the contrary, there were no statistically noteworthy differences in the length of hospital stay (LOS) between the two teams (WMD - 0.05, 95% CI - 0.14 to 0.04; p = 0.25), nerve sparing (unilateral or bilateral) (OR 0.96, 95% CI 0.68-1.35; p = 0.8), postoperative complications (OR 1.15, 95% CI 0.50-2.64; p = 0.75), or positive surgical margins (PSM) (OR 1.08, 95% CI 0.76-1.54; p = 0.68). Although DaVinci offers shorter operating times (OT) and increased pelvic lymph node dissection rates, Hugo RAS demonstrates lower estimated blood loss (EBL). Overall, Hugo RAS Robot-Assisted Radical Prostatectomy (RARP) results seem to be similar to those obtained with the DaVinci system. Further research and long-term follow-up are necessary to ascertain durable oncological and functional outcomes, allowing doctors to switch between robotic systems and use their skills. These findings are crucial for patients, surgeons, and healthcare policymakers and warrant future studies with extended follow-up.

Pseudorabies Virus UL4 protein promotes the ASC-dependent inflammasome activation and pyroptosis to exacerbate inflammation.

Pseudorabies virus (PRV) infection causes systemic inflammatory responses and inflammatory damages in infected animals, which are associated with the activation of inflammasome and pyroptosis in infected tissues. Here, we identified a critical function of PRV non-structural protein UL4 that enhanced ASC-dependent inflammasome activation to promote pyroptosis. Whereas, the deficiency of viral UL4 was able to reduce ASC-dependent inflammasome activation and the occurrences of pyroptosis. Mechanistically, the 132-145 aa of UL4 permitted its translocation from the nucleus to the cytoplasm to interact with cytoplasmic ASC to promote the activation of NLRP3 and AIM2 inflammasome. Further research showed that UL4 promoted the phosphorylation levels of SYK and JNK to enhance the ASC phosphorylation, which led to the increase of ASC oligomerization, thus promoting the activation of NLRP3 and AIM2 inflammasome and enhanced GSDMD-mediated pyroptosis. In vivo experiments further showed that PRV UL4 (132DVAADAAAEAAAAE145) mutated strain (PRV-UL4mut) infection did not lead to a significant decrease in viral titers at 12 h. p. i, but it induced lower levels of IL-1ß, IL-18, and GSDMD-NT, which led to an alleviated inflammatory infiltration and pathological damage in the lungs and brains, and a lower death rate compared with wild-type PRV strain infection. Taken together, our findings unravel that UL4 is an important viral regulator to manipulate the inflammasome signaling and pyroptosis of host cells to promote the pathogenicity of PRV, which might be further exploited as a new target for live attenuated vaccines or therapeutic strategies against pseudorabies in the future.

The development of anti-PD-1 antibody-induced spinal cord injury in bone marrow transplant C57BL/6 Rag1-/- mouse model.

Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI).Methods: Bone marrow transplant Rag1-/- mice were used to establish SCI model.Results: Anti-PD-1 results in SCI via CD8+ T-cells activation, while excessive activation of CD8+ T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8+ T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8+ T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8+ T-cells activation via perforin/GrB/PI-9/FasL pathways.Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.

What is this article about? In the process of treating cancer, immune checkpoint inhibitors such as anti-programmed death 1 (anti-PD-1) therapy, as a form of immunotherapy, have developed rapidly and changed the way to manage cancers significantly. However, some cancer patients who receive immune checkpoint blockade treatment suffer from severe adverse effects including spinal cord injury (SCI). This article for the first time constructed a bone marrow transplant mouse model to explore the toxicity mechanism of anti-PD-1 therapy-caused SCI.What were the results? We found that anti-PD-1 therapy can induce the activation of immune cells, while immune cell activation further promotes self-destruction of nerve cells by regulating cell death pathways.What do the results of the study mean? The mechanism of anti-PD-1 therapy-caused SCI is to activate of immune cells through regulating cell death pathways, thereby inducing self-destruction of nerve cells. These findings provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1 therapy.

Comparison of single-port versus multi-port robotic assisted partial nephrectomy: a systematic review and meta-analysis of perioperative and oncological outcomes.

