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Background: Proteins are commonly used in the healthcare industry to treat various health conditions, and most proteins are sensitive to physical and chemical changes. Lyophilization, also known as freeze-drying, involves sublimating water in the form of ice from a substance at low pressure, forming a freeze-dried powder that increases its shelf life. Extreme pressure and varying temperatures in the freeze-drying process may damage the protein's structural integrity. Lyoprotectants are commonly used to protect protein conformations. It is important to choose a suitable lyoprotectant to ensure optimal effectiveness. Method: Twenty articles screened from Scopus, Web of Science, and PubMed were included in this review that discussed potential lyoprotectants and their effectiveness with different protein models. Results: Lyoprotectants were categorized into sugars, polyols, surfactants, and amino acids. Lyoprotectants can exhibit significant protective effects towards proteins, either singularly or in combination with another lyoprotectant. They exert various interactions with the protein to stabilize it, such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and osmoprotection. Conclusions: This review concludes that disaccharides are the most effective lyoprotectants, while other groups of lyoprotectants are best used in combination with other lyoprotectants. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that pose significant environmental and health risks. These compounds originate from both natural phenomena, such as volcanic activity and wildfires, and anthropogenic sources, including vehicular emissions, industrial processes, and fossil fuel combustion. Their classification as carcinogenic, mutagenic, and teratogenic substances link them to various cancers and health disorders. PAHs are categorized into low-molecular-weight (LMW) and high-molecular-weight (HMW) groups, with HMW PAHs exhibiting greater resistance to degradation and a tendency to accumulate in sediments and biological tissues. Soil serves as a primary reservoir for PAHs, particularly in areas of high emissions, creating substantial risks through ingestion, dermal contact, and inhalation. Coastal and aquatic ecosystems are especially vulnerable due to concentrated human activities, with PAH persistence disrupting microbial communities, inhibiting plant growth, and altering ecosystem functions, potentially leading to biodiversity loss. In plants, PAH contamination manifests as a form of abiotic stress, inducing oxidative stress, cellular damage, and growth inhibition. Plants respond by activating antioxidant defenses and stress-related pathways. A notable aspect of plant defense mechanisms involves plant-derived extracellular vesicles (PDEVs), which are membrane-bound nanoparticles released by plant cells. These PDEVs play a crucial role in enhancing plant resistance to PAHs by facilitating intercellular communication and coordinating defense responses. The interaction between PAHs and PDEVs, while not fully elucidated, suggests a complex interplay of cellular defense mechanisms. PDEVs may contribute to PAH detoxification through pollutant sequestration or by delivering enzymes capable of PAH degradation. Studying PDEVs provides valuable insights into plant stress resilience mechanisms and offers potential new strategies for mitigating PAH-induced stress in plants and ecosystems. [ABSTRACT FROM AUTHOR]

The wound healing mechanism is dynamic and well-orchestrated; yet, it is a complicated process. The hallmark of wound healing is to promote wound regeneration in less time without invading skin pathogens at the injury site. This study developed a sodium–carboxymethylcellulose (Na-CMC) bilayer scaffold that was later integrated with silver nanoparticles/graphene quantum dot nanoparticles (AgNPs/GQDs) as an acellular skin substitute for future use in diabetic wounds. The bilayer scaffold was prepared by layering the Na-CMC gauze onto the ovine tendon collagen type 1 (OTC-1). The bilayer scaffold was post-crosslinked with 0.1% (w/v) genipin (GNP) as a natural crosslinking agent. The physical and chemical characteristics of the bilayer scaffold were evaluated. The results demonstrate that crosslinked (CL) groups exhibited a high-water absorption capacity (>1000%) and an ideal water vapour evaporation rate (2000 g/m2 h) with a lower biodegradation rate and good hydrophilicity, compression, resilience, and porosity than the non-crosslinked (NC) groups. The minimum inhibitory concentration (MIC) of AgNPs/GQDs presented some bactericidal effects against Gram-positive and Gram-negative bacteria. The cytotoxicity tests on bilayer scaffolds demonstrated good cell viability for human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Therefore, the Na-CMC bilayer scaffold could be a potential candidate for future diabetic wound care. [ABSTRACT FROM AUTHOR]

Traumatic damage to the spinal cord (SCI) frequently leads to irreversible neurological deficits, which may be related to apoptotic neurodegeneration in nerve tissue. The MLC901 treatment possesses neuroprotective and neuroregenerative activity. This study aimed to explore the regenerative potential of MLC901 and the molecular mechanisms promoting neurogenesis and functional recovery after SCI in rats. A calibrated forceps compression injury for 15 s was used to induce SCI in rats, followed by an examination of the impacts of MLC901 on functional recovery. The Basso, Beattie, and Bresnahan (BBB) scores were utilized to assess neuronal functional recovery; H&E and immunohistochemistry (IHC) staining were also used to observe pathological changes in the lesion area. Somatosensory Evoked Potentials (SEPs) were measured using the Nicolet® Viking Quest™ apparatus. Additionally, we employed the Western blot assay to identify PI3K/AKT/GSK-3β pathway-related proteins and to assess the levels of GAP-43 and GFAP through immunohistochemistry staining. The study findings revealed that MLC901 improved hind-limb motor function recovery, alleviating the pathological damage induced by SCI. Moreover, MLC901 significantly enhanced locomotor activity, SEPs waveform, latency, amplitude, and nerve conduction velocity. The treatment also promoted GAP-43 expression and reduced reactive astrocytes (GFAP). MLC901 treatment activated p-AKT reduced p-GSK-3β expression levels and showed a normalized ratio (fold changes) relative to β-tubulin. Specifically, p-AKT exhibited a 4-fold increase, while p-GSK-3β showed a 2-fold decrease in T rats compared to UT rats. In conclusion, these results suggest that the treatment mitigates pathological tissue damage and effectively improves neural functional recovery following SCI, primarily by alleviating apoptosis and promoting neurogenesis. The underlying molecular mechanism of this treatment mainly involves the activation of the PI3K/AKT/GSK-3β pathway. [ABSTRACT FROM AUTHOR]

