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1.
Biometals ; 37(2): 389-403, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38055071

RESUMEN

The bio-mediated synthesis of nanoparticles offers a sustainable and eco-friendly approach. In the present study, silver nanoparticles (AgNPs) were synthesized using Joshanda extract, a commercially available herbal formulation derived from a traditional medicinal plant, as a reducing and stabilizing agent. The as-synthesized AgNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), X-ray Diffraction (XRD) study, and Fourier-transform infrared (FTIR) analysis. UV-Vis spectroscopy exhibited a prominent absorption peak at 430 nm, confirming the formation of AgNPs. DLS analysis revealed the size distribution of the nanoparticles, ranging from 80 to 100 nm, and zeta potential measurements indicated a surface charge of - 14.4 mV. The XRD analysis provide evidence for the presence of a face-centered cubic structure within the silver nanoparticles. FTIR analysis further elucidated the interaction of bioactive compounds from the Joshanda extract with the AgNPs' surface. Strong peaks at 765-829 cm-1 indicated C-Cl stretching vibrations of alkyl halides, while the stretching of alkenes C=C was observed at 1641 cm-1. Moreover, the presence of alcohols and phenol (OH) groups was identified at 3448 cm-1, suggesting their involvement in nanoparticle stabilization. The antimicrobial potential of the synthesized AgNPs was evaluated against both gram-negative Pseudomonas aeruginosa and gram-positive Streptococcus mutans using zone of inhibition assays. The AgNPs exhibited remarkable inhibitory effects against both types of bacteria. Additionally, AgNPs-treated groups demonstrated a significant increase in reactive oxygen species (ROS) levels, indicating potential of as-synthesized AgNPs in disruption of the target microbial membranes. Furthermore, the as-synthesized AgNPs exhibited notable anti-biofilm properties by effectively hindering the development of mature biofilms. This study highlights the efficient green synthesis of AgNPs using Joshanda extract and also provides insights into their physico-chemical properties of as-synthesized nanoparticles. The demonstrated antimicrobial activity against both gram-negative and gram-positive bacteria, along with biofilm inhibition potential, underscores the promising applications of the as-synthesized AgNPs in the field of biomedical and environmental sciences. The study bridges traditional knowledge with contemporary nanotechnology, offering a novel avenue for the development of eco-friendly antimicrobial agents.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Preparaciones de Plantas , Antibacterianos/farmacología , Antibacterianos/química , Plata/farmacología , Plata/química , Bacterias Gramnegativas , Nanopartículas del Metal/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Bacterias Grampositivas , Antiinfecciosos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier
2.
Molecules ; 28(5)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36903437

RESUMEN

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Dietilnitrosamina/farmacología , ARN Interferente Pequeño/farmacología , Ciclooxigenasa 2 , Apoptosis , Carcinogénesis
3.
J Biol Chem ; 293(29): 11310-11324, 2018 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-29853634

RESUMEN

Amyloids are associated with many neurodegenerative diseases, motivating investigations into their structure and function. Although not linked to a specific disease, albumins have been reported to form many structural aggregates. We were interested in investigating host immune responses to amyloid fibrils assembled from the model protein ovalbumin. Surprisingly, upon subjecting ovalbumin to standard denaturing conditions, we encountered giant protein nanosheets harboring amyloid-like features and hypothesized that these nanosheets might have potential in clinical or therapeutic applications. We found that the nanosheets, without the administration of any additional adjuvant, evoked a strong antibody response in mice that was higher than that observed for native ovalbumin. This suggests that amyloid nanosheets have a self-adjuvanting property. The nanosheet-induced immune response was helper T cell 2 (Th2) biased and negligibly inflammatory. While testing whether the nanosheets might form depots for the sustained release of precursor proteins, we did observe release of ovalbumin that mimicked the conformation of native protein. Moreover, the nanosheets could load the anticancer drug doxorubicin and release it in a slow and sustained manner. Taken together, our results suggest that amyloid nanosheets should be further investigated as either an antigen delivery vehicle or a multifunctional antigen and drug co-delivery system, with potential applications in simultaneous immunotherapy and chemotherapy.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Amiloide/farmacología , Antibióticos Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/farmacología , Doxorrubicina/administración & dosificación , Ovalbúmina/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/química , Amiloide/administración & dosificación , Amiloide/química , Amiloide/inmunología , Animales , Formación de Anticuerpos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Femenino , Inmunización , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Ovalbúmina/administración & dosificación , Ovalbúmina/química , Ovalbúmina/inmunología , Desnaturalización Proteica , Células Th2/inmunología
4.
J Cell Physiol ; 234(5): 6951-6964, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30443899

