Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.

Triple-Networked Hybrid Hydrogels Reinforced with Montmorillonite Clay and Graphene Nanoplatelets for Soft and Hard Tissue Regeneration.

Hydrogel is a three-dimensional (3D) soft and highly hydrophilic, polymeric network that can swell in water and imbibe a high amount of water or biological fluids. Hydrogels have been used widely in various biomedical applications. Hydrogel may provide a fluidic tissue-like 3D microenvironment by maintaining the original network for tissue engineering. However, their low mechanical performances limit their broad applicability in various functional tissues. This property causes substantial challenges in designing and preparing strong hydrogel networks. Therefore, we report the triple-networked hybrid hydrogel network with enhanced mechanical properties by incorporating dual-crosslinking and nanofillers (e.g., montmorillonite (MMT), graphene nanoplatelets (GNPs)). In this study, we prepared hybrid hydrogels composed of polyacrylamide, poly (vinyl alcohol), sodium alginate, MMT, and MMT/GNPs through dynamic crosslinking. The freeze-dried hybrid hydrogels showed good 3D porous architecture. The results exhibited a magnificent porous structure, interconnected pore-network surface morphology, enhanced mechanical properties, and cellular activity of hybrid hydrogels.

Plasticized poly(vinylalcohol) and poly(vinylpyrrolidone) based patches with tunable mechanical properties for cardiac tissue engineering applications.

Polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) are the two most investigated biopolymers for various tissue engineering applications. However, their poor tensile strength renders them unsuitable for cardiac tissue engineering (CTE). In this study, we developed and evaluated PVA-PVP-based patches, plasticized with glycerol or propylene glycol (0.1%-0.4%; v:v), for their application in CTE. The cardiac patches were evaluated for their physico-chemical (weight, thickness, folding endurance, FT-IR, and swelling behavior) and mechanical properties. The optimized patches were characterized for their ability to support in vitro attachment, viability, proliferation, and beating behavior of neonatal mouse cardiomyocytes (CMs). In vivo evaluation of the cardiac patches was done under the subcutaneous skin pouch and heart of rat models. Results showed that the optimized molar ratio of PVA:PVP with plasticizers (0.3%; v-v) resulted in cardiac patches, which were dry at room temperature and had desirable folding endurance of at least 300, a tensile strength of 6-23 MPa and, percentage elongation at break of more than 250%. Upon contact with phosphate-buffered saline, these PVA-PVP patches formed hydrogel patches having the tensile strength of 1.3-3.0 MPa. The patches supported the attachment, viability, and proliferation of primary neonatal mouse CMs and were nonirritant and noncorrosive to cardiac cells. In vivo transplantation of cardiac patches into a subcutaneous pouch and on the heart of rat models revealed them to be biodegradable, biocompatible, and safe for use in CTE applications.

Pesticides in mixture disrupt metabolic regulation: in silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice.

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRß) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight.

Development of carrageenan-immobilized lytic coliphage vB_Eco2571-YU1 hydrogel for topical delivery of bacteriophages in wound dressing applications.

Bacteriophages are employed as cost-effective and efficient antibacterial agents to counter the emergence of antibiotic-resistant bacteria and other host bacteria in phage therapy. The increasing incidence of skin wounds is a significant concern in clinical practice, especially considering the limitations of antibiotic therapy. Furthermore, the lack of an effective delivery system that preserves the stability of bacteriophages hampers their clinical implementation. In recent years, there has been a growing amount of research on bacteriophage applications in veterinary and biomedical sciences. In our study, lytic coliphage vB_Eco2571-YU1 was isolated against pathogenic Escherichia coli host bacteria, and hydrogel wound dressing materials were fabricated with marine polysaccharide carrageenan (carr-vB_Eco2571-YU1) for their antibacterial activity. Transmission electron microscopy (TEM) morphology identified it as a Myoviridae coliphage with an icosahedral head length and width of approximately 60 and 56.8 nm, respectively, and a tail length of 119.7 nm. The one-step growth curve of coliphage revealed a latent period of 10 min, a rise period of 15 min, and a burst size of 120 virions per cell. The bacteriolytic activity of unimmobilized coliphages was observed within 2 h; however, strain-specific phage resistance was acquired after 9 h. In contrast, carr-vB_Eco2571-YU1 showed a sharp decline in the growth of bacteria in the log phase after 2 h and did not allow for the acquisition of phage resistance by the E. coli strain. The stability of coliphage under different pH, temperature, osmolarity, detergents, and organic solvents was evaluated. We also studied the long-term storage of carr-vB_Eco2571-YU1 hydrogels at 4 °C and found that the titer value decreased during a time-dependent period of 28 days. These hydrogels were also found to be hemocompatible using a hemolysis assay. The addition of plasticizer (0.6 % (w/v)) to the carrageenan (2 % (w/v)) to prepare carr-vB_Eco2571-YU1 hydrogels showed a decrease in compressive strength with enhanced elasticity. This phage therapy using polymeric immobilization of bacteriophages is a promising next-generation wound dressing biomaterial alternative to conventional wound and skin care management.