Platelet-derived extracellular vesicles (pEVs) are emerging as pivotal players in numerous physiological and pathological processes, extending beyond their traditional roles in hemostasis and thrombosis. As one of the most abundant vesicle types in human blood, pEVs transport a diverse array of bioactive molecules, including growth factors, cytokines, and clotting factors, facilitating crucial intercellular communication, immune regulation, and tissue healing. The unique ability of pEVs to traverse tissue barriers and their biocompatibility position them as promising candidates for targeted drug delivery and regenerative medicine applications. Recent studies have underscored their involvement in cancer progression, viral infections, wound healing, osteoarthritis, sepsis, cardiovascular diseases, rheumatoid arthritis, and atherothrombosis. For instance, pEVs promote tumor progression and metastasis, enhance tissue repair, and contribute to thrombo-inflammation in diseases such as COVID-19. Despite their potential, challenges remain, including the need for standardized isolation techniques and a comprehensive understanding of their mechanisms of action. Current research efforts are focused on leveraging pEVs for innovative anti-cancer treatments, advanced drug delivery systems, regenerative therapies, and as biomarkers for disease diagnosis and monitoring. This review highlights the necessity of overcoming technical hurdles, refining isolation methods, and establishing standardized protocols to fully unlock the therapeutic potential of pEVs. By understanding the diverse functions and applications of pEVs, we can advance their use in clinical settings, ultimately revolutionizing treatment strategies across various medical fields and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a significant public health challenge, with 5-fluorouracil (5-FU) resistance being a major obstacle to effective treatment. Despite advancements, resistance to 5-FU remains formidable due to complex mechanisms such as alterations in drug transport, evasion of apoptosis, dysregulation of cell cycle dynamics, tumor microenvironment (TME) interactions, and extracellular vesicle (EV)-mediated resistance pathways. Traditional chemotherapy often results in high toxicity, highlighting the need for alternative approaches with better efficacy and safety. Phytochemicals (PCs) and EVs offer promising CRC therapeutic strategies. PCs, derived from natural sources, often exhibit lower toxicity and can target multiple pathways involved in cancer progression and drug resistance. EVs can facilitate targeted drug delivery, modulate the immune response, and interact with the TME to sensitize cancer cells to treatment. However, the potential of PCs and engineered EVs in overcoming 5-FU resistance and reshaping the immunosuppressive TME in CRC remains underexplored. Addressing this gap is crucial for identifying innovative therapies with enhanced efficacy and reduced toxicities. This review explores the multifaceted mechanisms of 5-FU resistance in CRC and evaluates the synergistic effects of combining PCs with 5-FU to improve treatment efficacy while minimizing adverse effects. Additionally, it investigates engineered EVs in overcoming 5-FU resistance by serving as drug delivery vehicles and modulating the TME. By synthesizing the current knowledge and addressing research gaps, this review enhances the academic understanding of 5-FU resistance in CRC, highlighting the potential of interdisciplinary approaches involving PCs and EVs for revolutionizing CRC therapy. Further research and clinical validation are essential for translating these findings into improved patient outcomes. [ABSTRACT FROM AUTHOR]

Regenerative medicine represents a paradigm shift in healthcare, aiming to restore tissue and organ function through innovative therapeutic strategies. Among these, bioprinting and extracellular vesicles (EVs) have emerged as promising techniques for tissue rejuvenation. EVs are small lipid membrane particles secreted by cells, known for their role as potent mediators of intercellular communication through the exchange of proteins, genetic material, and other biological components. The integration of 3D bioprinting technology with EVs offers a novel approach to tissue engineering, enabling the precise deposition of EV-loaded bioinks to construct complex three-dimensional (3D) tissue architectures. Unlike traditional cell-based approaches, bioprinted EVs eliminate the need for live cells, thereby mitigating regulatory and financial obstacles associated with cell therapy. By leveraging the synergistic effects of EVs and bioprinting, researchers aim to enhance the therapeutic outcomes of skin regeneration while addressing current limitations in conventional treatments. This review explores the evolving landscape of bioprinted EVs as a transformative approach for skin regeneration. Furthermore, it discusses the challenges and future directions in harnessing this innovative therapy for clinical applications, emphasizing the need for interdisciplinary collaboration and continued scientific inquiry to unlock its full therapeutic potential. [ABSTRACT FROM AUTHOR]

Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes. EVs are described as a membrane-enclosed cargo of functional biomolecules not limited to lipids, nucleic acid, and proteins. Interestingly, studies have correlated the biological role of MSC-EVs to the paracrine activity of MSCs. This key evidence has led to rigorous studies on MSC-EVs as an acellular alternative. Using EVs as a therapy was proposed as a model leading to improvements through increased safety; enhanced bioavailability due to size and permeability; reduced heterogeneity by selective and quantifiable properties; and prolonged shelf-life via long-term freezing or lyophilization. Yet, the identity and potency of EVs are still relatively unknown due to various methods of preparation and to qualify the final product. This is reflected by the absence of regulatory strategies overseeing manufacturing, quality control, clinical implementation, and product registration. In this review, the authors review the various production processes and the proteomic profile of MSC-EVs. [ABSTRACT FROM AUTHOR]

Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms and devising effective therapeutic strategies. This review provides a comprehensive overview of the intricate landscape of extracellular vesicles (EVs) in the context of breast cancer, highlighting their diverse subtypes, biogenesis, and roles in intercellular communication within the tumour microenvironment (TME). The discussion spans various aspects, from EVs and stromal cells in breast cancer to their influence on angiogenesis, immune response, and chemoresistance. The impact of EV production in different culture systems, including two dimensional (2D), three dimensional (3D), and organoid models, is explored. Furthermore, this review delves into the therapeutic potential of EVs in breast cancer, presenting emerging strategies such as engineered EVs for gene delivery, nanoplatforms for targeted chemotherapy, and disrupting tumour derived EVs as a treatment approach. Understanding these complex interactions of EV within the breast cancer milieu is crucial for identifying resistance mechanisms and developing new therapeutic targets. [ABSTRACT FROM AUTHOR]

