MXene-based composites in smart wound healing and dressings.

MXenes, a class of two-dimensional materials, exhibit considerable potential in wound healing and dressing applications due to their distinctive attributes, including biocompatibility, expansive specific surface area, hydrophilicity, excellent electrical conductivity, unique mechanical properties, facile surface functionalization, and tunable band gaps. These materials serve as a foundation for the development of advanced wound healing materials, offering multifunctional nanoplatforms with theranostic capabilities. Key advantages of MXene-based materials in wound healing and dressings encompass potent antibacterial properties, hemostatic potential, pro-proliferative attributes, photothermal effects, and facilitation of cell growth. So far, different types of MXene-based materials have been introduced with improved features for wound healing and dressing applications. This review covers the recent advancements in MXene-based wound healing and dressings, with a focus on their contributions to tissue regeneration, infection control, anti-inflammation, photothermal effects, and targeted therapeutic delivery. We also discussed the constraints and prospects for the future application of these nanocomposites in the context of wound healing/dressings.

Advancing personalized medicine: Integrating statistical algorithms with omics and nano-omics for enhanced diagnostic accuracy and treatment efficacy.

Medical laboratory services enable precise measurement of thousands of biomolecules and have become an inseparable part of high-quality healthcare services, exerting a profound influence on global health outcomes. The integration of omics technologies into laboratory medicine has transformed healthcare, enabling personalized treatments and interventions based on individuals' distinct genetic and metabolic profiles. Interpreting laboratory data relies on reliable reference values. Presently, population-derived references are used for individuals, risking misinterpretation due to population heterogeneity, and leading to medical errors. Thus, personalized references are crucial for precise interpretation of individual laboratory results, and the interpretation of omics data should be based on individualized reference values. We reviewed recent advancements in personalized laboratory medicine, focusing on personalized omics, and discussed strategies for implementing personalized statistical approaches in omics technologies to improve global health and concluded that personalized statistical algorithms for interpretation of omics data have great potential to enhance global health. Finally, we demonstrated that the convergence of nanotechnology and omics sciences is transforming personalized laboratory medicine by providing unparalleled diagnostic precision and innovative therapeutic strategies.

Biotin-functionalized nanoparticles: an overview of recent trends in cancer detection.

Electrochemical bio-sensing is a potent and efficient method for converting various biological recognition events into voltage, current, and impedance electrical signals. Biochemical sensors are now a common part of medical applications, such as detecting blood glucose levels, detecting food pathogens, and detecting specific cancers. As an exciting feature, bio-affinity couples, such as proteins with aptamers, ligands, paired nucleotides, and antibodies with antigens, are commonly used as bio-sensitive elements in electrochemical biosensors. Biotin-avidin interactions have been utilized for various purposes in recent years, such as targeting drugs, diagnosing clinically, labeling immunologically, biotechnology, biomedical engineering, and separating or purifying biomolecular compounds. The interaction between biotin and avidin is widely regarded as one of the most robust and reliable noncovalent interactions due to its high bi-affinity and ability to remain selective and accurate under various reaction conditions and bio-molecular attachments. More recently, there have been numerous attempts to develop electrochemical sensors to sense circulating cancer cells and the measurement of intracellular levels of protein thiols, formaldehyde, vitamin-targeted polymers, huwentoxin-I, anti-human antibodies, and a variety of tumor markers (including alpha-fetoprotein, epidermal growth factor receptor, prostate-specific Ag, carcinoembryonic Ag, cancer antigen 125, cancer antigen 15-3, etc.). Still, the non-specific binding of biotin to endogenous biotin-binding proteins present in biological samples can result in false-positive signals and hinder the accurate detection of cancer biomarkers. This review summarizes various categories of biotin-functional nanoparticles designed to detect such biomarkers and highlights some challenges in using them as diagnostic tools.

Amine-functionalized mesoporous silica nanoparticles decorated by silver nanoparticles for delivery of doxorubicin in breast and cervical cancer cells.

