RESUMO
Mesoporous silica nanoparticles (MSNPs) are inorganic nanoparticles that have been comprehensively investigated and are intended to deliver therapeutic agents. MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. In this article, the viability of MSNPs' administration for lung cancer therapy has been reviewed. However, certain challenges lay ahead in the successful translation such as toxicology, immunology, large-scale production, and regulatory matters have made it extremely difficult to translate such discoveries from the bench to the bedside. This review highlights recent developments, characteristics, mechanism of action and customization for targeted delivery. This review also covers the most recent data that sheds light on MSNPs' extraordinary therapeutic potential in fighting lung cancer as well as future hurdles.
[Box: see text].
Assuntos
Neoplasias Pulmonares , Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Porosidade , Portadores de Fármacos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Sistemas de Liberação de Medicamentos/métodosRESUMO
Thiacloprid, a hazardous neonicotinoid insecticide, prevalent in daily agricultural practices, raises concerns due to the harmful effects of its residues on food items, and on unintended organisms poses a significant threat to human health. Introduced in 1990, Thiacloprid have gained popularity for its perceived effectiveness and reduced risks to non-target animals. However, emerging research in recent years reports significant toxic effects of Thiacloprid on non-target species, spanning neurotoxicity, immunotoxicity, hepatotoxicity, nephrotoxicity, and reproductive issues. Mammalian studies, particularly involving rodents, reveal cognitive impairment, hippocampal damage, and hepatic abnormalities upon Thiacloprid exposure. Reproductive toxicity and DNA damage are imminent concerns, disrupting gestational epigenetic reprogramming and suggesting persistent effects on future generations. Genotoxic effects, Embryotoxic, and observed reproductive toxicity accentuate the need for caution in the utilization of Thiacloprid. This review highlights reported toxic effects produced by Thiacloprid in recent years, challenging the initial belief in its lower toxicity for vertebrates.
RESUMO
Autophagy is a fundamental pillar of cellular resilience, indispensable for maintaining cellular health and vitality. It coordinates the meticulous breakdown of cytoplasmic macromolecules as a guardian of cell metabolism, genomic integrity, and survival. In the complex play of biological warfare, autophagy emerges as a firm defender, bravely confronting various pathogenic, infectious, and cancerous adversaries. Nevertheless, its role transcends mere defense, wielding both protective and harmful effects in the complex landscape of disease pathogenesis. From the onslaught of infectious outbreaks to the devious progression of chronic lifestyle disorders, autophagy emerges as a central protagonist, convolutedly shaping the trajectory of cellular health and disease progression. In this article, we embark on a journey into the complicated web of molecular and immunological mechanisms that govern autophagy's profound influence over disease. Our focus sharpens on dissecting the impact of various autophagy-associated proteins on the kaleidoscope of immune responses, spanning the spectrum from infectious outbreaks to chronic lifestyle ailments. Through this voyage of discovery, we unveil the vast potential of autophagy as a therapeutic linchpin, offering tantalizing prospects for targeted interventions and innovative treatment modalities that promise to transform the landscape of disease management.
RESUMO
Antibacterial photodynamic therapy (APDT) has received increased attention as a treatment for multidrug-resistant bacterial infections caused by antibiotic abuse. However, photosensitizers used in APDT have disadvantages such as water insolubility, self-aggregation, and photobleaching. To address these limitations, metal complexes have been explored. However, the use of such complexes tends to confine their antibacterial effectiveness specific bacterial strains. In this study, we report iron (Fe)- and copper (Cu)-based metallosurfactants as unique moieties for antibacterial photodynamic therapy (PDT) under the illumination of visible light. Briefly, our formulated Fe and Cu metallosurfactants, when combined with a fluorescein photosensitizer, exhibit nearly 100% antibacterial efficacy. This high efficiency is primarily attributed to the enhanced generation of singlet oxygen using FL in the presence of metallosurfactants when targeting bacteria such as Escherichia coli and Staphylococcus aureus under laser light. In vitro experiments further confirmed the superior antimicrobial activity of these metallosurfactants against a diverse range of microbial cultures, encompassing Gram-negative and Gram-positive bacteria as well as fungi. This performance outpaces conventional surfactants like cetyltrimethylammonium chloride and cetylpyridinium chloride. The compelling results from MTT assays and flow cytometry endorsed the substantial enhancement in antimicrobial properties achieved through Fe and Cu doping, all without the need for additional secondary agents. Notably, this synergistic antibacterial approach using metallosurfactants in PDT holds significant promise for the elimination of various bacteria in vivo, with the added advantage of mitigating the emergence of multidrug resistance.
