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1.
Sci Rep ; 14(1): 16437, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013991

RESUMEN

Inhalable microparticle-based anti TB drug delivery systems are being investigated extensively for Tuberculosis [TB] treatment as they offer efficient and deep lung deposition with several advantages over conventional routes. It can reduce the drug dose, treatment duration and toxic effects and optimize the drug bioavailability. Yeast derived ß-glucan is a ß-[1-3/1-6] linked biocompatible polymer and used as carrier for various biomolecules. Due to presence of glucan chains, particulate glucans act as PAMP and thereby gets internalized via receptor mediated phagocytosis by the macrophages. In this study, ß-glucan microparticles were prepared by adding l-leucine as excipient, and exhibited 70% drug [Rifabutin] loading efficiency. Further, the sizing and SEM data of particles revealed a size of 2-4 µm with spherical dimensions. The FTIR and HPLC data confirmed the ß-glucan composition and drug encapsulations efficiency of the particles. The mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD] data indicated that these particles are inhalable in nature and have better thermal stability as per DSC thermogram. These particles were found to be non-toxic upto a concentration of 80 µg/ml and were found to be readily phagocytosed by human macrophage cells in-vitro as well as in-vivo by lung alveolar macrophage. This study provides a framework for future design of inhalable ß-glucan particle based host-directed drug delivery system against pulmonary TB.


Asunto(s)
Sistemas de Liberación de Medicamentos , Rifabutina , beta-Glucanos , Rifabutina/administración & dosificación , Rifabutina/farmacocinética , Rifabutina/química , beta-Glucanos/química , Humanos , Administración por Inhalación , Tuberculosis Pulmonar/tratamiento farmacológico , Tamaño de la Partícula , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Portadores de Fármacos/química , Antituberculosos/administración & dosificación , Antituberculosos/farmacocinética , Antituberculosos/química
2.
Front Cell Infect Microbiol ; 14: 1408569, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035353

RESUMEN

A complex structure known as a biofilm is formed when a variety of bacterial colonies or a single type of cell in a group sticks to a surface. The extracellular polymeric compounds that encase these cells, often consisting of proteins, eDNA, and polysaccharides, exhibit strong antibiotic resistance. Concerns about biofilm in the pharmaceutical industry, public health, and medical fields have sparked a lot of interest, as antibiotic resistance is a unique capacity exhibited by these biofilm-producing bacteria, which increases morbidity and death. Biofilm formation is a complicated process that is controlled by several variables. Insights into the processes to target for the therapy have been gained from multiple attempts to dissect the biofilm formation process. Targeting pathogens within a biofilm is profitable because the bacterial pathogens become considerably more resistant to drugs in the biofilm state. Although biofilm-mediated infections can be lessened using the currently available medications, there has been a lot of focus on the development of new approaches, such as bioinformatics tools, for both treating and preventing the production of biofilms. Technologies such as transcriptomics, metabolomics, nanotherapeutics and proteomics are also used to develop novel anti-biofilm agents. These techniques help to identify small compounds that can be used to inhibit important biofilm regulators. The field of appropriate control strategies to avoid biofilm formation is expanding quickly because of this spurred study. As a result, the current article addresses our current knowledge of how biofilms form, the mechanisms by which bacteria in biofilms resist antibiotics, and cutting-edge treatment approaches for infections caused by biofilms. Furthermore, we have showcased current ongoing research utilizing the CRISPR/Cas9 gene editing system to combat bacterial biofilm infections, particularly those brought on by lethal drug-resistant pathogens, concluded the article with a novel hypothesis and aspirations, and acknowledged certain limitations.