Harnessing the power of biological macromolecules in hydrogels for controlled drug release in the central nervous system: A review.

Hydrogels have immense potential in revolutionizing central nervous system (CNS) drug delivery, improving outcomes for neurological disorders. They serve as promising tools for controlled drug delivery to the CNS. Available hydrogel types include natural macromolecules (e.g., chitosan, hyaluronic acid, alginate), as well as hybrid hydrogels combining natural and synthetic polymers. Each type offers distinct advantages in terms of biocompatibility, mechanical properties, and drug release kinetics. Design and engineering considerations encompass hydrogel composition, crosslinking density, porosity, and strategies for targeted drug delivery. The review emphasizes factors affecting drug release profiles, such as hydrogel properties and formulation parameters. CNS drug delivery applications of hydrogels span a wide range of therapeutics, including small molecules, proteins and peptides, and nucleic acids. However, challenges like limited biodegradability, clearance, and effective CNS delivery persist. Incorporating 3D bioprinting technology with hydrogel-based CNS drug delivery holds the promise of highly personalized and precisely controlled therapeutic interventions for neurological disorders. The review explores emerging technologies like 3D bioprinting and nanotechnology as opportunities for enhanced precision and effectiveness in hydrogel-based CNS drug delivery. Continued research, collaboration, and technological advancements are vital for translating hydrogel-based therapies into clinical practice, benefiting patients with CNS disorders. This comprehensive review article delves into hydrogels for CNS drug delivery, addressing their types, design principles, applications, challenges, and opportunities for clinical translation.

Gelatin/Polyacrylamide-Based Antimicrobial and Self-Healing Hydrogel Film for Wound Healing Application.

In this study, a self-healing, adhesive, and superabsorbent film made of gelatin, poly(acrylamide), and boric acid (GelAA) was successfully synthesized using a free radical reaction mechanism. The optimized film showed a remarkable 2865 ± 42% water absorptivity and also exhibited excellent self-healing behavior. The GelAA films were further loaded with silver nanoclusters (AgNCs) and ursodeoxycholic acid (UDC) (loading efficiency = 10%) to develop UDC/Ag/GelAA films. The loading of AgNCs in UDC/Ag/GelAA films helped in exhibiting 99.99 ± 0.01% antibacterial activity against both Gram-positive and Gram-negative bacteria, making them very effective against bacterial infections. Additionally, UDC/Ag/GelAA films had 77.19 ± 0.52% porosity and showed 90% of UDC release in 30 h, which helps in improving the cell proliferation. Our research provides an easy but highly effective process for synthesizing a hydrogel film, which is an intriguing choice for wound healing applications without the use of antibiotics.

Multicomponent decellularized extracellular matrix of caprine small intestine submucosa based bioactive hydrogel promoting full-thickness burn wound healing in rabbits.

Effective treatment for full-thickness burn wounds has remained challenging for clinicians. Among various strategies, extracellular gel-based dressing materials have gained attention to promote effective and rapid wound healing. These gel-based materials are porous and have antioxidant, antibacterial, hydrophilic, biodegradation, and biocompatible properties and hence can be used to alleviate burn wound healing. In concurrence with these findings, the present study evaluates thermo-responsive and self-assembled decellularized extracellular matrix (ECM) of caprine small intestine submucosa (DG-SIS) gel-based dressing material for burn wound healing. To expedite healing and efficiently tackle excessive free radicals and bioburden at the burn wound site, DG-SIS gel is fortified with antibacterial components (zinc oxide nanoparticles; ZnO) and a potent antioxidant agent (Vitamin-C;Vt-C). ZnO- and Vt-C-enriched DG-SIS (DG-SIS/ZnO/Vt-C) gels significantly increased the antioxidant and antibacterial activity of the therapeutic hydrogel. Additionally, the fabricated DG-SIS/ZnO/Vt-C bioactive gel resulted in significant full-thickness burn wound contraction (97.75 % in 14 days), a lower inflammatory effect, and enhanced angiogenesis with the highest collagen synthesis (1.22 µg/mg in 14 days) at the wound site. The outcomes from this study demonstrate a synergistic effect of ZnO/Vt-C in the bioactive gel as an effective and inexpensive therapeutic approach for full-thickness burn wound treatment.

Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.

Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.

Recent Advances in Drug Delivery Systems Targeting Insulin Signalling for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-ß plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3ß, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.

Piezoelectric Biosensors and Nanomaterials-based Therapeutics for Coronavirus and Other Viruses: A Mini-review.

Since late 2019, the novel coronavirus (COVID-19) pandemic has caused considerable mortality worldwide. This pandemic raised concerns and provoked research on the diagnosis and treatment of viruses-based diseases. The accurate diagnosis of a virus requires high specificity and sensitivity. Piezoelectric sensors are analytical devices that work on mass-sensitivity-based micromechanical transducers. The change in the mass by the interaction between biological elements and the frequency is recorded by measuring the alternate current and voltage. In addition to diagnosis, antiviral intervention strategies for mitigating various viral diseases are required. Nanomaterialsbased antiviral therapy is efficient, particularly with carbon/metal/metal oxide (organic/inorganic) nanoparticles. Metal/metal oxide nanoparticles, such as gold (Au), silver (Ag), copper (Cu), selenium (Se), zinc oxide (ZnO), magnesium oxide (MgO), carbon dots (CDs), and carbon quantum dots (CQDs), are promising candidates for antiviral therapy. This review discusses the piezoelectric sensors used to detect various viruses, including COVID-19, and the various organic and inorganic nanoparticles involved in the antiviral therapy.

Therapeutics for the Management of Cytokine Release Syndrome in COVID-19.

Coronavirus disease (COVID-19) is the greatest pandemic of this era and has affected more than 10 million people across 213 nations. However, the etiology, management, and treatment of COVID-19 remain unknown. A better understanding of the novel virus would help in developing accurate diagnostic methods and efficacious drugs for the treatment of patients of all age groups. To control the pandemic urgently, many drugs are being repurposed and several clinical trials are in progress for the same. As cytokine storm has been observed to be one of the common mechanisms of immune response in COVID-19 patients, several drugs are under trials to control the cytokine storm. In this review, we discuss the different categories of drugs in clinical trials for the management of cytokine storms in COVID-19 patients. Hitherto, several promising candidates such as IL-1 and IL-6 inhibitors have failed to display efficacy in the trials. Only corticosteroid therapy has shown benefit so far, albeit limited to patients on ventilator support. Thus, it is crucial to seek novel strategies to combat hyperinflammation and increase survival in COVID-19 afflicted patients.

Photocatalytic Degradation, Anticancer, and Antibacterial Studies of Lysinibacillus sphaericus Biosynthesized Hybrid Metal/Semiconductor Nanocomposites.

The biological synthesis of nanocomposites has become cost-effective and environmentally friendly and can achieve sustainability with high efficiency. Recently, the biological synthesis of semiconductor and metal-doped semiconductor nanocomposites with enhanced photocatalytic degradation efficiency, anticancer, and antibacterial properties has attracted considerable attention. To this end, for the first time, we biosynthesized zinc oxide (ZnO) and silver/ZnO nanocomposites (Ag/ZnO NCs) as semiconductor and metal-doped semiconductor nanocomposites, respectively, using the cell-free filtrate (CFF) of the bacterium Lysinibacillus sphaericus. The biosynthesized ZnO and Ag/ZnO NCs were characterized by various techniques, such as ultraviolet-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, and photoluminescence spectroscopy. The photocatalytic degradation potential of these semiconductor NPs and metal-semiconductor NCs was evaluated against thiazine dye, methylene blue (MB) degradation, under simulated solar irradiation. Ag/ZnO showed 90.4 ± 0.46% photocatalytic degradation of MB, compared to 38.18 ± 0.15% by ZnO in 120 min. The cytotoxicity of ZnO and Ag/ZnO on human cervical HeLa cancer cells was determined using an MTT assay. Both nanomaterials exhibited cytotoxicity in a concentration- and time-dependent manner on HeLa cells. The antibacterial activity was also determined against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus). Compared to ZnO, Ag/ZnO NCs showed higher antibacterial activity. Hence, the biosynthesis of semiconductor nanoparticles could be a promising strategy for developing hybrid metal/semiconductor nanomaterials for different biomedical and environmental applications.

