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1.
Genome Biol Evol ; 16(7)2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38752399

RESUMO

Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protein are frequent in tumors, and that RIP-2 modulates immune and inflammatory responses, we investigated alternative splicing events that result in partial deletions of the kinase domain at the N-terminus of RIP-2. We also investigated the structure and expression of the RIPK2 truncated variants and isoforms in different environments. In addition, we searched data throughout Supraprimates evolution that could support the biological importance of RIPK2 alternatively spliced products. We observed that human variants and isoforms were differentially regulated following temperature stress, and that the truncated transcript was more expressed than the long transcript in tumor samples. The inverse was found for the longer protein isoform. The truncated variant was also detected in chimpanzee, gorilla, hare, pika, mouse, rat, and tree shrew. The fact that the same variant has been preserved in mammals with divergence times up to 70 million years raises the hypothesis that it may have a functional significance.


Assuntos
Processamento Alternativo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Animais , Humanos , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Evolução Molecular , Isoformas de Proteínas/genética , Camundongos , Neoplasias/genética , Ratos
3.
Drug Deliv Transl Res ; 14(1): 62-79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37566362

RESUMO

The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resistance for the 0.3% TFC formulation. The addition of TPC percentages did not result in a significant difference (p > 0.05) in swelling capacity and disintegration rate. The results confirmed that TPC were able to modulate the morphological, morphometric, and mechanical properties of scaffolds. Thus, this study describes a potential new material to improve the regeneration of major tracheal structures after surgical tumor removal.


Assuntos
Fibroínas , Neoplasias , Psidium , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Fibroínas/química , Colágeno/química , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier
4.
J Tradit Complement Med ; 13(6): 575-587, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38020546

RESUMO

Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

5.
Drug Deliv Transl Res ; 13(12): 3223-3238, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37474880

RESUMO

Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound healing. The aim of this study was to develop and analyze the healing properties of GelMA containing AEPG, gallic acid, or ellagic acid in a rodent model. GelMA hydrogels containing 5% AEPG (GelMA-PG), 1.6% gallic acid (GelMA-GA), or 2.1% ellagic acid (GelMA-EA) were produced and their mechanical properties, enzymatic degradation, and thermogravimetric profile determined. Wound closure rates, healing histological grading, and immunohistochemical counts of myofibroblasts were assessed over time. The swelling of hydrogels varied between 50 and 90%, and GelMA exhibited a higher swelling than the other groups. The GPG samples showed higher compression and Young's moduli than GelMA, GGA, and GAE. All samples degraded around 95% in 48 h. GPG and GGA significantly accelerated wound closure, improved collagenization, increased histological grading, and hastened myofibroblast differentiation in comparison to the control, GelMA, and GEA. GelMA containing AEPG (GPG) improved wound healing, and although gallic acid is the major responsible for such biological activity, a potential synergic effect played by other polyphenols present in the extract is evident.


Assuntos
Gelatina , Hidrogéis , Hidrogéis/química , Gelatina/química , Ácido Elágico/farmacologia , Cicatrização , Ácido Gálico , Metacrilatos/química
6.
Sci Rep ; 13(1): 8588, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237049

RESUMO

Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views-differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores Tumorais/metabolismo , Metabolômica/métodos , Espectroscopia de Ressonância Magnética , Microambiente Tumoral
7.
Toxics ; 11(4)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37112602

RESUMO

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

8.
Biomedicines ; 11(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36979661

RESUMO

HPV infection is one of the most important risk factors for head and neck squamous cell carcinoma among younger patients. YRNAs are short non-coding RNAs involved in DNA replication. YRNAs have been found to be dysregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the role of YRNAs in HPV-positive HNSCC using publicly available gene expression datasets from HNSCC tissue, where expression patterns of YRNAs in HPV(+) and HPV(-) HNSCC samples significantly differed. Additionally, HNSCC cell lines were treated with YRNA1-overexpressing plasmid and RNA derived from these cell lines was used to perform a NGS analysis. Additionally, a deconvolution analysis was performed to determine YRNA1's impact on immune cells. YRNA expression levels varied according to cancer pathological and clinical stages, and correlated with more aggressive subtypes. YRNAs were mostly associated with more advanced cancer stages in the HPV(+) group, and YRNA3 and YRNA1 expression levels were found to be correlated with more advanced clinical stages despite HPV infection status, showing that they may function as potential biomarkers of more advanced stages of the disease. YRNA5 was associated with less-advanced cancer stages in the HPV(-) group. Overall survival and progression-free survival analyses showed opposite results between the HPV groups. The expression of YRNAs, especially YRNA1, correlated with a vast number of proteins and cellular processes associated with viral infections and immunologic responses to viruses. HNSCC-derived cell lines overexpressing YRNA1 were then used to determine the correlation of YRNA1 and the expression of genes associated with HPV infections. Taken together, our results highlight the potential of YRNAs as possible HNSCC biomarkers and new molecular targets.