The animal gut microbiota, comprising a diverse array of microorganisms, plays a pivotal role in shaping host health and physiology. This review explores the intricate dynamics of the gut microbiome in animals, focusing on its composition, function, and impact on host–microbe interactions. The composition of the intestinal microbiota in animals is influenced by the host ecology, including factors such as temperature, pH, oxygen levels, and nutrient availability, as well as genetic makeup, diet, habitat, stressors, and husbandry practices. Dysbiosis can lead to various gastrointestinal and immune-related issues in animals, impacting overall health and productivity. Extracellular vesicles (EVs), particularly exosomes derived from gut microbiota, play a crucial role in intercellular communication, influencing host health by transporting bioactive molecules across barriers like the intestinal and brain barriers. Dysregulation of the gut–brain axis has implications for various disorders in animals, highlighting the potential role of microbiota-derived EVs in disease progression. Therapeutic approaches to modulate gut microbiota, such as probiotics, prebiotics, microbial transplants, and phage therapy, offer promising strategies for enhancing animal health and performance. Studies investigating the effects of phage therapy on gut microbiota composition have shown promising results, with potential implications for improving animal health and food safety in poultry production systems. Understanding the complex interactions between host ecology, gut microbiota, and EVs provides valuable insights into the mechanisms underlying host–microbe interactions and their impact on animal health and productivity. Further research in this field is essential for developing effective therapeutic interventions and management strategies to promote gut health and overall well-being in animals. [ABSTRACT FROM AUTHOR]

This paper sheds light on the alarming issue of antibiotic resistance (ABR) in aquatic environments, exploring its detrimental effects on ecosystems and public health. It examines the multifaceted role of antibiotic use in aquaculture, agricultural runoff, and industrial waste in fostering the development and dissemination of resistant bacteria. The intricate interplay between various environmental factors, horizontal gene transfer, and bacterial extracellular vesicles (BEVs) in accelerating the spread of ABR is comprehensively discussed. Various BEVs carrying resistance genes like blaCTX-M, tetA, floR, and sul/I, as well as their contribution to the dominance of multidrug-resistant bacteria, are highlighted. The potential of BEVs as both a threat and a tool in combating ABR is explored, with promising strategies like targeted antimicrobial delivery systems and probiotic-derived EVs holding significant promise. This paper underscores the urgency of understanding the intricate interplay between BEVs and ABR in aquatic environments. By unraveling these unseen weapons, we pave the way for developing effective strategies to mitigate the spread of ABR, advocating for a multidisciplinary approach that includes stringent regulations, enhanced wastewater treatment, and the adoption of sustainable practices in aquaculture. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common form of PH. In PH-LHD, changes in the pulmonary vasculature are assumed to be mainly caused by pulmonary venous congestion. However, the underlying mechanisms of this form of PH are poorly understood. We aimed to establish a model of PH associated with pulmonary venous congestion. Wistar–Kyoto rats underwent partial occlusion of the left pulmonary vein to induce pulmonary venous congestion or sham surgery and were assessed at various time points post-surgery (3, 6, 9, 12 weeks). In vivo cardiopulmonary phenotyping was performed by using echocardiography along with heart catheterization. Histomorphometry methods were used to assess pulmonary vascular remodeling (e.g., wall thickness, degree of muscularization). Left pulmonary vein banding (PVB) resulted in mildly elevated right ventricular systolic pressure and moderate right ventricular hypertrophy. In PVB rats, small- and medium-sized pulmonary vessels in the left lung were characterized by increased wall thickness and muscularization. Taken together, our data demonstrate that left PVB-induced pulmonary venous congestion is associated with pulmonary vascular remodeling and mild PH. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that affects nearly 3.41 million people globally, with 90% of the cases affecting women of childbearing age. SLE is a complex disease due to the interplay of various immunological pathways and mechanisms. This scoping review aims to highlight the latest research findings on the therapeutic mechanisms of action of EVs in SLE. Relevant research articles were identified using the PRISMA framework from databases such as PubMed/MEDLINE (National Library of Medicine), Scopus (Elsevier), and Web of Science: Core Collection (Clarivate Analytics) from July 2023 to October 2023. Eleven studies met the inclusion criteria and thus were included in this scoping review. The findings showed that EVs have therapeutic effects on ameliorating the disease progression of SLE. EVs can reduce the pro-inflammatory cytokines and increase the anti-inflammatory cytokines. Moreover, EVs can increase the levels of regulatory T cells, thus reducing inflammation. EVs also have the potential to regulate B cells to alleviate SLE and reduce its adverse effects. The scoping review has successfully analysed the therapeutic potential in ameliorating the disease progression of SLE. The review also includes prospects to improve the effects of EVs further to increase the therapeutic effects on SLE. [ABSTRACT FROM AUTHOR]