The safety and efficacy of single-port and multi-port robot-assisted partial nephrectomy (SP-RAPN and MP-RAPN, respectively) were assessed for treating partial nephrectomy in this study. A systematic review of PubMed, Cochrane Library, and Web of Science databases was conducted up to June 2024 to compare studies on SP-RAPN and MP-RAPN. Primary outcomes included perioperative results, complications, and oncological outcomes. Eight studies involving 1014 patients were analyzed. For binary outcomes, comparisons were performed using odds ratios (OR), and for continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CI). The search failed to discover significant meaningful variations in operating times (p = 0.54), off-clamp procedure (P = 0.36), blood loss (p = 0.31), positive surgical margins (PSMs) (p = 0.78), or major complications (Clavien-Dindo grade ≥ 3) (p = 0.68) between SP-RAPN and MP-RAPN. However, shorter hospital stays (WMD - 0.26 days, 95% CI - 0.36 to - 0.15; p < 0.00001) and longer warm ischemia times (WIT) (WMD 3.13 min, 95% CI 0.81-5.46; p = 0.008) were related to SP-RAPN, and higher transfusion rate (OR 2.99, 95% CI 1.31-6.80; p = 0.009) compared to MP-RAPN. SP-RAPN performed better in terms of hospital stay but had slightly higher rates of transfusion, off-clamp procedures, and warm ischemia time (WIT) compared to MP-RAPN. As an emerging technology, preliminary research suggests that SP-RAPN is a feasible and safe method for carrying out a nephrectomy partial. However, compared to MP-RAPN, it shows inferior outcomes regarding (WIT) and transfusion rates.

Inhibition of Proliferation and Induction of Apoptosis in Prostatic Carcinoma DU145 Cells by Polysaccharides from Yunnan Rosa roxburghii Tratt.

OBJECTIVE: This study aimed to investigate methodologies for the extraction and purification of polysaccharides from Rosa roxburghii Tratt fruits and their impact on various cellular processes in prostate cancer DU145 cells, including survival rate, migration, invasion, cell cycle, and apoptosis. RESULTS: Compared to the control group, the polysaccharide exhibited a significant reduction in the viability, migration, and invasion rates of DU145 cells in a time- and dose-dependent manner within the polysaccharide-treated groups. Additionally, it effectively arrested the cell cycle of DU145 cells at the G0/G1 phase by downregulating the expressions of CDK-4, CDK-6, and Cyclin D1. Furthermore, it induced apoptosis by upregulating the expressions of Caspase 3, Caspase 8, Caspase 9, and BAX. METHODS: Polysaccharides were extracted from Rosa roxburghii Tratt sourced from Yunnan, China. Extraction and decolorization methods were optimized using response surface methodology, based on a single-factor experiment. Polysaccharide purification was carried out using DEAE-52 cellulose and Sephadex G-100 column chromatography. The optimal dosage of R. roxburghii Tratt polysaccharide affecting DU145 cells was determined using the CCK-8 assay. Cell migration and invasion were assessed using transwell and scratch assays. Flow cytometry was employed to analyze the effects on the cell cycle and apoptosis. Western blotting and Quantitative real-time PCR were utilized to examine protein and mRNA expressions in DU145 cells, respectively. CONCLUSIONS: Rosa roxburghii Tratt polysaccharides, consisting of D-mannose, L-rhamnose, N-acetyl-D-glucosamine, D-galacturonic acid, D-glucose, D-galactcose, D-xylose, L-arabinose, and L-fucose, possess the ability to hinder DU145 cell proliferation, migration, and invasion while inducing apoptosis through the modulation of relevant protein and gene expressions.

Imaging and monitoring of granzyme B in the immune response.

Significant progress has been made in tumor immunotherapy that uses the human immune response to kill and remove tumor cells. However, overreactive immune response could lead to various autoimmune diseases and acute rejection. Accurate and specific monitoring of immune responses in these processes could help select appropriate therapies and regimens for the patient and could reduce the risk of side effects. Granzyme B (GzmB) is an ideal biomarker for immune response, and its peptide substrate could be coupled with fluorescent dyes or contrast agents for the synthesis of imaging probes activated by GzmB. These small molecules and nanoprobes based on PET, bioluminescence imaging, or fluorescence imaging have proved to be highly GzmB specific and accuracy. This review summarizes the design of different GzmB-responsive imaging probes and their applications in monitoring of tumor immunotherapy and overreactive immune response. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Chemotherapy-Induced Neoantigen Nanovaccines Enhance Checkpoint Blockade Cancer Immunotherapy.