Asunto(s)
Antibacterianos , Biopelículas , Sistemas CRISPR-Cas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antibacterianos/farmacología , Humanos , Bacterias/efectos de los fármacos , Bacterias/genética , Farmacorresistencia Bacteriana/genética , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Edición Génica
3.
ACS Omega ; 9(25): 26762-26779, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38947816

RESUMEN

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, including being faster, safer, easier, and less expensive. In the real world, several medications have been repurposed, including aspirin, metformin, and chloroquine. However, doctors and scientists address numerous challenges when repurposing drugs, such as the fact that most drugs are not cost-effective and are resistant to bacteria. So the goal of this review is to gather information regarding repurposing pharmaceuticals to make them more cost-effective and harder for bacteria to resist. Cancer patients are more susceptible to bacterial infections. Due to their weak immune systems, antibiotics help protect them from a variety of infectious diseases. Although antibiotics are not immune boosters, they do benefit the defense system by killing bacteria and slowing the growth of cancer cells. Their use also increases the therapeutic efficacy and helps avoid recurrence. Of late, antibiotics have been repurposed as potent anticancer agents because of the evolutionary relationship between the prokaryotic genome and mitochondrial DNA of eukaryotes. Anticancer antibiotics that prevent cancer cells from growing by interfering with their DNA and blocking growth of promoters, which include anthracyclines, daunorubicin, epirubicin, mitoxantrone, doxorubicin, and idarubicin, are another type of FDA-approved antibiotics used to treat cancer. According to the endosymbiotic hypothesis, prokaryotes and eukaryotes are thought to have an evolutionary relationship. Hence, in this study, we are trying to explore antibiotics that are necessary for treating diseases, including cancer, helping people reduce deaths associated with various infections, and substantially extending people's life expectancy and quality of life.

4.
Front Pharmacol ; 15: 1406619, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957397

RESUMEN

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

5.
Microb Pathog ; 193: 106740, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38897360

RESUMEN

Biofilm-forming microbes can pose a major health risk that is difficult to combat. Nanotechnology, on the other hand, represents a novel technique for combating and eliminating biofilm-forming microbes. In this study, the selenium nanoparticles (SeNPs) were biosynthesized from moderate halophilic bacteria isolated from Pichavaram mangrove sediments. The bacterial strain S8 was found to be efficient for SeNPs synthesis and hence identified by 16s r RNA sequencing as Shewanella sp. In UV- spectral analysis the SeNPs displayed a peak at 320 nm due to surface plasmon resonance (SPR). The cell-free extract of Shewanella sp. and SeNPs indicates that the various functional groups in the cell-free extract were mainly involved in the synthesis and stabilization of SeNPs. The SeNPs had a spherical form with average diameter of 49 ± 0.01 nm, according to the FESEM analysis. The EDX shows the distinctive peaks of selenium at 1.37, 11.22.12.49 Kev. In the agar well diffusion method, the SeNPs show inhibitory activity against all the test pathogens with the highest activity noted against P.aeruginosa with a zone of inhibition of 22.7 ± 0.3 mm. The minimal inhibitory concentration (MIC) value of 80 µg/ml, minimal bactericidal concentration (MBC) of 160 µg/ml, and susceptibility constant of 0.043 µg/ml show that SeNPs highly effective against P.aeruginosa. The Sub-MIC value of SeNPs of 20 µg/ml was found to inhibit P.aeruginosa biofilm by 85% as compared to the control. Further, the anti-virulence properties viz., pyocyanin, pyoverdine, hemolytic, and protease inhibition revealed the synthesized SeNPs from halophilic bacteria control the pathogenicity of P.aeruginosa.


Asunto(s)
Antibacterianos , Biopelículas , Pruebas de Sensibilidad Microbiana , Nanopartículas , ARN Ribosómico 16S , Selenio , Biopelículas/efectos de los fármacos , Selenio/farmacología , Selenio/química , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas/química , ARN Ribosómico 16S/genética , Bacterias/efectos de los fármacos , Nanopartículas del Metal/química , Resonancia por Plasmón de Superficie , Sedimentos Geológicos/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Virulencia/efectos de los fármacos
6.
Front Cell Dev Biol ; 12: 1399065, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933330