Respiratory diseases have a major impact on global health. The airway epithelium, which acts as a frontline defence, is one of the most common targets for inhaled allergens, irritants, or micro-organisms to enter the respiratory system. In the tissue engineering field, biomaterials play a crucial role. Due to the continuing high impact of respiratory diseases on society and the emergence of new respiratory viruses, in vitro airway epithelial models with high microphysiological similarities that are also easily adjustable to replicate disease models are urgently needed to better understand those diseases. Thus, the development of biomaterial scaffolds for the airway epithelium is important due to their function as a cell-support device in which cells are seeded in vitro and then are encouraged to lay down a matrix to form the foundations of a tissue for transplantation. Studies conducted in in vitro models are necessary because they accelerate the development of new treatments. Moreover, in comparatively controlled conditions, in vitro models allow for the stimulation of complex interactions between cells, scaffolds, and growth factors. Based on recent studies, the biomaterial scaffolds that have been tested in in vitro models appear to be viable options for repairing the airway epithelium and avoiding any complications. This review discusses the role of biomaterial scaffolds in in vitro airway epithelium models. The effects of scaffold, physicochemical, and mechanical properties in recent studies were also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last twenty years, minimally invasive surgery (MIS) has radically changed the surgical landscape. In the field of thoracic surgery, approaches such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) have become the new standards for the majority of procedures performed, especially for early-stage lung cancer. Despite these developments, there is still a lack of concrete data regarding treatment outcomes of these minimally invasive approaches compared to the conventional open surgery. In the future, the number of minimally invasive procedures will likely keep increasing as more lung cancer nodules are detected at early stages due to lung cancer screening initiatives. Therefore, data on short- and long-term outcomes of VATS and RATS in early-stage lung cancer is needed. In the last two decades, robotic-assisted thoracoscopic surgery (RATS) has gained popularity as a minimally invasive surgical (MIS) alternative to multi- and uniportal video-assisted thoracoscopic surgery (VATS). With this approach, the surgeon obviates the known drawbacks of conventional MIS, such as the reduced in-depth perception, hand-eye coordination, and freedom of motion of the instruments. Previous studies have shown that a robotic approach for operable lung cancer has treatment outcomes comparable to other MIS techniques such as multi-and uniportal VATS, but with less blood loss, a lower conversion rate to open surgery, better lymph node dissection rates, and improved ergonomics for the surgeon. The thoracic surgeon of the future is expected to perform more complex procedures. More patients will enter a multimodal treatment scheme making surgery more difficult due to severe inflammation. Furthermore, due to lung cancer screening programs, the number of patients presenting with operable smaller lung nodules in the periphery of the lung will increase. This, combined with the fact that segmentectomy is becoming an increasingly popular treatment for small peripheral lung lesions, indicates that the future thoracic surgeons need to have profound knowledge of segmental resections. New imaging techniques will help them to locate these lesions and to achieve a complete oncologic resection. Current robotic techniques exist to help the thoracic surgeon overcome these challenges. In this review, an update of the latest MIS approaches and nodule detection techniques will be given. [ABSTRACT FROM AUTHOR]

Background: The idea of exploring respiratory therapy in vitro predominantly guided by cell-secreted substances has gained ground in recent years. A conditioned medium (CM) consists of protein milieu that contains a diverse spectrum of cytokines, chemokines, angiogenic agents, and growth factors. This review evaluated the efficacy of using CM collected in an in vitro respiratory epithelial model. Methods: Twenty-six papers were included in this review: twenty-one cellular response studies on respiratory secretome application and five studies involving animal research. Results: The CM produced by differentiated cells from respiratory and non-respiratory systems, such as mesenchymal stem cells (MSC), exhibited the similar overall effect of improving proliferation and regeneration. Not only could differentiated cells from respiratory tissues increase proliferation, migration, and attachment, but the CM was also able to protect the respiratory epithelium against cytotoxicity. Most non-respiratory tissue CM was used as a treatment model to determine the effects of the therapy, while only one study used particle-based CM and reported decreased epithelial cell tight junctions, which harmed the epithelial barrier. Conclusion: As it resolves the challenges related to cell development and wound healing while simultaneously generally reducing the danger of immunological compatibility and tumorigenicity, CM might be a potential regenerative therapy in numerous respiratory illnesses. However, additional research is required to justify using CM in respiratory epithelium clinical practice. [ABSTRACT FROM AUTHOR]

Numerous biomaterials have been developed over the years to enhance the outcomes of endoscopic sinus surgery (ESS) for patients with chronic rhinosinusitis. These products are specifically designed to prevent postoperative bleeding, optimize wound healing, and reduce inflammation. However, there is no singular material on the market that can be deemed the optimal material for the nasal pack. We systematically reviewed the available evidence to assess the functional biomaterial efficacy after ESS in prospective studies. The search was performed using predetermined inclusion and exclusion criteria, and 31 articles were identified in PubMed, Scopus, and Web of Science. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess each study's risk of bias. The studies were critically analyzed and categorized into types of biomaterial and functional properties, according to synthesis without meta-analysis (SWiM) guidelines. Despite the heterogeneity between studies, it was observed that chitosan, gelatin, hyaluronic acid, and starch-derived materials exhibit better endoscopic scores and significant potential for use in nasal packing. The published data support the idea that applying a nasal pack after ESS improves wound healing and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Burns are a widespread global public health traumatic injury affecting many people worldwide. Non-fatal burn injuries are a leading cause of morbidity, resulting in prolonged hospitalization, disfigurement, and disability, often with resulting stigma and rejection. The treatment of burns is aimed at controlling pain, removing dead tissue, preventing infection, reducing scarring risk, and tissue regeneration. Traditional burn wound treatment methods include the use of synthetic materials such as petroleum-based ointments and plastic films. However, these materials can be associated with negative environmental impacts and may not be biocompatible with the human body. Tissue engineering has emerged as a promising approach to treating burns, and sustainable biomaterials have been developed as an alternative treatment option. Green biomaterials such as collagen, cellulose, chitosan, and others are biocompatible, biodegradable, environment-friendly, and cost-effective, which reduces the environmental impact of their production and disposal. They are effective in promoting wound healing and reducing the risk of infection and have other benefits such as reducing inflammation and promoting angiogenesis. This comprehensive review focuses on the use of multifunctional green biomaterials that have the potential to revolutionize the way we treat skin burns, promoting faster and more efficient healing while minimizing scarring and tissue damage. [ABSTRACT FROM AUTHOR]

Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers. However, these treatments cause a significant number of side effects, as they damage both the cancer cells and the actively dividing normal cells indiscriminately. Hence, a new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8+ T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects. However, the progression of cell-based immunotherapy is hindered by the combined action of TME and TD-EVs, which render the cancer cells less immunogenic. Recently, there has been an increase in interest in using immune cell derivatives to treat cancers. One of the highly potential immune cell derivatives is the NK cell-derived EVs (NK-EVs). As an acellular product, NK-EVs are resistant to the influence of TME and TD-EVs, and can be designed for "off-the-shelf" use. In this systematic review, we examine the safety and efficacy of NK-EVs to treat various cancers in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Hydroxytyrosol (HT) is an olive polyphenol with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of HT treatment on epithelial–mesenchymal transition (EMT) in primary human respiratory epithelial cells (RECs) isolated from human nasal turbinate. HT dose–response study and growth kinetic study on RECs was performed. Several approaches on HT treatment and TGFβ1 induction with varying durations and methods was studied. RECs morphology and migration ability were evaluated. Vimentin and E-cadherin immunofluorescence staining and Western blotting [E-cadherin, vimentin, SNAIL/SLUG, AKT, phosphorylated (p)AKT, SMAD2/3 and pSMAD2/3] were performed after 72-h treatment. In silico analysis (molecular docking) of HT was performed to evaluate the potential of HT to bind with the TGFβ receptor. The viability of the HT-treated RECs was concentration-dependent, where the median effective concentration (EC50) was 19.04 μg/mL. Testing of the effects of 1 and 10 µg/mL HT revealed that HT suppressed expression of the protein markers vimentin and SNAIL/SLUG while preserving E-cadherin protein expression. Supplementation with HT protected against SMAD and AKT pathway activation in the TGFβ1-induced RECs. Furthermore, HT demonstrated the potential to bind with ALK5 (a TGFβ receptor component) in comparison to oleuropein. TGFβ1-induced EMT in RECs and HT exerted a positive effect in modulating the effects of EMT. [ABSTRACT FROM AUTHOR]

