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Nanotizing biosealant components offer a multitude of chemical functionalities for superior adhesion-cohesion, delivering unique properties for comprehensive wound healing that are otherwise impossible to achieve using commercial variants. For the first time, a two-step controlled hydrothermal pyrolysis is reported to nanotize dopamine, phloroglucinol, and glutaraldehyde into carbon dot (CD) to be subsequently converted into carbonized polymer dot (CPD) with gelatin as a co-substrate. Chemical crosslinking of CD with gelatin through Schiff base formation before the second pyrolysis step ensures a complex yet porous polymeric network. The retention of chemical functionalities indigenous to CD substrates and gelatin along with the preservation of CD photoluminescence in CPD for optical tracking is achieved. A unique nanoformulation is created with the CPD through tannic acid (TA) grafting evolving CPD-TA nanoglue demonstrating ≈1.32 MPa strength in lap shear tests conducted on porcine skin, surpassing traditional bioadhesives. CPD-TA nanoglue uploaded insulin as chosen cargo disbursal at the wound site for healing normal and in vitro diabetic wound models using HEKa cells with extraordinary biocompatibility. Most importantly, CPD-TA can generate reactive oxygen species (ROS) and scavenge simultaneously under ambient conditions (23 W white LED or dark) for on-demand sterilization or aiding wound recovery through ROS scavenging.
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Targeted delivery has not been achieved for anthelmintic treatment, resulting in the requirement of excess drug dose leading to side effects and therapeutic resistance. Gastrointestinal helminths take up lipid droplets from digestive fluid for energy production, egg development, and defense which inspired us to develop biocompatible and orally administrable albendazole-loaded solid lipid nanoparticles (SLN-A) that were derived from beeswax and showed drug loading efficiency of 83.3 ± 6.5 mg/g and sustained-release properties with 84.8 ± 2.5% of drug released at pH 6.4 within 24 h at 37 °C. Rhodamine B-loaded SLN showed time-dependent release and distribution of dye in-vitro in Haemonchus contortus. The sustained-release property was shown by the particles that caused enhancement of albendazole potency up to 50 folds. Therefore, this formulation has immense potential as an anthelminthic drug delivery vehicle that will be able to reduce the dose and drug-induced side effects by enhancing the bioavailability of the drug.
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Haemonchus , Animales , Albendazol/farmacología , Preparaciones de Acción RetardadaRESUMEN
In this article, we have reported the effect of varying concentration of europium (Eu) in (50 - x)% P2 O5 -25% Na2 O-24% CaO-% Eu2 O3 , where x = 1, 3, 5. The glass samples were synthesised via conventional melt-quench method. The impact of europium ion (Eu3+ ) on the structural, optical and luminescent properties of phosphate soda lime glasses has been studied using X-ray diffraction (XRD), Fourier-transformed infrared (FTIR) spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy coupled with energy-dispersive spectroscopy and photoluminescent techniques. The amorphous nature of glass samples was confirmed by XRD patterns. FTIR confirmed the presence of various functional groups. The emission spectra of synthesised samples exhibited intense emission peaks corresponding to Eu3+ under excitation at 393 nm. Among all the peaks, the maximum intensity was observed for 5 D0 â 7 F2 transition. Judd-Ofelt (J-O) parameters (Ω2 , Ω4 ) and other radiative parameters such as band width, radiative transition probabilities, stimulated emission cross-sections and branching ratio were determined from emission spectra. The other photometric parameters such as CIE coordinates and colour purity were also determined. Furthermore, cytotoxic studies were carried out on normal cell line human embryonic kidney cells (HEK-293) using MTT assay. Results showed that the prepared samples significantly enhanced growth in glass sample-treated cells as compared to control cells. These findings suggest that synthesised glass samples are biocompatible in nature and have potential for applications in display devices and biomedical research area.