9.
Pharmaceutics ; 15(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36839993

RESUMO

Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 µg/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil (Copaifera sabulicola) in liposomes (conventional and PEGylated), which was also checked against pheochromocytoma PC12 cells. Its safety was verified in normal rat astrocytes. The results indicate that liposomes encapsulating copaiba oil showed cytotoxic activity against the studied tumor strains in a dose-dependent fashion, demonstrating their potential applications as a chemotherapeutic bioactive formulation.

10.
Int J Pharm ; 634: 122648, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36709832

RESUMO

Chitosan films are commonly used for wound dressing, provided that this polymer has healing, mucoadhesiveness and antimicrobial properties. These properties can be further reinforced by the combination of chitosan with polysaccharides and glycoproteins present in aloe vera, together with copaiba oleoresin's pharmacological activity attributed to sesquiterpenes. In this work, we developed chitosan films containing either aloe vera, copaiba oil or both, by casting technique, and evaluated their microbial permeation, antimicrobial activity, cytotoxicity, and in vivo healing potential in female adult rats. None of the developed chitosan films promoted microbial permeation, while the cytotoxicity in Balb/c 3 T3 clone A31 cell line revealed no toxicity of films produced with 2 % of chitosan and up to 1 % of aloe vera and copaiba oleoresin. Films obtained with either 0.5 % chitosan or 0.5 % copaiba oleoresin induced cell proliferation which anticipate their potential for closure of wound and for the healing process. The in vivo results confirmed that tested films (0.5 % copaiba-loaded chitosan film and 0.5 % aloe vera-loaded chitosan film) were superior to a commercial dressing film. For all tested groups, a fully formed epithelium was seen, while neoformation of vessels seemed to be greater in formulations-treated groups than those treated with the control. Our work confirms the added value of combining chitosan with aloe vera and copaiba oil in the healing process of wounds.


Assuntos
Aloe , Anti-Infecciosos , Quitosana , Feminino , Ratos , Animais , Anti-Infecciosos/farmacologia , Bandagens
11.
Int J Pharm ; 631: 122497, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36529360

RESUMO

The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and ß-cyclodextrin (ERKA:ß-CD) in rodents. ERKA:ß-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:ß-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:ß-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:ß-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:ß-CD300-treated animals. The ERKA:ß-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity.


Assuntos
Mikania , Neoplasias , Sarcoma 180 , beta-Ciclodextrinas , Camundongos , Animais , Mikania/química , Sarcoma 180/tratamento farmacológico , NF-kappa B , Antígeno Ki-67 , beta-Ciclodextrinas/química , Desenvolvimento de Medicamentos
12.
J Control Release ; 353: 802-822, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36521691

RESUMO

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g., micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects.


Assuntos
Neoplasias , Poloxâmero , Humanos , Poloxâmero/química , Polímeros/química , Sistemas de Liberação de Medicamentos , Micelas , Neoplasias/tratamento farmacológico
13.
Int J Pharm ; 628: 122301, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36270554