Glottic insufficiency is widespread in the elderly population and occurs as a result of secondary damage or systemic disease. Tissue engineering is a viable treatment for glottic insufficiency since it aims to restore damaged nerve tissue and revitalize aging muscle. After injection into the biological system, injectable biomaterial delivers cost- and time-effectiveness while acting as a protective shield for cells and biomolecules. This article focuses on injectable biomaterials that transport cells and biomolecules in regenerated tissue, particularly adipose, muscle, and nerve tissue. We propose Wharton's Jelly mesenchymal stem cells (WJMSCs), induced pluripotent stem cells (IP-SCs), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor-1 (IGF-1) and extracellular vesicle (EV) as potential cells and macromolecules to be included into biomaterials, with some particular testing to support them as a promising translational medicine for vocal fold regeneration. [ABSTRACT FROM AUTHOR]

Collagen is the most abundant structural protein found in humans and mammals, particularly in the extracellular matrix (ECM). Its primary function is to hold the body together. The collagen superfamily of proteins includes over 20 types that have been identified. Yet, collagen type I is the major component in many tissues and can be extracted as a natural biomaterial for various medical and biological purposes. Collagen has multiple advantageous characteristics, including varied sources, biocompatibility, sustainability, low immunogenicity, porosity, and biodegradability. As such, collagen-type-I-based bioscaffolds have been widely used in tissue engineering. Biomaterials based on collagen type I can also be modified to improve their functions, such as by crosslinking to strengthen the mechanical property or adding biochemical factors to enhance their biological activity. This review discusses the complexities of collagen type I structure, biosynthesis, sources for collagen derivatives, methods of isolation and purification, physicochemical characteristics, and the current development of collagen-type-I-based scaffolds in tissue engineering applications. The advancement of additional novel tissue engineered bioproducts with refined techniques and continuous biomaterial augmentation is facilitated by understanding the conventional design and application of biomaterials based on collagen type I. [ABSTRACT FROM AUTHOR]

Simple Summary: Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Is the landscape in this hotly debated stage changing the role for surgery as immunotherapy and targeted therapies are being investigated and implemented? A review on multimodality therapeutic options for stage IIIA-N2 NSCLC is presented. For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement. [ABSTRACT FROM AUTHOR]

Electronic nicotine delivery systems (ENDS) containing synthetic nicotine have yet to be classified as tobacco products; consequently, there is ambiguity over whether Food and Drug Administration (FDA) regulatory authority can be extended to include tobacco-free nicotine (TFN) e-cigarettes. In recent years, a more significant number of e-cigarette companies have been manufacturing TFN-containing e-cigarettes and e-liquids to circumvent FDA regulations. While studies have shown that aerosols generated from tobacco-derived nicotine-containing e-cigarettes contain significant reactive oxygen species (ROS) levels, no comparison studies have been conducted using TFN e-cigarettes. This study uses a single puff aerosol generator to aerosolize TFN and tobacco-derived nicotine-containing vape products and subsequently involves semi-quantifying the ROS generated by these vape products in H2O2 equivalents. We found that the differences between ROS levels generated from TFN and tobacco-derived nicotine-containing vape products vary by flavor. TFN tobacco flavored and fruit flavored products are more toxic in terms of ROS generation than menthol/ice and drink/beverage flavored products using TFN. Our study provides further insight into understanding how flavoring agents used in vape products impact ROS generation from e-cigarettes differently in TFN e-cigarettes than e-cigarettes using tobacco-derived nicotine. [ABSTRACT FROM AUTHOR]

Pathological conditions of the tracheal epithelium, such as postoperative injuries and chronic conditions, often compromise the functionality of the respiratory epithelium. Although replacement of the respiratory epithelium using various types of tracheal transplantation has been attempted, there is no predictable and dependable replacement method that holds for safe and practicable long-term use. Therefore, we used a tissue engineering approach for ex vivo regeneration of the respiratory epithelium (RE) construct. Collagen type I was isolated from sheep tendon and it was fabricated in a three-dimensional (3D) scaffold format. Isolated human respiratory epithelial cells (RECs) and fibroblasts from nasal turbinate were co-cultured on the 3D scaffold for 48 h, and epithelium maturation was allowed for another 14 days in an air–liquid interface culture system. The scanning electron microscope results revealed a fabricated porous-structure 3D collagen scaffold. The scaffold was found to be biocompatible with RECs and fibroblasts and allows cells attachment, proliferation, and migration. Immunohistochemical analysis showed that the seeded RECs and fibroblasts were positive for expression of cytokeratin 14 and collagen type I markers, respectively, indicating that the scaffold supports the native phenotype of seeded cells over a period of 14 days. Although a longer maturation period is needed for ciliogenesis to occur in RECs, the findings suggest that the tissue-engineered RE construct is a potential candidate for direct use in tracheal epithelium replacement or tracheal tube reengineering. [ABSTRACT FROM AUTHOR]

