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.

Internet-of-things-integrated molecularly imprinted polymer-based electrochemical nano-sensors for pesticide detection in the environment and food products.

To ensure environmental and health safety, relevant pollutants such as pesticides must be screened thoroughly to set their permissible limit. Various approaches have been used to identify pesticides such as capillary electrophoresis, gas and liquid-liquid chromatography, high-performance liquid chromatography, and enzyme-linked immune-absorbent tests. However, these techniques have some drawbacks, including time-consuming difficult steps, expensive bulky equipment, expert personnel, and a lack of selectivity. Recent advances in the field of biosensing have introduced biosensors for the onsite detection of pesticides which offer several advantages including rapid, simple, selective, sensitive, low-cost operation, and on-site detection. With the advent of molecularly imprinted polymer which substituted the traditional biorecognition elements (BREs) such as enzymes and antibodies, biosensors' sensitivity, selectivity, and reproducibility enhanced many folds. Molecularly imprinted polymers (MIP) are artificial polymer molecules that resemble natural BREs. They are synthesized when functional monomers are polymerized in the presence of a target analyte. Owing to the advantages of MIP, in this paper, the development of MIP-based electrochemical biosensors for pesticide detection is reviewed critically. A brief introduction to pesticides and the use of MIPs-based electrochemical sensors for pesticide detection is presented along with pros and cons. Further, Internet of Things (IoT) integrated MIP-based nanosensors for pesticide detection and information distribution have been discussed. In the end, future perspectives and challenges while implementing MIP-based nanosensors for onsite pesticide recognition have eventually been highlighted.

Nanomaterials in electrochemical nanobiosensors of miRNAs.

Nanomaterial-based biosensors have received significant attention owing to their unique properties, especially enhanced sensitivity. Recent advancements in biomedical diagnosis have highlighted the role of microRNAs (miRNAs) as sensitive prognostic and diagnostic biomarkers for various diseases. Current diagnostics methods, however, need further improvements with regards to their sensitivity, mainly due to the low concentration levels of miRNAs in the body. The low limit of detection of nanomaterial-based biosensors has turned them into powerful tools for detecting and quantifying these biomarkers. Herein, we assemble an overview of recent developments in the application of different nanomaterials and nanostructures as miRNA electrochemical biosensing platforms, along with their pros and cons. The techniques are categorized based on the nanomaterial used.

Hearing Loss Prevalence, Years Lived With Disability, and Hearing Aid Use in the United States From 1990 to 2019: Findings From the Global Burden of Disease Study.

OBJECTIVES: This article describes key data sources and methods used to estimate hearing loss in the United States, in the Global Burden of Disease study. Then, trends in hearing loss are described for 2019, including temporal trends from 1990 to 2019, changing prevalence over age, severity patterns, and utilization of hearing aids. DESIGN: We utilized population-representative surveys from the United States to estimate hearing loss prevalence for the Global Burden of Disease study. A key input data source in modeled estimates are the National Health and Nutrition Examination Surveys (NHANES), years 1988 to 2010. We ran hierarchical severity-specific models to estimate hearing loss prevalence. We then scaled severity-specific models to sum to total hearing impairment prevalence, adjusted estimates for hearing aid coverage, and split estimates by etiology and tinnitus status. We computed years lived with disability (YLDs), which quantifies the amount of health loss associated with a condition depending on severity and creates a common metric to compare the burden of disparate diseases. This was done by multiplying the prevalence of severity-specific hearing loss by corresponding disability weights, with additional weighting for tinnitus comorbidity. RESULTS: An estimated 72.88 million (95% uncertainty interval (UI) 68.53 to 77.30) people in the United States had hearing loss in 2019, accounting for 22.2% (20.9 to 23.6) of the total population. Hearing loss was responsible for 2.24 million (1.56 to 3.11) YLDs (3.6% (2.8 to 4.7) of total US YLDs). Age-standardized prevalence was higher in males (17.7% [16.7 to 18.8]) compared with females (11.9%, [11.2 to 12.5]). While most cases of hearing loss were mild (64.3%, 95% UI 61.0 to 67.6), disability was concentrated in cases that were moderate or more severe. The all-age prevalence of hearing loss in the United States was 28.1% (25.7 to 30.8) higher in 2019 than in 1990, despite stable age-standardized prevalence. An estimated 9.7% (8.6 to 11.0) of individuals with mild to profound hearing loss utilized a hearing aid, while 32.5% (31.9 to 33.2) of individuals with hearing loss experienced tinnitus. Occupational noise exposure was responsible for 11.2% (10.2 to 12.4) of hearing loss YLDs. CONCLUSIONS: Results indicate large burden of hearing loss in the United States, with an estimated 1 in 5 people experiencing this condition. While many cases of hearing loss in the United States were mild, growing prevalence, low usage of hearing aids, and aging populations indicate the rising impact of this condition in future years and the increasing importance of domestic access to hearing healthcare services. Large-scale audiometric surveys such as NHANES are needed to regularly assess hearing loss burden and access to healthcare, improving our understanding of who is impacted by hearing loss and what groups are most amenable to intervention.