RESUMO

Circular economy, and concerns about environmental waste, is fostering the development of sustainable alternative products in a range of industries. In the dermo-cosmetic field, the market for sustainable anti-aging skincare products has increasingly grown over the last years. The innovation of this work was to develop chitosan films incorporating lemongrass essential oil (LEO) that could potentially be applied as a green cosmetic skin treatment due to their anti-oxidant and antimicrobial properties, using renewable and biodegradable materials. Different concentrations of LEO (i.e., 0.5, 1.0, and 1.5 % w/w) were formulated into chitosan filmogenic matrices, forming skincare bioactive films. Their antioxidant properties and water vapor permeability were strongly governed by the LEO concentration. Chitosan bioactive films containing 0.5 % LEO showed cellular viability over 70 %, while those with 1.5 % LEO had similar antioxidant capacity as NAC (N-acetyl-L-cysteine), used as the positive control to inactivate intracellular reactive oxygen species (ROS) in HaCat cells not treated with H2O2. The developed bioactive films showed activity against Escherichia coli and Staphylococcus aureus. Our LEO-loaded chitosan biofilms may be used as sheet masks with antioxidant and antimicrobial properties for skincare, with high flexibility and selected permeability, and without cytotoxic risks.


Assuntos
Anti-Infecciosos , Quitosana , Cymbopogon , Óleos Voláteis , Antioxidantes/farmacologia , Peróxido de Hidrogênio , Óleos Voláteis/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia
14.
Biomolecules ; 12(9)2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36139035

RESUMO

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients' quality of life with chronic diseases are discussed.


Assuntos
Técnicas Biossensoriais , Polímeros Responsivos a Estímulos , Doença Crônica , Sistemas de Liberação de Medicamentos , Humanos , Preparações Farmacêuticas , Qualidade de Vida
15.
Eur J Pharm Biopharm ; 178: 25-34, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35905803

RESUMO

Endoscopic submucosal dissection (ESD) and endoscopic submucosal resection (EMR) are non-invasive endoscopic techniques. They allow an early excised gastrointestinal (GI) mucosal precancerous lessions. For their application is necessary to use a submucosal injection that lifts the area to excise. The main objective of this study was the preparation of a microparticulate-based fluid for injection in the GI submucosa. Alginate microparticles (MPs) were developed by the solvent displacement technique and characterized by particle size, surface electrical properties, swelling, degradation, rheology, adhesion, leakage, syringeablity and stability. Furthermore, their potential to form a submucosal cushion was assayed in porcine stomach mucosa and porcine colon mucosa. Results showed MPs sizes below 160 µm, negative surface charge around -50 mV at pH = 6, high rates of swelling and good adhesion. The microparticulate-based fluid exhibited pseudoplastic behavior following the Ostwald-de Waele rheological model. A brief force is sufficient for its injection through a syringe. Finally, formulations were able to provide a submucosa elevation of 1.70 cm for more than 90 min and 120 min in the porcine stomach and colon, respectively.


Assuntos
Ressecção Endoscópica de Mucosa , Animais , Colo/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Mucosa Gástrica/cirurgia , Injeções , Mucosa Intestinal , Suínos
16.
Heliyon ; 8(5): e09337, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35540937

RESUMO

The potato is a root vegetable native to the Americas; it consists of the starchy tuber of the plant Solanum tuberosum. There are many varieties, and the flesh can have different colour ranging from yellow to red and purple. Coloured varieties have a denser texture and slightly nuttier, earthier flavour than other potatoes. The desirable quality characteristics of potatoes depends on the intended use, and the acceptability of raw potatoes is determined by size, shape, colour, and the quality of can be evaluated in terms of colour, flavour, and texture. Deep-frying is the century-old and it is among the most common cooking processes, still being used to prepare a variety of food products on both industrial and domestic scales. Frying the potatoes is among the tastiest and appreciated way to cook this vegetable. Purple fleshed potatoes are widely considered one of the best-tasting purple potatoes varieties, they have a nice taste and add colour to a meal. They are a source of beneficial health compounds which makes them interesting as functional food. The anthocyanins present in the Purple Majesty variety are interesting for their health promoting abilities, anti-oxidative activity, and even other health beneficial effects, e.g. anti-influenza virus activity, and anti-stomach cancer activity. The aim of this study has been to assess the effect of deep-frying of purple potato Purple Majesty using sunflower oil on the polyphenols, anthocyanins and to evaluate the antioxidant activity of the cooked matrix compared to the fresh one. The results seem to suggest that the healthy characteristics of this functional food are retained after the cooking by frying.

