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1.
ACS Omega ; 9(1): 16-32, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222657

RESUMO

Antibiotic resistance (AMR) is one of the pressing global public health concerns and projections indicate a potential 10 million fatalities by the year 2050. The decreasing effectiveness of commercially available antibiotics due to the drug resistance phenomenon has spurred research efforts to develop potent and safe antimicrobial agents. Iron oxide nanoparticles (IONPs), especially when doped with metals, have emerged as a promising avenue for combating microbial infections. Like IONPs, the antimicrobial activities of doped-IONPs are also linked to their surface charge, size, and shape. Doping metals on nanoparticles can alter the size and magnetic properties by reducing the energy band gap and combining electronic charges with spins. Furthermore, smaller metal-doped nanoparticles tend to exhibit enhanced antimicrobial activity due to their higher surface-to-volume ratio, facilitating greater interaction with bacterial cells. Moreover, metal doping can also lead to increased charge density in magnetic nanoparticles and thereby elevate reactive oxygen species (ROS) generation. These ROS play a vital role to disrupt bacterial cell membrane, proteins, or nucleic acids. In this review, we compared the antimicrobial activities of different doped-IONPs, elucidated their mechanism(s), and put forth opinions for improved biocompatibility.

2.
Environ Pollut ; 345: 123446, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38295931

RESUMO

Plastic pollution has become a major environmental concern globally, and novel and eco-friendly approaches like bioremediation are essential to mitigate the impact. Low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), and expanded polystyrene (EPS) are three of the most frequently used plastic types. This study examined biodegradation of these using Zophobas atratus larvae, followed by isolation and whole genome sequencing of gut bacteria collected from larvae frass. Over 36 days, 24.04 % LDPE, 20.01 % EPS, and 15.12 % LLDPE were consumed on average by the larvae, with survival rates of 85 %, 90 %, and 87 %, respectively. Fourier transform infrared spectroscopy (FTIR) analysis of fresh plastic types, consumed plastics, and larvae frass showed proof of plastic oxidation in the gut. Frass bacteria were isolated and cultured in minimal salt media supplemented with plastics as the sole carbon source. Two isolates of bacteria were sampled from these cultures, designated PDB-1 and PDB-2. PDB-1 could survive on LDPE and LLDPE as carbon sources, whereas PDB-2 could survive on EPS. Scanning Electron Microscopy (SEM) provided proof of degradation in both cases. Both isolates were identified as strains of Pseudomonas aeruginosa, followed by sequencing, assembly, and annotation of their genomes. LDPE- and LLDPE-degrading enzymes e.g., P450 monooxygenase, alkane monooxygenase, alcohol dehydrogenase, etc. were identified in PDB-1. Similarly, phenylacetaldehyde dehydrogenase and other enzymes involved in EPS degradation were identified in PDB-2. Genes of both isolates were compared with genomes of known plastic-degrading P. aeruginosa strains. Virulence factors, antibiotic-resistance genes, and rhamnolipid biosurfactant biosynthesis genes were also identified in both isolates. This study indicated Zophobas atratus larvae as potential LDPE, LLDPE, and EPS biodegradation agent. Additionally, the isolated strains of Pseudomonas aeruginosa provide a more direct and eco-friendly solution for plastic degradation. Confirmation and modification of the plastic-degrading pathways in the bacteria may create scope for metabolic engineering in the future.


Assuntos
Besouros , Polietileno , Animais , Polietileno/química , Poliestirenos/metabolismo , Larva/metabolismo , Biodegradação Ambiental , Bactérias/genética , Bactérias/metabolismo , Pseudomonas aeruginosa/metabolismo , Oxigenases de Função Mista/metabolismo , Carbono/metabolismo , Plásticos/metabolismo
3.
J Genet Eng Biotechnol ; 21(1): 162, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38055114