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The study is the first to formulate and investigate potential of papaya seed chloroform extract based solid lipid nanoparticles (PSCEN) as antifertility agents on male Bandicota bengalensis. The prepared nanoparticles were spherical of size 300-600 nm. The release kinetics showed a controlled release of the drug with major release over 48 h. To assess the antifertility effects of PSCEN, adult male rats were fed a diet containing two different concentrations of PSCEN (5% and 10%) for 15 days under bi-choice conditions. The mean total active ingredient ingestion of the rats in the two treated groups ranged from 2.13-3.31 and 3.92-5.87 g/100g body weight, respectively. No adverse effects of treatment on body weight were observed. Also, no mortality of rats was observed. The treatment had a significant effect on the weight of the testis and the epididymis, but not on the other organs. Sperm motility (%), sperm viability (%), sperm count (millions/ml), sperm mitochondrial activity (%), sperm nuclear chromatin de-condensation (%) and sperm hypo-osmotic swelling (%) were significantly decreased, and sperm abnormality (%) significantly increased compared to the vehicle control group. The reproductive success rates of male rats treated with 5% and 10% PSCEN and mated with untreated female rats were 20.00-66.67% and 16.67%, respectively, while in untreated female rats mated with male rats of vehicle control group, reproductive success rate was 33.33 to 80%. The study found a maximal antifertility effect of the 10% PSCEN containing bait, which was irreversible up to 105 days after stopping treatment, suggesting long-term efficacy.
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Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxide-producing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/ß-catenin signaling pathway, thereby increasing paclitaxel sensitivity. ROS here played a crucial role in modulating Akt activity when autophagy process was hindered by chloroquine, excessive ROS accumulation in the cell inhibited Akt activity. In addition, chloroquine pre-treatment followed by taxol (10 nM) treatment did not show significant toxicity towards non-carcinomas WI38 cells (lung fibroblast cells). Thus autophagy inhibition by CQ pre-treatment can be used as a fruitful strategy to combat the phenomenon of paclitaxel resistance development as well as metastasis in lung cancer.
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Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Cloroquina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Paclitaxel/farmacología , Especies Reactivas de Oxígeno/metabolismo , beta Catenina/metabolismo , Células A549 , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
The original version of this article unfortunately contained an error in acknowledgment text. The authors would like to include a statement: "Moumita Dasgupta is supported by Junior Research Fellowship from University Grant Commission, India." in acknowledgment section.
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Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2â¯nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values -7.48, 0.076, 3.84 kcal mol-1 and 6â¯×â¯105â¯s-1 respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to promote faster wound remodeling.
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Citocinas/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Insulina/farmacología , Nanopartículas del Metal/administración & dosificación , Cicatrización de Heridas , Animales , Movimiento Celular , Diabetes Mellitus Experimental/metabolismo , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Mediadores de Inflamación/metabolismo , Insulina/administración & dosificación , Insulina/química , Masculino , Nanopartículas del Metal/química , Ratas , Ratas Wistar , Plata/químicaRESUMEN
Porous hydroxyapatite (HAp) nanorods using surfactant templating proceeded via microwave irradiation method. Study of BET surface area measurement of the HAp nanorods showed that surface area of HAp nanorods with a mixture of cat-anionic surfactants was higher (56.16 m2/g) than their individual counterpart (for anionic 52.8 m2/g and for cationic 48.8 m2/g) as well as without surfactant (19.07 m2/g) due to higher synergistic effect and low critical aggregation concentration of the mixture. Surfactant-directed synthesis of porous HAp has been explored in literature, but the relation between the pore size distribution, surface area and morphology and choice of surfactant(s) was not fully understood and hence in this work we have explored those parameters. The rod shape morphology and the crystal structure of the synthesized HAp nanomaterial were observed by FESEM, HRTEM, and XRD. Due to the higher surface area, HAp nanorods synthesized from the cat-anionic mixture, act as a better adsorbent for dyes and metal ions. The maximum adsorption of dye (methylene blue) was found to be 833.3 mg/g whereas for heavy metal ions like Pb2+ and Cd2+ were 909 and 714.28 mg/g respectively. The kinetic mechanism, the effects of adsorbate pH, temperature, contact time and adsorbent concentration on the dye and metal ions removal were also explored. The antibacterial property of HAp nanorods after doping with silver was investigated against the gram-negative Escherichia coli and gram-positive Bacillus subtilis bacteria by measuring minimal inhibitory concentration (MIC) method.