Nanocarriers have demonstrated promising potential in the delivery of various anticancer drugs and in improving the efficiency of the treatment. In this study, silver nanoparticles (AgNPs) were green-synthesized using the extracts of different parts of the pomegranate plant, including the peel, flower petals, and calyx. To obtain the most efficient extract used for the green synthesis of AgNPs, all three types of synthesized nanoparticles were characterized. Then, (3-Aminopropyl) triethoxysilane-functionalized mesoporous silica nanoparticles (MSNs-APTES) decorated with AgNPs were fabricated via a one-pot green-synthesis method. AgNPs were directly coated on the surface of MSNs-APTES by adding pomegranate extract enriched with a source of reducing agent leading to converting the silver ion to AgNPs. The MSN-APTES-AgNPs (MSNs-AgNPs) have been thoroughly characterized using nanoparticle characterization techniques. In addition, DNA cleavage and hemolysis activities of the synthesized nanoparticles were analyzed, confirming the biocompatibility of synthesized nanoparticles. The Doxorubicin (DOX, as a breast/cervical anti-cancer drug) loading (42.8%) and release profiles were investigated via UV-visible spectroscopy. The fibroblast, breast cancer, and cervical cancer cells' viability against DOX-loaded nanoparticles were also studied. The results of this high drug loading, uniform shape, and small functionalized nanoparticles demonstrated its great potential for breast and cervical cancer management.

Glycosylated nanoplatforms: From glycosylation strategies to implications and opportunities for cancer theranostics.

Glycosylated nanoplatforms have emerged as promising tools in the field of cancer theranostics, integrating both therapeutic and diagnostic functionalities. These nanoscale platforms are composed of different materials such as lipids, polymers, carbons, and metals that can be modified with glycosyl moieties to enhance their targeting capabilities towards cancer cells. This review provides an overview of different modification strategies employed to introduce glycosylation onto nanoplatforms, including chemical conjugation, enzymatic methods, and bio-orthogonal reactions. Furthermore, the potential applications of glycosylated nanoplatforms in cancer theranostics are discussed, focusing on their roles in drug delivery, imaging, and combination therapy. The ability of these nanoplatforms to selectively target cancer cells through specific interactions with overexpressed glycan receptors is highlighted, emphasizing their potential for enhancing efficacy and reducing the side effects compared to conventional therapies. In addition, the incorporation of diagnostic components onto the glycosylated nanoplatforms provided the capability of simultaneous imaging and therapy and facilitated the real-time monitoring of treatment response. Finally, challenges and future perspectives in the development and translation of glycosylated nanoplatforms for clinical applications are addressed, including scalability, biocompatibility, and regulatory considerations. Overall, this review underscores the significant progress made in the field of glycosylated nanoplatforms and their potential to revolutionize cancer theranostics.

Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study.

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-α, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-ß, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (∼93%) was significantly greater than the control group (∼58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.

Innovative approaches for cancer treatment: graphene quantum dots for photodynamic and photothermal therapies.

Graphene quantum dots (GQDs) hold great promise for photodynamic and photothermal cancer therapies. Their unique properties, such as exceptional photoluminescence, photothermal conversion efficiency, and surface functionalization capabilities, make them attractive candidates for targeted cancer treatment. GQDs have a high photothermal conversion efficiency, meaning they can efficiently convert light energy into heat, leading to localized hyperthermia in tumors. By targeting the tumor site with laser irradiation, GQD-based nanosystems can induce selective cancer cell destruction while sparing healthy tissues. In photodynamic therapy, light-sensitive compounds known as photosensitizers are activated by light of specific wavelengths, generating reactive oxygen species that induce cancer cell death. GQD-based nanosystems can act as excellent photosensitizers due to their ability to absorb light across a broad spectrum; their nanoscale size allows for deeper tissue penetration, enhancing the therapeutic effect. The combination of photothermal and photodynamic therapies using GQDs holds immense potential in cancer treatment. By integrating GQDs into this combination therapy approach, researchers aim to achieve enhanced therapeutic efficacy through synergistic effects. However, biodistribution and biodegradation of GQDs within the body present a significant hurdle to overcome, as ensuring their effective delivery to the tumor site and stability during treatment is crucial for therapeutic efficacy. In addition, achieving precise targeting specificity of GQDs to cancer cells is a challenging task that requires further exploration. Moreover, improving the photothermal conversion efficiency of GQDs, controlling reactive oxygen species generation for photodynamic therapy, and evaluating their long-term biocompatibility are all areas that demand attention. Scalability and cost-effectiveness of GQD synthesis methods, as well as obtaining regulatory approval for clinical applications, are also hurdles that need to be addressed. Further exploration of GQDs in photothermal and photodynamic cancer therapies holds promise for advancements in targeted drug delivery, personalized medicine approaches, and the development of innovative combination therapies. The purpose of this review is to critically examine the current trends and advancements in the application of GQDs in photothermal and photodynamic cancer therapies, highlighting their potential benefits, advantages, and future perspectives as well as addressing the crucial challenges that need to be overcome for their practical application in targeted cancer therapy.