RESUMO

BACKGROUND: Human parainfluenza viruses (HPIVs) are common RNA viruses responsible for respiratory tract infections. Human parainfluenza virus 3 (HPIV-3) is particularly pathogenic, causing severe illnesses with no effective vaccine or therapy available. RESULTS: The current study employed a systematic immunoinformatic/reverse vaccinology approach to design a multiple epitope-based peptide vaccine against HPIV-3 by analyzing the virus proteome. On the basis of a number of therapeutic features, all three stable and antigenic proteins with greater immunological relevance, namely matrix protein, hemagglutinin neuraminidase, and RNA-directed RNA polymerase L, were chosen for predicting and screening suitable T-cell and B-cell epitopes. All of our desired epitopes exhibited no homology with human proteins, greater population coverage (99.26%), and high conservancy among reported HPIV-3 isolates worldwide. All of the T- and B-cell epitopes are then joined by putative ligands, yielding a 478-amino acid-long final construct. Upon computational refinement, validation, and thorough screening, several programs rated our peptide vaccine as biophysically stable, antigenic, allergenic, and non-toxic in humans. The vaccine protein demonstrated sufficiently stable interaction as well as binding affinity with innate immune receptors TLR3, TLR4, and TLR8. Furthermore, codon optimization and virtual cloning of the vaccine sequence in a pET32a ( +) vector showed that it can be readily expressed in the bacterial system. CONCLUSION: The in silico designed HPIV-3 vaccine demonstrated potential in evoking an effective immune response. This study paves the way for further preclinical and clinical evaluation of the vaccine, offering hope for a future solution to combat HPIV-3 infections.

4.
ACS Omega ; 8(17): 15152-15159, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37151486

RESUMO

Cobalt ferrite nanoparticles (CFNs) are promising materials for their enticing properties for different biomedical applications, including magnetic resonance imaging (MRI) contrast, drug carriers, biosensors, and many more. In our previous study, a chitosan-coated CFN (CCN) nanocomplex demonstrated potential as an MRI contrast dye by improving the biocompatibility of CFN. In this study, we report the progeny transfer effects of CCN following a single intravenous injection of CCN (20, 40, or 60 mg/kg) in pregnant albino Wistar rats. Biochemical and histological observation reveals that CCN is tolerated with respect to maternal organ functions (e.g., liver, kidney). Atomic absorption spectroscopy results showed that CCN or CCN-leached iron could cross the placental barrier and deposit in the fetus. Furthermore, this deposition accelerated lipid peroxidation in the placenta and fetus.

5.
Cancers (Basel) ; 15(6)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36980778

RESUMO

Radiation has been utilized for a long time for the treatment of cancer patients. However, radiotherapy (RT) has many constraints, among which non-selectivity is the primary one. The implementation of nanoparticles (NPs) with RT not only localizes radiation in targeted tissue but also provides significant tumoricidal effect(s) compared to radiation alone. NPs can be functionalized with both biomolecules and therapeutic agents, and their combination significantly reduces the side effects of RT. NP-based RT destroys cancer cells through multiple mechanisms, including ROS generation, which in turn damages DNA and other cellular organelles, inhibiting of the DNA double-strand damage-repair system, obstructing of the cell cycle, regulating of the tumor microenvironment, and killing of cancer stem cells. Furthermore, such combined treatments overcome radioresistance and drug resistance to chemotherapy. Additionally, NP-based RT in combined treatments have shown synergistic therapeutic benefit(s) and enhanced the therapeutic window. Furthermore, a combination of phototherapy, i.e., photodynamic therapy and photothermal therapy with NP-based RT, not only reduces phototoxicity but also offers excellent therapeutic benefits. Moreover, using NPs with RT has shown promise in cancer treatment and shown excellent therapeutic outcomes in clinical trials. Therefore, extensive research in this field will pave the way toward improved RT in cancer treatment.

