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1.
BMC Cancer ; 24(1): 396, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553708

RESUMO

BACKGROUND: Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. PATIENTS AND METHODS: Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy's effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. RESULTS: A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295-4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV-H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). CONCLUSIONS: The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. TRIAL REGISTRATION: Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/genética , Terapia Neoadjuvante , China , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Imunoterapia , Imunoglobulinas
2.
Endoscopy ; 56(8): 605-611, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38519045

RESUMO

BACKGROUND: Closure of gastrointestinal defects can reduce postprocedural adverse events. Over-the-scope clips and an over-the-scope suturing system are widely available, yet their use may be limited by defect size, location, operator skill level, and need to reinsert the endoscope with the device attached. The introduction of a through-the-scope helix tack suture system (TTSS) allows for closure of large irregular defects using a gastroscope or colonoscope, without the need for endoscope withdrawal. Since its approval 3 years ago, only a handful of studies have explored outcomes using this novel device. METHODS: Multiple databases were searched for studies looking at TTSS closure from inception until August 2023. The primary outcomes were the success of TTSS alone and TTSS with clips for complete defect closure. Secondary outcomes included complete closure based on procedure type (endoscopic mucosal resection [EMR], endoscopic submucosal dissection [ESD]) and adverse events. RESULTS: Eight studies met the inclusion criteria (449 patients, mean defect size 34.3 mm). Complete defect closure rates for TTSS alone and TTSS with adjunctive clips were 77.2% (95%CI 66.4-85.3; I2=79%) and 95.2% (95%CI 90.3-97.7; I2=42.5%), respectively. Complete defect closure rates for EMR and ESD were 99.2% (95%CI 94.3-99.9; I2 = 0%) and 92.1% (95%CI 85-96; I2=0%), respectively. The adverse event rate was 5.4% (95%CI 2.7-10.3; I2=55%). CONCLUSION: TTSS is a novel device for closure of postprocedural defects, with relatively high technical and clinical success rates. Comparative studies of closure devices are needed.


Assuntos
Técnicas de Sutura , Humanos , Técnicas de Sutura/instrumentação , Técnicas de Sutura/efeitos adversos , Ressecção Endoscópica de Mucosa/instrumentação , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Suturas/efeitos adversos , Endoscopia Gastrointestinal/instrumentação , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , Resultado do Tratamento
3.
Mol Biol Rep ; 51(1): 702, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822942

RESUMO

BACKGROUND: The development of cost-effective, simple, environment-friendly biographene is an area of interest. To accomplish environmentally safe, benign culturing that has advantages over other methods to reduce the graphene oxide (GO), extracellular metabolites from actinobacteria associated with mushrooms were used for the first time. METHODS: Bactericidal effect of GO against methicillin-resistant Staphylococcus aureus, antioxidant activity, and hydroxyapatite-like bone layer formation, gene expression analysis and appropriate biodegradation of the microbe-mediated synthesis of graphene was studied. RESULTS: Isolated extracellular contents Streptomyces achromogenes sub sp rubradiris reduced nano-GO to graphene (rGO), which was further examined by spectrometry and suggested an efficient conversion and significant reduction in the intensity of all oxygen-containing moieties and shifted crystalline peaks. Electron microscopic results also suggested the reduction of GO layer. In addition, absence of significant toxicity in MG-63 cell line, intentional free radical scavenging prowess, liver and kidney histopathology, and Wistar rat bone regeneration through modulation of OPG/RANKL/RUNX2/ALP pathways show the feasibility of the prepared nano GO. CONCLUSIONS: The study demonstrates the successful synthesis of biographene from actinobacterial extracellular metabolites, its potential biomedical applications, and its promising role in addressing health and environmental concerns.