Biomaterials-mediated CRISPR/Cas9 delivery: recent challenges and opportunities in gene therapy.

The use of biomaterials in delivering CRISPR/Cas9 for gene therapy in infectious diseases holds tremendous potential. This innovative approach combines the advantages of CRISPR/Cas9 with the protective properties of biomaterials, enabling accurate and efficient gene editing while enhancing safety. Biomaterials play a vital role in shielding CRISPR/Cas9 components, such as lipid nanoparticles or viral vectors, from immunological processes and degradation, extending their effectiveness. By utilizing the flexibility of biomaterials, tailored systems can be designed to address specific genetic diseases, paving the way for personalized therapeutics. Furthermore, this delivery method offers promising avenues in combating viral illnesses by precisely modifying pathogen genomes, and reducing their pathogenicity. Biomaterials facilitate site-specific gene modifications, ensuring effective delivery to infected cells while minimizing off-target effects. However, challenges remain, including optimizing delivery efficiency, reducing off-target effects, ensuring long-term safety, and establishing scalable production techniques. Thorough research, pre-clinical investigations, and rigorous safety evaluations are imperative for successful translation from the laboratory to clinical applications. In this review, we discussed how CRISPR/Cas9 delivery using biomaterials revolutionizes gene therapy and infectious disease treatment, offering precise and safe editing capabilities with the potential to significantly improve human health and quality of life.

Systemic allergic contact dermatitis to palladium, platinum, and titanium: mechanisms, clinical manifestations, prevalence, and therapeutic approaches.

Contact dermatitis (CD) is an inflammatory skin disease of eczema that is elicited by chemicals or metal ions that have toxic effects without eliciting a T-cell response (contact elicitation) or by small reactive chemicals that modify proteins and induce innate and adaptive immune responses (contact allergens). The clinical condition is characterized by localized skin rash, pruritus, redness, swelling, and lesions, which are mainly detected by patch tests and lymphocyte stimulation. Heavy metals such as palladium (Pd), platinum (Pt), and titanium (Ti) are ubiquitous in our environment. These heavy metals have shown CD effects as allergic agents. Immunological responses result from the interaction of cytokines and T cells. Occupational metal CD accounts for most cases of work-related cutaneous disorders. In this systematic review, the allergic effects of heavy metals, including Pd, Pt, and Ti, and the mechanisms, clinical manifestations, prevalence, and therapeutic approaches are discussed in detail. Furthermore, the therapeutic approaches introduced to treat CD, including corticosteroids, topical calcineurin inhibitors, systemic immunosuppressive agents, phototherapy, and antihistamines, can be effective in the treatment of these diseases in the future. Ultimately, the insights identified could lead to improved therapeutic and diagnostic pathways.

Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies.