Application of 3D, 4D, 5D, and 6D bioprinting in cancer research: what does the future look like?

The application of three- and four-dimensional (3D/4D) printing in cancer research represents a significant advancement in understanding and addressing the complexities of cancer biology. 3D/4D materials provide more physiologically relevant environments compared to traditional two-dimensional models, allowing for a more accurate representation of the tumor microenvironment that enables researchers to study tumor progression, drug responses, and interactions with surrounding tissues under conditions similar to in vivo conditions. The dynamic nature of 4D materials introduces the element of time, allowing for the observation of temporal changes in cancer behavior and response to therapeutic interventions. The use of 3D/4D printing in cancer research holds great promise for advancing our understanding of the disease and improving the translation of preclinical findings to clinical applications. Accordingly, this review aims to briefly discuss 3D and 4D printing and their advantages and limitations in the field of cancer. Moreover, new techniques such as 5D/6D printing and artificial intelligence (AI) are also introduced as methods that could be used to overcome the limitations of 3D/4D printing and opened promising ways for the fast and precise diagnosis and treatment of cancer.

Catalytic and biomedical applications of nanocelluloses: A review of recent developments.

Nanocelluloses exhibit immense potential in catalytic and biomedical applications. Their unique properties, biocompatibility, and versatility make them valuable in various industries, contributing to advancements in environmental sustainability, catalysis, energy conversion, drug delivery, tissue engineering, biosensing/imaging, and wound healing/dressings. Nanocellulose-based catalysts can efficiently remove pollutants from contaminated environments, contributing to sustainable and cleaner ecosystems. These materials can also be utilized as drug carriers, enabling targeted and controlled drug release. Their high surface area allows for efficient loading of therapeutic agents, while their biodegradability ensures safer and gradual release within the body. These targeted drug delivery systems enhance the efficacy of treatments and minimizes side effects. Moreover, nanocelluloses can serve as scaffolds in tissue engineering due to their structural integrity and biocompatibility. They provide a three-dimensional framework for cell growth and tissue regeneration, promoting the development of functional and biologically relevant tissues. Nanocellulose-based dressings have shown great promise in wound healing and dressings. Their ability to absorb exudates, maintain a moist environment, and promote cell proliferation and migration accelerates the wound healing process. Herein, the recent advancements pertaining to the catalytic and biomedical applications of nanocelluloses and their composites are deliberated, focusing on important challenges, advantages, limitations, and future prospects.

Assessment of Stiffness-Dependent Autophagosome Formation and Apoptosis in Embryonal Rhabdomyosarcoma Tumor Cells.

Remodeling of the extracellular matrix (ECM) eventually causes the stiffening of tumors and changes to the microenvironment. The stiffening alters the biological processes in cancer cells due to altered signaling through cell surface receptors. Autophagy, a key catabolic process in normal and cancer cells, is thought to be involved in mechano-transduction and the level of autophagy is probably stiffness-dependent. Here, we provide a methodology to study the effect of matrix stiffness on autophagy in embryonal rhabdomyosarcoma cells. To mimic stiffness, we seeded cells on GelMA hydrogel matrices with defined stiffness and evaluated autophagy-related endpoints. We also evaluated autophagy-dependent pathways, apoptosis, and cell viability. Specifically, we utilized immunocytochemistry and confocal microscopy to track autophagosome formation through LC3 lipidation. This approach suggests that the use of GelMA hydrogels with defined stiffness represents a novel method to evaluate the role of autophagy in embryonal rhabdomyosarcoma and other cancer cells.

