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  • 1
    Online Resource
    Online Resource
    Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial
    Elsevier BV ; 2023
    In:  eClinicalMedicine Vol. 57 ( 2023-03), p. 101898-
    Details
    In: eClinicalMedicine, Elsevier BV, Vol. 57 ( 2023-03), p. 101898-
    Type of Medium: Online Resource
    ISSN: 2589-5370
    URL: Article
    DOI: 10.1016/j.eclinm.2023.101898
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2946413-4
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  • 2
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    Association of FANCM Mutations with Familial and Early-Onset Breast Cancer Risk in a South American Population
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 4 ( 2023-02-17), p. 4041-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 4 ( 2023-02-17), p. 4041-
    Abstract: Breast cancer (BC) is the most common cancer among women worldwide. BRCA1/2 are responsible for 16–20% of the risk for hereditary BC. Other susceptibility genes have been identified; Fanconi Anemia Complementation Group M (FANCM) being one of these. Two variants in FANCM, rs144567652 and rs147021911, are associated with BC risk. These variants have been described in Finland, Italy, France, Spain, Germany, Australia, the United States, Sweden, Finnish, and the Netherlands, but not in the South American populations. Our study evaluated the association of the SNPs rs144567652 and rs147021911 with BC risk in non-carriers of BRCA1/2 mutations from a South American population. The SNPs were genotyped in 492 BRCA1/2-negative BC cases and 673 controls. Our data do not support an association between FANCM rs147021911 and rs144567652 SNPs and BC risk. Nevertheless, two BC cases, one with a family history of BC and the other with sporadic early-onset BC, were C/T heterozygotes for rs144567652. In conclusion, this is the first study related contribution of FANCM mutations and BC risk in a South American population. Nevertheless, more studies are necessary to evaluate if rs144567652 could be responsible for familial BC in BRCA1/2-negatives and for early-onset non-familial BC in Chilean BC cases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24044041
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Vaccine Design against Chagas Disease Focused on the Use of Nucleic Acids
    MDPI AG ; 2022
    In:  Vaccines Vol. 10, No. 4 ( 2022-04-12), p. 587-
    Details
    In: Vaccines, MDPI AG, Vol. 10, No. 4 ( 2022-04-12), p. 587-
    Abstract: Chagas disease is caused by the protozoan Trypanosoma cruzi and is endemic to Central and South America. However, it has spread around the world and affects several million people. Treatment with currently available drugs cause several side effects and require long treatment times to eliminate the parasite, however, this does not improve the chronic effects of the disease such as cardiomyopathy. A therapeutic vaccine for Chagas disease may be able to prevent the disease and improve the chronic effects such as cardiomyopathy. This vaccine would be beneficial for both infected people and those which are at risk in endemic and non-endemic areas. In this article, we will review the surface antigens of T. cruzi, in order to choose those that are most antigenic and least variable, to design effective vaccines against the etiological agent of Chagas disease. Also, we discuss aspects of the design of nucleic acid-based vaccines, which have been developed and proven to be effective against the SARS-CoV-2 virus. The role of co-adjuvants and delivery carriers is also discussed. We present an example of a chimeric trivalent vaccine, based on experimental work, which can be used to design a vaccine against Chagas disease.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines10040587
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2703319-3
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  • 4
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    Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 24, No. 1 ( 2022-12-20), p. 1-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 1 ( 2022-12-20), p. 1-
    Abstract: Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3′ massive analysis of cDNA ends (3′MACE). We found 〉 30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-β-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/β-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24010001
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Aging Hallmarks and the Role of Oxidative Stress
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 3 ( 2023-03-06), p. 651-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 3 ( 2023-03-06), p. 651-