Medulloblastoma (MB) is a major pediatric malignant brain tumor that arises in the cerebellum. MB tumors exhibit highly heterogeneous driven by diverse genetic alterations and could be divided into four major subgroups based on their different biological drivers and molecular features (Wnt, Sonic hedgehog (Shh), group 3, and group 4 MB). Even though the therapeutic strategies for each MB subtype integrate their pathogenesis and were developed to focus on their specific target sites, the unexpected drug non-selective cytotoxicity, low drug accumulation in the brain, and complexed MB tumor microenvironment still be huge obstacles to achieving satisfied MB therapeutic efficiency. This review discussed the current advances in modern MB therapeutic strategy development. Through the recent advances in knowledge of the origin, molecular pathogenesis of MB subtypes and their current therapeutic barriers, we particularly reviewed the current development in advanced MB therapeutic strategy committed to overcome MB treatment obstacles, focusing on novel signaling pathway targeted therapeutic agents and their combination discovery, advanced drug delivery systems design, and MB immunotherapy strategy development.

Therapeutic Potential of Oral-Derived Mesenchymal Stem Cells in Retinal Repair.

The retina has restricted regeneration ability to recover injured cell layer because of reduced production of neurotrophic factors and increased inhibitory molecules against axon regrowth. A diseased retina could be regenerated by repopulating the damaged tissue with functional cell sources like mesenchymal stem cells (MSCs). The cells are able to release neurotrophic factors (NFs) to boost axonal regeneration and cell maintenance. In the current study, we comprehensively explore the potential of various types of stem cells (SCs) from oral cavity as promising therapeutic options in retinal regeneration. The oral MSCs derived from cranial neural crest cells (CNCCs) which explains their broad neural differentiation potential and secret rich NFs. They are comprised of dental pulp SCs (DPSCs), SCs from exfoliated deciduous teeth (SHED), SCs from apical papilla (SCAP), periodontal ligament-derived SCs (PDLSCs), gingival MSCs (GMSCs), and dental follicle SCs (DFSCs). The Oral MSCs are becoming a promising source of cells for cell-free or cell-based therapeutic approach to recover degenerated retinal. These cells have various mechanisms of action in retinal regeneration including cell replacement and the paracrine effect. It was demonstrated that they have more neuroprotective and neurotrophic effects on retinal cells than immediate replacement of injured cells in retina. This could be the reason that their therapeutic effects would be weakened over time. It can be concluded that neuronal and retinal regeneration through these cells is most likely due to their NFs that dramatically suppress oxidative stress, inflammation, and apoptosis. Although, oral MSCs are attractive therapeutic options for retinal injuries, more preclinical and clinical investigations are required.

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol.

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.

Polysaccharides, proteins, and synthetic polymers based multimodal hydrogels for various biomedical applications: A review.

Nature-derived or biologically encouraged hydrogels have attracted considerable interest in numerous biomedical applications owing to their multidimensional utility and effectiveness. The internal architecture of a hydrogel network, the chemistry of the raw materials involved, interaction across the interface of counter ions, and the ability to mimic the extracellular matrix (ECM) govern the clinical efficacy of the designed hydrogels. This review focuses on the mechanistic viewpoint of different biologically driven/inspired biomacromolecules that encourages the architectural development of hydrogel networks. In addition, the advantage of hydrogels by mimicking the ECM and the significance of the raw material selection as an indicator of bioinertness is deeply elaborated in the review. Furthermore, the article reviews and describes the application of polysaccharides, proteins, and synthetic polymer-based multimodal hydrogels inspired by or derived from nature in different biomedical areas. The review discusses the challenges and opportunities in biomaterials along with future prospects in terms of their applications in biodevices or functional components for human health issues. This review provides information on the strategy and inspiration from nature that can be used to develop a link between multimodal hydrogels as the main frame and its utility in biomedical applications as the primary target.

Estimating mortality and disability in Peru before the COVID-19 pandemic: a systematic analysis from the Global Burden of the Disease Study 2019.