Synergistic applications of cyclodextrin-based systems and metal-organic frameworks in transdermal drug delivery for skin cancer therapy.

This review article explores the innovative field of eco-friendly cyclodextrin-based coordination polymers and metal-organic frameworks (MOFs) for transdermal drug delivery in the case of skin cancer therapy. We critically examine the significant advancements in developing these nanocarriers, with a focus on their unique properties such as biocompatibility, targeted drug release, and enhanced skin permeability. These attributes are instrumental in addressing the limitations inherent in traditional skin cancer treatments and represent a paradigm shift towards more effective and patient-friendly therapeutic approaches. Furthermore, we discuss the challenges faced in optimizing the synthesis process for large-scale production while ensuring environmental sustainability. The review also emphasizes the immense potential for clinical applications of these nanocarriers in skin cancer therapy, highlighting their role in facilitating targeted, controlled drug release which minimizes systemic side effects. Future clinical applications could see these nanocarriers being customized to individual patient profiles, potentially revolutionizing personalized medicine in oncology. With further research and clinical trials, these nanocarriers hold the promise of transforming the landscape of skin cancer treatment. With this study, we aim to provide a comprehensive overview of the current state of research in this field and outline future directions for advancing the development and clinical application of these innovative nanocarriers.

MOFs and MOF-Based Composites as Next-Generation Materials for Wound Healing and Dressings.

In recent years, there has been growing interest in developing innovative materials and therapeutic strategies to enhance wound healing outcomes, especially for chronic wounds and antimicrobial resistance. Metal-organic frameworks (MOFs) represent a promising class of materials for next-generation wound healing and dressings. Their high surface area, pore structures, stimuli-responsiveness, antibacterial properties, biocompatibility, and potential for combination therapies make them suitable for complex wound care challenges. MOF-based composites promote cell proliferation, angiogenesis, and matrix synthesis, acting as carriers for bioactive molecules and promoting tissue regeneration. They also have stimuli-responsivity, enabling photothermal therapies for skin cancer and infections. Herein, a critical analysis of the current state of research on MOFs and MOF-based composites for wound healing and dressings is provided, offering valuable insights into the potential applications, challenges, and future directions in this field. This literature review has targeted the multifunctionality nature of MOFs in wound-disease therapy and healing from different aspects and discussed the most recent advancements made in the field. In this context, the potential reader will find how the MOFs contributed to this field to yield more effective, functional, and innovative dressings and how they lead to the next generation of biomaterials for skin therapy and regeneration.

Contribution of Autophagy to Epithelial Mesenchymal Transition Induction during Cancer Progression.

Epithelial Mesenchymal Transition (EMT) is a dedifferentiation process implicated in many physio-pathological conditions including tumor transformation. EMT is regulated by several extracellular mediators and under certain conditions it can be reversible. Autophagy is a conserved catabolic process in which intracellular components such as protein/DNA aggregates and abnormal organelles are degraded in specific lysosomes. In cancer, autophagy plays a controversial role, acting in different conditions as both a tumor suppressor and a tumor-promoting mechanism. Experimental evidence shows that deep interrelations exist between EMT and autophagy-related pathways. Although this interplay has already been analyzed in previous studies, understanding mechanisms and the translational implications of autophagy/EMT need further study. The role of autophagy in EMT is not limited to morphological changes, but activation of autophagy could be important to DNA repair/damage system, cell adhesion molecules, and cell proliferation and differentiation processes. Based on this, both autophagy and EMT and related pathways are now considered as targets for cancer therapy. In this review article, the contribution of autophagy to EMT and progression of cancer is discussed. This article also describes the multiple connections between EMT and autophagy and their implication in cancer treatment.

Targeting vimentin: a multifaceted approach to combatting cancer metastasis and drug resistance.