Chemotherapeutics have the potential to increase the efficacy of cancer immunotherapies by stimulating the production of damage-associated molecular patterns (DAMPs) and eliciting mutations that result in the production of neoantigens, thereby increasing the immunogenicity of cancerous lesions. However, the dose-limiting toxicity and limited immunogenicity of chemotherapeutics are not sufficient to induce a robust antitumor response. We hypothesized that cancer cells in vitro treated with ultrahigh doses of various chemotherapeutics artificially increased the abundance, variety, and specificity of DAMPs and neoantigens, thereby improving chemoimmunotherapy. The in vitro chemotherapy-induced (IVCI) nanovaccines manufactured from cell lysates comprised multiple neoantigens and DAMPs, thereby exhibiting comprehensive antigenicity and adjuvanticity. Our IVCI nanovaccines exhibited enhanced immune responses in CT26 tumor-bearing mice, with a significant increase in CD4+/CD8+ T cells in tumors in combination with immune checkpoint inhibitors. The concept of IVCI nanovaccines provides an idea for manufacturing and artificial enhancement of immunogenicity vaccines to improve chemoimmunotherapy.

Chemotherapy-induced nanovaccines implement immunogenicity equivalence for improving cancer chemoimmunotherapy.

Several chemoimmunotherapies have been approved by the FDA for the treatment of various cancers. Chemotherapy has the potential to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of tumor cells, promoting the release of tumor associated antigens (TAAs), tumor specific antigens (TSAs) and damage associated molecular patterns (DAMPs), and disrupting immunosuppressive microenvironments by tumor debulking. Unfortunately, systemic administration of chemotherapeutics carries side effects of blunting anti-cancer immune response through systemic immunosuppression, which deserves to be explored as an inner contradiction in chemoimmunotherapy. Here, we proposed the hypothesis of "immunogenicity equivalence" in chemoimmunotherapy that chemotherapeutics-induced immunogenic antigens and DAMPs in vitro that can subsequently be incorporated into nanovaccines, which will possess comparable immunostimulatory potential when compared to tumors treated with systemic chemotherapy in vivo. The proteomic analysis confirmed that our nanovaccines contained TAAs, TSAs and DAMPs. Improvement in treatment outcomes in tumor-bearing mice receiving anti-PD-1 and chemotherapy-induced nanovaccines was then observed. Furthermore, we demonstrated the feasibility of replacing long-term chemotherapy with nanovaccines in chemoimmunotherapy. Our nanovaccine strategy would be a general choice for formulating cancer vaccines in personalized medicine.

Pseudorabies virus infection activates the NLRP3 and IFI16 inflammasomes to trigger pyroptosis.

Pseudorabies virus (PRV) preferably invades neural tissue and various organs, whereupon may result in multisystemic lesions. Pyroptosis mediated by proteolytic cleavage of gasdermin D (GSDMD) by inflammatory caspases (caspase-1/4/5/11), is closely associated with the activation of inflammasomes, a multiprotein proinflammatory complex. However, further studies on the mechanisms regarding PRV-induced pyroptosis in its natural host are required. Herein, it is demonstrated that PRV infection triggered GSDMD- not GSDME-mediated pyroptosis in porcine alveolar macrophage cells, resulting in increased secretion of IL-1ß and LDH. During this process, caspase-1 was activated and participated in the cleaving of GSDMD. Interestingly, we found that the viral replication process or protein production is required to induce pyroptotic cell death. Also, our findings showed that PRV triggered NLRP3 inflammasome activation, which was associated with the production of reactive oxygen species (ROS) and potassium efflux. In addition to the NLRP3 inflammasome, the IFI16 inflammasome was also activated. Importantly, the NLRP3- and IFI16- inflammasomes were both involved in pyroptosis during PRV infection. Finally, we observed that the cleaved GSDMD, activated caspase-1, increased IFI16 levels, and elevated NLRP3 protein in PRV-infected tissues (brain and lung), supporting the occurrence of pyroptosis and the activation of NLRP3- and IFI16- inflammasome in PRV-infected pigs. This research advances our understanding of the PRV-mediated inflammatory response and cell death pathways, providing a deeper knowledge of effective treatments for pseudorabies.

Open versus robot-assisted partial nephrectomy for highly complex renal masses: a meta-analysis of perioperitive and functional outcomes.