Assuntos
Regeneração Óssea , Grafite , Osteoprotegerina , Ligante RANK , Ratos Wistar , Grafite/farmacologia , Animais , Regeneração Óssea/efeitos dos fármacos , Ratos , Ligante RANK/metabolismo , Osteoprotegerina/metabolismo , Humanos , Materiais Biocompatíveis/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Actinobacteria/metabolismo , Antibacterianos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Transdução de Sinais/efeitos dos fármacos
4.
Mol Biol Rep ; 51(1): 990, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287730

RESUMO

BACKGROUND: Oxidative stress, a condition characterized by excessive production of reactive oxygen species (ROS), can cause significant damage to cellular macromolecules, leading to neurodegeneration. This underscores the need for effective antioxidant therapies that can mitigate oxidative stress and its associated neurodegenerative effects. KC14 peptide derived from liver-expressed antimicrobial peptide-2 A (LEAP 2 A) from Cyprinus carpio L. has been identified as a potential therapeutic agent. This study focuses on the antioxidant and neuroprotective properties of the KC14 peptide is to evaluate its effectiveness against oxidative stress and neurodegeneration. METHODS: The antioxidant capabilities of KC14 were initially assessed through in silico docking studies, which predicted its potential to interact with oxidative stress-related targets. Subsequently, the peptide was tested at concentrations ranging from 5 to 45 µM in both in vitro and in vivo experiments. In vivo studies involved treating H2O2-induced zebrafish larvae with KC14 peptide to analyze its effects on oxidative stress and neuroprotection. RESULTS: KC14 peptide showed a protective effect against the developmental malformations caused by H2O2 stress, restored antioxidant enzyme activity, reduced neuronal damage, and lowered lipid peroxidation and nitric oxide levels in H2O2-induced larvae. It enhanced acetylcholinesterase activity and significantly reduced intracellular ROS levels (p < 0.05) dose-dependently. Gene expression studies showed up-regulation of antioxidant genes with KC14 treatment under H2O2 stress. CONCLUSIONS: This study highlights the potent antioxidant activity of KC14 and its ability to confer neuroprotection against oxidative stress can provide a novel therapeutic agent for combating neurodegenerative diseases induced by oxidative stress.


Assuntos
Antioxidantes , Carpas , Peróxido de Hidrogênio , Fármacos Neuroprotetores , Estresse Oxidativo , Espécies Reativas de Oxigênio , Peixe-Zebra , Animais , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Carpas/metabolismo , Fármacos Neuroprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Proteínas de Peixes/farmacologia , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos/farmacologia , Óxido Nítrico/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo
5.
Mol Biol Rep ; 51(1): 89, 2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38184807

RESUMO

BACKGROUND: Kappaphycus alvarezii, a marine red algae species, has gained significant attention in recent years due to its versatile bioactive compounds. Among these, κ-carrageenan (CR), a sulfated polysaccharide, exhibits remarkable antimicrobial properties. This study emphasizes the synergism attained by functionalizing zinc oxide nanoparticles (ZnO NPs) with CR, thereby enhancing its antimicrobial efficacy and target specificity against dental pathogens. METHODS: In this study, we synthesized ZnO-CR NPs and characterized them using SEM, FTIR, and XRD techniques to authenticate their composition and structural attributes. Moreover, our investigation revealed that ZnO-CR NPs possess better free radical scavenging capabilities, as evidenced by their effective activity in the DPPH and ABTS assay. RESULTS: The antimicrobial properties of ZnO-CR NPs were systematically assessed using a zone of inhibition assay against dental pathogens of S. aureus, S. mutans, E. faecalis, and C. albicans, demonstrating their substantial inhibitory effects at a minimal concentration of 50 µg/mL. We elucidated the interaction between CR and the receptors of dental pathogens to further understand their mechanism of action. The ZnO-CR NPs demonstrated a dose-dependent anticancer effect at concentrations of 5 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL on KB cells, a type of Human Oral Epidermal Carcinoma. The mechanism by which ZnO-CA NPs induced apoptosis in KB cells was determined by observing an increase in the expression of the BCL-2, BAX, and P53 genes. CONCLUSION: Our findings unveil the promising potential of ZnO-CR NPs as a candidate with significant utility in dental applications. The demonstrated biocompatibility, potent antioxidant and antiapoptotic activity, along with impressive antimicrobial efficacy position these NPs as a valuable resource in the ongoing fight against dental pathogens and oral cancer.


