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1.
J Public Health Afr ; 14(9): 2334, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37942060

RESUMO

Cervical lesions, induced by high-risk oncogenic human papillomavirus (HR-HPV), in the context of HIV remains a global health challenge. We determined the effect of HR-HPV on the development of cervical lesions in women with and without HIV infection. A cross-sectional analytical study was conducted among 257 women living in Cameroon. HIV serology, HR-HPV genotyping and cervico-vaginal smear (CVS) were performed for all participants; among those declared HIV positive, plasma HIV viral load and CD4 count were measured. Statistical analyses were performed using Graph Pad version 6.0; P#x003C;0.05 was considered statistically significant. The mean age of the participants in our study was 37±6.5 years. According to HIV serology, 184 (71.59%) were HIV-positive vs. 73 (28.40%) HIV-negative. Among the HIV-positive women, the median CD4 count was 438 [IQR: 317-597] cells/mm3 and the median viremia was #x003C;40 [IQR: #x003C;40-2318] copies/ml. After successful genotyping, the prevalence of HR-HPV was 36.32% (73/201), with a significantly higher proportion in HIV-infected individuals (41.98% (55/131) vs. 25.71% (18/70); P=0.02; OR=2.1). The overall rate of cervical lesions was 23.34% (60/257), with a non-significantly higher proportion in HIV-infected participants (25.00% (46/184) vs. 19.17% (14/73); P=0.31). Relevantly, the presence of HR-HPV was significantly associated with cervical lesions (P#x003C;0.0001; OR=5.07), with a higher odds of cervical lesion in HIV-positive individuals (P#x003C;0.0001 and OR=5.67) compared to HIV-negative individuals (P=0.03 and OR=3.83). Although oncogenic HPV appears to be an independent factor in the development of cervical lesions, this study reveals higher odds of cervical lesions among HIV/HPV co-infection than in HPV infection alone.

2.
Pathogens ; 12(8)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37623992

RESUMO

BACKGROUND: Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic review aimed to identify HR-HPV genotypes and their associated factors among women in SSA. METHODS: A systematic review and meta-analysis of studies conducted in SSA on HR-HPV was conducted. Standard electronic databases were searched. R software version 3.6.0 was used for meta-analysis, with p < 0.05 considered statistically significant. RESULTS: We included 28 articles with a total of 22,652 participants. The overall pooled prevalence of HR-HPV genotypes was 55.13%, albeit high heterogeneity between studies. The overall pooled prevalence of HR-HPV genotypes in HIV-positive individuals was 75.51%, compared to 52.97% in HIV-negatives (OR = 4.68 (0.71-30.76)). HPV 16 (18%), 35 (10.12%), 52 (9.98%), 18 (9.7%) and 45 (6.82%) genotypes were the most prevalent. Twelve studies identified the most frequently reported risk factors associated with HR-HPV, with HIV infection (66.66%), multiple sexual partners (41.66%) and young age (41.66%) being the most reported risk factors. CONCLUSIONS: The combined prevalence of HR-HPV genotypes among women in general and HIV-infected women in particular remains high in SSA. The presence of several genotypes not covered by the vaccine is remarkable and suggests the need for revision of current vaccination policies to prevent HR-HPV infections.

3.
Front Immunol ; 14: 1239877, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37646023

RESUMO

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1ß) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4<500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1ß, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Gravidez , Humanos , Adolescente , Feminino , Criança , Masculino , Infecções por HIV/tratamento farmacológico , Fator de Necrose Tumoral alfa , Camarões , Estudos Transversais , Interleucina-4 , Interleucina-6 , Interleucina-12 , Citocinas , Antirretrovirais
4.
Front Mol Biosci ; 9: 1012359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465560