Autoimmune responses and therapeutic interventions for systemic lupus erythematosus: a comprehensive review.

Systemic Lupus Erythematosus (SLE) or Lupus is a multifactorial autoimmune disease of multiorgan malfunctioning of extremely heterogeneous and unclear etiology that affects multiple organs and physiological systems. Some racial groups and women of childbearing age are more susceptible to SLE pathogenesis. Impressive progress has been made towards a better understanding of different immune components contributing to SLE pathogenesis. Recent investigations have uncovered the detailed mechanisms of inflammatory responses and organ damage. Various environmental factors, pathogens, and toxicants, including ultraviolet light, drugs, viral pathogens, gut microbiome metabolites, and sex hormones trigger the onset of SLE pathogenesis in genetically susceptible individuals and result in the disruption of immune homeostasis of cytokines, macrophages, T cells, and B cells. Diagnosis and clinical investigations of SLE remain challenging due to its clinical heterogeneity and hitherto only a few approved antimalarials, glucocorticoids, immunosuppressants, and some nonsteroidal anti-inflammatory drugs (NSAIDs) are available for treatment. However, the adverse effects of renal and neuropsychiatric lupus and late diagnosis make therapy challenging. Additionally, SLE is also linked to an increased risk of cardiovascular diseases due to inflammatory responses and the risk of infection from immunosuppressive treatment. Due to the diversity of symptoms and treatment-resistant diseases, SLE management remains a challenging issue. Nevertheless, the use of next-generation therapeutics with stem cell and gene therapy may bring better outcomes to SLE treatment in the future. This review highlights the autoimmune responses as well as potential therapeutic interventions for SLE particularly focusing on the recent therapeutic advancements and challenges.

Polydopamine-Functionalized Bacterial Cellulose as Hydrogel Scaffolds for Skin Tissue Engineering.

Bacterial cellulose (BC) is a natural polysaccharide polymer hydrogel produced sustainably by the strain Gluconacetobacter hansenii under static conditions. Due to their biocompatibility, easy functionalization, and necessary physicochemical and mechanical properties, BC nanocomposites are attracting interest in therapeutic applications. In this study, we functionalized BC hydrogel with polydopamine (PDA) without toxic crosslinkers and used it in skin tissue engineering. The BC nanofibers in the hydrogel had a thickness of 77.8 ± 20.3 nm, and they could be used to produce hydrophilic, adhesive, and cytocompatible composite biomaterials for skin tissue engineering applications using PDA. Characterization techniques, namely Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and Raman spectroscopy, were performed to investigate the formation of polydopamine on the BC nanofibers. The XRD peaks for BC occur at 2θ = 14.65°, 16.69°, and 22.39°, which correspond to the planes of (100), (010), and (110) of cellulose type Iα. Raman spectroscopy confirmed the formation of PDA, as indicated by the presence of bands corresponding to the vibration of aromatic rings and aliphatic C-C and C-O stretching at 1336 and 1567 cm-1, respectively. FTIR confirmed the presence of peaks corresponding to PDA and BC in the BC/PDA hydrogel scaffolds at 3673, 3348, 2900, and 1052 cm-1, indicating the successful interaction of PDA with BC nanofibers, which was further corroborated by the SEM images. The tensile strength, swelling ratio, degradation, and surface wettability characteristics of the composite BC biomaterials were also investigated. The BC/PDA hydrogels with PDA-functionalized BC nanofibers demonstrated excellent tensile strength and water-wetting ability while maintaining the stability of the BC fibers. The enhanced cytocompatibility of the BC/PDA hydrogels was studied using the PrestoBlue assay. Culturing murine NIH/3T3 fibroblasts on BC/PDA hydrogels showed higher metabolic activity and enhanced proliferation. Additionally, it improved cell viability when using BC/PDA hydrogels. Thus, these BC/PDA composite biomaterials can be used as biocompatible natural alternatives to synthetic substitutes for skin tissue engineering and wound-dressing applications.

From sleep to cancer to neurodegenerative disease: the crucial role of Hsp70 in maintaining cellular homeostasis and potential therapeutic implications.

