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1.
Int J Mol Sci ; 21(16)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806551

RESUMO

Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial-mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.


Assuntos
Antineoplásicos/uso terapêutico , Cromonas/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Antineoplásicos/farmacologia , Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Sinergismo Farmacológico , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Paclitaxel/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/genética
2.
PLoS One ; 17(6): e0268945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657809

RESUMO

It is important to understand how to frame the formats for promoting HIV self-testing to increase uptake among young people. In this study, we used a culture-centered model to understand the narratives of HIV self-testing preferences among young people in Nigeria. We conducted a crowdsourcing contest to solicit ideas surrounding HIV self-testing promotion among young people (10-24 years) in Nigeria from October to November 2018 as part of the 2018 World AIDS Day event. We received 903 submissions and employed thematic content analysis to evaluate 769 eligible youth narratives. Thematic content analysis of the statements from the youth narratives was guided by the PEN-3 cultural model to examine the positive, existential, and negative perceptions (beliefs and values), enablers (resources), and nurturers (roles of friends and family) of HIV self-testing promotion among young people in Nigeria. Several themes emerged as factors that influence the uptake of HIV self-testing among young people in Nigeria. Specifically, seven themes emerged as perceptions: HIV testing accessibility, stigma reduction, and autonomy (positive); HIV self-testing kit packaging and advertisements (existential); lack of knowledge and increased stigma (negative). Seven themes emerged as enablers: social media, school, and government promotion (positive); gamification and animation (existential); high cost and access to linkage to care services (negative); And seven themes emerged as nurturers: peer, families, and faith-based communities (positive); parents and family-centered approach (existential); and partners and family (negative). Our data suggests that increased awareness around HIV self-testing on current youth-friendly platforms, de-stigmatization of HIV and HIV self-testing, decreased prices for HIV self-testing kits, reliability of testing kits, increased linkage to care services, and promotion of self-testing among family members and the community will be beneficial for HIV self-testing scale-up measures among young people in Nigeria.


Assuntos
Infecções por HIV , Autoteste , Adolescente , Infecções por HIV/diagnóstico , Teste de HIV , Humanos , Nigéria , Reprodutibilidade dos Testes
3.
Biochim Biophys Acta Rev Cancer ; 1875(1): 188494, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346129

RESUMO

Bacteria present in probiotics, particularly the common Lactobacillus and Bifidobacterium microbes, have been found to induce anti-cancer action by enhancing cancer cell apoptosis and protecting against oxidative stress. Probiotics supplements also decrease the cancer-producing microorganism Fusobacterium. Studies have demonstrated that gut microbiota modifies the effect of chemo/radiation therapy. Gut microbes not only enhance the action of chemotherapy drugs but also reduce the side effects of these medications. Additionally, gut microbes reduce immunotherapy toxicity, in particular, the presence of Bacteroidetes or Bifidobacterium decreases the development of colitis by ipilimumab therapy. Probiotics supplements containing Bifidobacterium also reduce chemotherapy-induced mucositis and radiation-induced diarrhea. This review focused on elucidating the mechanism behind the anti-cancer action of Bifidobacterium species. Available studies have revealed Bifidobacterium species decrease cancer cell proliferation via the inhibition of growth factor signaling as well as inducing mitochondrial-mediated apoptosis. Moreover, Bifidobacterium species reduce the adverse effects of chemo/immuno/radiation therapy by inhibiting proinflammatory cytokines. Further clinical studies are needed to identify the powerful and suitable Bifidobacterium strain for the development of adjuvant therapy to support chemo/immuno/radiation therapy.


Assuntos
Antineoplásicos/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Probióticos/uso terapêutico , Antineoplásicos/efeitos adversos , Bifidobacterium/efeitos dos fármacos , Citocinas/genética , Suplementos Nutricionais/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Lactobacillus/efeitos dos fármacos , Neoplasias/genética , Neoplasias/microbiologia , Neoplasias/patologia
4.
Implement Sci Commun ; 2(1): 126, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742357

RESUMO

BACKGROUND: Advances and proliferation of technologies such as mobile phones may provide opportunities to improve access to HIV/STI services and reach young people with high risk for HIV and STI. However, the reach, uptake, and sustainability of mobile health (mHealth) HIV/STI interventions targeting young people aged 10-24 years in low- and middle-income countries (LMICs) are largely unknown. To address this gap and to inform implementation science research, a review was conducted to summarize what is known, and what we need to know about implementing mhealth interventions for HIV/STI prevention targeting young people in LMICs. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for this review. Drawing upon Proctor's eight implementation outcome measures, we evaluated the acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, and sustainability of  m-health HIV/STI interventions targeting young people in LMICs. The search was performed from September 2020-January 2021 and updated on March 1, 2021, in Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, SCOPUS, Global Health, and Web of Science. Eligible studies were required to include an HIV/STI prevention outcome, target young people aged 10-24 years, include a comparison/control group, and reporting of atleast one implementation outcome as outlined by Proctor. RESULTS: A total of 1386 articles were located, and their titles and abstracts were screened. Of these, 57 full-text articles were reviewed and subsequently, and 11 articles representing 6 unique interventions were included in the systematic review. Acceptability 6 (100%), appropriateness 6 (100%), and feasibility 5(83%) were the most frequently evaluated implementation outcomes. Adoption 2 (33%), fidelity 1 (17%), and cost 1 (17%) were rarely reported; penetration and sustainability were not reported. CONCLUSIONS: This review contributes to implementation science literature by synthesizing key implementation outcomes of mHealth HIV/STI interventions targeting young people in LMICs. Future research is needed on m-health HIV/STI implementation outcomes, particularly the penetration, cost, and long-term sustainability of these interventions. Doing so will enhance the field's understanding of the mechanisms by which these interventions lead or do not lead to changes in high HIV/STI risk and vulnerability among young people in LMICs.

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