Nasal mucosa injury can be caused by trauma, radiotherapy, chronic infection such as sinusitis, and post sinus surgery. The rate of healing and its treatment are important in the recovery of patients especially in post sinus surgery, which introduces new injuries. In this review, the current knowledge in terms of the mechanism underlying nasal wound healing was initially discussed. The currently available treatment options for enhancement of wound healing following sinus surgery were discussed and these had included intravenous antibiotics or steroids, various nasal sprays, and nasal packing. In addition, emerging alternative therapies in nasal mucosa wound healing such as herbal medicine and the advancement of regenerative medicine therapies such as stem cells and their byproducts were also discussed. Despite the various available treatment options for wound healing in nasal mucosa, rigorous strong evidence of their efficacy is gravely warranted in order to recommend them as part of the treatment modality. [ABSTRACT FROM AUTHOR]

Simple Summary: The global coronavirus disease 2019 (COVID-19) pandemic has drastically changed the current practice of medicine worldwide. As more clinical data is collected and processed, we are beginning to have an understanding of which patients are more at risk for severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Preliminary data has shown that patients with lung cancer are disproportionally affected by the current COVID-19 pandemic. Furthermore, studies have shown that lung cancer patients are also significantly more likely to be admitted to the ICU and need mechanical ventilation. A specific subset of patients that are even more at risk for severe COVID-19 are those that require lung cancer surgery. To minimize the risk of SARS-CoV-2 infections in patients undergoing surgery, new treatment guidelines and preventive measures are necessary. In this review, we summarize the latest evidence regarding recommendations for patients undergoing lung cancer surgery in the COVID-19 era. The current coronavirus disease 2019 (COVID-19) pandemic has forced healthcare providers worldwide to adapt their practices. Our understanding of the effects of COVID-19 has increased exponentially since the beginning of the pandemic. Data from large-scale, international registries has provided more insight regarding risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has allowed us to delineate specific subgroups of patients that have higher risks for severe complications. One particular subset of patients that have significantly higher risks of SARS-CoV-2 infection with higher morbidity and mortality rates are those that require surgical treatment for lung cancer. Earlier studies have shown that COVID-19 infections in patients that underwent lung cancer surgery is associated with higher rates of respiratory failure and mortality. However, deferral of cancer treatments is associated with increased mortality as well. This creates difficult situations in which healthcare providers are forced to weigh the benefits of surgical treatment against the possibility of SARS-CoV-2 infections. A number of oncological and surgical organizations have proposed treatment guidelines and recommendations for patients planned for lung cancer surgery. In this review, we summarize the latest data and recommendations for patients undergoing lung cancer surgery in the COVID-19 circumstance. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase (AChE) is an important cholinesterase enzyme present in the synaptic clefts of living organisms. It maintains the levels of the neurotransmitter acetylcholine by catalyzing the hydrolysis reaction of acetylcholine to thiocholine. This catalytic activity of AChE is drastically inhibited by trace amounts of organophosphorus (OP) pesticides present in the environment. As a result, effective monitoring of OP pesticides in the environment is very desirable and has been done successfully in recent years with the use of nanomaterial-based AChE sensors. In such sensors, the enzyme AChE has been immobilized onto nanomaterials like multiwalled carbon nanotubes, gold nanoparticles, zirconia nanoparticles, cadmium sulphide nano particles or quantum dots. These nanomaterial matrices promote significant enhancements of OP pesticide determinations, with the thiocholine oxidation occurring at much lower oxidation potentials. Moreover, nanomaterial-based AChE sensors with rapid response, increased operational and long storage stability are extremely well suited for OP pesticide determination over a wide concentration range. In this review, the unique advantages of using nanomaterials as AChE immobilization matrices are discussed. Further, detection limits, sensitivities and correlation coefficients obtained using various electroanalytical techniques have also been compared with chromatographic techniques. [ABSTRACT FROM AUTHOR]

Catalase (CAT) is a heme enzyme with a Fe(III/II) prosthetic group at its redox centre. CAT is present in almost all aerobic living organisms, where it catalyzes the disproportionation of H2O2 into oxygen and water without forming free radicals. In order to study this catalytic mechanism in detail, the direct electrochemistry of CAT has been investigated at various modified electrode surfaces with and without nanomaterials. The results show that CAT immobilized on nanomaterial modified electrodes shows excellent catalytic activity, high sensitivity and the lowest detection limit for H2O2 determination. In the presence of nanomaterials, the direct electron transfer between the heme group of the enzyme and the electrode surface improved significantly. Moreover, the immobilized CAT is highly biocompatible and remains extremely stable within the nanomaterial matrices. This review discusses about the versatile approaches carried out in CAT immobilization for direct electrochemistry and electrochemical sensor development aimed as efficient H2O2 determination. The benefits of immobilizing CAT in nanomaterial matrices have also been highlighted. [ABSTRACT FROM AUTHOR]

Cardiac patch implantation helps maximize the paracrine function of grafted cells and serves as a reservoir of soluble proangiogenic factors required for the neovascularization of infarcted hearts. We have previously fabricated a cardiac patch, EF-HAM, composed of a human amniotic membrane (HAM) coated with aligned PLGA electrospun fibers (EF). In this study, we aimed to evaluate the biocompatibility and angiogenic effects of EF-HAM scaffolds with varying fiber thicknesses on the paracrine behavior of skeletal muscle cells (SkM). Conditioned media (CM) obtained from SkM-seeded HAM and EF-HAM scaffolds were subjected to multiplex analysis of angiogenic factors and tested on HUVECs for endothelial cell viability, migration, and tube formation analyses. All three different groups of EF-HAM scaffolds demonstrated excellent biocompatibility with SkM. CM derived from SkM-seeded EF-HAM 7 min scaffolds contained significantly elevated levels of proangiogenic factors, including angiopoietin-1, IL-8, and VEGF-C compared to plain CM, which was obtained from SkM cultured on the plain surface. CM obtained from all SkM-seeded EF-HAM scaffolds significantly increased the viability of HUVECs compared to plain CM after five days of culture. However, only EF-HAM 7 min CM induced a higher migration capacity in HUVECs and formed a longer and more elaborate capillary-like network on Matrigel compared with plain CM. Surface roughness and wettability of EF-HAM 7 min scaffolds might have influenced the proportion of skeletal myoblasts and fibroblasts growing on the scaffolds and subsequently potentiated the angiogenic paracrine function of SkM. This study demonstrated the angioinductive properties of EF-HAM composite scaffold and its potential applications in the repair and regeneration of ischemic tissues. [ABSTRACT FROM AUTHOR]