This comprehensive review explores vimentin as a pivotal therapeutic target in cancer treatment, with a primary focus on mitigating metastasis and overcoming drug resistance. Vimentin, a key player in cancer progression, is intricately involved in processes such as epithelial-to-mesenchymal transition (EMT) and resistance mechanisms to standard cancer therapies. The review delves into diverse vimentin inhibition strategies. Precision tools, including antibodies and nanobodies, selectively neutralize vimentin's pro-tumorigenic effects. DNA and RNA aptamers disrupt vimentin-associated signaling pathways through their adaptable binding properties. Innovative approaches, such as vimentin-targeted vaccines and microRNAs (miRNAs), harness the immune system and post-transcriptional regulation to combat vimentin-expressing cancer cells. By dissecting vimentin inhibition strategies across these categories, this review provides a comprehensive overview of anti-vimentin therapeutics in cancer treatment. It underscores the growing recognition of vimentin as a pivotal therapeutic target in cancer and presents a diverse array of inhibitors, including antibodies, nanobodies, DNA and RNA aptamers, vaccines, and miRNAs. These multifaceted approaches hold substantial promise for tackling metastasis and overcoming drug resistance, collectively presenting new avenues for enhanced cancer therapy.

Long-Term Major Adverse Cardiovascular Events in Patients with Moderate and Severe COVID-19: A Focus on Early Statin Use and Previous CVD.

Background: Limited data exist regarding the status of long-term cardiovascular disease (CVD) outcomes of hospitalized COVID-19 patients. We aimed to examine the efficacy of early statin use after SARS-CoV-2 pneumonia and the impact of prior CVD on the incidence of cardiovascular events. Methods: A prospective cohort study was performed on hospitalized COVID-19 patients. The primary endpoint was major adverse cardiovascular events (MACE) as a composite of cardiovascular mortality, stroke, heart failure, venous thromboembolism (VTE), revascularization, and nonfatal myocardial infarction (MI). The secondary endpoints comprised MACE components, all-cause mortality, readmission for COVID-19, and impaired functional classes. Results: The mean age of the 858 participants was 55.52±13.97 years, and the median follow-up time was 13 months (11.5-15). Men comprised 63.9% of the patients. Overall, MACE occurred in 84 subjects (9.8%), and 98 patients (11.4%) received ventilation. A multivariate Cox regression model was employed to explore the association between statin use and outcomes, and the following hazard ratios were obtained: MACE (0.831 [0.529 to 0.981]; P=0.044), All-cause mortality (1.098 [0.935 to 1.294]; P=0.255), stroke (0.118 [0.029 to 0.48]; P=0.003), revascularization (0.103 [0.029 to 0.367]; P<0.0001), poor functional capacity (0.827 [0.673 to 1.018]; P=0.073), nonfatal MI (0.599 [0.257 to 1.394]; P=0.234), VTE (0.376 [0.119 to 1.190]; P=0.096), and decompensated heart failure (0.137 [0.040 to 0.472]; P=0.002). Prior CVD predicted MACE (2.953 [1.393 to 6.271]; P=0.005), all-cause death (1.170 [0.960 to 1.412]; P=0.102), and VTE (2.770 [0.957 to 8.955]; P=0.051). Conclusion: Previous CVD is a robust predictor of long-term MACE and VTE. Early statin use might decrease the incidence rates of MACE, ischemic stroke, revascularization, and readmission for heart failure.

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

Atherogenic index of plasma: A valuable novel index to distinguish patients with unstable atherogenic plaques.