RESUMEN

In the recent past, various groups have proposed diverse biocompatible methods for the synthesis of metal nanoparticles (NPs). Besides culture biomass, culture supernatants (CS) are increasingly being explored for the synthesis of NPs; however, with the ever-increasing exploration of various CS in the biofabrication of NPs, it is equally important to explore the potential of various culture media (CMs) in the synthesis of metal NPs. Considering these aspects, in the present investigation, we explore the possible applicability of various CMs in the biofabrication of metal NPs. The synthesis of NPs was primarily followed by UV/VIS spectroscopy, and, thereafter, the NPs were characterized by various physiochemical techniques, including EM, EDX, FT_IR, X-ray diffraction, and DLS measurements, and finally, their anticancer potentialities were investigated against breast cancer. In addition, the NPs were examined in conjunction with artemisinin for therapeutic benefits against aggressive and highly metastatic MDA-MB-231 breast cancer cells. Cumulatively, the results of the present study collated the potentials of various bacterial CMs in the biofabrication of metal NPs and ascertained the efficacy of the as-synthesized silver nanoparticles, especially the combinatorial entity as intriguing breast cancer therapeutics. The data of the present study plausibly assist in advancing the therapeutic applicability of the combinatorial amalgam against aggressive and highly metastatic MDA-MB-231 breast cancer cells.


Asunto(s)
Artemisininas/química , Artemisininas/farmacología , Bacterias/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Medios de Cultivo/metabolismo , Nanopartículas del Metal/química , Antineoplásicos/farmacología , Línea Celular , Línea Celular Tumoral , Femenino , Células HEK293 , Humanos , Células MCF-7 , Tamaño de la Partícula , Plata/química
5.
Photochem Photobiol Sci ; 18(12): 3008-3015, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31696896

RESUMEN

A quinoline moiety was used as a building block for designing a probe for the selective detection of copper ions in a partially aqueous medium. We have developed a molecular sensing system which gives insight into the complex physiological and redox aspects of labile copper. The probe provides a colorimetric approach for distinguishing cuprous and cupric ions along with their simultaneous discrimination from other metal ions in the visible range of the spectrum. The chemosensor showed a remarkable fluorescence enhancement along with a significant bathochromic shift of about 35 nm. The detection limit of the probe was found to be 1.03 µM which is optimally favorable to be applied in real-time monitoring. Fabrication of paper strips with the probe was done to detect the presence of cuprous ions in the real sample. The value of the binding constant (1.37 × 104 M-1) suggests stable complex formation between the metal ion and the sensing probe. The photoluminescence and structural aspects of the chemosensor were characterized by using fluorescence, absorption, ESI-MS, and 1H NMR spectroscopy. Furthermore, the cytotoxic nature and bioimaging properties of the probe were interpreted in vitro on RAW 264.7 macrophage cell lines and peripheral blood mononuclear cells (PBMCs) respectively.


Asunto(s)
Colorimetría , Cobre/análisis , Quinolinas/química , Animales , Colorantes Fluorescentes/química , Humanos , Iones/química , Leucocitos Mononucleares/química , Leucocitos Mononucleares/citología , Límite de Detección , Macrófagos/química , Macrófagos/citología , Ratones , Microscopía Fluorescente , Células RAW 264.7
6.
Biochem J ; 475(3): 547-560, 2018 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-29301982