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Paclitaxel (Tx) is one of the first-line chemotherapeutic drugs used against lung cancer, but acquired resistance to this drug is a major challenge against successful chemotherapy. In this work, we have focused on the chronological changes of various cellular parameters and associated effect on Tx (10 nM) resistance development in A549 cell line. It was observed, at initial stage, the cell death percentage due to drug treatment had increased up to 20 days, and thereafter, it started declining and became completely resistant by 40 days. Expressions of ßIII tubulin and drug efflux pumps also increased over the period of resistance development. Changes in cellular autophagy and reactive oxygen species generation showed a biphasic pattern and increased gradually over the course of upto 20 days, thereafter declined gradually; however, their levels remained higher than untreated cells when resistance was acquired. Increase in extracellular acidification rates and oxygen consumption rates was found to be directly correlated with acquisition of resistance. The depolarisation of mitochondrial membrane potential was also biphasic; first, it increased with increase of cell death up to 20 days, thereafter, it gradually decreased to normal level along with resistance development. Increase in activity of catalase, glutathione peroxidase and glutathione content over these periods may attribute in bringing down the reactive oxygen species levels and normalisation of mitochondrial membrane potential in spite of comparatively higher reactive oxygen species production by the Tx-resistant cells.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Potencial de la Membrana Mitocondrial/fisiología , Paclitaxel/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células A549 , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Antineoplásicos Fitogénicos/farmacología , Autofagia , Caspasa 3/metabolismo , Ciclo Celular/fisiología , Resistencia a Antineoplásicos , Metabolismo Energético , Humanos , Neoplasias Pulmonares/patología , Microscopía FluorescenteRESUMEN
Muscle inflammation is often associated with its expansion. Bladder smooth muscle inflammation-induced cell death is accompanied by hyperplasia and hypertrophy as the primary cause for poor bladder function. In mice, DNA damage initiated by chemotherapeutic drug cyclophosphamide activated caspase 1 through the formation of the NLRP3 complex resulting in detrusor hyperplasia. A cyclophosphamide metabolite, acrolein, caused global DNA methylation and accumulation of DNA damage in a mouse model of bladder inflammation and in cultured bladder muscle cells. In correlation, global DNA methylation and NLRP3 expression was up-regulated in human chronic bladder inflammatory tissues. The epigenetic silencing of DNA damage repair gene, Ogg1, could be reversed by the use of demethylating agents. In mice, demethylating agents reversed cyclophosphamide-induced bladder inflammation and detrusor expansion. The transgenic knock-out of Ogg1 in as few as 10% of the detrusor cells tripled the proliferation of the remaining wild type counterparts in an in vitro co-culture titration experiment. Antagonizing IL-1ß with Anakinra, a rheumatoid arthritis therapeutic, prevented detrusor proliferation in conditioned media experiments as well as in a mouse model of bladder inflammation. Radiation treatment validated the role of DNA damage in the NLRP3-associated caspase 1-mediated IL-1ß secretory phenotype. A protein array analysis identified IGF1 to be downstream of IL-1ß signaling. IL-1ß-induced detrusor proliferation and hypertrophy could be reversed with the use of Anakinra as well as an IGF1 neutralizing antibody. IL-1ß antagonists in current clinical practice can exploit the revealed mechanism for DNA damage-mediated muscular expansion.
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Hiperplasia/metabolismo , Inflamación/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Interleucina-1beta/metabolismo , Músculo Liso/patología , Animales , Apoptosis/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Caspasa 1/metabolismo , Daño del ADN/efectos de los fármacos , ADN Glicosilasas/metabolismo , Humanos , Hiperplasia/patología , Inflamación/genética , Inflamación/patología , Factor I del Crecimiento Similar a la Insulina/genética , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Ratones , Músculo Liso/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal/efectos de los fármacos , Vejiga Urinaria/metabolismo , Vejiga Urinaria/patologíaRESUMEN
The MYC transcription factor plays a crucial role in the regulation of cell cycle progression, apoptosis, angiogenesis, and cellular transformation. Due to its oncogenic activities and overexpression in a majority of human cancers, it is an interesting target for novel drug therapies. MYC binding to the E-box (5'-CACGTGT-3') sequence at gene promoters contributes to more than 4000 MYC-dependent transcripts. Owing to its importance in MYC regulation, we designed a novel sequence-specific DNA-binding pyrrole-imidazole (PI) polyamide, Myc-5, that recognizes the E-box consensus sequence. Bioinformatics analysis revealed that the Myc-5 binding sequence appeared in 5'- MYC binding E-box sequences at the eIF4G1, CCND1, and CDK4 gene promoters. Furthermore, ChIP coupled with detection by quantitative PCR indicated that Myc-5 has the ability to inhibit MYC binding at the target gene promoters and thus cause downregulation at the mRNA level and protein expression of its target genes in human Burkitt's lymphoma model cell line, P493.6, carrying an inducible MYC repression system and the K562 (human chronic myelogenous leukemia) cell line. Single i.v. injection of Myc-5 at 7.5 mg/kg dose caused significant tumor growth inhibition in a MYC-dependent tumor xenograft model without evidence of toxicity. We report here a compelling rationale for the identification of a PI polyamide that inhibits a part of E-box-mediated MYC downstream gene expression and is a model for showing that phenotype-associated MYC downstream gene targets consequently inhibit MYC-dependent tumor growth.