6.
Curr Med Chem ; 30(15): 1756-1775, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36214302

RESUMO

Cobalt ferrite nanoparticles (CFN) have drawn attention as a theranostic agent. Unique physicochemical features of CFN and magnetic properties make CFN an outstanding candidate for biomedical, agricultural, and environmental applications. The extensive use of CFN may result in intentional inoculation of humans for disease diagnosis and therapeutic purposes or unintentional penetration of CFN via inhalation, ingestion, adsorption, or other means. Therefore, understanding the potential cytotoxicity of CFN may pave the way for their future biomedical and agricultural applications. This review scrutinized CFN biocompatibility, possible effects, and cytotoxic mechanisms in different biological systems. Literature indicates CFN toxicity is linked with their size, synthesizing methods, coating materials, exposure time, route of administration, and test concentrations. Some in vitro cytotoxicity tests showed misleading results of CFN potency; this might be due to the interaction of CFN with cytotoxicity assay regents. To date, published research indicates that the biocompatibility of CFN outweighed its cytotoxic effects in plant or animal models, but the opposite outcomes were observed in aquatic Zebrafish.


Assuntos
Nanopartículas , Peixe-Zebra , Animais , Humanos , Nanopartículas/química , Compostos Férricos/toxicidade , Compostos Férricos/química , Cobalto/toxicidade , Cobalto/química
7.
Polymers (Basel) ; 14(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36365532

RESUMO

Polymeric hydrogels have drawn considerable attention as a biomedical material for their unique mechanical and chemical properties, which are very similar to natural tissues. Among the conventional hydrogel materials, self-healing hydrogels (SHH) are showing their promise in biomedical applications in tissue engineering, wound healing, and drug delivery. Additionally, their responses can be controlled via external stimuli (e.g., pH, temperature, pressure, or radiation). Identifying a suitable combination of viscous and elastic materials, lipophilicity and biocompatibility are crucial challenges in the development of SHH. Furthermore, the trade-off relation between the healing performance and the mechanical toughness also limits their real-time applications. Additionally, short-term and long-term effects of many SHH in the in vivo model are yet to be reported. This review will discuss the mechanism of various SHH, their recent advancements, and their challenges in tissue engineering, wound healing, and drug delivery.

8.
Mol Biotechnol ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307631

RESUMO

Dengue fever is a mosquito-borne disease that claims the lives of millions of people around the world. A number of factors like disease's non-specific symptoms, increased viral mutation, growing antiviral drug resistance due to reduced susceptibility, unavailability of an effective vaccine for dengue, weak immunity against the virus, and many more are involved. Dengue belongs to the Flaviviridae family of viruses. The two species of the vector transmitting dengue are Aedes aegypti and Aedes albopictus, with the former one being dominant. Serotypes 2 of dengue fever are spread to the human body and cause severe illness. Recently, dengue has imposed an aggressive effect synergistically with the COVID-19 pandemic. As a result, we concentrated our efforts on finding a potential therapeutic. For this, we chose natural compounds to fight dengue fever, which is currently regarded as successful among many drug therapies. Following this, we started the in silico experiment with 922 plant extracts as lead compounds to fight serotype 2. In this study, we used SwissADME for analyzing ligand drug-likeness, pkCSM for designing an ADMET profile, Autodock vina 4.2 and Swissdock tools for molecular docking, and finally Desmond for molecular dynamics simulation. Ultimately 45 were found effective against the 2'O methyltransferase protein of serotype 2. CHEMBL376820 was found as possible therapeutic candidates for inhibiting methyltransferase protein in this thorough analysis. Nevertheless, more in vitro and in vivo research are required to substantiate their potential therapeutic efficacy.

9.
ACS Omega ; 7(31): 27216-27229, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35967026

RESUMO

Nanotherapeutics has emerged as the most sought after approach to tackle the menace of drug-resistant pathogenic bacteria. Among others, biogenic silver nanoparticles (bAgNPs) synthesized using medicinal plant extracts demonstrate promising antibacterial propensity with excellent biocompatibility. Herein, bAgNPs were synthesized through the green chemistry approach using Syzygium cymosum leaf extract as a reducing agent at different pH values (i.e., 5, 7, 8, and 10). The average size of bAgNPs synthesized at pH 5, 7, 8, and 10 was 23.3, 21.3, 17.2, and 35.3 nm, respectively, and all the nanoparticles were negatively charged. Their antibacterial potential was investigated against Bacillus subtilis, Escherichia coli DH5α, E. coli K12, enteropathogenic E. coli, and Salmonella typhi. The highest antibacterial activity was exhibited by bAgNPs synthesized at pH 8 against all the tested bacterial strains, which can be attributed to their small size and greater surface area to volume ratio. The bAgNPs demonstrated the highest zone of inhibition (29.5 ± 0.8 mm) against B. subtilis through oxidation of membrane fatty acids that resulted in the formation of the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct. However, bAgNPs demonstrated excellent hemocompatibility with rat and human red blood cells. Biogenic AgNPs synthesized at pH 8 also exhibited biocompatibility in terms of liver and kidney function biomarkers. Furthermore, hematoxylin and eosin staining of the tissue sections of vital organs (i.e., liver, kidneys, lungs, heart, spleen, and brain) also confirmed the biocompatibility of bAgNPs.

