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3.
Pathol Res Pract ; 254: 155097, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38277745

RESUMO

Exosomes are nanometric membrane vesicles of late endosomal origin that are released by most, if not all, cell types as a sophisticated means of intercellular communication. They play an essential role in the movement of materials and information between cells, transport a variety of proteins, lipids, RNA, and other vital data, and over time, they become an essential part of the drug delivery system and a marker for the early detection of many diseases. Dendritic cells have generated interest in cancer immunotherapy due to their ability to initiate and modify effective immune responses. Apart from their cytokine release and direct interactions with other cell types, DCs also emit nanovesicles, such as exosomes, that contribute to their overall activity. Numerous studies have demonstrated exosomes to mediate and regulate immune responses against cancers. Dendritic cell-derived exosomes (DCs) have attracted a lot of attention as immunotherapeutic anti-cancer treatments since it was found that they contain functional MHC-peptide complexes along with a variety of other immune-stimulating components that together enable immune cell-dependent tumor rejection. By enhancing tumor and immunosuppressive immune cells or changing a pro-inflammatory milieu to inhibit tumor advancement, exosomes generated from dendritic cells can initiate and support tumor growth. This study reviewed the immunogenicity of dendritic cell-derived exosomes and strategies for expanding their immunogenic potential as novel and effective anti-cancer therapies.


Assuntos
Exossomos , Neoplasias , Humanos , Exossomos/genética , Células Dendríticas , Neoplasias/patologia , Imunidade , Imunoterapia
4.
Pathol Res Pract ; 252: 154888, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37948996

RESUMO

A severe global health concern is the rising incidence and mortality rate of colorectal cancer (CRC). Chemotherapy, which is typically used to treat CRC, is known to have limited specificity and can have noticeable side effects. A paradigm shift in cancer treatment has been brought about by the development of targeted therapies, which has led to the appearance of pharmacological agents with improved efficacy and decreased toxicity. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), and BRAF are among the molecular targets covered in this review that are used in targeted therapy for CRC. The current discussion also covers advancements in targeted therapeutic approaches, such as antibody-drug conjugates, immune checkpoint inhibitors, and chimeric antigen receptor (CAR) T-cell therapy. A review of the clinical trials and application of these particular therapies in treating CRC is also done. Despite the improvements in targeted therapy for CRC, problems such as drug resistance and patient selection remain to be solved. Despite this, targeted therapies have offered fresh possibilities for identifying and treating CRC, paving the way for the development of personalized medicine and extending the life expectancy and general well-being of CRC patients.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Humanos , Antineoplásicos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Pesquisa Translacional Biomédica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
5.
Life Sci ; 333: 122139, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37783266

RESUMO

AIMS: Pain is a profoundly debilitating symptom in cancer patients, leading to disability, immobility, and a marked decline in their quality of life. This study aimed to investigate the potential roles of miR-199a-3p in a murine model of bone cancer pain induced by tumor cell implantation in the medullary cavity of the femur. MATERIALS AND METHODS: We assessed pain-related behaviors, including the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF). To investigate miRNA expression and its targets in astrocytes, we employed a combination of RNA-seq analysis, qRT-PCR, Western blotting, EdU, TUNEL, ChIP, ELISA, and luciferase reporter assays in mice (C3H/HeJ) with bone cancer pain and control groups. KEY FINDINGS: On days 10, 14, 21, and 28 post-surgery, we observed significant differences in PWTL, PWMT, and NSF when compared to the sham group (P < 0.001). qRT-PCR assays and miRNA sequencing results confirmed reduced miR-199a-3p expression in astrocytes of mice with bone cancer pain. Gain- and loss-of-function experiments demonstrated that miR-199a-3p suppressed astrocyte activation and the expression of inflammatory cytokines. In vitro investigations revealed that miR-199a-3p mimics reduced the levels of inflammatory factors in astrocytes and MyD88/NF-κB proteins. Furthermore, treatment with a miR-199a-3p agonist resulted in reduced expression of MyD88, TAK1, p-p65, and inflammatory mediators, along with decreased astrocyte activation in the spinal cord. SIGNIFICANCE: Collectively, these findings demonstrate that upregulation of miR-199a-3p may offer a therapeutic avenue for mitigating bone cancer pain in mice by suppressing neuroinflammation and inhibiting the MyD88/NF-κB signaling pathway.