RESUMO

A balanced diet is critical for human health, and edible plants play an important role in providing essential micronutrients as well as specific microRNAs (miRNAs) that can regulate human gene expression. Here we present the effects of Moringa oleifera (MO) miRNAs (mol-miRs) on lipid metabolism. Through in silico studies we identified the potential genes involved in lipid metabolism targeted by mol-miRs. To this end, we tested the efficacy of an aqueous extract of MO seeds (MOES), as suggested in traditional African ethnomedicine, or its purified miRNAs. The biological properties of MO preparations were investigated using a human derived hepatoma cell line (HepG2) as a model. MOES treatment decreased intracellular lipid accumulation and induced apoptosis in HepG2. In the same cell line, transfection with mol-miRs showed similar effects to MOES. Moreover, the effect of the mol-miR pool was investigated in a pre-obese mouse model, in which treatment with mol-miRs was able to prevent dysregulation of lipid metabolism.

5.
IJID Reg ; 5: 130-136, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36313603

RESUMO

Background: The burden of human papillomavirus (HPV) is high in Cameroon, but knowledge on high-risk oncogenic HPV (HR-HPV) is limited. Our study sought to ascertain the HR-HPV genotypes circulating in Cameroon. Methods: A cross-sectional study was conducted among non-vaccinated women in Cameroon. Detection of HR-HPV was performed by real-time PCR on cervico-vaginal swabs. Predictors of HR-HPV were determined following logistic regression analysis, with p < 0.05 considered statistically significant. Results: In total, 364 women were enrolled, with a median age of 41 (34-50) years. Of these, 3.0% were smokers and 26.09% reported having more than three sexual partners. The overall HR-HPV positivity rate was 21.43% (95% CI 17.21-25.64). Predictors of HR-HPV were young age, i.e < 41 years (aOR (95% CI) 0.408 (0.194-0.862); p = 0.018), smoking (aOR 5.199 (1.314-20.575); p = 0.018), and having more than three sex partners (aOR: 2.335 (1.133-4.811); p = 0.022). Overall, 12 HR-HPV genotypes were identified, with 26.98% women coinfected with at least two HR-HPVs, including one case of a triple coinfection. According to to the circulating genotypes, potential vaccine effectiveness was 47% for the 4-valent vaccine and 70% for the 9-valent vaccine. Conclusion: Within the Cameroonian context, at least one out of five women is likely to be an HR-HPV carrier, especially among young people, smokers, and those with multiple sexual partners. Importantly, HR-HPV infection is highly diversified, with vaccine efficacy ranging from about 47% (4-valent) to 70% (9-valent).

6.
J Am Nutr Assoc ; 41(3): 250-265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33600292

RESUMO

OBJECTIVE: Preliminary findings suggest a relationship between lower serum 25-hydroxyvitamin D [25(OH)D] levels and incidence and severity of COVID-19. The aim of this study was to evaluate the relationship between vitamin D status at admission and different markers of inflammation, coagulation, and sepsis in hospitalized patients with COVID-19. METHOD: We conducted a retrospective study on 137 consecutive patients with SARS-CoV-2 infection and available data on serum 25(OH)D levels, who were admitted to our Institution between March 1 and April 30, 2020. Patients were divided into two groups: survivors (n = 78; 57%) and non-survivors (n = 59; 43%). RESULTS: At admission, all patients showed hypovitaminosis D. Median total serum 25(OH)D levels at admission were significantly higher in survivors than non-survivors (12 ng/mL vs 8 ng/mL; p < 0.01). Non-survivors exhibited significantly higher median levels of white blood cell (WBC) count, neutrophil-to-lymphocyte count ratio (NLR), high-sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6), D-dimer, fibrinogen, and procalcitonin (PCT) compared to survivors at three different time points during hospitalization. In a multivariate analysis performed by a logistic regression model, serum 25(OH)D levels were significantly inversely associated with risk of COVID-19-related in-hospital mortality (odds ratio, 0.91; 95% confidence interval, 0.85-0.98; p = 0.01). According to receiver operating characteristic curve analysis, hsCRP, NLR, ferritin, and D-dimer were the best predictive biomarkers for poor prognosis of COVID-19, whereas IL-6, PCT, fibrinogen, 25(OH)D, WBC count, and tumor necrosis factor alpha (TNF-α) may serve as supportive biomarkers for worse clinical course of the disease. CONCLUSIONS: We found a markedly high prevalence (100%) of hypovitaminosis D in patients admitted to hospital with COVID-19, suggesting a possible role of low vitamin D status in increasing the risk of SARS-CoV-2 infection and subsequent hospitalization. The inverse association between serum 25(OH)D levels and risk of in-hospital mortality observed in our cohort suggests that a lower vitamin D status upon admission may represent a modifiable and independent risk factor for poor prognosis in COVID-19.