Background: Estimating and analyzing trends and patterns of health loss are essential to promote efficient resource allocation and improve Peru's healthcare system performance. Methods: Using estimates from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study (2019), we assessed mortality and disability in Peru from 1990 to 2019. We report demographic and epidemiologic trends in terms of population, life expectancy at birth (LE), mortality, incidence, prevalence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by the major diseases and risk factors in Peru. Finally, we compared Peru with 16 countries in the Latin American (LA) region. Results: The Peruvian population reached 33.9 million inhabitants (49.9% women) in 2019. From 1990 to 2019, LE at birth increased from 69.2 (95% uncertainty interval 67.8-70.3) to 80.3 (77.2-83.2) years. This increase was driven by the decline in under-5 mortality (-80.7%) and mortality from infectious diseases in older age groups (+60 years old). The number of DALYs in 1990 was 9.2 million (8.5-10.1) and reached 7.5 million (6.1-9.0) in 2019. The proportion of DALYs due to non-communicable diseases (NCDs) increased from 38.2% in 1990 to 67.9% in 2019. The all-ages and age-standardized DALYs rates and YLLs rates decreased, but YLDs rates remained constant. In 2019, the leading causes of DALYs were neonatal disorders, lower respiratory infections (LRIs), ischemic heart disease, road injuries, and low back pain. The leading risk factors associated with DALYs in 2019 were undernutrition, high body mass index, high fasting plasma glucose, and air pollution. Before the COVID-19 pandemic, Peru experienced one of the highest LRIs-DALYs rates in the LA region. Conclusion: In the last three decades, Peru experienced significant improvements in LE and child survival and an increase in the burden of NCDs and associated disability. The Peruvian healthcare system must be redesigned to respond to this epidemiological transition. The new design should aim to reduce premature deaths and maintain healthy longevity, focusing on effective coverage and treatment of NCDs and reducing and managing the related disability.

Zeolitic imidazolate frameworks: From bactericidal properties to tissue regeneration.

Zeolitic imidazolate frameworks (ZIFs), as a very well-known subset of metal-organic frameworks (MOFs), have attracted considerable attention in biomedicine due to their unique structural features such as tunable pore size, high surface area, high thermal stability, biodegradability, and biocompatibility. Moreover, it is possible to load a wide variety of therapeutic agents, drugs, and biomolecules into ZIF structures during the fabrication process owing to the ZIFs' porous structure and concise synthesis methods under mild conditions. This review focuses on the most recent advances in the bioinspiration of ZIFs and ZIF-integrated nanocomposites in boosting antibacterial efficiencies and regenerative medicine capabilities. The first part summarizes the various synthesis routes and physicochemical properties of ZIFs, including size, morphology, surface, and pore size. The recent advancements in the antibacterial aspects of using ZIFs and ZIF-integrated nanocomposites as carriers for antibacterial agents and drug cargo are elaborated. Moreover, the antibacterial mechanisms based on the factors affecting the antibacterial properties of ZIFs such as oxidative stress, internal and external triggers, the effect of metal ions, and their associated combined therapies, are discussed. The recent trends of ZIFs and their composites in tissue regeneration, especially bone regeneration and wound healing, are also reviewed with in-depth perspectives. Finally, the biological safety aspects of ZIFs, the latest reports about their toxicity, and the future prospects of these materials in regenerative medicine have been discussed.

Current state of RNA delivery using lipid nanoparticles to extrahepatic tissues: A review towards clinical translation.

Genetic medicine, including ribonucleic acid (RNA) therapy, has delivered numerous progresses to the treatment of diseases thanks to the development of lipid nanoparticles (LNPs) as a delivery vehicle. However, RNA therapeutics are still limited by the lack of safe, precise, and efficient delivery outside of the liver. Thus, to fully realize the potential of genetic medicine, strategies to arm LNPs with extrahepatic targeting capabilities are urgently needed. This review explores the current state of next-generation LNPs that can bring RNA biomolecules to their targeted organ. The main approaches commonly used are described, including the modulation of internal lipid chemistries, the use of conjugated targeting moieties, and the designs of clinical administration. This work will demonstrate the advances in each approach and the remaining challenges in the field, focusing on clinical translation.

Heavy metals in contact dermatitis: A review.