10.
Cancers (Basel) ; 14(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35804818

RESUMO

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic drugs are losing their efficacy due to adverse effects, and many patients develop resistance against these drugs. To overcome these limitations, the development of novel potent and reliable theranostic agents is urgently needed to diagnose and combat HMs at an early stage. Recently, gold nanomaterials (GNMs) have shown promise in the diagnosis and treatment of HMs. Magnetic resonance and the surface-plasmon-resonance properties of GNMs have made them a suitable candidate in the diagnosis of HMs via magnetic-resonance imaging and colorimetric or electrochemical sensing of cancer-specific biomarkers. Furthermore, GNMs-based photodynamic therapy, photothermal therapy, radiation therapy, and targeted drug delivery enhanced the selectivity and efficacy of anticancer drugs or drug candidates. Therefore, surface-tuned GNMs could be used as sensitive, reliable, and accurate early HMs, metastatic HMs, and MRD-detection tools, as well as selective, potent anticancer agents. However, GNMs may induce endothelial leakage to exacerbate cancer metastasis. Studies using clinical patient samples, patient-derived HMs models, or healthy-animal models could give a precise idea about their theranostic potential as well as biocompatibility. The present review will investigate the theranostic potential of vectorized GNMs in HMs and future challenges before clinical theranostic applications in HMs.

11.
J Toxicol ; 2022: 8152820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875616

RESUMO

Alternanthera philoxeroides, a tropical herb and edible vegetable, has been popular as a medicinal plant. Applying in vitro approach, we initially attempted to assess the phytochemicals, bioactive chemicals, as well as antioxidant and anticoagulant activities of this plant. Following that, the in vivo toxicological effects of methanolic extracts of A. philoxeroides using different doses on the kidney, heart, lung, liver, stomach, brain, and blood of female Swiss Albino mice were investigated. We estimated phytochemicals content as well as antioxidant activity through DPPH, NO, CUPRAC, and reducing power assays, followed by the anticoagulant activities of PT and aPTT and bioactive compounds using HPLC. To confirm the biocompatibility of A. philoxeroides extracts, histopathological and hematological parameters were examined in a mice model. Total phenol, flavonoid, and tannin content in A. philoxeroides was 181.75 ± 2.47 mg/g, 101.5 ± 3 .53 mg/g, and 68.58 ± 0.80 mg/g, respectively. Furthermore, the HPLC study confirmed the presence of four phenolic compounds: catechin, tannic acid, gallic acid, and vanillic acid. The methanolic extract of A. philoxeroides showed considerable antioxidant activity in all four antioxidant assay methods when compared to the standard. In comparison to ascorbic acid, A. philoxeroides also demonstrated a minor concentration-dependent ferric and cupric reduction activity. In vivo evaluation indicated that A. philoxeroides extracts (doses: 250, 500, and 1000 mg/kg) had no negative effects on the relative organ or body weight, or hematological indicators. Our study concluded that A. philoxeroides had significant antioxidant and anticoagulant activities and demonstrated no negative effects on the body or relative organ weight, histopathological, and hematological indices in the mouse model.