Assuntos
COVID-19 , Deficiência de Vitamina D , Biomarcadores , Proteína C-Reativa , COVID-19/epidemiologia , Ferritinas , Hospitalização , Humanos , Interleucina-6 , Pró-Calcitonina , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Vitamina D , Deficiência de Vitamina D/complicações , Vitaminas
7.
Sci Rep ; 11(1): 9007, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903708

RESUMO

MicroRNAs constitute a class of noncoding small RNAs involved in the posttranscriptional regulation of many biological pathways. In recent years, microRNAs have also been associated with regulation across kingdoms, demonstrating that exogenous miRNAs can function in mammals in a fashion similar to mammalian miRNAs. The growing interest in microRNAs and the increasing amount of literature and molecular and biomedical data available make it difficult to identify records of interest and keep up to date with novel findings. For these reasons, we developed the microRNA Analysis Portal (MAP). MAP selects relevant miRNA-focused articles from PubMed, links biomedical and molecular data and applies bioinformatics modules. At the time of this writing, MAP represents the richest, most complete and integrated database focused on microRNAs. MAP also integrates an updated version of MirCompare (2.0), a computational platform used for selecting plant microRNAs on the basis of their ability to regulate mammalian genes. Both MAP and MirCompare functionalities were used to predict that microRNAs from Moringa oleifera have putative roles across kingdoms by regulating human genes coding for proteins of the immune system. Starting from a selection of 94 human microRNAs, MirCompare selected 6 Moringa oleifera functional homologs. The subsequent prediction of human targets and areas of functional enrichment highlighted the central involvement of these genes in regulating immune system processes, particularly the host-virus interaction processes in hepatitis B, cytomegalovirus, papillomavirus and coronavirus. This case of use showed how MAP can help to perform complex queries without any computational background. MAP is available at http://stablab.uniroma2.it/MAP .


Assuntos
MicroRNAs/genética , Análise de Sequência de RNA/métodos , Genes de Plantas , Moringa oleifera/genética , Análise de Componente Principal
8.
Cell Death Discov ; 6: 43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32550010

RESUMO

Human microvesicles are key mediators of cell-cell communication. Exosomes function as microRNA transporters, playing a crucial role in physiological and pathological processes. Plant microvesicles (MVs) display similar features to mammalian exosomes, and these MVs might enhance plant microRNA delivery in mammals. Considering that plant microRNAs have been newly identified as bioactive constituents in medicinal plants, and that their potential role as regulators in mammals has been underlined, in this study, we characterized MVs purified from Moringa oleifera seeds aqueous extract (MOES MVs) and used flow cytometry methods to quantify the ability to deliver their content to host cells. The microRNAs present in MOES MVs were characterized, and through a bioinformatic analysis, specific human apoptosis-related target genes of plant miRNAs were identified. In tumor cell lines, MOES MVs treatment reduced viability, increased apoptosis levels associated with a decrease in B-cell lymphoma 2 protein expression and reduced mitochondrial membrane potential. Interestingly, the effects observed with MOES MVs treatment were comparable to those observed with MOES treatment and transfection with the pool of small RNAs isolated from MOES, used as a control. These results highlight the role of microRNAs transported by MOES MVs as natural bioactive plant compounds that counteract tumorigenesis.