Contact dermatitis is an inflammatory skin reaction caused by direct contact with chemical substances in the environment and can either be irritant or allergic in nature. The clinical symptoms of contact dermatitis, include local skin rash, itching, redness, swelling, and lesions. Nowadays, 15-20% of people have some degree of contact dermatitis, which can be more or less severe. Immune responses in allergic contact dermatitis (ACD) are due to the effects of cytokines and allergen-specific CD4+ and CD8+ T cells on the skin. Acids and alkalis such as drain cleaners, plants such as poinsettias, hair colors, and nail polish remover, are all prominent causes of irritant contact dermatitis (ICDs). Heavy metals are metallic elements with a high atomic weight that are hazardous in low quantities and are known to cause dermatitis after systemic or local exposure. Nickel (Ni), chromium (Cr), lead (Pb), and copper (Cu) are among the most common heavy metals used in various industries. Metal allergies may cause ACD and also systemic contact dermatitis (SCD). Contact dermatitis is detected by laboratory tests such as patch testing, lymphocyte stimulation test (LST), and evaluation of cytokine production by primary cultures of peripheral blood mononuclear cells. This article presents an update on the epidemiological and clinical characteristics of ACD and SCD caused by three heavy metals (Cr, Cu, and Pb). Ni is not discussed due to recent coverage. Furthermore, the effects of contact sensitivity to some other heavy metals, such as gold (Au), cobalt (Co), palladium (Pd), and mercury (Hg) are discussed.

Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

DNA hydrogels and nanogels for diagnostics, therapeutics, and theragnostics of various cancers.

As an efficient class of hydrogel-based therapeutic drug delivery systems, deoxyribonucleic acid (DNA) hydrogels (particularly DNA nanogels) have attracted massive attention in the last five years. The main contributor to this is the programmability of these 3-dimensional (3D) scaffolds that creates fundamental effects, especially in treating cancer diseases. Like other active biological ingredients (ABIs), DNA hydrogels can be functionalized with other active agents that play a role in targeting drug delivery and modifying the half-life of the therapeutic cargoes in the body's internal environment. Considering the brilliant advantages of DNA hydrogels, in this survey, we intend to submit an informative collection of feasible methods for the design and preparation of DNA hydrogels and nanogels, and the responsivity of the immune system to these therapeutic cargoes. Moreover, the interactions of DNA hydrogels with cancer biomarkers are discussed in this account. Theragnostic DNA nanogels as an advanced species for both detection and therapeutic purposes are also briefly reviewed.

Extracellular vesicle-based biovectors in chronic wound healing: Biogenesis and delivery approaches.

Chronic wounds remain an unresolved medical issue because of major social and therapeutic repercussions that require extensive focus. Recent related theragnostic focuses only on wound management and is not effectively promoting chronic wound healing. The rising number of patients with either under-healing or over-healing wounds highlights the ineffectiveness of current wound-healing treatments, and thus, there is an unmet need to focus on alternative treatments. To cover this gap, extracellular vesicles (EVs), for targeted delivery of therapeutics, are emerging as a potential therapy to treat both acute and persistent wounds. To address these issues, we explore the core biology of EVs, associated pharmacology, comprehension of immunogenic outcomes, and potential for long-term wound treatment with improved effectiveness and their nonacceptable side effects. Additionally, the therapeutic role of EVs in severe wound infections through biogenetic moderation, in combination with biomaterials (functional in nature), as well as drug carriers that can offer opportunities for the development of new treatments for this long-term condition, are also carefully elaborated, with an emphasis on biomaterial-based drug delivery systems. It is observed that exploring difficulties and potential outcomes of clinical translation of EV-based therapeutics for wound management has the potential to be adopted as a future therapy.

A Novel Vision of Reinforcing Nanofibrous Masks with Metal Nanoparticles: Antiviral Mechanisms Investigation.