17.
Heliyon ; 8(2): e08893, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35198766

RESUMO

The use of natural products in sunscreen formulations as a prophylactic measure against skin cancer is receiving special attention attributed to the photoprotective and antioxidant properties of their chemical components. In this work, we describe the development of topical hydrogel formulations containing hydroalcoholic extract of red propolis (HERP), and the evaluation of the dermal sensitizing effect of the developed products. Sunscreen formulations composed of HERP in different concentrations (1.5, 2.5 or 3.5% w/w) alone or in combination with a chemical (octyl methoxycinnamate) and/or physical (titanium dioxide) filters were developed using poloxamer 407 as gel basis. The preliminary and accelerated stability tests, texture analysis and spreadability tests were performed. All formulations revealed to be stable in preliminary stability assessment. The formulations containing HERP 1.5 and 2.5% alone or associated with the filters showed intense modifications during accelerated stability test, which were confirmed by rheological analyses. The incorporation of HERP and filters in the poloxamer hydrogel decreased the toughness of product (p < 0.05) and the formulation containing HERP alone presented the lowest adhesivity (p < 0.001). The incorporation of HERP in the hydrogel decreased the poloxamer transition temperature, showing different rheological behavior with the increase of HERP concentration. The developed formulations were stable, exhibited non-Newtonian and pseudoplastic behavior, showing in vivo skin compatibility and no skin irritancy.

18.
BMC Med ; 20(1): 40, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35094705

RESUMO

BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.


Assuntos
Análise da Randomização Mendeliana , Neoplasias Orofaríngeas , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana/métodos , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Comportamento Sexual , Fumar/efeitos adversos , Fumar/epidemiologia
19.
Biochimie ; 192: 83-90, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34653542

RESUMO

Bacillus thuringiensis (Bt) is a ubiquitous bacterium that produces several proteins that are toxic to different invertebrates such as insects, nematodes, mites, and also some protozoans. Among these, Cry and Cyt proteins are most explored as biopesticides for their action against agricultural pests and vectors of human diseases. In 2000, a group of researchers from Japan isolated parasporal inclusion proteins from B. thuringiensis, and reported their cytotoxic action against human leukemia. Later, other proteins with similar antitumor properties were also isolated from this bacterium and these cytotoxic proteins with specific activity against human cancer cells were named parasporins. At present, nineteen different parasporins are registered and classified in six families. These parasporins have been described to have specific in vitro antitumor activity against several cancer cell lines. The antitumor activity makes parasporins possible candidates as anticancer agents. Various research groups around the world are involved in isolating and characterizing in vitro antitumor activity of these proteins and many articles reporting such activities in detail have been published. However, there are virtually no data regarding the antitumor activity of parasporins in vivo. This review summarizes the properties of these potentially useful antitumor agents of natural origin, focusing on their in vivo activity thus also highlighting the importance of testing these proteins in animal models for a possible application in clinical oncology.


Assuntos
Bacillus thuringiensis/química , Proteínas de Bactérias , Citotoxinas , Endotoxinas , Corpos de Inclusão Intranuclear/química , Leucemia/tratamento farmacológico , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/uso terapêutico , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/uso terapêutico , Endotoxinas/química , Endotoxinas/uso terapêutico , Humanos , Leucemia/metabolismo , Controle Biológico de Vetores
20.
Curr Pharm Des ; 28(2): 104-115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34348617

RESUMO

With the increasing worldwide rate of chronic diseases, such as cancer, the development of novel techniques to improve the efficacy of therapeutic agents is highly demanded. Nanoparticles are especially well suited to encapsulate drugs and other therapeutic agents, bringing additional advantages, such as less frequent dosage requirements, reduced side effects due to specific targeting, and therefore increased patient compliance. However, with the increasing use of nanoparticles and their recent launch on the pharmaceutical market, it is important to achieve high-quality control of these advanced systems. In this review, we discuss the properties of different nanoparticles, the pharmacokinetics, the biosafety issues of concern, and conclude with novel nanotherapeutics and nanotheragnostics for cancer drug delivery.


Assuntos
Nanopartículas , Neoplasias , Biofarmácia , Contenção de Riscos Biológicos , Sistemas de Liberação de Medicamentos , Humanos , Nanomedicina/métodos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico
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