9.
Virol J ; 17(1): 69, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430034

RESUMO

BACKGROUND: Human papillomavirus (HPV) is the leading cause of cervical cancers, causing 270.000 deaths annually worldwide of which 85% occur in developing countries with an increasing risk associated to HIV infection. This study aimed at comparing HPV's positivity and genotype distribution in women according to their HIV status and determinants. METHODS: A comparative study was carried out in 2012 at the Chantal BIYA International Reference Centre (CIRCB) among 278 women enrolled consecutively at the General Hospital and the Gynaeco-Obstetric and Paediatric Hospital of the City of Yaoundé. HPV genotyping was performed by real-time PCR, HIV serological screening by serial algorithm, CD4 T cell phenotyping by flow cytometry and HIV viral load by Abbott m2000RT. Statistical analyses were performed using Microsoft Excel 2016 and Graph Pad version 6.0 software; with P < 0.05 considered statistically significant. RESULTS: Globally, mean age was 37 ± 3 years; median CD4-count for HIV+ was 414 cells/mm3 [IQR: 264.75-588] and median viremia was 50 RNA copies/mL [IQR: < 40-8288]. Overall HPV rate was 38.49% (107/278); 58.88% for single women vs. others (28.97% married, 2.80% divorced, 9.34% for widows), OR: 2.164; p = 0.0319. Following HIV status, HPV rate was 43.48% (80/184) among HIV+ vs. 28.72% (27/94) among HIV- (OR: 1.937; p < 0.0142); HPV genotypes among HIV+ vs. HIV- were respectively distributed as follows: genotype 16 (3.75% vs. 0.00%, p = 0.57), genotype 18 (3.75% vs. 3.70%, p = 1.00), co-infection 16 and others (8.75% vs. 7.40%, p = 1.00), co-infection 18 and others (8.75% vs. 11.11%, p = 0.71), co-infection 16, 18 and others (2.50% vs. 0.00%, p = 1.00) and other genotypes (72.50% vs. 77.78%, p = 0.80). Among HIV+ participants, HPV rate following CD4 was 62.88% (61/97) for CD4 < 500 vs. 35.71% (20/56) for CD4 ≥ 500 (OR: 3.05; p = 0.0012) while HPV rate following HIV viremia was 42.71% (41/96) with < 1000 RNA copies/ml vs. 66.00% (33/50) with > 1000 RNA copies/ml (OR = 0.384; p = 0.009). CONCLUSION: In Yaoundé, HPV rate appear to be very high, with higher rates of genotypes other than 16 and 18. In the event of HIV infection, the risk of HPV positivity is two times higher, favoured essentially by immunodeficiency. Thus, HIV-infected women should be closely monitored to prevent the emergence of cervical cancer.


Assuntos
Alphapapillomavirus/genética , Infecções por HIV/complicações , Infecções por HIV/virologia , Infecções por Papillomavirus/virologia , Adulto , Contagem de Linfócito CD4 , Camarões/epidemiologia , Coinfecção/virologia , Estudos Transversais , DNA Viral/genética , Feminino , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Carga Viral
10.
Pan Afr Med J ; 34: 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762906

RESUMO

INTRODUCTION: The number of HIV exposed uninfected (HEU) infants is increasing as vertical transmission is reducing. This subpopulation requires more investigations. This study aimed at comparing the expression level of soluble Fas receptors (FasR) and ligands (FasL) between HIV infected, HEU and unexposed children. METHODS: Eighty eight HIV-1infected, 86 HEU and 38 HIV unexposed children were recruited. Soluble FasR and FasL were measured in their plasma. Mann-Whitney U-Test was used to compare groups with 95% confidence. Spearman coefficient was used to test the correlation with CD4 and viral load (VL). RESULTS: Overall plasma levels of FasR were higher than that of FasL. The concentration of FasR and FasL were significantly higher in HIV-1 infected children in comparison to HEU and unexposed children. There was no difference in the plasma level of FasL in HIV infected compared to HEU children. A significant difference was observed between HIV infected children and HEU children (P=0.001) for the FasL. FasR were higher in both HIV infected and unexposed children compared to HEU children. There was a positive correlation (rs=+0.4; p=0.01) in ARV treated children between CD4 count and FasL concentration. Significant negative correlation (rs=-0.3; p=0.040) in ARV naïve children was observed between CD4 percentage and FasL. Significant and positive correlation (rs=+0.4; p=0.008) was observed between the VL and FasL in HIV infected, treated or not. CONCLUSION: HEU children differ from HIV infected and unexposed children as the level of FasL/R expression is concerned. HEU should be considered different from HIV unexposed although exempt from virus as some immune dysfunctions have been reported among them.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Proteína Ligante Fas/sangue , Infecções por HIV/epidemiologia , Receptor fas/sangue , Adolescente , Contagem de Linfócito CD4 , Camarões , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Masculino , Carga Viral
11.
Sci Rep ; 9(1): 10480, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324861