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Linfoma de Burkitt/genética , Elementos E-Box/efectos de los fármacos , Imidazoles/química , Nylons/química , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Pirroles/química , Animales , Apoptosis/efectos de los fármacos , Sitios de Unión/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/genética , Quinasa 4 Dependiente de la Ciclina/genética , Proteínas de Unión al ADN , Elementos E-Box/genética , Factor 4G Eucariótico de Iniciación/genética , Humanos , Ratones , Ratones SCID , Nylons/síntesis química , Regiones Promotoras Genéticas , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The present research aimed to explore the durability of MMO electrodes through electro-oxidation (EO) in purifying secondary treated actual sewage wastewater using batch and pilot-scale setups. The main aim is to inactivate bacteria in sewage treatment plants before they are released into the environment, thus contaminating water and soil. Process parameters such as current density (j), NaCl dose (n), and treatment time (t) were optimized using response surface methodology in a lab-scale EO reactor under batch conditions. The results showed that optimization of current density at 5.90 mA/cm2 and NaCl concentration at 1.31 g/L led to 93.90% of bacterial inactivation (Q1) within 8 min of treatment and 0.48 kWh/m3 energy consumption (Q2). Biological analysis was conducted to validate bacterial cell destruction and count coliform bacteria in the EO-treated sewage wastewater. XRD, cyclic voltammetry studies, and FE-SEM/EDS analysis were done to confirm the MMO anode's durability and stability after 100 recycles. The study prioritized bacterial inactivation along with organic matter degradation. Besides that, a small pilot-scale study on the actual sewage wastewater with a volume of 10-50 L was done in batch mode under previously optimized conditions to analyze the efficacy of the MMO anodes in terms of bacterial inactivation.
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Oxidación-Reducción , Eliminación de Residuos Líquidos , Aguas Residuales , Aguas Residuales/química , Eliminación de Residuos Líquidos/métodos , Aguas del Alcantarillado/química , Electrodos , Proyectos PilotoRESUMEN
Wound healing involves a carefully regulated sequence of events, encompassing pro-inflammatory and anti-inflammatory stages, tissue regeneration, and remodeling. However, in individuals with diabetes, this process gets disrupted due to dysregulation caused by elevated glucose levels and pro-inflammatory cytokines in the bloodstream. Consequently, the pro-inflammatory stage is prolonged, while the anti-inflammatory phase is delayed, leading to impaired tissue regeneration and remodeling with extended healing time. Furthermore, the increased glucose levels in open wounds create an environment conducive to microbial growth and tissue sepsis, which can escalate to the point of limb amputation. Managing diabetic wounds requires meticulous care and monitoring due to the lack of widely available preventative and therapeutic measures. Existing clinical interventions have limitations, such as slow recovery rates, high costs, and inefficient drug delivery methods. Therefore, exploring alternative avenues to develop effective wound-healing treatments is essential. Nature offers a vast array of resources in the form of secondary metabolites, notably polyphenols, known for their antimicrobial, anti-inflammatory, antioxidant, glucose-regulating, and cell growth-promoting properties. Additionally, nanoparticles synthesized through environmentally friendly methods hold promise for wound healing applications in diabetic and non-diabetic conditions. This review provides a comprehensive discussion and summary of the potential wound-healing abilities of specific natural polyphenols and their nanoparticles. It explores the mechanisms of action underlying their efficacy and presents effective formulations for promoting wound-healing activity.