Assuntos
Antibacterianos , Cobre , Luz , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Fármacos Fotossensibilizantes , Tensoativos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Tensoativos/química , Tensoativos/farmacologia , Tensoativos/síntese química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Cobre/química , Cobre/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Teste de Materiais , Staphylococcus aureus/efeitos dos fármacos , Tamanho da Partícula , Escherichia coli/efeitos dos fármacos , Estrutura Molecular , Ferro/química , Ferro/farmacologia , HumanosRESUMO
Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of polycarbonate plastics and epoxy resins, found in numerous consumer products. Despite its widespread use, its potential adverse health effects have raised significant concerns. This review explores the molecular mechanisms and evidence-based literature underlying BPA-induced toxicities and its implications for human health. BPA is an endocrine-disrupting chemical (EDC) which exhibits carcinogenic properties by influencing various receptors, such as ER, AhR, PPARs, LXRs, and RARs. It induces oxidative stress and contributes to cellular dysfunction, inflammation, and DNA damage, ultimately leading to various toxicities including but not limited to reproductive, cardiotoxicity, neurotoxicity, and endocrine toxicity. Moreover, BPA can modify DNA methylation patterns, histone modifications, and non-coding RNA expression, leading to epigenetic changes and contribute to carcinogenesis. Overall, understanding molecular mechanisms of BPA-induced toxicity is crucial for developing effective strategies and policies to mitigate its adverse effects on human health.
Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Fenóis , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Humanos , Disruptores Endócrinos/toxicidade , Animais , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Poluentes Ambientais/toxicidadeRESUMO
One of the serious challenges facing modern point-of-care (PoC) molecular diagnostic platforms relate to reliable detection of low concentration biomarkers such as nucleic acids or proteins in biological samples. Non-specific analyte-receptor interactions due to competitive binding in the presence of abundant molecules, inefficient mass transport and very low number of analyte molecules in sample volume, in general pose critical hurdles for successful implementation of such PoC platforms for clinical use. Focusing on these specific challenges, this work reports a unique PoC biosensor that combines the advantages of nanoscale biologically-sensitive field-effect transistor arrays (BioFET-arrays) realized in a wafer-scale top-down nanofabrication as high sensitivity electrical transducers with that of sophisticated molecular programs (MPs) customized for selective recognition of analyte miRNAs and amplification resulting in an overall augmentation of signal transduction strategy. The MPs realize a programmable universal molecular amplifier (PUMA) in fluidic matrix on chip and provide a biomarker-triggered exponential release of small nucleic acid sequences easily detected by receptor-modified BioFETs. A common miRNA biomarker LET7a was selected for successful demonstration of this novel biosensor, achieving limit of detection (LoD) down to 10 fM and wide dynamic ranges (10 pM-10 nM) in complex physiological solutions. As the determination of biomarker concentration is implemented by following the electrical signal related to analyte-triggered PUMA in time-domain instead of measuring the threshold shifts of BioFETs, and circumvents direct hybridization of biomarkers at transducer surface, this new strategy also allows for multiple usage (>3 times) of the biosensor platform suggesting exceptional cost-effectiveness for practical use.