Assuntos
Anti-Infecciosos , Neoplasias Bucais , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Carragenina/farmacologia , Staphylococcus aureus , Neoplasias Bucais/tratamento farmacológico , Apoptose , Candida albicans
6.
Mol Biol Rep ; 51(1): 352, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400866

RESUMO

BACKGROUND: Oral diseases are often attributed to dental pathogens such as S. aureus, S. mutans, E. faecalis, and C. albicans. In this research work, a novel approach was employed to combat these pathogens by preparing zinc oxide nanoparticles (ZnO NPs) capped with cinnamic acid (CA) plant compounds. METHODS: The synthesized ZnO-CA NPs were characterized using SEM, FTIR, and XRD to validate their composition and structural features. The antioxidant activity of ZnO-CA NPs was confirmed using DPPH and ABTS free radical scavenging assays. The antimicrobial effects of ZnO-CA NPs were validated using a zone of inhibition assay against dental pathogens. Autodock tool was used to identify the interaction of cinnamic acid with dental pathogen receptors. RESULTS: ZnO-CA NPs exhibited potent antioxidant activity in both DPPH and ABTS assays, suggesting their potential as powerful antioxidants. The minimal inhibitory concentration of ZnO-CA NPs against dental pathogens was found 25 µg/mL, indicating their effective antimicrobial properties. Further, ZnO-CA NPs showed better binding affinity and amino acid interaction with dental pathogen receptors. Also, the ZnO-CA NPs exhibited dose-dependent (5 µg/mL, 15 µg/mL, 25 µg/mL, and 50 µg/mL) anticancer activity against Human Oral Epidermal Carcinoma KB cells. The mechanism of action of apoptotic activity of ZnO-CA NPs on the KB cells was identified through the upregulation of BCL-2, BAX, and P53 genes. CONCLUSIONS: This research establishes the potential utility of ZnO-CA NPs as a promising candidate for dental applications. The potent antioxidant, anticancer, and effective antimicrobial properties of ZnO-CA NPs make them a valuable option for combating dental pathogens.


Assuntos
Anti-Infecciosos , Benzotiazóis , Carcinoma , Cinamatos , Nanopartículas Metálicas , Ácidos Sulfônicos , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas Metálicas/química , Antioxidantes/farmacologia , Staphylococcus aureus , Células KB , Anti-Infecciosos/farmacologia
7.
Mol Biol Rep ; 51(1): 730, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864973

RESUMO

BACKGROUND: Antimicrobial resistance has surged due to widespread antimicrobial drug use, prompting interest in biosynthesizing nanoparticles from marine-derived actinomycetes extracellular metabolites, valued for their diverse bioactive compounds. This approach holds promise for addressing the urgent need for novel antimicrobial agents. The current study aimed to characterize novel bioactive compounds from unexplored biodiversity hotspots, halophilic Streptomyces sp. isolated from mangrove sediment in the Pichavaram region, India. METHODS AND RESULTS: Streptomyces rochei SSCM102 was conclusively identified through morphological and molecular characterization. Synthesis of silver nanoparticles (AgNPs) from Streptomyces rochei SSCM102 was characterized using various techniques, including UV-Vis, XRD, SEM, EDX, and FT-IR. The UV-Vis spectrum of the reduced AgNPs exhibited a prominent peak at 380 nm, confirming the AgNPs. The UV-Vis spectrum confirmed the synthesis of AgNP, and SEM analysis revealed a cubic morphology with sizes ranging from 11 to 21 nm. The FTIR spectrum demonstrated a shift in frequency widths between 626 cm-1 and 3432 cm-1. The EDX analysis substantiated the presence of metallic silver, evident from a strong band at 1.44 keV. The synthesized AgNPs exhibited antibacterial efficacy against human pathogens Escherichia coli (64 ± 0.32 µg/ml), Klebsiella pneumoniae (32 ± 0.16 µg/ml), and Pseudomonas aeruginosa (16 ± 0.08 µg/ml) by MIC and MBC values of 128 ± 0.64 (µg/ml), 64 ± 0.32 (µg/ml) and 32 ± 0.16 (µg/ml), respectively. Additionally, at a concentration of 400 µg/ml, the AgNPs displayed a 72% inhibition of DPPH radicals, indicating notable antioxidant capacity. The LC50 value of 130 µg/mL indicates that the green-synthesized AgNPs have lower toxicity by Brine Shrimp Larvae assay. CONCLUSION: The study's novel approach to synthesizing eco-friendly silver nanoparticles using Halophilic Streptomyces rochei SSCM102 contributes significantly to the field of biomedical research and drug development. By demonstrating potent antibacterial properties and aligning with sustainability goals, these nanoparticles offer promising avenues for novel antibacterial therapies.


