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1.
Ecotoxicol Environ Saf ; 278: 116349, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38714081

RESUMO

BACKGROUND: Exposures to polyaromatic hydrocarbons (PAHs) contribute to cancer in the fire service. Fire investigators are involved in evaluations of post-fire scenes. In the US, it is estimated that there are up to 9000 fire investigators, compared to approximately 1.1 million total firefighting personnel. This exploratory study contributes initial evidence of PAH exposures sustained by this understudied group using worn silicone passive samplers. OBJECTIVES: Evaluate PAH exposures sustained by fire investigators at post-fire scenes using worn silicone passive samplers. Assess explanatory factors and health risks of PAH exposure at post-fire scenes. METHODS: As part of a cross-sectional study design, silicone wristbands were distributed to 16 North Carolina fire investigators, including eight public, seven private, and one public and private. Wristbands were worn during 46 post-fire scene investigations. Fire investigators completed pre- and post-surveys providing sociodemographic, occupational, and post-fire scene characteristics. Solvent extracts from wristbands were analyzed via gas chromatography-mass spectrometry (GC-MS). Results were used to estimate vapor-phase PAH concentration in the air at post-fire scenes. RESULTS: Fire investigations lasted an average of 148 minutes, standard deviation ± 93 minutes. A significant positive correlation (r=0.455, p<.001) was found between investigation duration and PAH concentrations on wristbands. Significantly greater time-normalized PAH exposures (p=0.039) were observed for investigations of newer post-fire scenes compared to older post-fire scenes. Regulatory airborne PAH exposure limits were exceeded in six investigations, based on exposure to estimated vapor-phase PAH concentrations in the air at post-fire scenes. DISCUSSION: Higher levels of off-gassing and suspended particulates at younger post-fire scenes may explain greater PAH exposure. Weaker correlations are found between wristband PAH concentration and investigation duration at older post-fire scenes, suggesting reduction of off-gassing PAHs over time. Exceedances of regulatory PAH limits indicate a need for protection against vapor-phase contaminants, especially at more recent post-fire scenes.


Assuntos
Bombeiros , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Silicones , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Exposição Ocupacional/análise , Estudos Transversais , North Carolina , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Monitoramento Ambiental/métodos , Poluentes Ocupacionais do Ar/análise , Cromatografia Gasosa-Espectrometria de Massas , Punho
2.
Curr Med Chem ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347787

RESUMO

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines. Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists. Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.

3.
Int J Mol Sci ; 24(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569520

RESUMO

This research introduces a novel pipeline that couples machine learning (ML), and molecular docking for accelerating the process of small peptide ligand screening through the prediction of peptide-protein docking. Eight ML algorithms were analyzed for their potential. Notably, Light Gradient Boosting Machine (LightGBM), despite having comparable F1-score and accuracy to its counterparts, showcased superior computational efficiency. LightGBM was used to classify peptide-protein docking performance of the entire tetrapeptide library of 160,000 peptide ligands against four viral envelope proteins. The library was classified into two groups, 'better performers' and 'worse performers'. By training the LightGBM algorithm on just 1% of the tetrapeptide library, we successfully classified the remaining 99%with an accuracy range of 0.81-0.85 and an F1-score between 0.58-0.67. Three different molecular docking software were used to prove that the process is not software dependent. With an adjustable probability threshold (from 0.5 to 0.95), the process could be accelerated by a factor of at least 10-fold and still get 90-95% concurrence with the method without ML. This study validates the efficiency of machine learning coupled to molecular docking in rapidly identifying top peptides without relying on high-performance computing power, making it an effective tool for screening potential bioactive compounds.