Assuntos
Técnicas Biossensoriais , Desenho de Equipamento , Limite de Detecção , MicroRNAs , Técnicas Biossensoriais/instrumentação , MicroRNAs/análise , Humanos , Biomarcadores , Transistores Eletrônicos , Sistemas Automatizados de Assistência Junto ao Leito , Dispositivos Lab-On-A-ChipRESUMO
Underutilized fruits are thought to be nutrient and antioxidant gold mines. Despite their high nutritive value, therapeutic properties, and ability to grow in adverse soil and climatic conditions, they have received little attention. However, these underutilized fruits are an important component of traditional foods, particularly in arid and semiarid regions of Rajasthan. Lasoda (Cordia myxa) contains numerous phytochemicals that contribute to its antioxidant potential, including tannins, flavonoids, phenolic acids, xanthones, terpenes, and saponins. The primary goal of this review is to emphasize the importance of extracting bioactive compounds from lasoda and evaluating their antioxidant potential. Furthermore, this review emphasizes the major areas for the application of lasoda and its extract as prospective positive health agents that can be used in the preparation of functional foods. The use of lasoda may also improve the value of bakery products and meat quality and prevent postharvest losses. This review is a pilot article that can aid in the nutritional profiling of Cordia fruits and seeds, and it provides information on the effective and efficient use of this underutilized fruit in the food and nutraceutical industries.
Assuntos
Antioxidantes , Frutas , Compostos Fitoquímicos , Antioxidantes/farmacologia , Frutas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Alimento Funcional , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Valor Nutritivo , Flavonoides/análise , Flavonoides/farmacologia , Flavonoides/isolamento & purificaçãoRESUMO
PURPOSE: This study aims to examine the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers. METHODS: This meta-analysis used PubMed and EMBASE databases to access published studies that met the eligibility criteria. Primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. Study quality was assessed using the Newcastle Ottawa Scale. Meta-analysis was conducted using R software. RESULTS: The meta-analysis included 61 studies, of which 53 were cohort studies and eight were case-control studies. Particulate matter 2.5 mm or less in diameter (PM2.5) was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. A pooled analysis of exposure reported in cohort and case-control studies and cancer incidence demonstrated a significant relationship (relative risk [RR], 1.04 [95% CI, 1.02 to 1.05]; I2, 88.93%; P < .05). A significant association was observed between exposure to pollutants such as PM2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I2, 68.52%) and nitrogen dioxide (NO2) (RR, 1.03 [95% CI, 1.01 to 1.05]; I2, 73.52%) and lung cancer incidence. The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I2, 94.77%; P < .001). Among the four pollutants, PM2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I2, 95.33%) and NO2 (RR, 1.05 [95% CI, 1.02 to 1.08]; I2, 89.98%) were associated with lung cancer mortality. CONCLUSION: The study confirms the association between air pollution exposure and lung cancer incidence and mortality. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Pulmonares , Humanos , Incidência , Dióxido de Nitrogênio/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Neoplasias Pulmonares/epidemiologiaRESUMO
The escalation of harmful pollutants, including heavy metals, due to industrialization and urbanization has become a global concern. To mitigate the negative impacts of heavy metal stress on germination and early plant development, growth regulators have been employed. This study aimed to evaluate the response of mung bean (Vigna radiata L.) to zinc stress in the presence of brassinosteroids, focusing on seedling growth and antioxidant potential. Mung bean seedlings were treated with three concentrations of 24-epibrassinolide (EBL) (0.1, 0.2, and 0.4 PPM) with or without zinc. Results demonstrated that the application of brassinosteroids, combined with zinc stress, significantly enhanced germination percentage (about 47.06, 63.64, and 120%), speed of germination (about 39.13, 50, and 100%), seedling growth (about 38% in case of treatment combined 0.4 PPM 24-EBL and 1.5 mM ZnSO4) and seedling vigor index (204% in case of treatment combined 0.4 PPM 24-EBL and 1.5 mM ZnSO4) compared to zinc-treated seedlings alone after 24 h. The activities of antioxidative enzymes (catalase, ascorbate peroxidase, polyphenol oxidase, and peroxidase) and total soluble protein content decreased, while lipid peroxidation and proline content exhibited a significant increase (p ≤ 0.05) when compared to the control. However, the negative effects induced by heavy metal stress on these parameters were significantly mitigated by EBL application. Notably, the most effective concentration of EBL in overcoming zinc stress was found to be 0.4 PPM. These findings underscore the potential of exogenously applied brassinosteroids as a valuable tool in phytoremediation projects by ameliorating heavy metal stress.