12.
Anticancer Drugs ; 33(1): 6-10, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261912

RESUMO

Anticancer drug discovery programmes use a large number of in-vitro assays to screen the potency of compound libraries. The accuracy and reliability of these in-vitro assays are vital in selecting potent lead candidates for further (pre)clinical studies. Among the commonly used cell viability assays, the sulforhodamine B (SRB) assay has been a popular choice due to its simplicity, accuracy, reliability and reproducibility. SRB dye interacts with protein's basic amino acids and viable cell number is determined based on the cellular protein content. In this study, the cytotoxic potency of the novel hydroxythiopyridone derivatives towards A549 and H522 cells was determined using the SRB assay. The known drugs oxaliplatin and vorinostat were also examined. The resulting EC50 values were accurate, reliable and reproducible. However, all EC50 values calculated in 6-well plates were higher compared to those determined from 96-well plates. Furthermore, results from 6-well plates were also more variable compared to 96-well plates. Our results confirm that SRB assay is a reliable technique in screening the potency of anticancer drug candidates but plating conditions need to be carefully considered.


Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Rodaminas , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Oxaliplatina/farmacologia , Reprodutibilidade dos Testes , Vorinostat/farmacologia
13.
Int J Biomater ; 2021: 4877344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691184

RESUMO

Thermal burns are a major cause of death and suffering around the globe. They can cause debilitating, life-altering injuries as well as lead to significant psychological and financial consequences. Several research works have been conducted in attempt to find a wound healing therapy that is successful. At present, hydrogels have been widely used in cutting-edge research for this purpose because they have suitable properties. This study aimed to see how therapy with chitosan-polyethylene glycol (Ch-Peg) based hydrogels affected the healing of burn wounds in rats. With the concern of public health, xanthan gum (X), boric acid (B), gelatin (Ge), polyethylene glycol (Peg), chitosan (Ch), glutaraldehyde (G), and HPLC-grade water were prepared using X : Ge : G, X : Ge : Peg : G, X : Ge : Ch : G, X : Ge : Peg : Ch : G, X : Ge : B : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch : G. The produced composite hydrogels were examined for swelling ability, biodegradability, rheological characteristics, and porosity. The 3D structure of the hydrogel was revealed by scanning electron microscopy (SEM). After that, the structural characterization technique named Fourier-transform infrared spectroscopy (FTIR) was used to describe the composites (SEM). Lastly, in a rat skin wound model, the efficacy of the produced hydrogels was studied. Swelling ability, biodegradability, rheological properties, and porosity were all demonstrated in composite hydrogels that contained over 90% water. Hydrogels with good polymeric networks and porosity were observed using SEM. The existence of bound water and free, intra- and intermolecule hydrogen-linked OH and NH in the hydrogels was confirmed using FTIR. In a secondary burned rat model, all hydrogels showed significant wound healing effectiveness when compared to controls. When compared to other composite hydrogels, wounds treated with X : Ge : Peg : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch:G recovered faster after 28 days. In conclusion, this research suggests that X : Ge : Peg : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch : G could be used to treat skin injuries in the clinic.

14.
Pharmaceutics ; 13(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34452256

RESUMO

Colorectal cancer (CRC) is one of the intimidating causes of death around the world. CRC originated from mutations of tumor suppressor genes, proto-oncogenes and DNA repair genes. Though platinum (Pt)-based anticancer drugs have been widely used in the treatment of cancer, their toxicity and CRC cells' resistance to Pt drugs has piqued interest in the search for alternative metal-based drugs. Ruthenium (Ru)-based compounds displayed promising anticancer activity due to their unique chemical properties. Ru-complexes are reported to exert their anticancer activities in CRC cells by regulating different cell signaling pathways that are either directly or indirectly associated with cell growth, division, proliferation, and migration. Additionally, some Ru-based drug candidates showed higher potency compared to commercially available Pt-based anticancer drugs in CRC cell line models. Meanwhile Ru nanoparticles coupled with photosensitizers or anticancer agents have also shown theranostic potential towards CRC. Ru-nanoformulations improve drug efficacy, targeted drug delivery, immune activation, and biocompatibility, and therefore may be capable of overcoming some of the existing chemotherapeutic limitations. Among the potential Ru-based compounds, only Ru (III)-based drug NKP-1339 has undergone phase-Ib clinical trials in CRC treatment.