Assuntos
Neoplasias Ósseas , Dor do Câncer , MicroRNAs , Osteossarcoma , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Ósseas/complicações , Neoplasias Ósseas/genética , Dor do Câncer/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos C3H , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , Osteossarcoma/genética , Qualidade de Vida
6.
Mol Cancer ; 22(1): 169, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814270

RESUMO

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos , Composição de Medicamentos
7.
Cancer Chemother Pharmacol ; 92(6): 439-453, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37768333

RESUMO

Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Autofagia/genética , Resistência a Medicamentos
8.
Pathol Res Pract ; 248: 154666, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37487316

RESUMO

In the entire world, prostate cancer (PCa) is one of the most common and deadly cancers. Treatment failure is still common among patients, despite PCa diagnosis and treatment improvements. Inadequate early diagnostic markers and the emergence of resistance to conventional therapeutic approaches, particularly androgen-deprivation therapy, are the causes of this. Long non-coding RNAs (lncRNAs), as an essential group of regulatory molecules, have been reported to be dysregulated through prostate tumorigenesis and hold great promise as diagnostic targets. Besides, lncRNAs regulate the malignant features of PCa cells, such as proliferation, invasion, metastasis, and drug resistance. These multifunctional RNA molecules interact with other molecular effectors like miRNAs and transcription factors to modulate various signaling pathways, including AR signaling. This study aimed to compile new knowledge regarding the role of lncRNA through prostate tumorigenesis in terms of their effects on the various malignant characteristics of PCa cells; in light of these characteristics and the significant potential of lncRNAs as diagnostic and therapeutic targets for PCa. AVAILABILITY OF DATA AND MATERIALS: Not applicable.


Assuntos
MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Masculino , Humanos , Neoplasias da Próstata/patologia , RNA Longo não Codificante/genética , Antagonistas de Androgênios , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica/genética
9.
Life Sci ; 329: 121968, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37487941

RESUMO

AIMS: Retinal ischemia/reperfusion (I/R) injury is a common pathological basis for various ophthalmic diseases. This study aimed to investigate the potential of sulforaphane (SFN) and Homer1a in regulating cell apoptosis induced by retinal I/R injury and to explore the underlying regulatory mechanism between them. MATERIALS AND METHODS: In in vivo experiments, C57BL/6J mice and Homer1flox/-/Homer1a+/-/Nestin-Cre+/- mice were used to construct retinal I/R injury models. In vitro experiments utilized the oxygen-glucose deprivation-reperfusion (OGD/R) injury model with primary retinal ganglion cells (RGCs). The effects of Homer1a and SFN on cell apoptosis were observed through pathological analyses, flow cytometry, and visual electrophysiological assessments. KEY FINDINGS: We discovered that after OGD/R injury, apoptosis of RGCs and intracellular Ca2+ activity significantly increased. However, these changes were reversed upon the addition of SFN, and similar observations were reproduced in in vivo studies. Furthermore, both in vivo and in vitro studies confirmed the upregulation of Homer1a after I/R, which could be further enhanced by the administration of SFN. Moreover, upregulation of Homer1a resulted in a reduction in cell apoptosis and pro-apoptotic proteins, while downregulation of Homer1a had the opposite effect. Flash visual evoked potential, oscillatory potentials, and escape latency measurements in mice supported these findings. Furthermore, the addition of SFN strengthened the neuroprotective effects in the OGD/R + H+ group but weakened them in Homer1flox/-/Homer1a+/-/Nestin-Cre+/- mice. SIGNIFICANCE: These results indicate that Homer1a plays a significant role in the therapeutic potential of sulforaphane for retinal I/R injury, thereby providing a theoretical basis for clinical treatment.