RESUMEN

Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and energy provision. Lipid metabolism is necessary for the maintenance of life since it regulates the balance between the processes of synthesis and breakdown. Increasing evidence suggests that cancer cells exhibit abnormal lipid metabolism, significantly affecting their malignant characteristics, including self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. Prominent oncogenic signaling pathways that modulate metabolic gene expression and elevate metabolic enzyme activity include phosphoinositide 3-kinase (PI3K)/AKT, MAPK, NF-kB, Wnt, Notch, and Hippo pathway. Conversely, when metabolic processes are not regulated, they can lead to malfunctions in cellular signal transduction pathways. This, in turn, enables uncontrolled cancer cell growth by providing the necessary energy, building blocks, and redox potentials. Therefore, targeting lipid metabolism-associated oncogenic signaling pathways could be an effective therapeutic approach to decrease cancer incidence and promote survival. This review sheds light on the interactions between lipid reprogramming and signaling pathways in cancer. Exploring lipid metabolism as a target could provide a promising approach for creating anticancer treatments by identifying metabolic inhibitors. Additionally, we have also provided an overview of the drugs targeting lipid metabolism in cancer in this review.

7.
ACS Appl Bio Mater ; 7(6): 3515-3534, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38787337

RESUMEN

Breast cancer is the most common type of cancer and the second leading cause of cancer-related mortality in females. There are many side effects due to chemotherapy and traditional surgery, like fatigue, loss of appetite, skin irritation, and drug resistance to cancer cells. Immunotherapy has become a hopeful approach toward cancer treatment, generating long-lasting immune responses in malignant tumor patients. Recently, hydrogel has received more attention toward cancer therapy due to its specific characteristics, such as decreased toxicity, fewer side effects, and better biocompatibility drug delivery to the particular tumor location. Researchers globally reported various investigations on hydrogel research for tumor diagnosis. The hydrogel-based multilayer platform with controlled nanostructure has received more attention for its antitumor effect. Chitosan and alginate play a leading role in the formation of the cross-link in a hydrogel. Also, they help in the stability of the hydrogel. This review discusses the properties, preparation, biocompatibility, and bioavailability of various research and clinical approaches of the multipolymer hydrogel made of alginate and chitosan for breast cancer treatment. With a focus on cases of breast cancer and the recovery rate, there is a need to find out the role of hydrogel in drug delivery for breast cancer treatment.


Asunto(s)
Alginatos , Materiales Biocompatibles , Neoplasias de la Mama , Quitosano , Hidrogeles , Inmunoterapia , Quitosano/química , Alginatos/química , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Hidrogeles/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Femenino , Ensayo de Materiales , Antineoplásicos/química , Antineoplásicos/farmacología , Tamaño de la Partícula , Animales
8.
ACS Omega ; 9(11): 12500-12514, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38524425

RESUMEN

Leishmaniasis, which is caused by a parasitic protozoan of the genus Leishmania, is still a major threat to global health, impacting millions of individuals worldwide in endemic areas. Chemotherapy has been the principal method for managing leishmaniasis; nevertheless, the evolution of drug resistance offers a significant obstacle to therapeutic success. Drug-resistant behavior in these parasites is a complex phenomenon including both innate and acquired mechanisms. Resistance is frequently related to changes in drug transportation, drug target alterations, and enhanced efflux of the drug from the pathogen. This review has revealed specific genetic mutations in Leishmania parasites that are associated with resistance to commonly used antileishmanial drugs such as pentavalent antimonials, miltefosine, amphotericin B, and paromomycin, resulting in changes in gene expression along with the functioning of various proteins involved in drug uptake, metabolism, and efflux. Understanding the genetic changes linked to drug resistance in Leishmania parasites is essential for creating approaches for tackling and avoiding the spread of drug-resistant variants. Based on which specific treatments focus on mutations and pathways could potentially improve treatment efficacy and help long-term leishmaniasis control. More study is needed to uncover the complete range of genetic changes generating medication resistance and to develop new therapies based on available information.