    Abstract: Aging is a complex biological process accompanied by a progressive decline in the physical function of the organism and an increased risk of age-related chronic diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases. Studies have established that there exist nine hallmarks of the aging process, including (i) telomere shortening, (ii) genomic instability, (iii) epigenetic modifications, (iv) mitochondrial dysfunction, (v) loss of proteostasis, (vi) dysregulated nutrient sensing, (vii) stem cell exhaustion, (viii) cellular senescence, and (ix) altered cellular communication. All these alterations have been linked to sustained systemic inflammation, and these mechanisms contribute to the aging process in timing not clearly determined yet. Nevertheless, mitochondrial dysfunction is one of the most important mechanisms contributing to the aging process. Mitochondria is the primary endogenous source of reactive oxygen species (ROS). During the aging process, there is a decline in ATP production and elevated ROS production together with a decline in the antioxidant defense. Elevated ROS levels can cause oxidative stress and severe damage to the cell, organelle membranes, DNA, lipids, and proteins. This damage contributes to the aging phenotype. In this review, we summarize recent advances in the mechanisms of aging with an emphasis on mitochondrial dysfunction and ROS production.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12030651
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 6
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    Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids
    Frontiers Media SA ; 2021
    In:  Frontiers in Cellular and Infection Microbiology Vol. 11 ( 2021-8-5)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 11 ( 2021-8-5)
    Abstract: Trypanosomatids are a group of primitive unicellular eukaryotes that can cause diseases in plants, insects, animals, and humans. Kinetoplast genome integrity is key to trypanosomatid cell survival and viability. Kinetoplast DNA (kDNA) is usually under attack by reactive oxygen and nitric species (ROS and RNS), damaging the DNA, and the cells must remove and repair those oxidatively generated lesions in order to survive and proliferate. Base excision repair (BER) is a well-conserved pathway for DNA repair after base damage, single-base loss, and single-strand breaks, which can arise from ROS, RSN, environmental genotoxic agents, and UV irradiation. A powerful BER system has been described in the T. cruzi kinetoplast and it is mainly carried out by DNA polymerase β (pol β) and DNA polymerase β-PAK (pol β-PAK), which are kinetoplast-located in T. cruzi as well as in other trypanosomatids. Both pol β and pol β-PAK belong to the X-family of DNA polymerases (pol X family), perform BER in trypanosomatids, and display intrinsic 5-deoxyribose phosphate (dRP) lyase and DNA polymerase activities. However, only Pol β-PAK is able to carry out trans-lesion synthesis (TLS) across 8oxoG lesions. T. cruzi cells overexpressing pol β are more resistant to ROS and are also more efficient to repair 8oxoG compared to control cells. Pol β seems to play a role in kDNA replication, since it associates with kinetoplast antipodal sites in those development stages in trypanosomatids which are competent for cell replication. ROS treatment of cells induces the overexpression of pol β, indicating that plays a role in kDNA repair. In this review, we will summarize the main features of trypanosomatid minicircle kDNA replication and the biochemical characteristics of pol β-like enzymes and their involvement in BER and kDNA replication. We also summarize key structural features of trypanosomatid pol β compared to their mammalian (human) counterpart.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    DOI: 10.3389/fcimb.2021.670564
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2619676-1
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  • 7
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    Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
    MDPI AG ; 2022
    In:  Genes Vol. 13, No. 2 ( 2022-01-26), p. 234-
    Details
    In: Genes, MDPI AG, Vol. 13, No. 2 ( 2022-01-26), p. 234-
    Abstract: Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly through the MED1 subunit, since estrogen receptor (ER) can interact with MED1 by specific protein–protein interactions; therefore, MED1 plays a fundamental role in ER-positive breast cancer (BC) etiology. Additionally, other MED subunits also play a role in BC etiology. On the other hand, microRNAs (miRNAs) are a family of small non-coding RNAs, which can regulate gene expression at the post-transcriptional level by binding in a sequence-specific fashion at the 3′ UTR of the messenger RNA. The miRNAs are also important factors that influence oncogenic signaling in BC by acting as both tumor suppressors and oncogenes. Moreover, miRNAs are involved in endocrine therapy resistance of BC, specifically to tamoxifen, a drug that is used to target ER signaling. In metazoans, very little is known about the transcriptional regulation of miRNA by the MED complex and less about the transcriptional regulation of miRNAs involved in BC initiation and progression. Recently, it has been shown that MED1 is able to regulate the transcription of the ER-dependent miR-191/425 cluster promoting BC cell proliferation and migration. In this review, we will discuss the role of MED1 transcriptional coactivator in the etiology of BC and in endocrine therapy-resistance of BC and also the contribution of other MED subunits to BC development, progression and metastasis. Lastly, we identified miRNAs that potentially can regulate the expression of MED subunits.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes13020234