Assuntos
Peptídeos , Proteínas , Ligantes , Simulação de Acoplamento Molecular , Proteínas/química , Peptídeos/metabolismo , Algoritmos , Aprendizado de Máquina , Ligação Proteica
4.
Anal Chem ; 95(36): 13488-13496, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37606488

RESUMO

Cervical cancers constitute a large disease burden in developing countries, with the human papillomavirus (HPV) being responsible for most cervical lesions. Many regions in low-resource countries lack adequate access to sensitive point-of-care (POC) screening tools, preventing timely diagnosis and treatment. To reduce screening barriers, we developed a POC HPV molecular test that detects 14 high-risk HPV types in 30 min in a single assay. We introduced innovations to the underlying amplification (recombinase polymerase amplification) and detection methodologies such as improved probe design, reagent lyophilization, and pipette-less processing to increase sensitivity while enabling minimally trained personnel to conduct reproducible testing. Based on 198 clinically derived samples, we demonstrated a sensitivity of 93% and a specificity of 73% compared to an FDA-approved polymerase chain reaction-based clinical method. Our modified pipette-less simplified assay had a sensitivity of 96% and a specificity of 83%. The application of our assay is intended as a near-patient screening tool with further evaluation by a clinician for confirmation.


Assuntos
Papillomavirus Humano , Infecções por Papillomavirus , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Infecções por Papillomavirus/diagnóstico , Testes Imediatos , Genótipo
5.
Pharmaceutics ; 15(7)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37514162

RESUMO

In vivo imaging has enabled impressive advances in biological research, both preclinical and clinical, and researchers have an arsenal of imaging methods available. Bioluminescence imaging is an advantageous method for in vivo studies that allows for the simple acquisition of images with low background signals. Researchers have increasingly been looking for ways to improve bioluminescent imaging for in vivo applications, which we sought to achieve by developing a bioluminescent probe that could specifically target cells of interest. We chose pancreatic ductal adenocarcinoma (PDAC) as the disease model because it is the most common type of pancreatic cancer and has an extremely low survival rate. We targeted the epidermal growth factor receptor (EGFR), which is frequently overexpressed in pancreatic cancer cells, using an EGFR-specific affibody to selectively identify PDAC cells and delivered a Gaussia luciferase (GLuc) bioluminescent protein for imaging by engineering a fusion protein with both the affibody and the bioluminescent protein. This fusion protein was then complexed with a G5-PAMAM dendrimer nanocarrier. The dendrimer was used to improve the protein stability in vivo and increase signal strength. Our targeted bioluminescent complex had an enhanced uptake into PDAC cells in vitro and localized to PDAC tumors in vivo in pancreatic cancer xenograft mice. The bioluminescent complexes could delineate the tumor shape, identify multiple masses, and locate metastases. Through this work, an EGFR-targeted bioluminescent-dendrimer complex enabled the straightforward identification and imaging of pancreatic cancer cells in vivo in preclinical models. This argues for the targeted nanocarrier-mediated delivery of bioluminescent proteins as a way to improve in vivo bioluminescent imaging.

6.
Elife ; 112022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454035

RESUMO

Background: MicroRNAs (miRNA) and other components contained in extracellular vesicles may reflect the presence of a disease. Lung tissue, sputum, and sera of individuals with idiopathic pulmonary fibrosis (IPF) show alterations in miRNA expression. We designed this study to test whether urine and/or tissue derived exosomal miRNAs from individuals with IPF carry cargo that can promote fibrosis. Methods: Exosomes were isolated from urine (U-IPFexo), lung tissue myofibroblasts (MF-IPFexo), serum from individuals with IPF (n=16) and age/sex-matched controls without lung disease (n=10). We analyzed microRNA expression of isolated exosomes and their in vivo bio-distribution. We investigated the effect on ex vivo skin wound healing and in in vivo mouse lung models. Results: U-IPFexo or MF-IPFexo expressed miR-let-7d, miR-29a-5p, miR-181b-3p and miR-199a-3p consistent with previous reports of miRNA expression obtained from lung tissue/sera from patients with IPF. In vivo bio-distribution experiments detected bioluminescent exosomes in the lung of normal C57Bl6 mice within 5 min after intravenous infusion, followed by distribution to other organs irrespective of exosome source. Exosomes labeled with gold nanoparticles and imaged by transmission electron microscopy were visualized in alveolar epithelial type I and type II cells. Treatment of human and mouse lung punches obtained from control, non-fibrotic lungs with either U-IPFexo or MF-IPFexo produced a fibrotic phenotype. A fibrotic phenotype was also induced in a human ex vivo skin model and in in vivo lung models. Conclusions: Our results provide evidence of a systemic feature of IPF whereby exosomes contain pro-fibrotic miRNAs when obtained from a fibrotic source and interfere with response to tissue injury as measured in skin and lung models. Funding: This work was supported in part by Lester and Sue Smith Foundation and The Samrick Family Foundation and NIH grants R21 AG060338 (SE and MKG), U01 DK119085 (IP, RS, MTC).