RESUMO
INTRODUCTION: Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder of the mature B-cells, mostly seen in men, and is characterized by cytopenia, splenomegaly, myelofibrosis, and the presence of atypical lymphoid cells showing the cytoplasmic hairy projection in the peripheral blood, bone marrow, and spleen. The immunophenotypic (IPT) profile shows the clonal expansion of B-cells with CD19, CD20, and CD22 showing bright expression. The diagnosis requires two hairy cell markers out of CD103, CD123, CD25, and CD11c to be positive. The HCL variant (HCL-v) has a different IPT profile with negative CD25 in most cases. AIM: The aim was to study the hematological and IPT of classical HCL and HCL variants. METHODS: This cross-sectional study included all the cases of HCL diagnosed over a retrospective period of eight years from 1st January 2015 to 31st December 2022 in a tertiary care hospital in north India. The patients included in the study were those for whom immunophenotyping; that is, flow cytometry and/or immunohistochemistry (IHC) were done for diagnosis. Bone marrow slides, IHC slides, and flow cytometric IPTs were reviewed. RESULTS: The study included 13 patients who were diagnosed to have HCL, of which 12 were classical HCL and one was HCL-variant (HCL-v). Among classical HCL, IPT was done by flow cytometry in 10 patients, while in two patients, it was done by IHC. CD19, CD20, and CD22 were positive in all patients of classical HCL (10/10, 10/10, and 5/5, respectively), while CD123, CD103, CD25, and CD11C were positive in 100%, 89%, 80%, and 100% cases, respectively. One patient of HCL-v had CD103 and CD123 positive, while CD25 and CD123 were negative. CONCLUSION: The diagnosis of HCL requires a multipronged approach. The use of clinical features, morphology, and immunophenotyping combined with ancillary techniques provides higher diagnostic accuracy and enables its distinction from other B-cell lymphoproliferative disorders (BCLPDs), leading to better patient management and treatment.
RESUMO
Background: The aim of the current study was to compare three different dose-calculating algorithms, i.e., superposition (SP), fast SP (FSP), and convolution (CV), for breast cancer patients treated with intensity-modulated radiotherapy (IMRT) and field-in-Field forward plan IMRT (FiF-FP-IMRT). Materials and Methods: The current retrospective study involved 100 postmastectomy breast cancer patients who were given radiotherapy using IMRT and FiF-FP-IMRT planning techniques. All the initially SP-calculated plans were recalculated with the same monitor units for FSP and CV algorithm without change in any of the other planning parameters. The isodose distribution and various plan evaluating parameters, for example, conformity index (CI), homogeneity index, and uniformity index target volume and normal structure doses were compared and analyzed for all the different algorithm calculated plans. Results: In the IMRT plans, all the target and normal structure dose-volume parameters showed a significant difference between all the three different algorithms with P < 0.05. In the FiF-FP-IMRT plans, CV algorithm showed a significant difference in most of the target and normal structure dose-volume parameters. Among quality indexes, only CI showed a significant difference between all the algorithms in both the planning techniques. R50 showed a significant difference with the CV algorithm in both the planning techniques. Conclusion: The change in the dose calculation algorithm resulted in dosimetric changes which must be evaluated by the medical physicists and oncologists while evaluating treatment plans. In the current study with breast patients, the results obtained for target and normal structure doses using the CV algorithm are overestimated as compared to SP and FSP algorithms, producing variable results in air and bony normal structures. However, the ipsilateral lung V5 parameter and the ipsilateral humeral head mean dose were found to be underestimated by the CV algorithm as compared to the SP and FSP algorithm in both the planning techniques.