RESUMEN

Peptidyl-tRNA hydrolase (Pth) catalyzes the breakdown of peptidyl-tRNA into peptide and tRNA components. Pth from Acinetobacter baumannii (AbPth) was cloned, expressed, purified and crystallized in a native unbound (AbPth-N) state and in a bound state with the phosphate ion and cytosine arabinoside (cytarabine) (AbPth-C). Structures of AbPth-N and AbPth-C were determined at 1.36 and 1.10 Šresolutions, respectively. The structure of AbPth-N showed that the active site is filled with water molecules. In the structure of AbPth-C, a phosphate ion is present in the active site, while cytarabine is bound in a cleft which is located away from the catalytic site. The cytarabine-binding site is formed with residues: Gln19, Trp27, Glu30, Gln31, Lys152, Gln158 and Asp162. In the structure of AbPth-N, the side chains of two active-site residues, Asn70 and Asn116, were observed in two conformations. Upon binding of the phosphate ion in the active site, the side chains of both residues were ordered to single conformations. Since Trp27 is present at the cytarabine-binding site, the fluorescence studies were carried out which gave a dissociation constant (KD) of 3.3 ± 0.8 × 10-7 M for cytarabine. The binding studies using surface plasmon resonance gave a KD value of 3.7 ± 0.7 × 10-7 M. The bacterial inhibition studies using the agar diffusion method and the biofilm inhibition assay established the strong antimicrobial potential of cytarabine. It also indicated that cytarabine inhibited Gram-negative bacteria more profoundly when compared with Gram-positive bacteria in a dose-dependent manner. Cytarabine was also effective against the drug-resistant bacteria both alone as well as in combination with other antibiotics.


Asunto(s)
Acinetobacter baumannii/enzimología , Biopelículas/efectos de los fármacos , Hidrolasas de Éster Carboxílico/química , Hidrolasas de Éster Carboxílico/genética , Acinetobacter baumannii/química , Acinetobacter baumannii/genética , Antibacterianos/química , Antibacterianos/farmacología , Sitios de Unión , Hidrolasas de Éster Carboxílico/farmacología , Catálisis , Dominio Catalítico , Cristalografía por Rayos X , Citarabina/química , Escherichia coli/genética , Dominios Proteicos , ARN de Transferencia/química , ARN de Transferencia/genética , Aminoacil-ARN de Transferencia/genética , Especificidad por Sustrato , Propiedades de Superficie
7.
Inflammopharmacology ; 26(2): 583-598, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28547701

RESUMEN

AIM OF THE STUDY: Terminalia arjuna is a medicinal plant well known as a cardiotonic in Ayurvedic system of medicine. We hypothesized that aqueous stem bark extract of T. arjuna (TAE) may inhibit IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway in Apo E-/- mice. MATERIALS AND METHODS: 12-week-old, male Apo E-/- mice divided into four groups (n = 6/group) fed with normal chow-diet were employed: GP I: phosphate buffer saline (PBS) (2 month); GP II: rIL-18 (1 month) followed by PBS (1 month); GP III: rIL-18 (1 month) followed by TAE (1 month); GP IV: rIL-18 (1 month) followed by atorvastatin (1 month). RESULTS: IL-18 treatment induced a significant increase (p < 0.001) in pro-inflammatory marker (IL-18) (170 ± 9.16 vs. 1178.66 ± 8.08, pg/ml), and downregulated cholesterol efflux gene (PPAR-γ) by ~0.6-fold vs. 1.00 in IL-18-treated mice as compared to the control animals, respectively. TAE treatment to both groups caused a significant reduction in IL-18 to 281.66 ± 9.60 vs. 1178.66 ± 8.08 (pg/ml), upregulated cholesterol efflux gene by ~1.5- vs. 0.6-fold in TAE-treated group, decreased atherogenic lipids, and percentage atherosclerotic lesion area, demonstrating comparable effects with atorvastatin. CONCLUSION: Our data demonstrate that TAE protects against IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway.