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In a bid to overcome hyperthermia resistance, a major obstacle in cancer treatment, this study explores manipulating autophagy, a cellular recycling mechanism, within the context of gastric cancer. We designed artemisinin-protected magnetic iron-oxide nanoparticles (ART-MNPs) to hyperactivate autophagy, potentially sensitizing cancer cells to hyperthermia. The synthesized ART-MNPs exhibited magnetic properties and the capability of raising the temperature by 7 °C at 580.3 kHz. Importantly, ART-MNPs displayed significant cytotoxicity against human gastric cancer cells (AGS), with an IC50 value of 1.9 µg mL-1, demonstrating synergistic effects compared to either MNPs or ART treatment alone (IC50 for MNPs is 9.7 µg mL-1 and for ART is 9.4 µg mL-1 respectively). Combination index studies further supported this synergy. Mechanistic analysis revealed a significant increase in autophagy level (13.58- and 15.08-fold increase compared to artemisinin and MNPs, respectively) upon ART-MNP treatment, suggesting that this hyperactivation is responsible for hyperthermia sensitization and minimized resistance (as evidenced by changes in viability compared to control under hyperthermic conditions). This work offers a promising strategy to modulate autophagy and overcome hyperthermia resistance, paving the way for developing hyperthermia as a standalone therapy for gastric cancer.
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Metallic nanoparticles have emerged as a promising option for various biological applications, owing to their distinct characteristics such as small size, optical properties, and ability to exhibit luminescence. In this study, we have successfully employed a one-pot method to synthesize multifunctional insulin-protected iron [Fe(II)] nanoparticles denoted as [IFe(II)NPs]. The formation of IFe(II)NPs is confirmed by the presence of FTIR bonds at 447.47 and 798.28 cm-1, corresponding to Fe-O and Fe-N bonds, respectively. Detailed analysis of the HR-TEM-EDS-SAED data reveals that the particles are spherical in shape, partially amorphous in nature, and have a diameter of 28.6 ± 5.2 nm. Additionally, Metal Ion Binding (MIB) and Protein Data Bank (PDB) analyses affirm the binding of iron ions to the insulin hexamer. Our findings underscore the potential of IFe(II)NPs as a promising new platform for a variety of biomedical applications due to their high signal-to-noise ratio, and minimal background fluorescence. The particles are highly luminescent, biocompatible, and have a significant quantum yield (0.632). Exemplar applications covered in this paper include insulin receptor recognition and protection against reactive oxygen species (ROS), harmful molecules known to inflict damage on cells and DNA. The IFe(II)NPs effectively mitigate ROS-induced inflammation, which is a hinderance to wound recovery, thereby facilitating enhanced wound recovery.
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Diabetic wounds represent a major issue in medical care and need advanced therapeutic and tissue imaging systems for better management. The utilization of nano-formulations involving proteins like insulin and metal ions plays significant roles in controlling wound outcomes by decreasing inflammation or reducing microbial load. This work reports the easy one-pot synthesis of extremely stable, biocompatible, and highly fluorescent insulin-cobalt core-shell nanoparticles (ICoNPs) with enhanced quantum yield for their highly specific receptor-targeted bioimaging and normal and diabetic wound healing in vitro (HEKa cell line). The particles were characterized using physicochemical properties, biocompatibility, and wound healing applications. FTIR bands at 670.35 cm-1, 849.79, and 973.73 indicating the Co-O bending, CoO-OH bond, and Co-OH bending, respectively, confirm the protein-metal interactions, which is further supported by the Raman spectra. In silico studies indicate the presence of cobalt binding sites on the insulin chain B at 8 GLY, 9 SER, and 10 HIS positions. The particles exhibit a magnificent loading efficiency of 89.48 ± 0.049% and excellent release properties (86.54 ± 2.15% within 24 h). Further, based on fluorescent properties, the recovery process can be monitored under an appropriate setup, and the binding of ICoNPs to insulin receptors was confirmed by bioimaging. This work helps synthesize effective therapeutics with numerous wound-healing promoting and monitoring applications.
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Prolonged inflammation can impede wound healing, which is regulated by several proteins and cytokines, including IL-4, IL-10, IL-13, and TGF-ß. Concentration-dependent effects of these molecules at the target site have been investigated by researchers to develop them as wound-healing agents by regulating signaling strength. Nanotechnology has provided a promising approach to achieve tissue-targeted delivery and increased effective concentration by developing protein-functionalized nanoparticles with growth factors (EGF, IGF, FGF, PDGF, TGF-ß, TNF-α, and VEGF), antidiabetic wound-healing agents (insulin), and extracellular proteins (keratin, heparin, and silk fibroin). These molecules play critical roles in promoting cell proliferation, migration, ECM production, angiogenesis, and inflammation regulation. Therefore, protein-functionalized nanoparticles have emerged as a potential strategy for improving wound healing in delayed or impaired healing cases. This review summarizes the preparation and applications of these nanoparticles for normal or diabetic wound healing and highlights their potential to enhance wound healing.