Robot-assisted partial nephrectomy (RAPN) is increasingly being used for the complex surgical management of renal masses. The comparison of RAPN with open partial nephrectomy (OPN) has not yet led to a unified conclusion with regard to perioperative outcomes. To conduct a systematic review and meta-analysis of the literature on the perioperative outcomes of RAPN compared with OPN. We performed a systematic search in PubMed, Embase, Web of Science, and Cochrane Library database for randomized control trials (RCTs) and non-RCTs that compare OPN to RAPN. The primary outcomes included perioperative, functional and oncologic. The odds ratio (OR) and weighted mean difference (WMD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CIs). Five studies, comprising 936 patients, were included in the meta-analysis. Our findings indicated that there were no significant differences in blood loss, minor complication rate, eGFR decline from baseline, positive surgical margin, and ischemia time between OPN and RAPN. However, RAPN was associated with a shorter hospital stay (WMD 1.64 days, 95% CI - 1.17 to 2.11; p < 0.00001), lower overall complication rate (OR 1.72, 95% CI 1.21-2.45; p < 0.002), lower transfusion rate (OR 2.64, 95% CI 1.39-5.02; p = 0.003) and lower major complication rate (OR 1.76, 95% CI 1.11-2.79; p < 0.02) compared to OPN. Additionally, the operation time for OPN was shorter than that for RAPN (WMD - 10.77 min, 95% CI - 18.49 to - 3.05, p = 0.006). In comparison with OPN, RAPN exhibits better results in terms of hospital stay, overall complications, blood transfusion rate, and major complications, with no significant difference in intraoperative blood loss, minor complications, PSM, ischemia time, and short-term postoperative eGFR decline. However, the operation time of OPN is slightly shorter than that of RAPN.

Perioperative results of single-port vs multi-port robotic-assisted radical prostatectomy via peritoneal approach: a meta-analysis.

To compare the perioperative outcomes of single-port robotic-assisted radical prostatectomy (SP-RARP) and multiport robotic-assisted radical prostatectomy (MP-RARP) via transperitoneal approach, we conducted a comprehensive database search of eligible studies up to October 2022 and compared their results. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and a leave-one-out sensitivity analysis was performed to control for heterogeneity and risk of bias. A total of six articles were included, involving 926 patients, among which 256 underwent SP-RARP and 670 underwent MP-RARP. Comparing the two, SP-RARP was associated with shorter hospitalization time (- 0.5 days; 95% CI - 1.02, - 0.06, p < 0.05) and less intraoperative blood loss (- 29.88 ml; 95% CI - 45.66, - 14.10, p < 0.05). However, there were no significant differences in any complications, operative time, positive surgical margins, or short-term follow-up outcomes (continence and potency at 3 months). These findings provide reference data for the selection of surgical methods in performing transperitoneal RP and support further research on the broad applicability of the SP platform.

Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments.

The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, responsible for severe economic losses to the swine industry worldwide. The interferon-inducible GTPase guanylate-binding protein 1 (GBP1) exhibits antiviral immunity. Our findings show that there is a robust upregulation in the expression of porcine GBP1 during PRV infection. GBP1 knockout promotes PRV infection, while GBP1 overexpression restricts it. Importantly, we found that GBP1 impeded the normal structure of actin filaments in a GTPase-dependent manner, preventing PRV virions from reaching the nucleus. We also discovered that viral US3 protein bound GBP1 to interfere with its GTPase activity. Finally, the interaction between US3 and GBP1 requires US3 serine/threonine kinase activity sites and the GTPase domain (aa 1 to 308) of GBP1. Taken together, this study offers fresh perspectives on how PRV manipulates the host's antiviral immune system.

Advances of functional nanomaterials for magnetic resonance imaging and biomedical engineering applications.

Functional nanomaterials have been widely used in biomedical fields due to their good biocompatibility, excellent physicochemical properties, easy surface modification, and easy regulation of size and morphology. Functional nanomaterials for magnetic resonance imaging (MRI) can target specific sites in vivo and more easily detect disease-related specific biomarkers at the molecular and cellular levels than traditional contrast agents, achieving a broad application prospect in MRI. This review focuses on the basic principles of MRI, the classification, synthesis and surface modification methods of contrast agents, and their clinical applications to provide guidance for designing novel contrast agents and optimizing the contrast effect. Furthermore, the latest biomedical advances of functional nanomaterials in medical diagnosis and disease detection, disease treatment, the combination of diagnosis and treatment (theranostics), multi-model imaging and nanozyme are also summarized and discussed. Finally, the bright application prospects of functional nanomaterials in biomedicine are emphasized and the urgent need to achieve significant breakthroughs in the industrial transformation and the clinical translation is proposed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Construction of a rabbit model with vinorelbine administration via peripherally inserted central catheter and dynamic monitoring of changes in phlebitis and thrombosis.