Asunto(s)
Apolipoproteínas E/metabolismo , Aterosclerosis/tratamiento farmacológico , Interleucina-18/metabolismo , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Extractos Vegetales/farmacología , Terminalia/química , Animales , Antioxidantes/metabolismo , Aterosclerosis/metabolismo , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Plantas Medicinales/química
8.
Mol Cell Biochem ; 428(1-2): 119-128, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28176248

RESUMEN

Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in atherosclerotic lesion formation. Endothelium may regulate leukocyte recruitment by expressing specific adhesion molecules. Interleukin-18 is a proinflammatory cytokine that plays an important role in vascular pathologies. The present study highlights the modulation of adhesion molecules and PPAR-γ by IL-18 and proposes a novel feedback mechanism by which PPAR-γ may regulate IL-18 expression. Three groups of normal chow diet-fed, male Apo E-/- mice, aged 12 weeks (n = 6/group) were employed: Gp I, phosphate-buffered saline (PBS) (2 mo): Gp II, recombinant IL-18 (rIL-18) (1 mo) followed by PBS (1 mo); Gp III, rIL-18 (1 mo) followed by pyrrolidine dithiocarbamate (PDTC) (1 mo). Significantly augmented mRNA expression of ICAM-1 (~5.7-fold), VCAM-1 (~3.6-fold), and NF-κB (~7-fold) was observed in Gp II mice as compared to Gp I, whereas PPAR-γ expression was not altered. PDTC treatment caused a significant downregulation of ICAM-1 (~4.2-fold), VCAM-1(~2-fold), and NF-κB (~4.5-fold) and upregulation of PPAR-γ expression (~5-fold) in Gp III mice. A similar trend was observed in protein expression. In vivo imaging results demonstrated a marked increase in probe (CF750 dye conjugated to VCAM-1 antibody) fluorescence intensity for VCAM-1 expression in Gp II mice, whereas it was moderately decreased in Gp III. PPAR-γ was found to significantly downregulate both IL-18 levels and IL-18-induced adhesion molecules. The underlying mechanism was found to be via inhibition of NF-κB activity by PDTC, thereby leading to decreased adherence of monocytes to the activated endothelial cells and a step to halt the progression and development of atherosclerotic lesions.


Asunto(s)
Apolipoproteínas E/genética , Aterosclerosis/genética , Retroalimentación Fisiológica/efectos de los fármacos , Interleucina-18/administración & dosificación , FN-kappa B/genética , PPAR gamma/genética , Animales , Adhesión Celular/efectos de los fármacos , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/farmacología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Interleucina-18/farmacología , Masculino , Ratones , Ratones Noqueados , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Transducción de Señal
9.
Nanomedicine ; 13(5): 1773-1783, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28216150

RESUMEN

Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues and high production costs. In this study, AmB complexes based on poly(gamma-glutamic acid) (PGGA) were prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone®) and liposomal AmB (AmBisome®). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (-45.5 to -51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 °C and 25 °C), and have a high drug loading (up to 35% w/w). In vitro, AmB/PGGA complexes exhibited a more favorable cytotoxicity profile than Fungizone® but comparable to AmBisome®, with respect to the hemolytic activity and the modulation of pro-inflammatory cytokines (TNF-α and IL-1ß). In-vivo, AmB/PGGA complexes were significantly more efficacious than both Fungizone® and AmBisome® against experimental murine candidiasis. These results provide strong evidence that AmB/PGGA complexes display better efficacy and safety features than the currently approved AmB products.


Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Anfotericina B/administración & dosificación , Animales , Antifúngicos/administración & dosificación , Candidiasis/tratamiento farmacológico , Ácido Glutámico , Ratones , Nanotecnología/métodos , Factor de Necrosis Tumoral alfa
10.
J Biol Chem ; 290(7): 4131-48, 2015 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-25512377

RESUMEN

Amyloids are highly organized protein aggregates that arise from inappropriately folded versions of proteins or polypeptides under both physiological as well as simulated ambiences. Once thought to be irreversible assemblies, amyloids have begun to expose their more dynamic and reversible attributes depending upon the intrinsic properties of the precursor protein/peptide and experimental conditions such as temperature, pressure, structural modifications in proteins, or presence of chemicals in the reaction mixture. It has been repeatedly proposed that amyloids undergo transformation to the bioactive peptide/protein forms under specific conditions. In the present study, amyloids assembled from the model protein ovalbumin (OVA) were found to release the precursor protein in a slow and steady manner over an extended time period. Interestingly, the released OVA from amyloid depot was found to exhibit biophysical characteristics of native protein and reacted with native-OVA specific monoclonal as well as polyclonal antibodies. Moreover, antibodies generated upon immunization of OVA amyloidal aggregates or fibrils were found to recognize the native form of OVA. The study suggests that amyloids may act as depots for the native form of the protein and therefore can be exploited as vaccine candidates, where slow antigen release over extended time periods is a pre-requisite for the development of desired immune response.