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Lactoferrin (LF) is a non-heme iron-binding glycoprotein involved in the transport of iron in blood plasma. In addition, it has many biological functions, including antibacterial, antiviral, antimicrobial, antiparasitic, and, importantly, antitumor properties. In this study, we have investigated the potential of employing lactoferrin-iron oxide nanoparticles (LF-IONPs) as a treatment modality for gastric cancer. The study confirms the formation of LF-IONPs with a spherical shape and an average size of 5 ± 2 nm, embedded within the protein matrix. FTIR and Raman analysis revealed that the Fe-O bond stabilized the protein particle interactions. Further, we conducted hyperthermia studies to ascertain whether the proposed composite can generate a sufficient rise in temperature at a low frequency. The results confirmed that we can achieve a temperature rise of about 7 °C at 242.4 kHz, which can be further harnessed for gastric cancer treatment. The particles were further tested for their anti-cancer activity on AGS cells, with and without hyperthermia. Results indicate that LF-IONPs (10 µg/ml) significantly enhance cytotoxicity, resulting in the demise of 67.75 ± 5.2% of cells post hyperthermia, while also exhibiting an inhibitory effect on cell migration compared to control cells, with the most inhibition observed after 36 h of treatment. These findings suggest the potential of LF-IONPs in targeted hyperthermia treatment of gastric cancer.
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Hipertermia Inducida , Nanosferas , Neoplasias Gástricas , Humanos , Lactoferrina/farmacología , Lactoferrina/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Hierro/metabolismo , Hipertermia Inducida/métodosRESUMEN
G-quadruplexes (G4) are non-canonical, four-stranded, nucleic acid secondary structures formed in the guanine-rich sequences, where guanine nucleotides associate with each other via Hoogsteen hydrogen bonding. These structures are widely found near the functional regions of the mammalian genome, such as telomeres, oncogenic promoters, and replication origins, and play crucial regulatory roles in replication and transcription. Destabilization of G4 by various carcinogenic agents allows oncogene overexpression and extension of telomeric ends resulting in dysregulation of cellular growth-promoting oncogenesis. Therefore, targeting and stabilizing these G4 structures with potential ligands could aid cancer prevention and therapy. The field of G-quadruplex targeting is relatively nascent, although many articles have demonstrated the effect of G4 stabilization on oncogenic expressions; however, no previous study has provided a comprehensive analysis about the potency of a wide variety of nutraceuticals and some of their derivatives in targeting G4 and the lattice of oncogenic cell signaling cascade affected by them. In this review, we have discussed bioactive G4-stabilizing nutraceuticals, their sources, mode of action, and their influence on cellular signaling, and we believe our insight would bring new light to the current status of the field and motivate researchers to explore this relatively poorly studied arena. Schematic diagram depicting nutraceuticals' role in attenuating cancer progression.
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Heteroatom doping on carbon dots (Cdots) has been developed as an efficient approach to modify its optical and electronic properties. The four different types of heteroatom-doped Cdots (undoped Cdots (u-Cdots, nitrogen-doped Cdots (N-Cdots), sulfur-doped Cdots (Cdots), nitrogen, sulfur codoped Cdots (N, S-Cdots)) have been synthesized through a simple heat treatment of 5 min. Among four different heteroatoms doped nanosensors, N, S-Cdots with MnO2 nanospheres (Mn NS) showed one of the best fluorescents "on-off-on" nanosensors for selective sensing of glutathione (GSH) and cell imaging. N, S-Cdots showed a high fluorescence quantum yield, good photostability, ionic strength, and pH stability. N, S-Cdots with Mn NS demonstrated extremely high fluorescence quenching efficiency and the maximum fluorescence recovery rate after adding GSH to the produced solution. The photophysical study of N, S-Cdots-Mn NS used as a sensor confirms the inner filter effect (IFE) quenching mechanism between them. The developed sensor has an 80 nM limit of detection (LOD) for GSH. The heteroatom-doped framework of Cdots plays a significant role in the sensitive detection of GSH. N, S-Cdots-Mn NS have good permeability, biocompatibility, and low toxicity, due to which it was used in the intracellular imaging of GSH in living cells. The prepared sensor is rapid, economical, less toxic, and highly applicable in diagnosing diseases.