RESUMO

High-throughput technologies have produced a large amount of experimental and biomedical data creating an urgent need for comprehensive and automated mining approaches. To meet this need, we developed SMAC (SMart Automatic Classification method): a tool to extract, prioritise, integrate and analyse biomedical and molecular data according to user-defined terms. The robust ranking step performed on Medical Subject Headings (MeSH) ensures that papers are prioritised based on specific user requirements. SMAC then retrieves any related molecular data from the Gene Expression Omnibus and performs a wide range of bioinformatics analyses to extract biological insights. These features make SMAC a robust tool to explore the literature around any biomedical topic. SMAC can easily be customised/expanded and is distributed as a Docker container ( https://hub.docker.com/r/hfx320/smac ) ready-to-use on Windows, Mac and Linux OS. SMAC's functionalities have already been adapted and integrated into the Breast Cancer Now Tissue Bank bioinformatics platform and the Pancreatic Expression Database.


Assuntos
Mineração de Dados , Expressão Gênica , Armazenamento e Recuperação da Informação , Publicações Periódicas como Assunto , Biologia Computacional/métodos , Sistemas Computacionais , Mineração de Dados/métodos , Humanos , Armazenamento e Recuperação da Informação/métodos , Sistemas de Informação , Medical Subject Headings , Metadados , Software
12.
Exp Ther Med ; 18(1): 5-17, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31258632

RESUMO

Moringa oleifera Lam. (MO) is one of the most well-known and widely distributed species of the Moringaceae family in African communities, and various preparations of M. oleifera are used for the treatment of several diseases. Due to the extensive worldwide use of MO products, and the use of MO aqueous extract in traditional African medicine, the aim of the present study was to investigate the anti-proliferative, cytotoxic and pro-apoptotic activities of different aqueous extracts from leaves and seeds of M. oleifera (MOE), which have been prepared using different protocols, in lymphoid and monocytoid cells. The results of the present study demonstrated the anti-proliferative and pro-apoptotic effects of the aqueous extracts obtained from M. oleifera leaves and seeds on tumour cells; however, not on peripheral blood mononuclear cells (PBMCs) from healthy donors. The pro-apoptotic effect of MO seed aqueous extract (MOE-S) was correlated with decreased B-cell lymphoma 2 (BCL2) and sirtuin-1 (SIRT1) protein expression, which are involved in apoptosis. Considering the effects of plant secondary metabolites on human cells and the role of plant microRNA in cross-kingdom interactions, the presence of secondary metabolites and microRNA in MOE was characterised. In conclusion, M. oleifera aqueous extracts appeared to be able to differentially regulate proliferation and apoptosis in healthy cells and cancer cells, and this ability could be associated with the microRNA present in the extracts. These results highlighted the possible use of MOE as an adjuvant in traditional cancer therapy.