Prevention of spreading viral respiratory disease, especially in case of a pandemic such as coronavirus disease of 2019 (COVID-19), has been proved impossible without considering obligatory face mask-wearing protocols for both healthy and contaminated populations. The widespread application of face masks for long hours and almost everywhere increases the risks of bacterial growth in the warm and humid environment inside the mask. On the other hand, in the absence of antiviral agents on the surface of the mask, the virus may have a chance to stay alive and be carried to different places or even put the wearers at risk of contamination when touching or disposing the masks. In this article, the antiviral activity and mechanism of action of some of the potent metal and metal oxide nanoparticles in the role of promising virucidal agents have been reviewed, and incorporation of them in an electrospun nanofibrous structure has been considered an applicable method for the fabrication of innovative respiratory protecting materials with upgraded safety levels.

A VEGFB-Based Peptidomimetic Inhibits VEGFR2-Mediated PI3K/Akt/mTOR and PLCγ/ERK Signaling and Elicits Apoptotic, Antiangiogenic, and Antitumor Activities.

Vascular endothelial growth factor receptor 2 (VEGFR2) mediates VEGFA signaling mainly through the PI3K/AKT/mTOR and PLCγ/ERK1/2 pathways. Here we unveil a peptidomimetic (VGB3) based on the interaction between VEGFB and VEGFR1 that unexpectedly binds and neutralizes VEGFR2. Investigation of the cyclic and linear structures of VGB3 (named C-VGB3 and L-VGB3, respectively) using receptor binding and cell proliferation assays, molecular docking, and evaluation of antiangiogenic and antitumor activities in the 4T1 mouse mammary carcinoma tumor (MCT) model showed that loop formation is essential for peptide functionality. C-VGB3 inhibited proliferation and tubulogenesis of human umbilical vein endothelial cells (HUVECs), accounting for the abrogation of VEGFR2, p-VEGFR2 and, subsequently, PI3K/AKT/mTOR and PLCγ/ERK1/2 pathways. In 4T1 MCT cells, C-VGB3 inhibited cell proliferation, VEGFR2 expression and phosphorylation, the PI3K/AKT/mTOR pathway, FAK/Paxillin, and the epithelial-to-mesenchymal transition cascade. The apoptotic effects of C-VGB3 on HUVE and 4T1 MCT cells were inferred from annexin-PI and TUNEL staining and activation of P53, caspase-3, caspase-7, and PARP1, which mechanistically occurred through the intrinsic pathway mediated by Bcl2 family members, cytochrome c, Apaf-1 and caspase-9, and extrinsic pathway via death receptors and caspase-8. These data indicate that binding regions shared by VEGF family members may be important in developing novel pan-VEGFR inhibitors that are highly relevant in the pathogenesis of angiogenesis-related diseases.

Nanobiotechnological approaches in antinociceptive therapy: Animal-based evidence for analgesic nanotherapeutics of bioengineered silver and gold nanomaterials.

Pain management is a major challenge in healthcare systems worldwide. Owing to undesirable side effects of current analgesic medications, there is an exceeding need to develop the effective alternative therapeutics. Nowadays, the application of nanomaterials is being highly considered, as their exceptional properties arising from the nanoscale dimensions are undeniable. With the increasing use of metal NPs, more biocompatible and costly methods of synthesis have been developed in which different biological rescores including microorganisms, plants and algae are employed. Nanobiotechnology-based synthesis of nanosized particles is an ecological approach offering safe production of nanoparticles (NPs) by biological resources eliminating the toxicity attributed to the conventional routes. This review provides an assessment of biosynthesized silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) as antinociceptive agents in recent studies. Living animal models (mice and rats) have been used for analyzing the effect of biogenic NPs on decreasing the nociceptive pain utilizing different methods such as acetic acid-induced writhing test, hot plate test, and formalin test. Potent analgesic activity exhibited by green fabricated AgNPs and AuNPs represents the bright future of nanotechnology in the management of pain and other social and medicinal issues followed by this unpleasant sensation. Moreover, there NPs showed a protective effects on liver, kidney, and body weight in animal models that make them attractive for clinical studies. However, further research is required to fully address the harmless antinociceptive effect of NPs for clinical usage.