Assuntos
Antibacterianos , Sedimentos Geológicos , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Prata , Streptomyces , Streptomyces/metabolismo , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Sedimentos Geológicos/microbiologia , Química Verde/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Índia , Bactérias/efeitos dos fármacos
8.
Antonie Van Leeuwenhoek ; 117(1): 95, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967683

RESUMO

The decline of new antibiotics and the emergence of multidrug resistance in pathogens necessitates a revisit of strategies used for lead compound discovery. This study proposes to induce the production of bioactive compounds with sub-lethal concentrations of silver nanoparticles (Ag-NPs). A total of Forty-two Actinobacteria isolates from four Saudi soil samples were grown with and without sub-lethal concentration of Ag-NPs (50 µg ml-1). The spent broth grown with Ag-NPs, or without Ag-NPs were screened for antimicrobial activity against four bacteria. Interestingly, out of 42 strains, broths of three strains grown with sub-lethal concentration of Ag-NPs exhibit antimicrobial activity against Staphylococcus aureus and Micrococcus luteus. Among these, two strains S4-4 and S4-21 identified as Streptomyces labedae and Streptomyces tirandamycinicus based on 16S rRNA gene sequence were selected for detailed study. The change in the secondary metabolites profile in the presence of Ag-NPs was evaluated using GC-MS and LC-MS analyses. Butanol extracts of spent broth grown with Ag-NPs exhibit strong antimicrobial activity against M. luteus and S. aureus. While the extracts of the controls with the same concentration of Ag-NPs do not show any activity. GC-analysis revealed a clear change in the secondary metabolite profile when grown with Ag-NPs. Similarly, the LC-MS patterns also differ significantly. Results of this study, strongly suggest that sub-lethal concentrations of Ag-NPs influence the production of secondary metabolites by Streptomyces. Besides, LC-MS results identified possible secondary metabolites, associated with oxidative stress and antimicrobial activities. This strategy can be used to possibly induce cryptic biosynthetic gene clusters for the discovery of new lead compounds.


Assuntos
Antibacterianos , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S , Prata , Staphylococcus aureus , Streptomyces , Streptomyces/metabolismo , Streptomyces/genética , Prata/farmacologia , Prata/química , Prata/metabolismo , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , RNA Ribossômico 16S/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Microbiologia do Solo , Metabolismo Secundário , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/crescimento & desenvolvimento , Descoberta de Drogas
9.
Int J Med Sci ; 21(2): 253-264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169567