Sleep is a fundamental process essential for reparatory and restorative mechanisms in all organisms. Recent research has linked sleep to various pathological conditions, including cancer and neurodegeneration, which are associated with various molecular changes in different cellular environments. Despite the potential significance of various molecules, the HSPA1A or Hsp70 protein, which has possible connections with sleep and different neuropsychological and pathological disorders, has been explored the least. This paper explores the potential for manipulating and discovering drugs related to the Hsp70 protein to alleviate sleep problems and improve the prognosis for various other health issues. This paper discusses the critical role of Hsp70 in cancer, neurodegeneration, apoptosis, sleep, and its regulation at the structural level through allosteric mechanisms and different substrates. The significant impact of Hsp70's connection to various conditions suggests that existing sleep medicine could be used to improve such conditions, leading to improved outcomes, minimized research costs, and a new direction for current research. Overall, this paper highlights the potential of Hsp70 protein as a key therapeutic target for developing new drugs for the treatment of sleep disorders, cancer, neurodegeneration, and other related pathological conditions. Further research into the molecular mechanisms of Hsp70 regulation and its interactions with other cellular pathways is necessary to develop targeted treatments for these conditions.Communicated by Ramaswamy H. Sarma.

Preparation, characterization, and bioactivity of reinforced monetite with chitosan-gelatin electrospun composite scaffold for bone tissue engineering.

In this study, chitosan-gelatin-monetite (CGM)-based electrospun scaffolds have been developed that closely mimicked the microstructure and chemical composition of the extracellular matrix of natural bone. CGM-based nanofibrous composite scaffolds were prepared with the help of the electrospinning technique, post-cross-linked using ethyl(dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide solution to improve their stability in an aqueous environment. The prepared chitosan/gelatin (CG) scaffold showed an average fiber diameter of 308 ± 17 nm, whereas 5 and 7 wt% monetite containing CGM5and CGM7scaffolds, exhibited an average fiber diameter of 287 ± 13 and 265 ± 9 nm, respectively, revealing the fine distribution of monetite particles on the fibrous surface. The distribution of monetite nanoparticles onto the CG nanofibrous surface was confirmed using x-ray diffraction, Fourier transform infrared, and EDAX. Moreover, the addition of 7 wt% monetite into the CG electrospun matrix increased their ultimate tensile strength from 7.62 ± 0.13 MPa in the CG scaffold to 14.34 ± 0.39 MPa in the CGM7scaffold. Simulated body fluid study and staining with alizarin red S (ARS) confirmed the higher mineralization ability of monetite-containing scaffolds compared to that revealed by the CG scaffold. The monetite incorporation into the CG matrix improved its osteogenic properties, including pre-osteoblast MG-63 cell adhesion, proliferation, and differentiation, when seeded with the cells. A higher degree of cellular adhesion, spreading, and migration was observed on the monetite-incorporated CG scaffold than that on the CG scaffold. From 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide) MTT assay, alkaline phosphatase activity, ARS staining, and immunocytochemistry study, the cultured cells discovered a more conducive microenvironment to proliferate and subsequently differentiate into osteoblast lineage in contact with CGM7nanofibers rather than that in CGM0and CGM5.In-vitroresults indicated that electrospun CGM-based composite scaffolds could be used as a potential candidate to repair and regenerate new bone tissues.

A Comprehensive Review of Emerging Trends and Innovative Therapies in Epilepsy Management.

Epilepsy is a complex neurological disorder affecting millions worldwide, with a substantial number of patients facing drug-resistant epilepsy. This comprehensive review explores innovative therapies for epilepsy management, focusing on their principles, clinical evidence, and potential applications. Traditional antiseizure medications (ASMs) form the cornerstone of epilepsy treatment, but their limitations necessitate alternative approaches. The review delves into cutting-edge therapies such as responsive neurostimulation (RNS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), highlighting their mechanisms of action and promising clinical outcomes. Additionally, the potential of gene therapies and optogenetics in epilepsy research is discussed, revealing groundbreaking findings that shed light on seizure mechanisms. Insights into cannabidiol (CBD) and the ketogenic diet as adjunctive therapies further broaden the spectrum of epilepsy management. Challenges in achieving seizure control with traditional therapies, including treatment resistance and individual variability, are addressed. The importance of staying updated with emerging trends in epilepsy management is emphasized, along with the hope for improved therapeutic options. Future research directions, such as combining therapies, AI applications, and non-invasive optogenetics, hold promise for personalized and effective epilepsy treatment. As the field advances, collaboration among researchers of natural and synthetic biochemistry, clinicians from different streams and various forms of medicine, and patients will drive progress toward better seizure control and a higher quality of life for individuals living with epilepsy.