Assuntos
Exossomos , Fibrose Pulmonar Idiopática , Nanopartículas Metálicas , MicroRNAs , Animais , Camundongos , Humanos , Ouro , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fibrose
7.
Nanomaterials (Basel) ; 12(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36558293

RESUMO

Metal nanoparticles are effective radiosensitizers that locally enhance radiation doses in targeted cancer cells. Compared with other metal nanoparticles, gold nanoparticles (GNPs) exhibit high biocompatibility, low toxicity, and they increase secondary electron scatter. Herein, we investigated the effects of active-targeting GNPs on the radiation-induced bystander effect (RIBE) in prostate cancer cells. The impact of GNPs on the RIBE presents implications for secondary cancers or spatially fractionated radiotherapy treatments. Anti-prostate-specific membrane antigen (PSMA) antibodies were conjugated with PEGylated GNPs through EDC-NHS chemistry. The media transfer technique was performed to induce the RIBE on the non-irradiated bystander cells. This study focused on the LNCaP cell line, because it can model a wide range of stages relating to prostate cancer progression, including the transition from androgen dependence to castration resistance and bone metastasis. First, LNCaP cells were pretreated with phosphate buffered saline (PBS) or PSMA-targeted GNPs (PGNPs) for 24 h and irradiated with 160 kVp X-rays (0-8 Gy). Following that, the collected culture media were filtered (sterile 0.45 µm polyethersulfone) in order to acquire PBS- and PGNP- conditioned media (CM). Then, PBS- and PGNP-CM were transferred to the bystander cells that were loaded with/without PGNPs. MTT, γ-H2AX, clonogenic assays and reactive oxygen species assessments were performed to compare RIBE responses under different treatments. Compared with 2 Gy-PBS-CM, 8 Gy-PBS-CM demonstrated a much higher RIBE response, thus validating the dose dependence of RIBE in LNCaP cells. Compared with PBS-CM, PGNP-CM exhibited lower cell viability, higher DNA damage, and a smaller survival fraction. In the presence of PBS-CM, bystander cells loaded with PGNPs showed increased cell death compared with cells that did not have PGNPs. These results demonstrate the PGNP-boosted expression and sensitivity of RIBE in prostate cancer cells.

8.
Clin Transl Gastroenterol ; 13(12): e00547, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36413804

RESUMO

Crohn's disease (CD) is an idiopathic inflammatory condition of the gastrointestinal tract with the primary method of diagnosis and follow-up being colonoscopy. A disturbed host-microbiome interaction, including the presence of pathobionts, is implicated in initiation and perpetuation of inflammation. As such, we hypothesized that bacterial quorum-sensing (QS) molecules (QSMs), small molecules bacteria generate to regulate gene expression, would be elevated in patients with CD. We collected serum at the time of colonoscopy from patients with CD and healthy controls, determining through biosensors for QSMs that patients with CD had significantly elevated levels of QSMs in serum. Expansion of these studies may allow for QSM levels in serum to serve as a biomarker for intestinal inflammation in patients with CD.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/microbiologia , Bactérias , Inflamação , Gerenciamento Clínico
9.
J Inflamm Res ; 15: 2795-2801, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535052