9.
Heliyon ; 10(6): e27724, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38500979

RESUMEN

Lead (Pb) is a highly toxic contaminant that is ubiquitously present in the ecosystem and poses severe environmental issues, including hazards to soil-plant systems. This review focuses on the uptake, accumulation, and translocation of Pb metallic ions and their toxicological effects on plant morpho-physiological and biochemical attributes. We highlight that the uptake of Pb metal is controlled by cation exchange capacity, pH, size of soil particles, root nature, and other physio-chemical limitations. Pb toxicity obstructs seed germination, root/shoot length, plant growth, and final crop-yield. Pb disrupts the nutrient uptake through roots, alters plasma membrane permeability, and disturbs chloroplast ultrastructure that triggers changes in respiration as well as transpiration activities, creates the reactive oxygen species (ROS), and activates some enzymatic and non-enzymatic antioxidants. Pb also impairs photosynthesis, disrupts water balance and mineral nutrients, changes hormonal status, and alters membrane structure and permeability. This review provides consolidated information concentrating on the current studies associated with Pb-induced oxidative stress and toxic conditions in various plants, highlighting the roles of different antioxidants in plants mitigating Pb-stress. Additionally, we discussed detoxification and tolerance responses in plants by regulating different gene expressions, protein, and glutathione metabolisms to resist Pb-induced phytotoxicity. Overall, various approaches to tackle Pb toxicity have been addressed; the phytoremediation techniques and biochar amendments are economical and eco-friendly remedies for improving Pb-contaminated soils.

10.
Mol Biotechnol ; 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38502429

RESUMEN

Prostate cancer incidences are rising worldwide at an alarming rate. Drug resistance and relapse are two major challenges in the treatment of prostate cancer. Therefore, new multimodal, safe, and effective therapeutic agents are urgently required which could effectively mitigate the menace of tumor recurrence and chemo-resistance. Plant-derived products are increasingly being utilized due to their antioxidant, antibacterial, and anti-tumor potential. In the current study, 3-acetyl-11-keto-ß-boswellic acid, a triterpenoid isolated from plant Boswellia, was utilized to ascertain its chemotherapeutic potential against human prostate cancer cells. Various in vitro assays including cell viability, nuclear staining, mitochondria potential, reactive oxygen species (ROS) generation, and quantification of apoptosis, were performed for the evaluation of the cytotoxic potential of AKBA. We observed that AKBA (10-50 µM) dose-dependently suppressed cell proliferation and caused programmed cell death in PC3 cells via both intrinsic and extrinsic pathway. Intriguingly, AKBA was also found to chemosensitize PC3 cells in synergistic combination with doxorubicin. To the best of our knowledge, this is the first study to document the synergistic chemosensitizing impact of AKBA when combined with doxorubicin in prostate cancer cells.This showcases the potential of AKBA in combinatorial therapy or adjuvant therapy for the management of prostate cancer. In sum, our results suggested that AKBA is a promising drug-like molecule against prostate cancer. Our investigation introduces a novel perspective, elucidating a previously unexplored dimension, and uncovering a compelling chemosensitizing phenomenon along with a strong synergistic effect arising from the concurrent application of these two agents.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38457040

RESUMEN

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

13.
Heliyon ; 10(1): e24009, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38230238

RESUMEN

Dia/betes is a serious health concern in many countries with high blood glucose, obesity, and multiple organ failures in late stages. Treating diabetes with effective drugs is still a challenging issue since most of the available diabetic drugs are not effective in combating diabetes, especially in secondary disease complications like obesity, retinopathy, and nephropathy associated with diabetes. Hence search for effective antidiabetic medication, especially from natural sources is mandatory with no adverse side effects. In the present study, a combined herbal aqueous extract of Tribulus terrestris and Curcuma amada was administered to diabetic-induced rats for 37 days. During experimentation, the mean blood glucose level was estimated and at the end of the experiment on the 37th day, the animal was sacrificed and observed for weight gain, plasma insulin, glycogen, glycated hemoglobin, urea, and creatinine level. The results revealed that TT and CA extract-treated diabetic groups significantly lowered the mean blood glucose level followed by increased glycogen and insulin level. Urea, creatinine, and HbA1c levels were considerably reduced in TT and CA-treated diabetic animals as compared to that of antidiabetic drug Glibenclamide-treated groups. TT and CA-treated diabetic animals showed considerable net body weight gain at the end of the experimental day. A concluding remark of the study shows that TT and CA herbal extract is effective against diabetes and it can be considered as an antidiabetic agent in ayurvedic medicine practice.