13.
Sci Rep ; 8(1): 12413, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120339

RESUMO

Functional foods include compounds with nutritional and health properties. The human diet could play a stronger role in cancer prevention. Only a few studies have described the presence of plant small RNA, in humans who were fed with plant foods, which demonstrated the ability of these molecules to modulate consumer's genes and evidenced the existence of a plant-animal regulation. Through in silico prediction, Olea europaea small RNAs (sRs), which had been previously reported as miRNAs, were identified, each with functional homology to hsa-miR34a. According to this initial funding, we investigated the ability of oeu-sRs to regulate tumorigenesis in human cells. The transfection of these synthetic oeu-sRs reduced the protein expression of hsa-miR34a mRNA targets, increased apoptosis and decreased proliferation in different tumor cells; by contrast, no effect was observed in PBMCs from healthy donors. The introduction of oeu-small RNA in hsa-miR34a-deficient tumor cells restores its function, whereas cells with normal expression of endogenous hsa-miR34a remained unaffected. The natural oeu-small RNAs that were extracted from O. europaea drupes induce the same effects as synthetic sRs. Careful research on the small RNA sequences executed for mapping and annotation in the genome of O. europaea var. Sylvestris and var. Farga led to the hypothesis that RNA fragments with functional homology to human miRNAs could be generated from the degradation of regions of RNA transcripts. These results indicate the possibility of developing novel natural non-toxic drugs that contain active plant-derived tumor-suppressing small RNA with functional homology to hsa-miRNAs and that can support antineoplastic strategies.


Assuntos
Evolução Molecular , MicroRNAs/genética , Neoplasias/genética , Olea/genética , Interferência de RNA , RNA de Plantas/genética , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/química , RNA de Plantas/química , Homologia de Sequência do Ácido Nucleico , Transfecção
14.
J Comput Biol ; 23(12): 976-989, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27428722

RESUMO

MicroRNAs (miRNAs) are a class of small noncoding RNAs that act as efficient post-transcriptional regulators of gene expression. In 2012, the first cross-kingdom miRNA-based interaction had been evidenced, demonstrating that exogenous miRNAs act in a manner of mammalian functional miRNAs. Starting from this evidence, we defined the concept of cross-kingdom functional homology between plant and mammalian miRNAs as a needful requirement for vegetal miRNA to explicit a regulation mechanism into the host mammalian cell, comparable to the endogenous one. Then, we proposed a new dedicated algorithm to compare plant and mammalian miRNAs, searching for functional sequence homologies between them, and we developed a web software called MirCompare. We also predicted human genes regulated by the selected plant miRNAs, and we determined the role of exogenous miRNAs in the perturbation of intracellular interaction networks. Finally, as already performed by Pirrò and coworkers, the ability of MirCompare to select plant miRNAs with functional homologies with mammalian ones has been experimentally confirmed by evaluating the ability of mol-miR168a to downregulate the protein expression of SIRT1, when its mimic is transfected into human hepatoma cell line G2 (HEPG2) cells. This tool is implemented into a user-friendly web interface, and the access is free to public through the website http://160.80.35.140/MirCompare.


Assuntos
Algoritmos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , MicroRNAs/genética , Moringa oleifera/genética , Células Hep G2 , Humanos , Mapeamento de Interação de Proteínas , RNA Mensageiro/genética , Sirtuína 1/genética , Sirtuína 1/metabolismo , Software
15.
PLoS One ; 11(3): e0149495, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26930203

RESUMO

Moringa oleifera is a widespread plant with substantial nutritional and medicinal value. We postulated that microRNAs (miRNAs), which are endogenous, noncoding small RNAs regulating gene expression at the post-transcriptional level, might contribute to the medicinal properties of plants of this species after ingestion into human body, regulating human gene expression. However, the knowledge is scarce about miRNA in Moringa. Furthermore, in order to test the hypothesis on the pharmacological potential properties of miRNA, we conducted a high-throughput sequencing analysis using the Illumina platform. A total of 31,290,964 raw reads were produced from a library of small RNA isolated from M. oleifera seeds. We identified 94 conserved and two novel miRNAs that were validated by qRT-PCR assays. Results from qRT-PCR trials conducted on the expression of 20 Moringa miRNA showed that are conserved across multiple plant species as determined by their detection in tissue of other common crop plants. In silico analyses predicted target genes for the conserved miRNA that in turn allowed to relate the miRNAs to the regulation of physiological processes. Some of the predicted plant miRNAs have functional homology to their mammalian counterparts and regulated human genes when they were transfected into cell lines. To our knowledge, this is the first report of discovering M. oleifera miRNAs based on high-throughput sequencing and bioinformatics analysis and we provided new insight into a potential cross-species control of human gene expression. The widespread cultivation and consumption of M. oleifera, for nutritional and medicinal purposes, brings humans into close contact with products and extracts of this plant species. The potential for miRNA transfer should be evaluated as one possible mechanism of action to account for beneficial properties of this valuable species.