Asunto(s)
Amiloide/inmunología , Anticuerpos Monoclonales/inmunología , Ovalbúmina/inmunología , Péptidos/inmunología , Linfocitos T/inmunología , Amiloide/química , Amiloide/metabolismo , Animales , Anticuerpos Monoclonales/sangre , Dicroismo Circular , Citocinas/metabolismo , Femenino , Inmunización , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Óxido Nítrico/metabolismo , Ovalbúmina/química , Ovalbúmina/metabolismo , Péptidos/química , Péptidos/metabolismo , Conformación Proteica , Multimerización de Proteína
11.
Dig Dis ; 33(5): 675-82, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26398762

RESUMEN

Liver cancer results in enormous human toll worldwide. Over the years, various chemotherapeutic entities have been employed for treatment of advanced HCC; however, as of yet none embody attributes to improve overall survival. Following rapid advancement in nanotechnology, it is envisage that nanoscale systems may emerge as intriguing platforms to improve chemotherapeutic strategies against various cancers including liver cancer; with better insight in the understanding of pathophysiology of liver cancer and material science, the field of nanotechnology may bring newer hope to liver cancer treatment. Reckoning with these, we detailed the arsenal of nanoformulations that are in various stages of clinical development/ preclinical settings for the treatment of liver cancer together with providing a glimpse of the attributes of nanotechnology in revolutionizing the status of chemotherapeutic modalities.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124564, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38824756

RESUMEN

In our research we explore the world of PACDs, carbon dots synthesized from pamoic acid through a single step pyrolysis method. Our findings reveal that PACDs have capabilities of serving as sensitive and selective sensors in both colorimetric and fluorescent modes. They are particularly effective, at colorimetrically and fluorometrically detecting ferric ions and can also act as fluorometric sensors for pH. When ferric ions are introduced an interesting transformation occurs. A noticeable change in color unfolds before our eyes, under 365 nm UV light the fluorescence shifts from green to blue while in daylight it changes from a yellow to a deep ink blue. Notably these detection techniques can precisely measure ferric ions within concentrations ranging from 5 µM to 80 µM with a detection limit of 0.1 µM for fluorescence response. Additionally, they can detect ferric ions colorimetrically within the range of 5 µM to 45 µM with a detection limit of 3.8 µM. Furthermore, the PACDs exhibit a capability to adapt to different pH levels. In alkaline environments with a pH range between 8 and 11 the fluorescence signal demonstrates a response that directly correlates with pH levels and slightly shifts its position. In contrast under acidic conditions a noticeable shift, towards blue is observed in the fluorescence signal leading to a change in color from green to blue when exposed to UV light. This shift persists as the fluorescence signal directly correlates with decreasing pH levels in settings. Apart from their proficiency in ferric ion detection and pH monitoring, the PACDs also demonstrate potential in cancer research. Through an assessment using the MTT assay it was discovered that the PACDs exhibit cytotoxic effects against five different cancer cell lines; HCT 116, MDA MB 231, Hep3B, MCF 7 and HeLa. The findings are promising as the PACDs show IC50 values of 12.5 µg/ml 6.25 µg/ml 25 µg/ml 50 µg/ml and 100 µg/ml for these cell lines. This research highlights the versatility and potential of PACDs as a tool, in both sensing applications and oncology research.


Asunto(s)
Carbono , Puntos Cuánticos , Espectrometría de Fluorescencia , Humanos , Carbono/química , Puntos Cuánticos/química , Concentración de Iones de Hidrógeno , Colorimetría/métodos , Límite de Detección , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/análisis
13.
Mini Rev Med Chem ; 24(13): 1238-1251, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38185891

RESUMEN

BACKGROUND: Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is also known as benzpyridine, benzopyridine, and 1-azanaphthalene. It has a benzene ring fused with a pyridine ring, and both rings share two carbon atoms. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. OBJECTIVE: This article is expected to have a significant impact on the advancement of effective antitubercular drugs. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. METHODS: Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility comes from their ability to bind with the receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, anti-tumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. RESULTS: Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain nitrogen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of significant properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. CONCLUSION: This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study emphasizes the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.