RESUMO
Monoaromatic hydrocarbons such as benzene, toluene, ethylbenzene, and o, m, and p-xylenes (BTEX) are high-risk pollutants because of their mutagenic and carcinogenic nature. These pollutants are found with elevated levels in groundwater and soil in Canada at several contaminated sites. The intrinsic microbes present in the subsurface have the potential to degrade pollutants by their metabolic pathways and convert them to non-toxic products. However, the low subsurface temperature (5-10 °C) limits their growth and degradation ability. This study examined the feasibility of subsurface heat augmentation using geothermal heating for BTEX bioremediation. Novel potent BTEX-degrading bacterial strains were isolated from soil at 3.0, 42.6, and 73.2 m depths collected from a geothermal borehole during installation and screened using an enrichment technique. The selected strains were identified with Sanger sequencing and phylogenetic tree analysis, revealing that all the strains except Bacillus subtilis are novel with respective to BTEX degradation. The isolates, Microbacterium esteraromaticum and Bacillus infantis showed the highest degradation with 67.98 and 65.2% for benzene, 72.8 and 71.02% for toluene, 77.52 and 76.44% for ethylbenzene, and 74.58 and 74.04% for xylenes respectively. Further, temperature influence at 15 ± 1 °C, 28 ± 1 °C and 40 ± 1 °C was observed, which showed increased growth by two-fold and on average 35-49% more biodegradation at higher temperatures. Results showed that temperature is a positive stimulant for bioremediation, hence geothermal heating could also be a stimulant for in-situ bioremediation.
Assuntos
Poluentes Ambientais , Xilenos , Xilenos/metabolismo , Benzeno/metabolismo , Filogenia , Derivados de Benzeno/metabolismo , Tolueno/metabolismo , Biodegradação AmbientalRESUMO
This report describes the status of introductions globally for eight World Health Organization (WHO)-recommended new and underutilized vaccines, comprising 10 individual vaccine antigens. By 2021, among 194 countries worldwide, 33 (17%) provided all of these 10 WHO-recommended antigens as part of their routine immunization schedules; only one low-income country had introduced all of these recommended vaccines. Universal hepatitis B birth dose; human papillomavirus vaccine; rotavirus vaccine; and diphtheria, tetanus, and pertussis-containing vaccine first booster dose have been introduced by 57%, 59%, 60%, and 72% of all countries worldwide, respectively. Pneumococcal conjugate vaccine, rubella-containing vaccine, measles-containing vaccine second dose, and Haemophilus influenzae type b vaccine have been introduced by 78%, 89%, 94%, and 99% of all countries, respectively. The annual rate of new vaccine introductions declined precipitously when the COVID-19 pandemic started, from 48 in 2019 to 15 in 2020 before rising to 26 in 2021. Increased efforts to accelerate new and underutilized vaccine introductions are urgently needed to improve universal equitable access to all recommended vaccines to achieve the global Immunization Agenda 2021-2030 (IA2030) targets.
Assuntos
COVID-19 , Vacinas Anti-Haemophilus , Humanos , Lactente , Vacina contra Difteria, Tétano e Coqueluche , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Vacina contra Sarampo , Vacina contra Rubéola , Esquemas de Imunização , Vacina Antipólio de Vírus Inativado , Vacinas contra Hepatite B , Vacinas CombinadasRESUMO
Hepatitis C Virus (HCV) is estimated to affect nearly 180 million people worldwide, culminating in â¼0.7 million yearly casualties. However, a safe vaccine against HCV is not yet available. This study endeavored to identify a multi-genotypic, multi-epitopic, safe, and globally competent HCV vaccine candidate. We employed a consensus epitope prediction strategy to identify multi-epitopic peptides in all known envelope glycoprotein (E2) sequences, belonging to diverse HCV genotypes. The obtained peptides were screened for toxicity, allergenicity, autoimmunity and antigenicity, resulting in two favorable peptides viz., P2 (VYCFTPSPVVVG) and P3 (YRLWHYPCTV). Evolutionary conservation analysis indicated that P2 and P3 are highly conserved, supporting their use as part of a designed multi-genotypic vaccine. Population coverage analysis revealed that P2 and P3 are likely to be presented by >89% Human Leukocyte Antigen (HLA) molecules from six geographical regions. Indeed, molecular docking predicted the physical binding of P2 and P3 to various representative HLAs. We designed a vaccine construct using these peptides and assessed its binding to toll-like receptor 4 (TLR-4) by molecular docking and simulation. Subsequent analysis by energy-based and machine learning tools predicted high binding affinity and pinpointed the key binding residues (i.e. hotspots) in P2 and P3. Also, a favorable immunogenic profile of the construct was predicted by immune simulations. We encourage the scientific community to validate our vaccine construct in vitro and in vivo.Communicated by Ramaswamy H. Sarma.