14.
J Alzheimers Dis ; 97(3): 1299-1312, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38277291

RESUMEN

BACKGROUND: The present study investigates the interrelated pathophysiology of depression and Alzheimer's disease (AD), with the objective of elucidating common underlying mechanisms. OBJECTIVE: Our objective is to identify previously undiscovered biogenic compounds from the NuBBE database that specifically interact with GluR3. This study examines the bidirectional association between depression and AD, specifically focusing on the role of depression as a risk factor in the onset and progression of the disease. METHODS: In this study, we utilize pharmacokinetics, homology modeling, and molecular docking-based virtual screening techniques to examine the GluR3 AMPA receptor subunit. RESULTS: The compounds, namely ZINC000002558953, ZINC000001228056, ZINC000000187911, ZINC000003954487, and ZINC000002040988, exhibited favorable pharmacokinetic profiles and drug-like characteristics, displaying high binding affinities to the GluR3 binding pocket. CONCLUSIONS: These findings suggest that targeting GluR3 could hold promise for the development of therapies for depression and AD. Further validation through in vitro, in vivo, and clinical studies is necessary to explore the potential of these compounds as lead candidates for potent and selective GluR3 inhibitors. The shared molecular mechanisms between depression and AD provide an opportunity for novel treatment approaches that address both conditions simultaneously.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Simulación del Acoplamiento Molecular , Enfermedad de Alzheimer/tratamiento farmacológico , Depresión/tratamiento farmacológico , Simulación de Dinámica Molecular
15.
J Biomol Struct Dyn ; 42(5): 2738-2745, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37194307

RESUMEN

Respiratory allergies have become a major public health concern and affect one-third of the world's population. Several factors like environmental changes, industrialization, and immunologic interactions are reported to contribute to allergic respiratory diseases. Immunological reactions because of mosquito bite (allergic proteins) have been reported to have a high contribution to IgE-mediated allergic airway disease but they are largely ignored. In this study, we aim to predict the potential allergens (proteins) from Aedes aegypti that might play a role in the reactions of IgE-mediated allergic airway diseases. The allergens are identified from an extensive literature search and the 3D structures were prepared using the SwissDock server. Computational studies were performed to identify the potential allergens that might be responsible for IgE-mediated allergies. Our docking and molecular dynamics (MD) simulation results suggest that ADE-3, an allergen from Aedes aegypti, has the highest docking score and is predicted to be responsible for IgE-mediated allergic reaction(s). Overall, this study highlights the importance of immunoinformatics, and the obtained information can be used for designing prophylactic peptide vaccine candidates and inhibitors for controlling IgE-mediated inflammations.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Aedes , Hipersensibilidad , Mordeduras y Picaduras de Insectos , Animales , Humanos , Alérgenos/química , Aedes/metabolismo , Inmunoglobulina E/metabolismo
16.
J Biomol Struct Dyn ; 42(3): 1368-1380, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37191027