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
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  • 8
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    Enzymatic Protein Biopolymers as a Tool to Synthetize Eukaryotic Messenger Ribonucleic Acid (mRNA) with Uses in Vaccination, Immunotherapy and Nanotechnology
    MDPI AG ; 2020
    In:  Polymers Vol. 12, No. 8 ( 2020-07-23), p. 1633-
    Details
    In: Polymers, MDPI AG, Vol. 12, No. 8 ( 2020-07-23), p. 1633-
    Abstract: Multi-subunit enzymes are protein biopolymers that are involved in many cellular processes. The enzyme that carries out the process of transcription of mRNAs is RNA polymerase II (RNAPII), which is a multi-subunit enzyme in eukaryotes. This protein biopolymer starts the transcription from specific sites and is positioned by transcription factors, which form a preinitiation complex (PIC) on gene promoters. To recognize and position the RNAPII and the transcription factors on the gene promoters are needed specific DNA sequences in the gene promoters, which are named promoter elements. Those gene promoter elements can vary and therefore several kinds of promoters exist, however, it appears that all promoters can use a similar pathway for PIC formation. Those pathways are discussed in this review. The in vitro transcribed mRNA can be used as vaccines to fight infectious diseases, e.g., in immunotherapy against cancer and in nanotechnology to deliver mRNA for a missing protein into the cell. We have outlined a procedure to produce an mRNA vaccine against the SARS-CoV-2 virus, which is the causing agent of the big pandemic, COVID-19, affecting human beings all over the world. The potential advantages of using eukaryotic RNAPII to synthetize large transcripts are outlined and discussed. In addition, we suggest a method to cap the mRNA at the 5′ terminus by using enzymes, which might be more effective than cap analogs. Finally, we suggest the construction of a future multi-talented RNAPII, which would be able to synthetize large mRNA and cap them in the test tube.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym12081633
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527146-5
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  • 9
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    Genetic Variation in MicroRNA-423 Promotes Proliferation, Migration, Invasion, and Chemoresistance in Breast Cancer Cells
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 23, No. 1 ( 2021-12-29), p. 380-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 1 ( 2021-12-29), p. 380-
    Abstract: MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C 〉 A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C 〉 A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C 〉 A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23010380
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 10
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    Therapeutic Perspectives of HIV-Associated Chemokine Receptor (CCR5 and CXCR4) Antagonists in Carcinomas
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 24, No. 1 ( 2022-12-28), p. 478-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 1 ( 2022-12-28), p. 478-
    Abstract: The interaction between malignant cells and the tumor microenvironment is critical for tumor progression, and the chemokine ligand/receptor axes play a crucial role in this process. The CXCR4/CXCL12 and CCR5/CCL5 axes, both related to HIV, have been associated with the early (epithelial–mesenchymal transition and invasion) and late events (migration and metastasis) of cancer progression. In addition, these axes can also modulate the immune response against tumors. Thus, antagonists against the receptors of these axes have been proposed in cancer therapy. Although preclinical studies have shown promising results, clinical trials are needed to include these drugs in the oncological treatment protocols. New alternatives for these antagonists, such as dual CXCR4/CCR5 antagonists or combined therapy in association with immunotherapy, need to be studied in cancer therapy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24010478
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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