Assuntos
Hepacivirus , Hepatite C , Humanos , Hepacivirus/genética , Simulação de Acoplamento Molecular , Glicoproteínas/genética , Antígenos HLA/química , Hepatite C/prevenção & controle , Peptídeos/genética , Vacinas de Subunidades Antigênicas , Genótipo , Epitopos de Linfócito T , Epitopos de Linfócito B , Biologia Computacional/métodosRESUMO
Photodynamic therapy (PDT) is facing challenges such as poor solubility, precise delivery, self-aggregation, and photobleaching of photosensitizers with cancer cells due to their less tendency to accumulate in tumor tissues. To address these challenges, we have explored a Rose Bengal (RB)-loaded metallocatanionic vesicles (MCVs) nanosystem for the phototoxicity of cancer cells. Different sets of MCVs were prepared by two different cationic single-chain metallosurfactants, i.e., hexadecylpyridinium trichlorocuprate (CuCPC I) and hexadecylpyridinium trichloroferrate (FeCPC I) in combination with anionic double-chain sodium bis(2-ethylhexyl)sulfosuccinate (AOT) surfactant in phosphate buffer saline of pH 7.4. The RB-loaded CuCPC I:AOT and FeCPC I:AOT vesicles enhanced the maximum singlet oxygen (1O2) generation by 1-fold and 3-fold, respectively, compared to pure RB. Upon irradiation with a 532 nm laser for 10 min, these RB-loaded CuCPC I:AOT and FeCPC I:AOT MCVs significantly decreased the metabolic activity of U-251 cells by 70% and 85% at MCVs concentration of 0.75 µM, respectively. Furthermore, RB-loaded MCVs showed the highest intracellular 1O2-mediated membrane damage and cell-killing effect as confirmed by singlet oxygen sensor green and differential nuclear staining assay, which is attributed to the cellular uptake profile of different RB-loaded MCVs fractions. Caspase 3/7 assay confirmed the apoptotic pathway of cell death by activating caspase. Therefore, the photoactivation of RB-loaded MCVs led to a significant reduction in the viability of U-251 cells (maximum 85%), which resulted in cell death. Our study demonstrated the advantage of using these dual-charge and biocompatible metallocatanionic vesicles as a promising delivery system of photodynamic therapy that can enhance 1O2 generation from PS and can be further utilized in photomedicine.
Assuntos
Neoplasias , Fotoquimioterapia , Rosa Bengala/farmacologia , Oxigênio Singlete/metabolismo , Cetilpiridínio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
Purpose: The purpose of the study was to consider and calculate dosimetric parameters during treatment planning to improve radiobiological outcomes for cervical cancer patients treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT). Material and methods: In the present study, dose volume histograms (DVH) of 30 cervical cancer patients treated with HDR brachytherapy using computer tomography (CT)-based planning were analyzed. High-risk clinical target volume (HR-CTV) was contoured as the main target volume for all the patients, with an assumption that there was no presence of gross tumor at the time of brachytherapy. Values of target coverage volumes (100%, 150%, and 200%) were obtained from DVH, which was used to calculate different quality indices (QIs), including coverage index (CI), dose homogeneity index (DHI), overdose volume index (ODI), and dose non-uniformity ratio (DNR). Values of these QIs were further used to calculate tumor control probability (TCP). Statistical correlation between all QIs with TCP was established. Also, normal tissue complication probabilities for bladder (NTCP_B) and rectum (NTCP_R) were calculated. Results: The mean values of the various calculated parameters, including CI, DHI, ODI, DNR, TCP, NTCP_B and NTCP_R were 0.92 ±0.07, 0.26 ±0.10, 0.50 ±0.10, 0.74 ±0.10, 0.92 ±0.07, 0.08 ±0.25, and 0.36 ±0.27, respectively. Pearson's product moment correlation coefficient between CI, DHI, ODI, and DNR with regards to TCP was +0.85, -0.85, +0.84, and +0.85, respectively. Conclusions: The correlation between dosimetric and radiobiological parameters was found statistically significant, which shows the influence of dosimetric parameters on the radiobiological outcome. Therefore, these parameters should be considered during the treatment planning to improve the radiobiological outcome.