RESUMEN

A revival interest has been given to natural products as sources of phytocompounds to be used as alternative treatment against infectious diseases. In this context, we aimed to investigate the antimicrobial potential of Ziziphus honey (ZH) against twelve clinical bacterial strains and several yeasts and molds using in vitro and computational approaches. The well-diffusion assay revealed that ZH was able to induce growth inhibition of most Gram-positive and Gram-negative bacteria. The high mean growth inhibition zone (mGIZ) was recorded in E. coli (Clinical strain, 217), S. aureus followed by E. coli ATCC 10536 (mGIZ values: 41.00 ± 1 mm, 40.67 ± 0.57 mm, and 34.67 ± 0.57 mm, respectively). The minimal bactericidal concentrations (MBCs) and minimal fungicidal concentration values (MFCs) from approximately 266.33 mg/mL to over 532.65 mg/mL. Molecular docking results revealed that the identified compounds maltose, 2-furoic acid, isopropyl ester, 2,4-imidazolidinedione, 5-(2-methylpropyl)-(S)- and 3,4,5-trihydroxytoluene, S-Methyl-L-Cysteine, 2-Furancarboxylic acid, L-Valine-N-ethoxycarbonyl, Hexanoic acid, 3,5,5-trimethyl-, Methyl-beta-D-thiogalactoside, gamma-Sitosterol, d-Mannose, 4-O-Methylmannose, 2,4-Imidazolidinedione, 5-(2-methylpropyl)- (S) were found to have good affinity for targeted receptor, respectively. Through a 100-ns dynamic simulation research, binding interactions and stability between promising phytochemicals and the active residues of the studied enzymes were confirmed. The ADMET profiling of all identified compounds revealed that most of them could be qualified as biologically active with good absorption and permeation. Overall, the results highlighted the efficiency of ZH against the tested clinical pathogenic strains. The antimicrobial potential and the potency displayed by the identified compounds could imply their further pharmacological applications.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Antiinfecciosos , Miel , Ziziphus , Antibacterianos/farmacología , Staphylococcus aureus , Cromatografía de Gases y Espectrometría de Masas , Bacterias Gramnegativas , Escherichia coli , Simulación del Acoplamiento Molecular , Bacterias Grampositivas , Antiinfecciosos/farmacología , Antiinfecciosos/química , Fitoquímicos/farmacología , Fitoquímicos/química
17.
J Biomol Struct Dyn ; : 1-10, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38127429

RESUMEN

Unpleasant side effects of standard inflammatory drugs urges search for novel therapeutic candidates. This study aims in identifying novel anti-inflammatory NF-κB inhibitor by high-throughput computational and in-vitro pre-clinical approaches. Lead candidate selection was conducted by the use of computational docking molecular-dynamic simulations. The RBL-2H3 cell line, derived from rat basophils, was used to evaluate the release of cytokines and degranulation. The study focused on the study of neutrophil elastase and its role in cellular motility. Flow cytometry was utilized to evaluate the activation of basophils and the expression of critical signaling proteins. High throughput screening identified CSB-0914 to stably bind NF-κB-p50 subunit. Dose based loss in T NF-α and IL-2 release were observed in RBL-2H3 cells in addition to degranulation inhibition by CSB-0914. The compound demonstrated significant efficacy in reducing basophil activation assay induced by FcεRI receptors, with an IC50 value of 98.41 nM.. A dose dependent decrease in neutrophil migration and elastase were observed when treated with CSB- 0914. The compound was effective in decreasing. Upon stimulation, RBL-2H3 cells exhibited phosphorylation of NF-κB p-65 as well as upregulation of the Nrf2 and HO-1 signaling pathways. Collectively, our study has successfully identified a novel inhibitor called CSB-0914 that effectively regulates inflammatory responses. These reactions are primarily mediated by the interplay between NF-κB, Nrf2, and HO-1. The findings of this study provide support for the need to conduct more research on CSB-0914 with the aim of its development as a pharmaceutical agent for anti-inflammatory purposes.Communicated by Ramaswamy H. Sarma.

18.
Cell Mol Biol (Noisy-le-grand) ; 69(13): 83-88, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38158684

RESUMEN

Allergies due to honeybee venom (HBV) are reported to be the second most common form of allergy to Hymenoptera venom that occurs after being stung. Indeed, 15-20% of people test IgE positive after being stung. However, accurate data on the incidence of honey bee allergens is missing and estimated to be less than 0.001%. Beekeeping is an ancient and widely practiced activity across the Kingdom of Saudi Arabia. Still, studies on the allergenic effect of the different subspecies of honey bees are very rare in Saudi Arabia. Hence, in this study, using the In-silico approach, we aimed to study and evaluate the effect of allergens from honey bees in Ha'il City, Saudi Arabia on IgE-mediated allergies. A list of potential allergens from Apis mellifera was prepared, and the 3D structure was prepared using the SWISS-MODEL web server and the PDB database was used for retrieving the structure of the immunoglobulin E- fragment antigen-binding (IgE-Fab) region. Molecular docking (clusPro webserver) and molecular dynamics (Schrödinger) results revealed that the B2D0J5 protein from Apis mellifera might be the key protein associated with IgE-mediated allergic response. Overall, the identified knowledge can be used for exploring prophylactic vaccine candidates and improving the diagnosis of allergic reactions to honey bees in the Ha'il region of Saudi Arabia.