15.
Infect Genet Evol ; 93: 104951, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34089909

RESUMO

The devastating outbreak of COVID-19 has spread all over the world and has become a global health concern. There is no specific therapeutics to encounter the COVID-19. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control human viral infections employing post-transcriptional gene silencing (PTGS) through neutralizing target complementary mRNA. RNA-dependent RNA polymerase (RdRp) encoded by the viral RdRp gene as a part of the replication-transcription complex can be adopted as an acceptable target for controlling SARS-CoV-2 mediated infection. Therefore, in the current study, accessible siRNA designing tools, including significant algorithms and parameters, were rationally used to design the candidate siRNAs against SARS-COV-2 encoded RdRp. The designed siRNA molecules possessed adequate nucleotide-based and other features for potent gene silencing. The targets of the designed siRNAs revealed no significant matches within the whole human genome, ruling out any possibilities for off-target silencing by the siRNAs. Characterization with different potential parameters of efficacy allowed selecting the finest siRNA among all the designed siRNA molecules. Further, validation assessment and target site accessibility prediction also rationalized the suitability of this siRNA molecule. Molecular docking study between the selected siRNA molecule and component of RNA interference (RNAi) pathway gave an excellent outcome. Molecular dynamics of two complexes: siRNA and argonaute complex, guide RNA, and target protein complex, have shown structural stability of these proteins. Therefore, the designed siRNA molecule might act as an effective therapeutic agent against the SARS-CoV-2 at the genome level and can prevent further outbreaks of COVID-19 in humans.


Assuntos
RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA Interferente Pequeno/genética , SARS-CoV-2/genética , Proteínas Argonautas/química , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Composição de Bases , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Inativação Gênica , Genoma Humano , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/química , Alinhamento de Sequência
16.
Curr Med Chem ; 28(39): 8098-8115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33645474

RESUMO

Approximately 85% of all lungs cancer cases are classified as non-small cell lung cancer (NSCLC). Kirsten rat sarcoma (KRAS) viral oncogene homolog mutations frequently occur in NSCLC patients resulting in a decreased overall survival. Additionally, currently used chemotherapeutic drugs lack selectivity,and patients experience side effects. Therefore, potent therapeutic agents are urgently needed for these patients. Plant- based compounds could be a potential option to treat KRAS-mutated NSCLC. These compounds are reported to be effective against the KRAS-linked up-stream and downstream signaling pathways that are directly or indirectly linked with cell proliferation, division, and apoptosis. Additionally, plant phytochemicals also suppressed different cell cycle phases of KRAS-mutant NSCLC cells. Furthermore, phytochemicals have a wider therapeutic index compared to chemotherapeutic drugs. Therefore, phytochemicals could benefit NSCLC patients as sole agents or as a combination therapy with approved chemotherapies. The current review aims to summarize the potential benefit of natural compounds in KRAS-mutant NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais
17.
Biomedicines ; 9(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513800

RESUMO

Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a-1c and 3-hydroxy-4-thiopyridones 1d-1f as well as their Ru(η6-p-cymene)Cl complexes 2a-2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d-1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low µM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.

18.
Curr Drug Metab ; 21(8): 579-598, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520684

RESUMO

BACKGROUND: Breast cancer is a heterogeneous disease typically prevalent among women and is the second-largest cause of death worldwide. Early diagnosis is the key to minimize the cancer-induced complication, however, the conventional diagnostic strategies have been sluggish, complex, and, to some extent, non-specific. Therapeutic tools are not so convenient and side effects of current therapies offer the development of novel theranostic tool to combat this deadly disease. OBJECTIVE: This article aims to summarize the advances in the diagnosis and treatment of breast cancer with gold nanoparticles (GNP or AuNP). METHODS: A systematic search was conducted in the three popular electronic online databases including PubMed, Google Scholar, and Web of Science, regarding GNP as breast cancer theranostics. RESULTS: Published literature demonstrated that GNPs tuned with photosensitive moieties, nanomaterials, drugs, peptides, nucleotide, peptides, antibodies, aptamer, and other biomolecules improve the conventional diagnostic and therapeutic strategies of breast cancer management with minimum cytotoxic effect. GNP derived diagnosis system assures reproducibility, reliability, and accuracy cost-effectively. Additionally, surface-modified GNP displayed theranostic potential even in the metastatic stage of breast cancer. CONCLUSION: Divergent strategies have shown the theranostic potential of surface tuned GNPs against breast cancer even in the metastatic stage with minimum cytotoxic effects both in vitro and in vivo.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Nanopartículas Metálicas , Animais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Desenvolvimento de Medicamentos , Feminino , Ouro , Humanos , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Nanomedicina Teranóstica
19.
ACS Appl Bio Mater ; 3(11): 7722-7733, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-35019512