RESUMO

Periodontal regeneration refers to procedures aimed at restitution of lost supporting tissue around the periodontally compromised tooth. Regenerative procedures very often include the use of barrier materials to encourage the growth of key surrounding tissues. The current study aimed to evaluate the effectiveness of autogenous periosteal graft as a barrier membrane for the treatment of intrabony defects in chronic periodontitis patients. A total of four data bases MEDLINE (by PubMed), Cochrane database, EBSCO, and Google Scholar were explored to identify the studies in English up to December 2022. An additional hand search of relevant journals was also done. A team of three independent reviewers screened the retrieved articles using the inclusion criteria. Randomized control trials (RCTs) evaluating the effectiveness of autogenous periosteal grafts in the treatment of intrabony defects in chronic periodontitis cases were included in the study. A total of six relevant articles were recognized for data procurement. A total of 117 patients with 68 sites with an age range between 18 years and 55 years were selected. Outcome variables examined were pocket depth (PD), clinical attachment level (CAL), radiographic bone defect fill (BDF), gingival recession (GR), plaque index (PI), gingival index (GI) and bleeding on probing (BOP). Data were analyzed using Revman 5.3 software. The mean differences and 95% confidence interval were used to illustrate the estimate of effect size. There is an equal effect in both groups for the PI, GI, and BOP reduction. For PD reduction, the result was in the favor of periosteal graft with open flap debridement (OFD) group. For CAL gain, radiographic BDF and GR, results also favored the periosteal graft, but no statistically significant difference was found amongst the groups. Within the limitation of the study, it seems that the autogenous periosteal graft can be used successfully along with OFD to treat intrabony defects in chronic periodontitis patients.


Assuntos
Perda do Osso Alveolar , Periodontite Crônica , Retração Gengival , Adolescente , Humanos , Perda do Osso Alveolar/cirurgia , Periodontite Crônica/cirurgia , Retração Gengival/cirurgia , Resultado do Tratamento , Adulto Jovem , Adulto , Pessoa de Meia-Idade
10.
BMC Oral Health ; 24(1): 715, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907185

RESUMO

BACKGROUND: Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations. METHODS: We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells. RESULTS: ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53. CONCLUSIONS: This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice.


Assuntos
Alcaloides , Apoptose , Benzodioxóis , Biofilmes , Neoplasias Bucais , Piperidinas , Alcamidas Poli-Insaturadas , Óxido de Zinco , Proteína X Associada a bcl-2 , Humanos , Alcaloides/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/efeitos dos fármacos , Benzodioxóis/farmacologia , Biofilmes/efeitos dos fármacos , Linhagem Celular Tumoral , Células KB , Nanopartículas Metálicas/uso terapêutico , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Nanopartículas , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/efeitos dos fármacos , Difração de Raios X , Óxido de Zinco/farmacologia
11.
Int J Mol Sci ; 24(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37445822

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor outcomes when diagnosed at an advanced stage. Current curative treatments are most effective in early-stage HCC, highlighting the importance of early diagnosis and intervention. However, existing diagnostic methods, such as radiological imaging, alpha-fetoprotein (AFP) testing, and biopsy, have limitations that hinder early diagnosis. AFP elevation is absent in a significant portion of tumors, and imaging may have low sensitivity for smaller tumors or in the presence of cirrhosis. Additionally, as our understanding of the molecular pathogenesis of HCC grows, there is an increasing need for molecular information about the tumors. Biopsy, although informative, is invasive and may not always be feasible depending on tumor location. In this context, liquid biopsy technology has emerged as a promising approach for early diagnosis, enabling molecular characterization and genetic profiling of tumors. This technique involves analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived exosomes. CTCs are cancer cells shed from the primary tumor or metastatic sites and circulate in the bloodstream. Their presence not only allows for early detection but also provides insights into tumor metastasis and recurrence. By detecting CTCs in peripheral blood, real-time tumor-related information at the DNA, RNA, and protein levels can be obtained. This article provides an overview of CTCs and explores their clinical significance for early detection, prognosis, treatment selection, and monitoring treatment response in HCC, citing relevant literature.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , alfa-Fetoproteínas , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/metabolismo , Biópsia Líquida/métodos
12.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37373394