RESUMO
Photodynamic therapy (PDT) is an innovative technique for cancer treatment with minimal side effects, based on the use of a photosensitizer, oxygen, and light. Photosensitizers (PSs) have several limitations, that may limit their clinical use, like poor solubilization, self-aggregation, and lack of specific targeting, which can be addressed with the use of nanomaterials. Herein, a unique type of catansomes (CaSs) was prepared using a gemini imidazolium-based surfactant (1,3-bis[(3-octadecyl-1-imidazolio)methyl]benzene dibromide (GBIB) and a double chain surfactant, diaoctyl sodium sulfosuccinate or Aerosol OT (AOT). The formation of CaS GBIB/AOT was optimized in various ethanol/water (E/W) solvent ratios by employing a facile, quick, and most reliable solution-solution mixing method. The CaS was characterized by dynamic light scattering (DLS) and field emission gun scanning electron microscopy (FEG-SEM) techniques. The experimental results reveal that stable CaSs with a spherical shape were obtained at lower concentration (100 µM). Rose Bengal (RB), a PS of the xanthene family, was incorporated into these prepared CaSs, as proven by fluorescence spectroscopy, UV-visible absorption spectroscopy, and confocal laser scanning microscopy. Singlet oxygen (1O2) generation studies revealed the relevant role of the E/W solvent ratio as there was a 4-fold boost in the 1O2 production for GBIB/AOT in E/W = 50:50 and around 3-fold in E/W = 30:70. Also, the GBIB-rich 80:20 fraction was more efficient in increasing the 1O2 generation as compared to the AOT rich fraction (20:80). Further, their phototoxicity was tested in a water-rich solvent ratio (E/W = 30:70) against MCF-7 cells. Upon irradiation with a 532 nm laser (50 mW) for 5 min, RB@GBIB/AOT(20:80) fraction caused 50% decrease in the metabolic activity of MCF-7 cells, and RB@GBIB/AOT(80:20) fraction produced a maximum 85% decrease in cell viability. Furthermore, the enhancement in intracellular 1O2 generation by RB@GBIB/AOT, as compared to pure RB, was confirmed with singlet oxygen sensor green (SOSG). This new type of CaS based on gemini surfactants exhibiting a large amount of 1O2 generation, holds great interest for several applications, such as use in photomedicine in future.
Assuntos
Neoplasias , Rosa Bengala , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Rosa Bengala/química , Rosa Bengala/farmacologia , Rosa Bengala/uso terapêutico , Oxigênio Singlete/química , Oxigênio Singlete/uso terapêutico , Solventes/uso terapêutico , Tensoativos/farmacologia , ÁguaRESUMO
BACKGROUND: The treatment of the peri-implantitis remains complex and challenging with no consensus on which is the best treatment approach. PURPOSE: To examine the key local and systemic factors associated with implant loss, disease progression, or favorable outcomes after surgical peri-implantitis therapy. MATERIALS AND METHODS: Records of patients treated for peri-implantitis were screened. Patient-, implant- and surgery-related variables on and prior to the day of the surgery were collected (T0: time of peri-implantitis treatment). If the treated implant was still in function when the data was collected, the patient invited to participate for a recall study visit (T1, longest follow-up after treatment). Impacts of the variables on the implant survival, success, and peri-implant bone change after treatment were investigated. RESULTS: Eighty patients with 121 implants with a mean follow-up of 42.6 ± 26.3 months were included. A total of 22 implants (18.2%) were removed during the follow-up period. When relative bone loss (%) was in range 25%-50%, risk for implant removal increased 15 times compared to lower bone loss <25% (OR = 15.2; CI: 2.06-112.7; p = 0.008). Similarly, relative bone loss of >50% increased 20 times the risk of implant failure compared to the <25% (OR = 20.2; CI: 2.42-169.6; p = 0.006). For post-treatment success rate, history of periodontitis significantly increased the risk of unsuccess treatment (OR = 3.07; p = 0.04) after resective surgery). CONCLUSION: Severe bone loss (>50%) poses significantly higher risk of treatment failure.