Peripherally inserted central catheters (PICCs) are used for the administration of chemotherapy drugs, including vinorelbine. The present study aimed to construct a rabbit model with vinorelbine administration via PICC, and to dynamically monitor the formation of phlebitis and thrombosis. PICC was inserted into 48 rabbits following specific clinical procedures. The rabbits were randomly divided (n=6 per group) into the following eight groups: i) Control (PICC in place for 1 day); ii) 2nd day of PICC placement (received the first cycle of vinorelbine administration); iii) 3rd day of PICC placement; iv) 7th day of PICC placement; v) 14th day of PICC placement; vi) 21st day of PICC placement; vii) 23rd day of PICC placement (received the second cycle of vinorelbine administration); and viii) 24th day of PICC placement. Hematoxylin and eosin staining was performed on catheter, ear vein and anterior vena specimens. Prothrombin time was measured using an automatic coagulation analyzer, followed by routine blood tests. Serum levels of inflammation- and thrombosis-related factors, including C-reactive protein, D-dimer, interleukin-2, interleukin-6, P-selectin and E-selectin, were measured using ELISAs. X-ray examination confirmed that the rabbit model with vinorelbine administration via PICC was successfully constructed. On the 1st and 23rd day of PICC placement, thrombosis was observed in the catheter. Furthermore, on the 1st day of PICC placement, thrombosis was clearly observed in the ear vein and anterior vena samples. After vinorelbine administration, phlebitis occurred in the ear vein and anterior vena cava samples. With increasing time after vinorelbine administration via PICC, thrombosis and phlebitis were notably ameliorated. Moreover, on the day of vinorelbine administration, prothrombin time was significantly decreased and the serum levels of inflammation- and thrombosis-related factors were significantly increased compared with previous days. Collectively, the present study observed the formation and specific evolution of phlebitis and venous thrombosis after vinorelbine administration, providing a reference for the early prediction, timely prevention and treatment of PICC-related chemotherapy complications.

Advances of Nanomedicine in Radiotherapy.

Radiotherapy (RT) remains one of the current main treatment strategies for many types of cancer. However, how to improve RT efficiency while reducing its side effects is still a large challenge to be overcome. Advancements in nanomedicine have provided many effective approaches for radiosensitization. Metal nanoparticles (NPs) such as platinum-based or hafnium-based NPs are proved to be ideal radiosensitizers because of their unique physicochemical properties and high X-ray absorption efficiency. With nanoparticles, such as liposomes, bovine serum albumin, and polymers, the radiosensitizing drugs can be promoted to reach the tumor sites, thereby enhancing anti-tumor responses. Nowadays, the combination of some NPs and RT have been applied to clinical treatment for many types of cancer, including breast cancer. Here, as well as reviewing recent studies on radiotherapy combined with inorganic, organic, and biomimetic nanomaterials for oncology, we analyzed the underlying mechanisms of NPs radiosensitization, which may contribute to exploring new directions for the clinical translation of nanoparticle-based radiosensitizers.

Establishment of incontinence-associated dermatitis rat models and assessment of the therapeutic effects of zinc oxide, painless skin protective film and silicone dressing.

The aim of the present study was to construct incontinence-associated dermatitis (IAD) rat models and observe the therapeutic effects of zinc oxide, painless skin protective film and silicone dressing on IAD. A total of 54 rats were randomly divided into nine groups: i) Control group; ii) trypsin model group; iii) model + zinc oxide group; iv) model + painless skin protective film group; v) model + silicon dressing group; vi) synthetic urine combined with trypsin model group (joint model group); vii) joint model + zinc oxide group; viii) joint model + painless skin protective film group; and ix) joint model + silicone dressing group. A total of 4 days after applying the zinc oxide, protective film or silicon dressing intervention, IAD scores and pH values in skin tissues were examined. Skin tissues and blood samples were collected. Hematoxylin and eosin staining, immunohistochemical staining of major histocompatibility complex class II (MHC-II) and western blot analysis of MHC-II, NF-κB/p65, phosphorylated (p)-NF-κB/p65, STAT1 and p-STAT1 were carried out in skin tissue. Serum IFN-γ, IL-1ß, IL-2 and TNF-α levels were determined using ELISA. The results demonstrated that IAD scores and pH values were both higher in the model groups than the control, which were significantly ameliorated by silicone dressing. The skin tissue structure of IAD rats both in trypsin model group and joint model group was severely damaged, the wounds were not covered by epidermis, and numerous inflammatory cell infiltrations were observed. After treatment, dermatitis was improved. Skin tissue from the trypsin and joint IAD models had higher MHC-II, NF-κB p65, p-NF-κB p65, STAT1 and p-STAT1 expression than controls, which was decreased by protective film and silicon dressing. Zinc oxide reduced NF-κB p65, p-NF-κB p65, STAT1 and p-STAT1 expression. However, no significant differences were observed in NF-κB/p-NF-κB ratio and STAT1/p-STAT1 ratio among groups. Furthermore, serum IFN-γ, IL-1ß, IL-2 and TNF-α levels were significantly elevated in trypsin and joint IAD rats. The upregulation of these cytokines was significantly inhibited after all three treatments. Among the three treatment methods, silicone dressing had the best therapeutic effect. Thus, these findings revealed that zinc oxide, painless skin protective film and silicone dressing could ameliorate the severity of IAD rat models, and that silicone dressing possessed the best therapeutic effect.