Assuntos
Potenciais Evocados Visuais , Traumatismo por Reperfusão , Camundongos , Animais , Nestina/farmacologia , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Apoptose
10.
Poult Sci ; 102(8): 102852, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37354617

RESUMO

Major viral infections, such as Newcastle disease virus, infectious bronchitis virus, avian influenza virus, and infectious bursal disease virus, inflict significant injury to small poultry and tremendous economic damage to the poultry sector. This research aims to develop a multiplex reverse transcriptase polymerase chain reaction (m-RT-PCR) approach to simultaneously determine these important viral pathogens. The conserved segment of various viral genetic sequences was used to design and synthesize specific primers. Moreover, as positive controls, recombinant vectors were synthesized in this investigation. The d-optimal approach was used to improve PCR conditions in this investigation. Positive controls and clinical samples were used to assess the m-PCR assay's specificity, sensitivity, repeatability, and reproducibility. According to the sensitivity test findings, the m-PCR technique could generate the 8 target genes from viral genomes using 1 × 102. In addition, 8 viral pathogens were detected from the infected samples. The findings also suggest that live animal oral swabs were not significantly different from tissue sampling of a dead animal (P < 0.05), and this kit had a high sensitivity for analyzing both types of samples. The suggested m-PCR test may detect and evaluate viral infection in birds with excellent specificity, sensitivity, and throughput.


Assuntos
Doenças das Aves , Doenças das Aves Domésticas , Infecções Respiratórias , Viroses , Animais , Aves Domésticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Reprodutibilidade dos Testes , Transcrição Reversa , Galinhas , Sensibilidade e Especificidade , Viroses/veterinária , Infecções Respiratórias/veterinária , Reação em Cadeia da Polimerase/veterinária , Reação em Cadeia da Polimerase Multiplex/veterinária , Reação em Cadeia da Polimerase Multiplex/métodos , Doenças das Aves Domésticas/diagnóstico
11.
Diversitas perspectiv. psicol ; 15(1): 39-50, ene.-jun. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1001870

RESUMO

Resumen Las diferencias de oportunidades de género en el campo de la ciencia y tecnología son aún una brecha, a esto se suma las probables afectaciones psicológicas, emocionales que son de interés en el estudio porque analiza y relaciona de forma objetiva las implicaciones de género y riesgos por predisposición a conductas ansiosas en estudiantes de ciencia y tecnología de la universidad. Los participantes fueron de 4to. y 5to. año, de diferentes especialidades, la muestra estuvo constituida por 368 (192 mujeres y 176 hombres), que realizan actividades de investigación. Se aplicaron el cuestionario sobre Implicaciones de género y la escala del IDARE (Inventario de Ansiedad Rasgo-Estado) para medir ansiedad. Los resultados ponen de manifiesto que las estudiantes participan más en actividades de investigación pero también obtienen mayores niveles de ansiedad "estado". Se evaluó la vida familiar, el vivir solos, con familiares, tareas dentro del hogar, participación y aportes al conocimiento científico. Los estudiantes muestran mayor ansiedad "estado" al participar en círculos de estudio, por ser parte de investigaciones financiadas, frente a la paternidad y por responsabilidad económica en el hogar. Resaltar que hay claros indicios de afectaciones (ansiedad) a la salud psicológica-emocional por segregación vertical y horizontal de género.


Abstract The differences in gender opportunities in the field of science and technology are still a gap, in addition to the probable psychological and emotional effects that are of interest in the study because it analyzes and objectively relates the implications of gender and risks for predisposition to anxious behavior in university science and technology students. The participants are 4th and 5th year, of different specialties, the sample was constituted by 368 (192 women and 176 men), who carry out research activities. Methods: Two instruments were applied: a questionnaire on Gender Implications and the IDARE scale to measure anxiety. Results show that students participate more in research activities but also obtain higher levels of "state" anxiety. Family life, living alone, with relatives, tasks within the home, participation and contributions to scientific knowledge were evaluated. Students show greater anxiety "status" when participating in study circles, as part of funded research, as opposed to paternity and economic responsibility in the home. Highlight that there are clear indications of affectations (anxiety) to psychological health emotional by vertical and horizontal segregation of gender.

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