RESUMO

Despite colorectal cancer remaining a leading worldwide cause of cancer-related death, there remains a paucity of effective treatments for advanced disease. The molecular mechanisms underlying the development of colorectal cancer include altered cell signaling and cell cycle regulation that may result from epigenetic modifications of gene expression and function. Acting as important transcriptional regulators of normal biological processes, zinc finger proteins also play key roles in regulating the cellular mechanisms underlying colorectal neoplasia. These actions impact cell differentiation and proliferation, epithelial-mesenchymal transition, apoptosis, homeostasis, senescence, and maintenance of stemness. With the goal of highlighting promising points of therapeutic intervention, we review the oncogenic and tumor suppressor roles of zinc finger proteins with respect to colorectal cancer tumorigenesis and progression.


Assuntos
Transformação Celular Neoplásica , Neoplasias Colorretais , Humanos , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Carcinogênese/genética , Neoplasias Colorretais/patologia , Dedos de Zinco , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
13.
Int J Mol Sci ; 24(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36768686

RESUMO

The emerging field of immuno-oncology has brought exciting developments in the treatment of hepatocellular carcinoma (HCC). It has also raised urgent questions about the role of immunotherapy in the setting of liver transplantation, both before and after transplant. A growing body of evidence points to the safety and efficacy of immunotherapeutic agents as potential adjuncts for successful down-staging of advanced HCCs to allow successful transplant in carefully selected patients. For patients with recurrent HCC post-transplant, immunotherapy has a limited, yet growing role. In this review, we describe optimal regimens in the setting of liver transplantation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Imunoterapia
14.
Int J Mol Sci ; 24(11)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37298090

RESUMO

Recent studies in nanomedicine have intensively explored the prospective applications of surface-tailored graphene oxide (GO) as anticancer entity. However, the efficacy of nonfunctionalized graphene oxide nanolayers (GRO-NLs) as an anticancer agent is less explored. In this study, we report the synthesis of GRO-NLs and their in vitro anticancer potential in breast (MCF-7), colon (HT-29), and cervical (HeLa) cancer cells. GRO-NLs-treated HT-29, HeLa, and MCF-7 cells showed cytotoxicity in the MTT and NRU assays via defects in mitochondrial functions and lysosomal activity. HT-29, HeLa, and MCF-7 cells treated with GRO-NLs exhibited substantial elevations in ROS, disturbances of the mitochondrial membrane potential, an influx of Ca2+, and apoptosis. The qPCR quantification showed the upregulation of caspase 3, caspase 9, bax, and SOD1 genes in GRO-NLs-treated cells. Western blotting showed the depletion of P21, P53, and CDC25C proteins in the above cancer cell lines after GRO-NLs treatment, indicating its function as a mutagen to induce mutation in the P53 gene, thereby affecting P53 protein and downstream effectors P21 and CDC25C. In addition, there may be a mechanism other than P53 mutation that controls P53 dysfunction. We conclude that nonfunctionalized GRO-NLs exhibit prospective biomedical application as a putative anticancer entity against colon, cervical, and breast cancers.


Assuntos
Neoplasias da Mama , Proteína Supressora de Tumor p53 , Humanos , Feminino , Linhagem Celular Tumoral , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Nanomedicina , Apoptose , Células MCF-7 , Colo/metabolismo
15.
Molecules ; 28(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38138469