RESUMO

Acne is the most common skin condition in the United States and affects approximately 85% of people ages 12-24. As a multifactorial disease, the pathogenesis of acne involves overproduction of sebum, irregular shedding of the cutaneous cells, accretion of Cutibacterium acnes at the pilosebaceous unit, and inflammation. To date, conventional therapies for acne include topical retinoids, over-the-counter bactericidal agents, and systematic treatments, such as oral antibiotics and isotretinoin. However, the potential for significant side effects and risk of antibiotic resistance remain limitations in these therapies, in turn reducing patient compliance and adherence to acne treatment regimens. Therefore, the use of natural plant-derived treatments or phytotherapeutics as an alternative or adjuvant to conventional treatments is attractive to patients due to their safety and minimal risk for side effects. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid of the Cannabis sativa (hemp) plant. The therapeutic use of CBD has been implicated in many diseases with an inflammatory aspect, including cancers, neurodegeneration, immunological disorders, and dermatological diseases. However, the use of CBD for acne treatment remains a novel window of opportunity. Herein, we summarize the available and relevant data, highlighting the potential use of CBD in acne for its anti-inflammatory properties. To that extent, CBD and other cannabis constituents such as cannabis seeds were found to reduce inflammation and expression of inflammatory cytokines including TNF-α and IL-1ß when evaluated in acne-like conditions. Treatment with these cannabis extracts was also found to be safe and well tolerated, further strengthening the prospect of CBD as an anti-inflammatory therapeutic for acne.

10.
Biofactors ; 48(3): 665-682, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35084073

RESUMO

The CD36/FAT scavenger receptor/fatty acids transporter regulates cellular lipid accumulation important for inflammation, atherosclerosis, lipotoxicity, and initiation of cellular senescence. Here we compared the regulatory effects of the vitamin E analogs alpha-tocopherol (αT), alpha-tocopheryl phosphate (αTP), and αTP/ßCD (a nanocarrier complex between αTP and ß-cyclodextrin [ßCD]) and investigated their regulatory effects on lipid accumulation, phagocytosis, and senescence in THP-1 monocytes and macrophages. Both, αTP and αTP/ßCD inhibited CD36 surface exposition stronger than αT leading to more pronounced CD36-mediated events such as inhibition of DiI-labeled oxLDL uptake, phagocytosis of fluorescent Staphylococcus aureus bioparticles, and cell proliferation. When compared to ßCD, the complex of αTP/ßCD extracted cholesterol from cellular membranes with higher efficiency and was associated with the delivery of αTP to the cells. Interestingly, both, αTP and more so αTP/ßCD inhibited lysosomal senescence-associated beta-galactosidase (SA-ß-gal) activity and increased lysosomal pH, suggesting CD36-mediated uptake into the endo-lysosomal phagocytic compartment. Accordingly, the observed pH increase was more pronounced with αTP/ßCD in macrophages whereas no significant increase occurred with αT, alpha-tocopheryl acetate (αTA) or ßCD. In contrast to αT and αTA, the αTP molecule is di-anionic at neutral pH, but upon moving into the acidic endo-lysosomal compartment becomes protonated and thus is acting as a base. Moreover, it is expected to be retained in lysosomes since it still carries one negative charge, similar to lysosomotropic drugs. Thus, treatment with αTP or αTP/ßCD and/or inhibition of conversion of αTP to αT as it occurs in aged cells may counteract CD36-mediated overlapping inflammatory, senescent, and atherosclerotic events.


Assuntos
Monócitos , Vitamina E , Antígenos CD36/genética , Antígenos CD36/metabolismo , Lipoproteínas LDL/farmacologia , Macrófagos , Fagocitose , Vitamina E/metabolismo , Vitamina E/farmacologia
11.
Pharmaceutics ; 13(12)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34959441