Assuntos
Perda do Osso Alveolar , Implantes Dentários , Peri-Implantite , Periodontite , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/cirurgia , Implantes Dentários/efeitos adversos , Progressão da Doença , Humanos , Peri-Implantite/etiologia , Peri-Implantite/cirurgia , Periodontite/cirurgia , PrognósticoRESUMO
In clinics, photodynamic therapy (PDT) is established as a non-invasive therapeutic modality for certain types of cancers and skin disease. However, due to poor water solubility, photobleaching, and the dark toxicity of photosensitizers (PSs), further developments are required to improve the efficiency of PDT. Herein, we report the role of metallocatanionic vesicles (MCVs) in enhancing the phototoxicity of methylene blue (MB) against cancer cells. These MCVs were prepared via a facile and quick solution-solution mixing method using a cationic single-chain metallosurfactant (FeCPC I) in combination with anionic sodium oleate (Na Ol). For singlet oxygen (1O2) generation and PDT studies, two fractions of FeCPC I : Na Ol, i.e., 30 : 70 (V37) and 70 : 30 (V73), were chosen based on their long-term stability in aqueous media. A cationic PS MB was loaded into these vesicles. The MB-loaded MCV 30 : 70 and 70 : 30 fractions enhanced the 1O2 generation by 0.10- and 0.40-fold, respectively, compared with MB alone. Upon illumination using a 650 nm laser, these MB-loaded V73 and V37 MCVs significantly decreased the metabolic activity of MCF-7 cells by ≤50% at a concentration of 0.75 µM. Furthermore, the SOSG assay revealed that the synthesized MCVs enhanced the intracellular 1O2 compared with MB alone. The MB-loaded V73 MCVs showed the highest 1O2-mediated membrane damage and cell-killing effect, as confirmed using the differential nuclear staining assay (DNS), which is attributed to the cellular uptake profile of the different MCV fractions. Altogether, this work shows the advantage of using these biocompatible and dual-charge MCVs as promising delivery vehicles that can enhance the 1O2 generation from the PS. This work suggests the future application of these Fe-MCVs in magnetically guided PDT.
Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Luz , Azul de Metileno/farmacologia , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete/metabolismoRESUMO
Background: Surface/skin dose measurement is one of the most challenging tasks for clinical dosimetry in radiotherapy and comparison with almost all the commercially available treatment planning systems (TPSs) brings a significant variation with the measured dose. Aims and Objectives: In the current study, doses calculated from the TPS in the near-surface region for conformal plans (both three-dimensional conformal radiotherapy [3DCRT] and intensity-modulated radiotherapy [IMRT]) of 35 breast cancer patients were evaluated and compared with the doses measured with Markus chamber. Materials and Methods: The computed tomography (CT) images of a solid water slab phantom with a Markus chamber (at different depths ranging from 1 mm to 5 mm from the surface) were taken and imported into the TPS. All the conformal treatment plans made in TPS were executed on a linear accelerator and dose agreements between TPS calculated and chamber measured doses were analysed. Results: Results showed that this TPS underestimated the calculated doses in the superficial region by up to 26% and 21%, respectively, with respect to mean and maximum dose values obtained within the effective volume of the chamber used. Conclusion: The uncertainty of doses in the superficial region should be kept in mind when evaluating treatment plans for superficial tumours in TPS.