Nanotechnology has become an emerging technology in the medical field and is widely applicable for various clinical applications. The potential use of nanoparticles as antimicrobial agents is greatly explored and taken into consideration as alternative methods to overcome the challenges faced by healthcare workers and patients in preventing infections caused by pathogenic microorganisms. Among microorganisms, bacterial infections remain a major hurdle and are responsible for high morbidity and mortality globally, especially involving those with medical conditions and elderly populations. Over time, these groups are more vulnerable to developing resistance to antibiotics, as bacterial biofilms are difficult to destroy or eliminate via antibiotics; thus, treatment becomes unsuccessful or ineffective. Mostly, bacterial biofilms and other microbes can be found on medical devices and wounds where they disperse their contents which cause infections. To inhibit biofilm formations and overcome antibiotic resistance, antimicrobial-loaded nanoparticles alone or combined with other substances could enhance the bactericidal activity of nanomaterials. This includes killing the pathogens effectively without harming other cells or causing any adverse effects to living cells. This review summarises the mechanisms of actions employed by the different types of nanoparticles which counteract infectious agents in reducing biofilm formation and improve antibiotic therapy for clinical usage. [ABSTRACT FROM AUTHOR]

Studies have shown that aerosols generated from flavored e-cigarettes contain Reactive Oxygen Species (ROS), promoting oxidative stress-induced damage within pulmonary cells. Our lab investigated the ROS content of e-cigarette vapor generated from disposable flavored e-cigarettes (vape bars) with and without nicotine. Specifically, we analyzed vape bars belonging to multiple flavor categories (Tobacco, Minty Fruit, Fruity, Minty/Cool (Iced), Desserts, and Drinks/Beverages) manufactured by various vendors and of different nicotine concentrations (0–6.8%). Aerosols from these vape bars were generated via a single puff aerosol generator; these aerosols were then individually bubbled through a fluorogenic solution to semi-quantify ROS generated by these bars in H2O2 equivalents. We compared the ROS levels generated by each vape bar as an indirect determinant of their potential to induce oxidative stress. Our results showed that ROS concentration (μM) within aerosols produced from these vape bars varied significantly among different flavored vape bars and identically flavored vape bars with varying nicotine concentrations. Furthermore, our results suggest that flavoring chemicals and nicotine play a differential role in generating ROS production in vape bar aerosols. Our study provides insight into the differential health effects of flavored vape bars, in particular cool (iced) flavors, and the need for their regulation. [ABSTRACT FROM AUTHOR]

Telomere repeat binding factor 2 (TRF2) has a well-known function at the telomeres, which acts to protect the telomere end from being recognized as a DNA break or from unwanted recombination. This protection mechanism prevents DNA instability from mutation and subsequent severe diseases caused by the changes in DNA, such as cancer. Since TRF2 actively inhibits the DNA damage response factors from recognizing the telomere end as a DNA break, many more studies have also shown its interactions outside of the telomeres. However, very little has been discovered on the mechanisms involved in these interactions. This review aims to discuss the known function of TRF2 and its interaction with the DNA damage response (DDR) factors at both telomeric and non-telomeric regions. In this review, we will summarize recent progress and findings on the interactions between TRF2 and DDR factors at telomeres and outside of telomeres. [ABSTRACT FROM AUTHOR]

Vocal fold injection is a preferred treatment in glottic insufficiency because it is relatively quick and cost-saving. However, researchers have yet to discover the ideal biomaterial with properties suitable for human vocal fold application. The current systematic review employing PRISMA guidelines summarizes and discusses the available evidence related to outcome measures used to characterize novel biomaterials in the development phase. The literature search of related articles published within January 2010 to March 2021 was conducted using Scopus, Web of Science (WoS), Google Scholar and PubMed databases. The search identified 6240 potentially relevant records, which were screened and appraised to include 15 relevant articles based on the inclusion and exclusion criteria. The current study highlights that the characterization methods were inconsistent throughout the different studies. While rheologic outcome measures (viscosity, elasticity and shear) were most widely utilized, there appear to be no target or reference values. Outcome measures such as cellular response and biodegradation should be prioritized as they could mitigate the clinical drawbacks of currently available biomaterials. The review suggests future studies to prioritize characterization of the viscoelasticity (to improve voice outcomes), inflammatory response (to reduce side effects) and biodegradation (to improve longevity) profiles of newly developed biomaterials. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling. [ABSTRACT FROM AUTHOR]

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings. [ABSTRACT FROM AUTHOR]

Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C (cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an N-terminal peptide of cMyBP-C. Previously, we reported that the presence of C0-C1f is pathogenic within cardiac tissue and is able to activate macrophages. Fibroblasts also play a crucial role in cardiac remodeling arising from ischemic events, as they contribute to both inflammation and scar formation. To understand whether C0-C1f directly modulates fibroblast phenotype, we analyzed the impact of C0-C1f on a human fibroblast cell line in vitro by performing mRNA microarray screening, immunofluorescence staining, and quantitative real-time PCR. The underlying signaling pathways were investigated by KEGG analysis and determined more precisely by targeted inhibition of the potential signaling cascades in vitro. C0-C1f induced pro-inflammatory responses that might delay TGFβ-mediated myofibroblast conversion. TGFβ also counteracted C0-C1f-mediated fibroblast activation. Inhibition of TLR4 or NFκB as well as the delivery of miR-146 significantly reduced C0-C1f-mediated effects. In conclusion, C0-C1f induces inflammatory responses in human fibroblasts that are mediated via TRL4 signaling, which is decreased in the presence of TGFβ. Specific targeting of TLR4 signaling could be an innovative strategy to modulate C0-C1f-mediated inflammation. [ABSTRACT FROM AUTHOR]