A Biosynthesized Near-Infrared-Responsive Nanocomposite Biomaterial for Antimicrobial and Antibiofilm Treatment.

Photodynamic inactivation (PDI) has become an appealing alternative strategy to treat infections without developing resistance to microbes. In PDI treatment, near-infrared (NIR) light is preferred because it causes less damage to normal tissues and leads to better penetration in deep tissues. Here, we develop an NIR-responsive nanomedicine for efficient broad-spectrum antimicrobial photodynamic treatment. By harnessing the biosynthetic capability of a bacterial cellulose-producing microorganism, we construct a nanocomposite biomaterial to deliver and recycle the nanomedicine. Our simple one-step biosynthetic approach does not impede the antimicrobial potency of the nanomedicine under NIR activation and requires no chemical modification. The resulting nanocomposite has been tested in antimicrobial treatment of different microorganisms, exhibiting a great potential to eliminate pathogens in biofilms and to treat in vivo infections.

Nanotechnology's application in Type 1 diabetes.

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the immune system attacking islet cells. T1D, with a long prediabetes period, and the incidence of T1D increases with age during childhood and peaks at 10-14 years. And once it gets overt, it requires lifelong insulin replace treatment. Therefore, the diagnosis of early-stage T1D and effective treatments are important for the management of T1D patients. The imaging methods, such as magnetic resonance imaging (MRI) and so on, were applied in diagnosis of the early stage T1D and its development tracking. The addition of nanomaterials, especially in MRI, can improve the quality of T1D imaging for the diagnosis of T1D at early stage and cause less harm to human body. Meantime, among various treatment options, islet transplantation and immunotherapy are promising, effective, and less independent on insulin. The addition of nanotechnology can effectively reduce the attack of the immune system on drugs and cells, making the therapeutic drug more targeted in the body and prolonging the action time between drugs and cells, thus its addition makes these therapy safer and more efficient. In this review, we attempt to summarize the recent advances in the development of nanotechnology advances of T1D including using nanomaterials for the diagnosis and immunological imaging of T1D, protecting the transplanted islet cells from immune system attack, and delivering relevant molecules to targeted immunocytes. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

Preventive application of low molecular weight heparin ameliorates peripherally inserted central catheter-related venous thrombosis.

OBJECTIVE: Peripherally inserted central catheter (PICC) is being increasingly used in critical care settings. However, PICC is associated with various complications, particularly venous thrombosis. Our aim was to observe the effects of preventive application of low molecular weight heparin on venous thrombosis in a PICC model. METHODS: All rabbits were randomly divided into four groups: a control group, and low/medium/high concentration of low molecular weight heparin groups. All rabbits were injected prophylactically with normal saline or low molecular weight heparin once a day for 7 days. A PICC model was constructed. The pathologic changes of ear vein, anterior vena cava, and venous thrombosis were investigated using hematoxylin and eosin (H&E). Biochemical testing was performed including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Serum D-dimer (D2D) and fibrinogen (FG) levels were detected using Enzyme-linked immunosorbent assay (ELISA). RESULTS: X-ray results showed that the PICC model was successfully constructed. H&E results showed that preventive application of low molecular weight heparin significantly ameliorated the pathologic damage to ear vein and anterior vena cava in the PICC model. Furthermore, we found that preventive application of low molecular weight heparin inhibited venous thrombosis in the model by H&E stain. Moreover, it significantly reduced serum FG and D2D levels in PICC model. Biochemical testing results showed that PT, APTT, and TT were significantly elevated in the PICC model. CONCLUSION: Our findings revealed that preventive application of low molecular weight heparin significantly ameliorates venous thrombosis in a PICC model.