Background: Plaque instability is a leading cause of morbidity and mortality in coronary artery disease (CAD) patients. Numerous efforts have been made to figure out and manage unstable plaques prior to major cardiovascular events incidence. The current study aims to assess the values of the atherogenic index of plasma (AIP) to detect unstable plaques. Materials and Methods: The current case-control study was conducted on 435 patients who underwent percutaneous coronary intervention due to chronic stable angina (stable plaques, n = 145) or acute coronary syndrome (unstable plaques, n = 290). The demographic, comorbidities, chronic medications, biochemical and hematological characteristics of the patients were entered into the study checklist. The baseline AIP was measured according to the formula of triglycerides/high-density lipoprotein logarithm. Binary logistic regression was applied to investigate the standalone association of AIP with plaque instability. Receiver operating curve (ROC) was depicted to determine a cut-off, specificity, and sensitivity of AIP in unstable plaques diagnosis. Results: AIP was an independent predictor for atherogenic plaque unstability in both crude (odds ratio [OR]: 3.677, 95% confidence interval [CI]: 1.521-8.890; P = 0.004) and full-adjusted models (OR: 15, 95% CI: 2.77-81.157; P = 0.002). According to ROC curve, at cut-point level of 0.62, AIP had sensitivity and specificity of 89.70% and 34% to detect unstable plaques, respectively (area under the curve: 0.648, 95% CI: 0.601-0.692, P < 0.001). Conclusion: According to this study, at the threshold of 0.62, AIP as an independent biomarker associated with plaque instability can be considered a screening tool for patients at increased risk for adverse events due to unstable atherosclerotic plaques.

The Iranian Society of Echocardiography (ISE) Statement on Performing Echocardiography During the COVID-19 Pandemic.

Corona virus disease 2019(COVID-19) pandemic has caused a significant burden on the global health system. Considerable cardiovascular involvement has been reported among COVID-19 patients with higher ICU admission and mortality rates among patients with cardiovascular comorbidities. Consequently, diagnostic cardiovascular evaluations such as echocardiography are a crucial part of the disease management. On the other hand, providing safety for the patients and the healthcare personnel is a matter of great concern in the pandemic state. In this document, we have provided recommendations on performing echocardiography in hospital echocardiography labs and outpatient echocardiography clinics during the current COVID-19 (Coronavirus disease of 2019) outbreak.

Pulmonary endarteritis and endocarditis complicated with septic embolism: a case report and review of the literature.

BACKGROUND: Pulmonary endarteritis is a rare clinical phenomenon with congenital heart that can potentially lead to major complications. CASE PRESENTATION: We report a 47-year-old man with pulmonary endarteritis. This patient presented with hypertension, chest pain and a previous history of pulmonary valve disease during childhood. Also, eight-months prior, he was hospitalized with dyspnea (Functional Class III), cough, phlegm, and night sweats without fever. Echocardiographic diagnosis in the first transtransthoracic echocardiography (TTE) was intense pulmonary valve stenosis (PVS) an, thus, the pulmonary valve vegetation and PVS, established by transesophageal echocardiography (TEE). He was referred for surgery after 1 weeks of intravenous antibiotic therapy for removal of the vegetation. CONCLUSIONS: Finally he was asymptomatic at 3-months of follow-up and was clinically in good condition. Therefore, the detection of infective endocarditis of the lung valve must not lengthy be prolonged.

Investigation of chitosan-g-PEG grafted nanoparticles as a half-life enhancer carrier for tissue plasminogen activator delivery.

Tissue plasminogen activator (tPA) a thrombolytic agent is commonly used for digesting the blood clot. tPA half-life is low (4-6 min) and its administration needs a prolonged continuous infusion. Improving tPA half-life could reduce enzyme dosage and enhance patient compliance. Nano-carries could be used as delivery systems for the protection of enzymes physically, enhancing half-life and increasing the stability of them. In this study, chitosan (CS) and polyethylene glycol (PEG) were used for the preparation of CS-g-PEG/tPA nanoparticles (NPs) via the ion gelation method. Particles' size and loading capacity were optimised by central composite design. Then, NPs cytotoxicity, release profile, enzyme activity and in vivo half-life and coagulation time were investigated. The results showed that NPs does not have significant cytotoxicity. Release study revealed that a burst effect happened in the first 5 min and resulted in releasing 30% of tPA. Loading tPA in NPs could decrease 25% of its activity but the half-life of it increases in comparison to free tPA in vivo. Also, blood coagulation time has significantly affected (p-value = 0.041) by encapsulated tPA in comparison to free tPA. So, CS-g-PEG/tPA could increase enzyme half-life during the time and could be used as a non-toxic candidate delivery system for tPA.