RESUMO

Gene therapy is a good alternative for determined congenital disorders; however, there are numerous limitations for gene delivery in vivo including targeted cellular uptake, intracellular trafficking, and transport through the nuclear membrane. Here, a modified G5 polyamidoamine (G5 PAMAM) dendrimer-DNA complex was developed, which will allow cell-specific targeting to skeletal muscle cells and transport the DNA through the intracellular machinery and the nuclear membrane. The G5 PAMAM nanocarrier was modified with a skeletal muscle-targeting peptide (SMTP), a DLC8-binding peptide (DBP) for intracellular transport, and a nuclear localization signaling peptide (NLS) for nuclear uptake, and polyplexed with plasmid DNA containing the GFP-tagged microdystrophin (µDys) gene. The delivery of µDys has been considered as a therapeutic modality for patients suffering from a debilitating Duchenne muscular dystrophy (DMD) disorder. The nanocarrier-peptide-DNA polyplexes were prepared with different charge ratios and characterized for stability, size, surface charge, and cytotoxicity. Using the optimized nanocarrier polyplexes, the transfection efficiency in vitro was determined by demonstrating the expression of the GFP and the µDys protein using fluorescence and Western blotting studies, respectively. Protein expression in vivo was determined by injecting an optimal nanocarrier polyplex formulation to Duchenne model mice, mdx4Cv. Ultimately, these nanocarrier polyplexes will allow targeted delivery of the microdystrophin gene to skeletal muscle cells and result in improved muscle function in Duchenne muscular dystrophy patients.

12.
Ecotoxicol Environ Saf ; 228: 112929, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34768049

RESUMO

Carcinogens are emitted in significant quantities at fire scenes and are a major contributor in the increased cancer risk observed in firefighters when compared to the general population. A knowledge gap exists in the current understanding of the distribution of these toxic compounds within a localized fire incident response arena. Here, we employ stationary silicone-based passive samplers at controlled live fire trainings to evaluate the deposition behavior of polyaromatic hydrocarbons (PAHs) emitted by fires. Our findings indicate significantly greater total PAH exposure in fires fueled by biomass and wood compared to fires burning cleaner fuels, such as propane. A 22% increase in total PAH deposition and a 68% increase in high molecular weight PAH deposition was recorded for biomass fueled fires compared to propane fueled fires. Furthermore, we observe that heavier molecular weight PAHs exhibit a pronounced deposition front within a certain radius of the hot zone, whereas low molecular weight PAHs are more uniformly distributed throughout the area. These findings highlight that the warm zones and cold zones of fire situations yield elevated levels of carcinogen exposure to first responders within them. We anticipate that these findings will help inform decisions made by emergency personnel when evaluating risk for the hot zone, warm zone, and cold zone of urban fires helping ease the carcinogenic risk experienced.

13.
ACS Appl Bio Mater ; 4(1): 229-251, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34250454

RESUMO

Polymeric biomaterials have been used in a variety of applications, like cargo delivery and tissue scaffolding, because they are easily synthesized and can be adapted to many systems. However, there is still a need to further enhance and improve their functions to progress their use in the biomedical field. A promising solution is to modify the polymer surfaces with peptides that can increase biocompatibility, cellular interactions, and receptor targeting. In recent years, peptide modifications have been used to overcome many challenges to polymer biomaterial development. This review discusses recent progress in developing peptide-modified polymers for therapeutic applications including cell-specific targeting and tissue engineering. Furthermore, we will explore some of the most frequently studied base components of these biomaterials.


Assuntos
Biopolímeros/química , Peptídeos/química , Animais , Células Apresentadoras de Antígenos/citologia , Células Apresentadoras de Antígenos/metabolismo , Biopolímeros/metabolismo , Biopolímeros/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Engenharia Tecidual , Alicerces Teciduais/química
14.
Biosens Bioelectron ; 191: 113471, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34246123