Asunto(s)
Antituberculosos , Quinolinas , Quinolinas/química , Quinolinas/farmacología , Antituberculosos/farmacología , Antituberculosos/química , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Animales , Estructura Molecular
14.
Eur J Pharmacol ; 975: 176637, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38729416

RESUMEN

Macrophages play a pivotal role in safeguarding against a broad spectrum of infections, from viral, bacterial, fungal to parasitic threats and contributing to the immune defense against cancer. While morphine's immunosuppressive effects on immune cells are extensively documented, a significant knowledge gap exists regarding its influence on macrophage polarization and differentiation. Hence, we conducted a study that unveils that prior exposure to morphine significantly impedes the differentiation of bone marrow cells into macrophages. Furthermore, the polarization of macrophages toward the M1 phenotype under M1-inducing conditions experiences substantial impairment, as evidenced by the diminished expression of CD80, CD86, CD40, iNOS, and MHCII. This correlates with reduced expression of M1 phenotypical markers such as iNOS, IL-1ß, and IL-6, accompanied by noticeable morphological, size, and phagocytic alterations. Further, we also observed that morphine affected M2 macrophages. These findings emphasize the necessity for a more comprehensive understanding of the impact of morphine on compromising macrophage function and its potential ramifications for therapeutic approaches.


Asunto(s)
Diferenciación Celular , Inmunosupresores , Macrófagos , Morfina , Morfina/farmacología , Animales , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Diferenciación Celular/efectos de los fármacos , Inmunosupresores/farmacología , Polaridad Celular/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratones Endogámicos C57BL , Fagocitosis/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Masculino , Interleucina-1beta/metabolismo
15.
Int J Biol Macromol ; 274(Pt 1): 133188, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38880456

RESUMEN

Morphine addiction poses a significant challenge to global healthcare. Current opioid substitution therapies, such as buprenorphine, naloxone and methadone are effective but often lead to dependence. Thus, exploring alternative treatments for opioid addiction is crucial. We have developed a novel vaccine that presents morphine and Pam3Cys (a TLR-2 agonist) on the surface of Acr1 nanoparticles. This vaccine has self-adjuvant properties and targets TLR-2 receptors on antigen-presenting cells, particularly dendritic cells. Our vaccination strategy promotes the proliferation and differentiation of morphine-specific B-cells and Acr1-reactive CD4 T-cells. Additionally, the vaccine elicited the production of high-affinity anti-morphine antibodies, effectively eliminating morphine from the bloodstream and brain in mice. It also reduced the expression of addiction-associated µ-opioid receptor and dopamine genes. The significant increase in memory CD4 T-cells and B-cells indicates the vaccine's ability to induce long-lasting immunity against morphine. This vaccine holds promise as a prophylactic measure against morphine addiction.


Asunto(s)
Células Dendríticas , Morfina , Nanopartículas , Receptor Toll-Like 2 , Vacunas , Animales , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Morfina/farmacología , Ratones , Vacunas/inmunología , Receptor Toll-Like 2/metabolismo , Nanopartículas/química , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Dependencia de Morfina/inmunología , Dependencia de Morfina/tratamiento farmacológico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Receptores Opioides mu/inmunología , Receptores Opioides mu/metabolismo , Nanovacunas
16.
Polymers (Basel) ; 15(6)2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36987161

RESUMEN

Recently, polymeric nanofiber veils have gained lot of interest for various industrial and research applications. Embedding polymeric veils has proven to be one of the most effective ways to prevent delamination caused by the poor out-of-plane properties of composite laminates. The polymeric veils are introduced between plies of a composite laminate, and their targeted effects on delamination initiation and propagation have been widely studied. This paper presents an overview of the application of nanofiber polymeric veils as toughening interleaves in fiber-reinforced composite laminates. It presents a systematic comparative analysis and summary of attainable fracture toughness improvements based on electrospun veil materials. Both Mode I and Mode II tests are covered. Various popular veil materials and their modifications are considered. The toughening mechanisms introduced by polymeric veils are identified, listed, and analyzed. The numerical modeling of failure in Mode I and Mode II delamination is also discussed. This analytical review can be used as guidance for veil material selection, for estimation of the achievable toughening effect, for understanding the toughening mechanism introduced by veils, and for the numerical modeling of delamination.