RESUMO

This work reports the influence of antimony substitution in a cerium molybdate lattice for improved dielectric and photocatalytic properties. For this purpose, a series of Ce2-xSbx(MoO4)3 (x = 0.00, 0.01, 0.03, 0.05, 0.07, and 0.09) were synthesized through a co-precipitation route. The as-synthesized materials were characterized for their optical properties, functional groups, chemical oxidation states, structural phases, surface properties, and dielectric characteristics using UV-Vis spectroscopy (UV-Vis), Fourier transform infrared (FTIR) and Raman spectroscopies, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis, and impedance spectroscopy, respectively. UV-Vis study showed a prominent red shift of absorption maxima and a continuous decrease in band gap (3.35 eV to 2.79 eV) by increasing the dopant concentration. The presence of Ce-O and Mo-O-Mo bonds, detected via FTIR and Raman spectroscopies, are confirmed, indicating the successful synthesis of the desired material. The monoclinic phase was dominant in all materials, and the crystallite size was decreased from 40.29 nm to 29.09 nm by increasing the Sb content. A significant increase in the dielectric constant (ε' = 2.856 × 108, 20 Hz) and a decrease in the loss tan (tanδ = 1.647, 20 Hz) were exhibited as functions of the increasing Sb concentration. Furthermore, the photocatalytic efficiency of pristine cerium molybdate was also increased by 1.24 times against diclofenac potassium by incorporating Sb (x = 0.09) in the cerium molybdate. The photocatalytic efficiency of 85.8% was achieved within 180 min of UV light exposure at optimized conditions. The photocatalytic reaction followed pseudo-first-order kinetics with an apparent rate constant of 0.0105 min-1, and the photocatalyst was recyclable with good photocatalytic activity even after five successive runs. Overall, the as-synthesized Sb-doped cerium molybdate material has proven to be a promising candidate for charge storage devices and a sustainable photocatalyst for wastewater treatment.

16.
J Am Chem Soc ; 144(33): 15175-15184, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35959925

RESUMO

Surface and bulk molecular modulators are the key to improving the efficiency and stability of hybrid perovskite solar cells. However, due to their low concentration, heterogeneous environments, and low sample mass, it remains challenging to characterize their structure and dynamics at the atomic level, as required to establish structure-activity relationships. Nuclear magnetic resonance (NMR) spectroscopy has revealed a wealth of information on the atomic-level structure of hybrid perovskites, but the inherent insensitivity of NMR severely limits its utility to characterize thin-film samples. Dynamic nuclear polarization (DNP) can enhance NMR sensitivity by orders of magnitude, but DNP methods for perovskite materials have so far been limited. Here, we determined the factors that limit the efficiency of DNP NMR for perovskite samples by systematically studying layered hybrid perovskite analogues. We find that the fast-relaxing dynamic cation is the major impediment to higher DNP efficiency, while microwave absorption and particle morphology play a secondary role. We then show that the former can be mitigated by deuteration, enabling 1H DNP enhancement factors of up to 100, which can be harnessed to enhance signals from dopants or additives present in very low concentrations. Specifically, using this new DNP methodology at a high magnetic field and with small sample volumes, we have recorded the NMR spectrum of the 20 nm (6 µg) passivating layer on a single perovskite thin film, revealing a two-dimensional (2D) layered perovskite structure at the surface that resembles the n = 1 homologue but which has greater disorder than in bulk layered perovskites.

17.
Chem Rec ; 22(7): e202100274, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35103379

RESUMO

Graphene-based nanocomposites with inorganic (metal and metal oxide) nanoparticles leads to materials with high catalytic activity for a variety of chemical transformations. Graphene and its derivatives such as graphene oxide, highly reduced graphene oxide, or nitrogen-doped graphene are excellent support materials due to their high surface area, their extended π-system, and variable functionalities for effective chemical interactions to fabricate nanocomposites. The ability to fine-tune the surface composition for desired functionalities enhances the versatility of graphene-based nanocomposites in catalysis. This review summarizes the preparation of graphene/inorganic NPs based nanocomposites and their use in catalytic applications. We discuss the large-scale synthesis of graphene-based nanomaterials. We have also highlighted the interfacial electronic communication between graphene/inorganic nanoparticles and other factors resulting in increased catalytic efficiencies.

18.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36499412

RESUMO

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.