Epithelial–Mesenchymal Transition (EMT) was first discovered during the transition of cells from the primitive streak during embryogenesis in chicks. It was later discovered that EMT holds greater potential in areas other than the early development of cells and tissues since it also plays a vital role in wound healing and cancer development. EMT can be classified into three types based on physiological functions. EMT type 3, which involves neoplastic development and metastasis, has been the most thoroughly explored. As EMT is often found in cancer stem cells, most research has focused on its association with other factors involving cancer progression, including telomeres. However, as telomeres are also mainly involved in aging, any possible interaction between the two would be worth noting, especially as telomere dysfunction also contributes to cancer and other age-related diseases. Ascertaining the balance between degeneration and cancer development is crucial in cell biology, in which telomeres function as a key regulator between the two extremes. The essential roles that EMT and telomere protection have in aging reveal a potential mutual interaction that has not yet been explored, and which could be used in disease therapy. In this review, the known functions of EMT and telomeres in aging are discussed and their potential interaction in age-related diseases is highlighted. [ABSTRACT FROM AUTHOR]

The current strategy for rapid wound healing treatment involves combining a biomaterial and cell-secreted proteins or biomolecules. This study was aimed at characterizing 3-dimensional (3D) collagen hydrogels fortified with dermal fibroblast-conditioned medium (DFCM) as a readily available acellular skin substitute. Confluent fibroblasts were cultured with serum-free keratinocyte-specific medium (KM1 and KM2) and fibroblast-specific medium (FM) to obtain DFCM. Subsequently, the DFCM was mixed with collagen (Col) hydrogel and chondroitin-4-sulphate (C4S) to fabricate 3D constructs termed Col/C4S/DFCM-KM1, Col/C4S/DFCM-KM2, and Col/C4S/DFCM-FM. The constructs successfully formed soft, semi-solid and translucent hydrogels within 1 h of incubation at 37 °C with strength of <2.5 Newton (N). The Col/C4S/DFCM demonstrated significantly lower turbidity compared to the control groups. The Col/C4S/DFCM also showed a lower percentage of porosity (KM1: 35.15 ± 9.76%; KM2: 6.85 ± 1.60%; FM: 14.14 ± 7.65%) compared to the Col (105.14 ± 11.87%) and Col/C4S (143.44 ± 27.72%) constructs. There were no changes in both swelling and degradation among all constructs. Fourier transform infrared spectrometry showed that all groups consisted of oxygen–hydrogen bonds (O-H) and amide I, II, and III. In conclusion, the Col/C4S/DFCM constructs maintain the characteristics of native collagen and can synergistically deliver essential biomolecules for future use in skin therapeutic applications. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches. [ABSTRACT FROM AUTHOR]

Fibroblasts secrete many essential factors that can be collected from fibroblast culture medium, which is termed dermal fibroblast conditioned medium (DFCM). Fibroblasts isolated from human skin samples were cultured in vitro using the serum-free keratinocyte-specific medium (Epilife (KM1), or define keratinocytes serum-free medium, DKSFM (KM2) and serum-free fibroblast-specific medium (FM) to collect DFCM-KM1, DFCM-KM2, and DFCM-FM, respectively). We characterised and evaluated the effects of 100–1600 µg/mL DFCM on keratinocytes based on attachment, proliferation, migration and gene expression. Supplementation with 200–400 µg/mL keratinocyte-specific DFCM-KM1 and DFCM-KM2 enhanced the attachment, proliferation and migration of sub-confluent keratinocytes, whereas 200–1600 µg/mL DFCM-FM significantly increased the healing rate in the wound healing assay, and 400–800 µg/mL DFCM-FM was suitable to enhance keratinocyte attachment and proliferation. A real-time (RT2) profiler polymerase chain reaction (PCR) array showed that 42 genes in the DFCM groups had similar fold regulation compared to the control group and most of the genes were directly involved in wound healing. In conclusion, in vitro keratinocyte re-epithelialisation is supported by the fibroblast-secreted proteins in 200–400 µg/mL DFCM-KM1 and DFCM-KM2, and 400–800 µg/mL DFCM-FM, which could be useful for treating skin injuries. [ABSTRACT FROM AUTHOR]

Poly(d,l–lactide–co–glycolide) (PLGA) has been extensively explored for bone regeneration applications; however, its clinical use is limited by low osteointegration. Therefore, approaches that incorporate osteoconductive molecules are of great interest. Graphene oxide (GO) is gaining popularity for biomedical applications due to its ability to bind biological molecules and present them for enhanced bioactivity. This study reports the preparation of PLGA microparticles via Pickering emulsification using GO as the sole surfactant, which resulted in hybrid microparticles in the size range of 1.1 to 2.4 µm based on the ratio of GO to PLGA in the reaction. Furthermore, this study demonstrated that the hybrid GO-PLGA microparticles were not cytotoxic to either primary human fetal cartilage rudiment cells or the human osteoblast-like cell line, Saos-2. Additionally, the GO-PLGA microparticles promoted the osteogenic differentiation of the human fetal cartilage rudiment cells in the absence of exogenous growth factors to a greater extent than PLGA alone. These findings demonstrate that GO-PLGA microparticles are cytocompatible, osteoinductive and have potential as substrates for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein. [ABSTRACT FROM AUTHOR]

In this work, we present a potentiometric pH sensor on textile substrate for wearable applications. The sensitive (thick film graphite composite) and reference electrodes (Ag/AgCl) are printed on cellulose-polyester blend cloth. An excellent adhesion between printed electrodes allow the textile-based sensor to be washed with a reliable pH response. The developed textile-based pH sensor works on the basis of electrochemical reaction, as observed through the potentiometric, cyclic voltammetry (100 mV/s) and electrochemical impedance spectroscopic (10 mHz to 1 MHz) analysis. The electrochemical double layer formation and the ionic exchanges of the sensitive electrode-pH solution interaction are observed through the electrochemical impedance spectroscopic analysis. Potentiometric analysis reveals that the fabricated textile-based sensor exhibits a sensitivity (slope factor) of 4 mV/pH with a response time of 5 s in the pH range 6–9. The presented sensor shows stable response with a potential of 47 ± 2 mV for long time (2000 s) even after it was washed in tap water. These results indicate that the sensor can be used for wearable applications. [ABSTRACT FROM AUTHOR]