17.
Polymers (Basel) ; 15(6)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36987354

RESUMEN

The problem of icing for surfaces of engineering structures requires attention more and more every year. Active industrialization in permafrost zones is currently underway; marine transport in Arctic areas targets new goals; the requirements for aerodynamically critical surfaces of wind generators and aerospace products, serving at low temperatures, are increasing; and fiber-reinforced polymer composites find wide applicability in these structural applications demanding the problem of anti/de-icing to be addressed. The traditional manufacturing approaches are superimposed with the new technologies, such as 3D printers and robotics for laying heat wires or cheap and high-performance Thermal Sprayed methods for metallic cover manufacturing. Another next step in developing heaters for polymer structures is nano and micro additives to create electrically conductive heating networks within. In our study, we review and comparatively analyze the modern technologies of structure heating, based on resistive heating composites.

18.
Chin J Integr Med ; 29(6): 549-555, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37017881

RESUMEN

Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.


Asunto(s)
COVID-19 , Tinospora , Humanos , Tinospora/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Antioxidantes/farmacología , Antioxidantes/química
19.
Cureus ; 15(4): e37914, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37220467

RESUMEN

Soft tissue chondroma is a relatively rare, slowly growing, benign cartilaginous tumor. This solitary mass can imitate chondrosarcomas in radiologic and histological characteristics. The diagnosis is hard to establish on clinical presentation and relies on careful radiological examination. The lesion is equally prevalent in both genders and primarily affects people in their forties and sixties. They may occur in any part of the body; however, they are most commonly observed in hand and foot. We report the case of a 61-year-old female who presented with heavily ossified soft tissue chondroma within the plantar fascia of her left foot. A conclusive diagnosis was established via histopathological examination. The chondroma was marginally excised, and the postoperative period was uneventful.

20.
J Int Soc Prev Community Dent ; 13(6): 469-476, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38304537

RESUMEN

Aim: To quantify and compare the metal ions released from different bracket-wire combinations and to assess their cytotoxicity. Materials and Methods: A total of 360 fabricated sectional fixed orthodontic appliances were divided into 6 groups. The first three groups consisted of stainless-steel brackets with stainless-steel, snickel-titanium (NiTi), and titanium-molybdenum alloy (TMA) archwires, and the other three groups were fabricated using ceramic brackets (polycrystalline alumina) with stainless-steel, NiTi, and TMA archwires. These appliances were immersed in artificial saliva (pH 6.5 ± 0.5, 37°C), for 1 week, 2 weeks, and 1 month. The nickel and chromium ions released in the artificial saliva were quantified using a flame atomic absorption spectrometer, and cytotoxicity assessment was performed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay on human cervical cancer cell line. Results: The stainless-steel bracket groups displayed a significantly greater release of nickel and chromium ions compared to the ceramic bracket groups (P < 0.05). However, no significant differences were identified when comparing the three archwire types within the stainless-steel/ceramic bracket groups. At the end of 1 month, the % cell viability demonstrated by the appliances was in the decreasing order of stainless-steel-TMA > ceramic-stainless steel > stainless-steel-NiTi > ceramic-NiTi > stainless-steel-stainless steel > ceramic-TMA. Conclusion: Considerably greater release of nickel and chromium ions was observed from the appliances utilizing stainless-steel brackets compared to those employing ceramic brackets. However, no remarkable difference in the levels of nickel and chromium ions was observed when comparing the three archwires: stainless steel, NiTi, and TMA. In the cytotoxicity assessment, the ceramic-TMA combination displayed the highest level of cytotoxicity, while the stainless-steel-TMA combination displayed the least cytotoxicity.

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