RESUMO

The design of a new class of selective and high affinity antibody mimetics termed clamp peptide (CP) that incorporate three short peptides structurally and mechanically mimicking a clamp is proposed as sensing elements for a reliable detection sensor platform. The CPs consist of two short peptides functioning as arms that recognize two different epitopes in the target protein and are connected by a third short peptide that acts as a hinge between the peptide arms. For the construction of CPs, we employed a rational design combined with computational methods. To illustrate our approach, we designed a CP that binds selectively to the envelope protein of the Zika virus (ZIKV). The virtual docking cycles were run maximizing the discrimination between ZIKV and Dengue virus (DENV) envelope proteins. DENV was chosen among the flavivirus family because it has high structural similarity with ZIKV. When employed in a colorimetric binding assay or in label-free electrochemical impedance sensor format, the CP was selective for ZIKV vs DENV particles showing detection limit under 104 copies/mL, comparable to anti-ZIKV antibodies. Apparent dissociation binding constants (Kd) confirmed a better performance of CPs than mono-arm peptides (Kd of best CP = 162 nM ± 23 nM; Kd of best mono-arm peptide = 11.15 ± 2.76 µM). The performance of the assays based on CPs was also verified in serum and urine (diluted 1:10 and 1:1 respectively). The detection limits of CPs decreased about one order of magnitude for ZIKV detection in serum or urine, with a distinct analytical signal starting from 105 copies/mL of ZIKV.


Assuntos
Técnicas Biossensoriais , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Anticorpos Antivirais , Reações Cruzadas , Humanos , Peptídeos , Infecção por Zika virus/diagnóstico
15.
Head Neck ; 43(11): 3618-3630, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34331493

RESUMO

Human papilloma virus (HPV) infection is a key risk factor and etiology for oropharyngeal squamous cell carcinoma (OPSCC). HPV-induced OPSCC is rapidly increasing in incidence, with men experiencing increased mortality. When identified at an early stage, HPV-induced OPSCC can be successfully treated. Diagnosis of HPV-related OPSCC relies on an expert physical examination and invasive biopsy. Since saliva bathes the oropharyngeal mucosa and can be collected noninvasively, saliva obtained via salivary risings is an attractive body fluid for early detection of HPV-induced OPSCC. A plethora of DNA, RNA, and protein salivary biomarkers have been explored. This review discusses these markers and their robustness for detecting oncogenic HPV in OPSCC saliva samples. Methods detecting HPV DNA were more reliable than those detecting RNA, albeit both require time-consuming analyses. Salivary HPV proteomics are a new, promising focus of HPV detection research, and while more practical, lag behind nucleic acid detection methods in their development.


Assuntos
Alphapapillomavirus , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Biomarcadores , Humanos , Masculino , Neoplasias Orofaríngeas/diagnóstico , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço
16.
Cancers (Basel) ; 14(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35008322

RESUMO

BACKGROUND: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. LITERATURE REVIEW: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. CONCLUSION: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.

17.
Immunotargets Ther ; 9: 131-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903924

RESUMO

The immune-suppressive effects of cannabidiol (CBD) are attributed to the modulation of essential immunological signaling pathways and receptors. Mechanistic understanding of the pharmacological effects of CBD emphasizes the therapeutic potential of CBD as a novel immune modulator. Studies have observed that the antagonists of CB1 and CB2 receptors and transient receptor potential vanilloid 1 reverse the immunomodulatory effects of CBD. CBD also inhibits critical activators of the Janus kinase/signal transducer and activator of transcription signaling pathway, as well as the nucleotide-binding oligomerization domain-like receptor signaling pathway, in turn decreasing pro-inflammatory cytokine production. Furthermore, CBD protects against cellular damage incurred during immune responses by modulating adenosine signaling. Ultimately, the data overwhelmingly support the immunosuppressive effects of CBD and this timely review draws attention to the prospective development of CBD as an effective immune modulatory therapeutic.

18.
Ecotoxicol Environ Saf ; 205: 111100, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32911453

RESUMO

Compared to the general population, firefighters are known to sustain greater levels of exposure to hazardous compounds, despite their personal protective equipment, also known as turnout gear. Among the most significant toxins that firefighters are chronically exposed to are polycyclic aromatic hydrocarbons (PAHs). Additionally, firefighters have also been noted to exhibit an increased incidence of certain types of cancer. Considering a probable link between exposure to PAHs and increased rates of cancer in the fire service, we aim to document ambient chemical concentrations in the firefighter work environment. Our strategy involves the use of silicone-based wristbands that have the capacity to passively sorb PAHs. To determine if wristbands can serve as an effective chemical monitoring device for the fire service, silicone wristbands were pilot-tested as personal sampling devices for work environment risk monitoring in active-duty firefighters. Recovered wristbands underwent multiple extraction steps, followed by GC-MS analysis to demonstrate their efficacy in monitoring PAHs in the firefighter environment. Initial findings from all wristband samples taken from firefighters showed multiple exposures to various PAHs of concern for the health of the firefighters when in a fire environment. In addition to PAH monitoring, we examined known and potential sources of PAH contamination in their work environment. To that end, profiles of elevated PAH concentrations were documented at various fire stations throughout South Florida, for individual firefighters both during station duties and active fire response.