Assuntos
MicroRNAs/genética , Moringa oleifera/genética , Plantas Medicinais/genética , RNA de Plantas/genética , Sequência de Bases , Sequência Conservada , Regulação da Expressão Gênica de Plantas , Genômica , Células Hep G2 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , MicroRNAs/química , MicroRNAs/farmacologia , Moringa oleifera/química , Plantas Medicinais/química , RNA de Plantas/química , RNA de Plantas/farmacologia , Análise de Sequência de RNA/métodos , Transfecção
16.
Curr HIV Res ; 14(2): 165-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26419862

RESUMO

AIM: To investigate the prevalence and genotypic profile of overt and occult hepatitis-B infection (OBI) among HIV-infected individuals in Cameroon. METHODS: 212 HIV-infected Cameroonians, aged 37.6 [IQR: 32.6-46.6] followed-up at the University Health Centre in Yaoundé, were tested for HBsAg, anti-HBs, anti-HBc IgG/IgM, HBV-DNA and anti-HCV IgG. HBV positive cases were tested for Hepatitis Delta virus (HDV) using anti-HDV IgG and HDV-RNA. Liver function was assessed by alanine and aspartate aminotransaminases. OBI was defined as negative-HBsAg and detectable HBV-DNA. In occult or overt HBVinfected participants, HBV reverse transcriptase (RT)/surface (S) sequences were analyzed for drug resistance, immuneescape mutants, and phylogeny. RESULTS: Overall, 78.3% (166/212) participants had past/ongoing HBV-exposure, with 39.1% (83/212) carrying "HBcAbpositive alone". Prevalence of overt HBV (positive-HBsAg) was 11.8% (25/212), prevalence of HBV and HDV was respectively 6.9% (12/175) and 12% (3/25). Phylogeny of HBV-RT/S revealed the co-circulation of genotypes A and E. All HBV-coinfected participants harbored HBV strains with at least one immune-escape mutation. Of note, one HBV variant carried the vaccine-escape mutation G145R that hinders HBsAg neutralization by antibodies. For the first time, a novel 9 aa-deletion (s115-s123), located in the HBsAg "a" determinant, was found concomitantly with OBI. A stop codon in the S region (associated with increased risk of hepatocellular carcinoma) was found in six cases. CONCLUSION: High prevalence of overt/occult HBV-infection and circulating atypical strains highlight the importance of HBV-surveillance among HIV-infected Cameroonians and strategies to detect OBI in highly endemic countries.


Assuntos
Infecções por HIV/complicações , Hepatite B/epidemiologia , Adulto , Camarões/epidemiologia , Coinfecção , DNA Viral/análise , Feminino , Genótipo , Hepatite B/genética , Hepatite B/virologia , Anticorpos Anti-Hepatite B/análise , Antígenos de Superfície da Hepatite B , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
18.
J Med Virol ; 87(6): 893-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25783989

RESUMO

Zaire Ebola virus (EBOV) is an enveloped non-segmented negative strand RNA virus of 19 kb in length belonging to the family Filoviridae. The virus was isolated and identified in 1976 during the epidemic of hemorrhagic fever in Zaire. The most recent outbreak of EBOV among humans, was that occurred in the forested areas of south eastern Guinea, that began in February 2014 and is still ongoing. The recent Ebola outbreak, is affecting other countries in West Africa, in addiction to Guinea: Liberia, Nigeria, and Sierra Leone. In this article, a selective pressure analysis and homology modeling based on the G Glycoprotein (GP) sequences retrieved from public databases were used to investigate the genetic diversity and modification of antibody response in the recent outbreak of Ebola Virus. Structural and the evolutionary analysis underline the 2014 epidemic virus being under negative selective pressure does not change with respect to the old epidemic in terms of genome adaptation.