Asunto(s)
Hipersensibilidad , Mordeduras y Picaduras de Insectos , Humanos , Abejas , Animales , Alérgenos/química , Simulación del Acoplamiento Molecular , Inmunoglobulina E
19.
Front Cell Infect Microbiol ; 13: 1295593, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38099219

RESUMEN

Introduction: Zinc oxide nanoparticles (ZnO-NPs) have garnered considerable interest in biomedical research primarily owing to their prospective therapeutic implications in combatting pathogenic diseases and microbial infections. The primary objective of this study was to examine the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) using chicken egg white (albumin) as a bio-template. Furthermore, this study aimed to explore the potential biomedical applications of ZnO NWs in the context of infectious diseases. Methods: The NWs synthesized through biological processes were observed using electron microscopy, which allowed for detailed examination of their characteristics. The results of these investigations indicated that the NWs exhibited a size distribution ranging from approximately 10 to 100 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) mapping analyses successfully corroborated the size, dimensions, and presence of biological constituents during their formation. In this study, XTT assay and confocal imaging were employed to provide evidence of the efficacy of ZnO-NWs in the eradication of bacterial biofilms. The target bacterial strains were Staphylococcus aureus and Escherichia coli. Furthermore, we sought to address pertinent concerns regarding the biocompatibility of the ZnO-NWs. This was achieved through comprehensive evaluation of the absence of cytotoxicity in normal HEK-293T and erythrocytes. Results: The findings of this investigation unequivocally confirmed the biocompatibility of the ZnO-NWs. The biosynthesized ZnO-NWs demonstrated a noteworthy capacity to mitigate the dermatitis-induced consequences induced by Staphylococcus aureus in murine models after a therapeutic intervention lasting for one week. Discussion: This study presents a comprehensive examination of the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) derived from chicken egg whites. These findings highlight the considerable potential of biosynthesized ZnO-NWs as a viable option for the development of therapeutic agents targeting infectious diseases. The antibacterial efficacy of ZnO-NWs against both susceptible and antibiotic-resistant bacterial strains, as well as their ability to eradicate biofilms, suggests their promising role in combating infectious diseases. Furthermore, the confirmed biocompatibility of ZnO-NWs opens avenues for their safe use in biomedical applications. Overall, this research underscores the therapeutic promise of ZnO-NWs and their potential significance in future biomedical advancements.


Asunto(s)
Enfermedades Transmisibles , Dermatitis , Nanopartículas del Metal , Óxido de Zinc , Animales , Ratones , Óxido de Zinc/farmacología , Óxido de Zinc/química , Pollos , Clara de Huevo , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus , Espectroscopía Infrarroja por Transformada de Fourier , Extractos Vegetales/farmacología
20.
Mol Biotechnol ; 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37914864

RESUMEN

Cancer is a group of heterogeneous diseases that occur when cells in the body proliferate and divide uncontrollably. As the current treatment modalities have pros and cons, the discovery of new chemotherapeutic agents with the least side effects is one of the most investigated research areas. In this context, plant-based natural products are a rich source of drugs and have served humanity for ages. Frankincense essential oils (FEOs) are among the most promising plant-based oils in Gulf countries. In addition to their high cultural value, FEOs are also famous for their engaging biological activities, including anti-cancerous. However, the practical application of FEOs is often hindered/by their low water solubility, limited bioavailability, high volatility, and sensitivity toward heat, humidity, light, or oxygen. Thus, a significant demand for technological advancement would improve their ability to target particular cells and tissues. Nanotechnology emerged as an exciting approach in this context. Through suitable nano-formulation (functionalization or encapsulation into a nanostructure), issues arising due to solubility, targeting capability, and delivery can be controlled.

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