RESUMO

Among metallic nanoparticles, silver nanoparticles (AgNPs) have a wide spectrum of medical applications. Herein, biogenic silver nanoparticles (bAgNPs) were prepared from extracts of Caesalpinia digyna leaf as a reducing agent at different pH values (i.e., 5, 7, 8, and 10). The as-synthesized bAgNPs were characterized using UV-vis and Fourier transform infrared (FTIR) spectroscopies, scanning transmission electron microscopy, powder X-ray diffraction analysis, dynamic light scattering, and ζ-potential analysis. The sizes of bAgNPs prepared at pH 5, 7, 8, and 10 were 45.4, 11.3, 11.4, and 40.8 nm, respectively, and all of the nanoparticles were negatively charged. The antimicrobial activity of the as-prepared bAgNPs was investigated against Bacillus subtilis, Escherichia coli DH5α, E. coli K12, enteropathogenic E. coli (EPEC), and Salmonella typhi. The bAgNPs prepared at pH 8 showed the highest antibacterial propensity against all of the bacterial strains as exhibited in the zone of inhibition (ZOI) as well as the CellTox green assay, which can be due to their relatively small size, stability, and higher surface area-to-volume ratio. The bAgNPs synthesized at pH 8 showed the highest ZOI against B. subtilis, which was ∼25 mm in diameter. The lipid peroxidation assay demonstrated the formation of the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct while treating the bacteria with bAgNPs due to the oxidation of fatty acids present in the membrane. The highest amount of MDA-TBA adduct was observed when Gram-positive B. subtilis was exposed to bAgNPs. On the contrary, rats treated with bAgNPs demonstrated no significant toxicity in terms of hematological and biochemical parameters. The bAgNPs also showed excellent compatibility with human red blood cells. Overall, bAgNPs synthesized at pH 8 have superior antimicrobial activity and excellent biocompatibility and, therefore, can be used as potential antibacterial agents.

20.
ACS Appl Bio Mater ; 3(11): 7952-7964, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-35019535

RESUMO

Cobalt ferrite nanoparticle (CFN) has received attention in magnetic resonance imaging (MRI) as a promising contrast agent due to its higher saturation magnetization and magneto-crystalline anisotropy. However, the in vitro cytotoxicity of CFN has raised concern for its biomedical application as a diagnostic agent. The coating of CFN by a biocompatible polymer such as chitosan (CH) might lessen the biocompatibility concern. Therefore, in this study, we examined the applicability of chitosan-coated cobalt ferrite nanoparticle (CCN) as an MRI contrast dye and investigated its biocompatibility in vivo. Phantom MRI images revealed that the relaxivity of CCN was 121 (±8) mM-1s-1, indicating the potential of CCN as a T2-weighted contrast agent. A single intravenous (iv) administration of CCN (10 mg/kg) improved the contrast of magnetic-resonance-imaging-based angiography (MRA) and brain-MRI in male albino Wistar rats compared to the control. Furthermore, toxicity studies dependent on dose (1-20 mg/kg) and time (1-28 days) in male albino Wistar rats confirmed the in vivo biocompatibility of CCN. The physical, hematological, biochemical, and histopathological observation assured that a single iv injection of CCN up to 20 mg/kg was well adjusted with liver, kidney, heart, and brain functions. The findings of the current study consolidate CCN as a promising candidate for MRI contrast dye.

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