Assuntos
Aminoácidos/genética , Ebolavirus/genética , Doença pelo Vírus Ebola/virologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , África Ocidental/epidemiologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Bases de Dados Factuais , Bases de Dados de Ácidos Nucleicos , Conjuntos de Dados como Assunto , Ebolavirus/química , Epidemias , Variação Genética , Doença pelo Vírus Ebola/epidemiologia , Humanos , Modelos Moleculares , Mutação , Seleção Genética , Fatores de Tempo , Proteínas do Envelope Viral/imunologia
19.
PLoS One ; 9(8): e103999, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25090613

RESUMO

BACKGROUND: The vast majority of the population around the world has always used medicinal plants as first source of health care to fight infectious and non infectious diseases. Most of these medicinal plants may have scientific evidence to be considered in general practice. OBJECTIVE: The aim of this work was to investigate the antioxidant capacities and anti-inflammatory activities of ethanol extracts of leaves of Cassia alata, Eleusine indica, Carica papaya, Eremomastax speciosa and the stem bark of Polyscias fulva, collected in Cameroon. METHODS: Chemiluminescence was used to analyze the antioxidant activities of plant extracts against hydrogen peroxide or superoxide anion. Comet assays were used to analyze the protection against antioxidant-induced DNA damage induced in white blood cells after treating with hydrogen peroxide. Flow cytometry was used to measure γδ T cells proliferation and anti-inflammatory activity of γδ T cells and of immature dendritic cells (imDC) in the presence of different concentrations of plant extracts. RESULTS: Ethanol extracts showed strong antioxidant properties against both hydrogen peroxide and superoxide anion. Cassia alata showed the highest antioxidant activity. The effect of plant extracts on γδ T cells and imDC was evidenced by the dose dependent reduction in TNF-α production in the presence of Cassia alata, Carica papaya, Eremomastax speciosa Eleusine indica, and Polyscias fulva. γδ T cells proliferation was affected to the greatest extent by Polyscias fulva. CONCLUSION: These results clearly show the antioxidant capacity and anti-inflammatory activities of plant extracts collected in Cameroon. These properties of leaves and stem bark extracts may contribute to the value for these plants in traditional medicine and in general medical practice.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Acanthaceae/química , Araliaceae/química , Camarões , Carica/química , Cassia/química , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Eleusine/química , Humanos , Lipopolissacarídeos/farmacologia , Luminescência , Malondialdeído/metabolismo , Substâncias Protetoras/farmacologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
20.
Int J Oncol ; 43(3): 956-64, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23817892

RESUMO

African ethnomedicine is essentially based on the traditional use of vegetal extracts. Since these natural drugs have shown health giving properties, in the present study we increased further the scientific basis supporting these data. We investigated the effects, on murine B16F10 melanoma cells, of plant extracts that were directly obtained by a Cameroon 'traditional healer'. After a preliminary study on the antioxidant functions of these compounds, already abundant in literature, Moringa oleifera Lam., Eremomastax speciosa (Hochst.) Cufod and Aframomum melegueta K. Schum extracts were individually analyzed. We performed laboratory assessments on these medicinal preparations in order to clearly demonstrate their antineoplastic features. All the treatments caused in tumor cells a great reduction in growth and proliferation rate, cell cycle arrest, increase of p53, p21WAF1/Cip1 and p27Kip1 protein levels and induction of differentiation. These results, on the bioactivity and the biochemical characteristics of African plant extracts, may increase the comprehension of indigenous therapeutic practices and represent the first step for the individuation of new inexpensive and natural drugs able to prevent and contrast cancer onset.


Assuntos
Antioxidantes/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/administração & dosagem , África , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antioxidantes/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Humanos , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Extratos Vegetais/química , Plantas Medicinais/química
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