Assuntos
Nanocompostos , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Nanocompostos/uso terapêutico , Imageamento por Ressonância Magnética , Óxidos de Nitrogênio , Nitrogênio
19.
Molecules ; 27(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36432023

RESUMO

Cross contamination of ß-lactams is one of the highest risks for patients using pharmaceutical products. Penicillin and some non-penicillin ß-lactams may cause potentially life-threatening allergic reactions. The trace detection of ß-lactam antibiotics in cleaning rinse solutions of common reactors and manufacturing aids in pharmaceutical facilities is very crucial. Therefore, the common facilities adopt sophisticated cleaning procedures and develop analytical methods to assess traces of these compounds in rinsed solutions. For this, a highly sensitive and reproducible ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the analysis of Cephapirin and Ceftiofur. As per the FDA guidelines described in FDA-2011-D-0104, the contamination of these ß-lactam antibiotics must be regulated. The analysis was performed on an XBridge C18 column with 100 mm length, 4.6 mm diameter, and 3.5 µm particle size at an oven temperature of about 40 °C. The mobile phase was composed of 0.15% formic acid in water and acetonitrile as mobile phases A and B, and a flow rate was set to 0.6 mL/min. The method was validated for Cephapirin and Ceftiofur. The quantification precision and accuracy were determined to be the lowest limit of detection 0.15 parts per billion (ppb) and the lowest limit of quantification 0.4 ppb. This method was linear in the range of 0.4 to 1.5 ppb with the determination of coefficient (R2 > 0.99). This sensitive and fast method was fit-for-purpose for detecting and quantifying trace amounts of ß-lactam contamination, monitoring cross contamination in facility surface cleaning, and determining the acceptable level of limits for regulatory purposes.


Assuntos
Cefapirina , Humanos , Espectrometria de Massas em Tandem/métodos , Antibacterianos/análise , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , beta-Lactamas , Monobactamas , Penicilinas
20.
Molecules ; 28(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36615440

RESUMO

Green syntheses of metallic nanoparticles using plant extracts as effective sources of reductants and stabilizers have attracted decent popularity due to their non-toxicity, environmental friendliness and rapid nature. The current study demonstrates the ecofriendly, facile and inexpensive synthesis of silver nanoparticles (AP-AgNPs) using the extract of aerial parts of the Anthemis pseudocotula Boiss. plant (AP). Herein, the aerial parts extract of AP performed a twin role of a reducing as well as a stabilizing agent. The green synthesized AP-AgNPs were characterized by several techniques such as XRD, UV-Vis, FT-IR, TEM, SEM and EDX. Furthermore, the antimicrobial and antibiofilm activity of as-prepared AP-AgNPs were examined by a standard two-fold microbroth dilution method and tissue culture plate methods, respectively, against several Gram-negative and Gram-positive bacterial strains and fungal species such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and Acinetobacter baumannii (MDR-AB), methicillin-resistant S. aureus (MRSA) and Candida albicans (C. albicans) strains. The antimicrobial activity results clearly indicated that the Gram-negative bacteria MDR-PA was most affected by AgNPs as compared to other Gram-negative and Gram-positive bacteria and fungi C. albicans. Whereas, in the case of antibiofilm activity, it has been found that AgNPs at 0.039 mg/mL, inhibit biofilms formation of Gram-negative bacteria i.e., MDR-PA, E. coli, and MDR-AB by 78.98 ± 1.12, 65.77 ± 1.05 and 66.94 ± 1.35%, respectively. On the other hand, at the same dose (i.e., 0.039 mg/mL), AP-AgNPs inhibits biofilm formation of Gram-positive bacteria i.e., MRSA, S. aureus and fungi C. albicans by 67.81 ± 0.99, 54.61 ± 1.11 and 56.22 ± 1.06%, respectively. The present work indicates the efficiency of green synthesized AP-AgNPs as good antimicrobial and antibiofilm agents against selected bacterial and fungal species.


Assuntos
Anthemis , Anti-Infecciosos , Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Candida albicans , Escherichia coli , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa , Prata/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus
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