Assuntos
Poluentes Ocupacionais do Ar/análise , Bombeiros , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Carcinógenos/análise , Monitoramento Ambiental , Florida , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Neoplasias , Exposição Ocupacional/estatística & dados numéricos , Silicones/análise
19.
Obes Surg ; 30(11): 4331-4338, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32860570

RESUMO

PURPOSE: A subpopulation of weight loss surgery (WLS) patients endorse cannabis and/or opioid use; however, impact on post-WLS anxiety and depression is unclear. This study examined the influence of the independent and combined use of cannabis and opioids on (1) depression and anxiety, (2) duodenum serotonin and cortisol, and (3) total percent weight loss. MATERIALS AND METHODS: A cross-sectional analysis was conducted among patients (N = 18) who had biomarkers of serotonin and cortisol collected from the duodenum during WLS. Cannabis and opioid use was determined by self-reported lifetime, past-year, and past 30-day use. The Beck Anxiety Inventory and Depression Inventory-II assessed depression and anxiety symptoms. Total percent weight loss was calculated from pre-WLS and post-WLS weight (kg). Chi-squared analyses and t tests were conducted. RESULTS: Over a quarter (27.8%) were cannabis-only users and 16.7% used a combination of cannabis and opioids. None reported using only opioids in this sample. Combination users presented with greater depressive symptoms (22.7%, p = 0.01) and greater total percent weight loss (34.1%, p = 0.04) than cannabis users (7.8, 23.2%, respectively). Cannabis users had greater serotonin (p = 0.02) and cortisol (p = 0.01) levels than combination users and never users. CONCLUSIONS: Cannabis users had greater cortisol levels than never users and combination users. Combination users had greater weight loss and depression symptoms than cannabis users. Future studies should consider a larger sample size, utilization of a cohort design to address causality, and examination of the type, dose, and route of cannabis and opioid administration to further understand the impact of the combined use of cannabis and opioids post-WLS.


Assuntos
Cirurgia Bariátrica , Cannabis , Obesidade Mórbida , Analgésicos Opioides , Biomarcadores , Estudos Transversais , Humanos , Saúde Mental , Obesidade Mórbida/cirurgia , Redução de Peso
20.
J Occup Environ Med ; 62(11): e611-e615, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32826549

RESUMO

OBJECTIVE: Characterize objective measurements of carcinogenic exposure using passive sampling silicone-based wristbands among Dominican firefighters. METHODS: Firefighters from a metropolitan fire service in the Dominican Republic were asked to wear a silicone-based wristband during one typical 24-hour shift. A pre- and post-shift survey collected work shift characteristics. Wristbands were processed for the type and quantity of polycyclic aromatic hydrocarbons (PAHs), a family of known carcinogenic compounds. RESULTS: Fifteen firefighters wore a wristband, of which 73.3% responded to a fire with an average of 3.7 calls during the shift. Total PAH exposure was significantly higher among firefighters who responded to a fire versus firefighters with no fire during their shift (261 parts per billion [ppb] vs 117 ppb, P = 0.003). CONCLUSIONS: Silicone-based wristbands as objective passive samplers documented exposure to carcinogenic compounds during a typical 24-hour firefighter shift.


Assuntos
Poluentes Ocupacionais do Ar , Carcinógenos , Bombeiros , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Ocupacionais do Ar/análise , Carcinógenos/análise , República Dominicana , Monitoramento Ambiental , Humanos , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Silicones
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