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1.
Front Reprod Health ; 5: 1107215, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36890798

RESUMO

Prior research has substantiated the vital role of telomeres in human fertility. Telomeres are prerequisites for maintaining the integrity of chromosomes by preventing the loss of genetic material following replication events. Little is known about the association between sperm telomere length and mitochondrial capacity involving its structure and functions. Mitochondria are structurally and functionally distinct organelles that are located on the spermatozoon's midpiece. Mitochondria produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), which is necessary for sperm motility and generate reactive oxygen species (ROS). While a moderate concentration of ROS is critical for egg-sperm fusion, and fertilization, excessive ROS generation is primarily related to telomere shortening, sperm DNA fragmentation, and alterations in the methylation pattern leading to male infertility. This review aims to highlight the functional connection between mitochondria biogenesis and telomere length in male infertility, as mitochondrial lesions have a damaging impact on telomere length, leading both to telomere lengthening and reprogramming of mitochondrial biosynthesis. Furthermore, it aims to shed light on how both inositol and antioxidants can positively affect male fertility.

2.
Diagnostics (Basel) ; 12(4)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35454022

RESUMO

Several SARS-CoV-2 variants have emerged and early detection for monitoring their prevalence is crucial. Many identification strategies have been implemented in cases where sequencing data for confirmation is pending or not available. The presence of B.1.1.318 among prevalent variants was indicated by an unusual amplification pattern in various RT-qPCR commercial assays. Positive samples for SARS-CoV-2, as determined using the Allplex SARS-CoV-2 Assay, the Viasure SARS-CoV-2 Real Time Detection Kit and the GeneFinder COVID-19 Plus RealAmp Kit, presented a delay or failure in the amplification of the N gene, which was further investigated. Whole-genome sequencing was used for variant characterization. The differences between the mean Ct values for amplification of the N gene vs. other genes were calculated for each detection system and found to be at least 14 cycles. Sequencing by WGS revealed that all the N gene dropout samples contained the B.1.1.318 variant. All the isolates harbored three non-synonymous mutations in the N gene, which resulted in four amino acid changes (R203K, G204R, A208G, Met234I). Although caution should be taken when the identification of SARS-CoV-2 variants is based on viral gene amplification failure, such patterns could serve as a basis for rapid and cost-effective screening, functioning as indicators of community circulation of specific variants, requiring subsequent verification via sequencing.

3.
Diagnostics (Basel) ; 11(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34943612

RESUMO

The detection of actionable mutations in tumor tissue is a prerequisite for treatment customization in patients with metastatic colorectal cancer (mCRC). Analysis of circulating tumor DNA (ctDNA) for the identification of such mutations in patients' plasma is an attractive alternative to invasive tissue biopsies. Despite having the high analytical sensitivity required for ctDNA analysis, digital polymerase chain reaction (dPCR) technologies can only detect a very limited number of hotspot mutations, whilst a broader mutation panel is currently needed for clinical decision making. Recent advances in next-generation sequencing (NGS) have led to high-sensitivity platforms that allow screening of multiple genes at a single assay. Our goal was to develop a small, cost- and time-effective NGS gene panel that could be easily integrated in the day-to-day clinical routine in the management of patients with mCRC. We designed a targeted panel comprising hotspots in six clinically relevant genes (KRAS, NRAS, MET, BRAF, ERBB2 and EGFR) and validated it in a total of 68 samples from 30 patients at diagnosis, first and second disease progression. Results from our NGS panel were compared against plasma testing with BEAMing dPCR regarding the RAS gene status. The overall percent of agreement was 83.6%, with a positive and negative percent agreement of 74.3% and 96.2%, respectively. Further comparison of plasma NGS with standard tissue testing used in the clinic showed an overall percent agreement of 86.7% for RAS status, with a positive and negative percent agreement of 81.2% and 92.8%, respectively. Thus, our study strongly supports the validity and efficiency of an affordable targeted NGS panel for the detection of clinically relevant mutations in patients with mCRC.

4.
Comput Struct Biotechnol J ; 19: 5546-5555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712399

RESUMO

Artificial Intelligence (AI) has recently altered the landscape of cancer research and medical oncology using traditional Machine Learning (ML) algorithms and cutting-edge Deep Learning (DL) architectures. In this review article we focus on the ML aspect of AI applications in cancer research and present the most indicative studies with respect to the ML algorithms and data used. The PubMed and dblp databases were considered to obtain the most relevant research works of the last five years. Based on a comparison of the proposed studies and their research clinical outcomes concerning the medical ML application in cancer research, three main clinical scenarios were identified. We give an overview of the well-known DL and Reinforcement Learning (RL) methodologies, as well as their application in clinical practice, and we briefly discuss Systems Biology in cancer research. We also provide a thorough examination of the clinical scenarios with respect to disease diagnosis, patient classification and cancer prognosis and survival. The most relevant studies identified in the preceding year are presented along with their primary findings. Furthermore, we examine the effective implementation and the main points that need to be addressed in the direction of robustness, explainability and transparency of predictive models. Finally, we summarize the most recent advances in the field of AI/ML applications in cancer research and medical oncology, as well as some of the challenges and open issues that need to be addressed before data-driven models can be implemented in healthcare systems to assist physicians in their daily practice.

5.
J Dev Biol ; 9(2)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066950

RESUMO

Applications and indications of assisted reproduction technology are expanding, but every new approach is under scrutiny and thorough consideration. Recently, groups of assisted reproduction experts have presented data that support the clinical use of mosaic preimplantation embryos at the blastocyst stage, previously excluded from transfer. In the light of published contemporary studies, with or without clinical outcomes, there is growing evidence that mosaic embryos have the capacity for further in utero development and live birth. Our in-depth discussion will enable readers to better comprehend current developments. This expansion into the spectrum of ART practices requires further evidence and further theoretical documentation, basic research, and ethical support. Therefore, if strict criteria for selecting competent mosaic preimplantation embryos for further transfer, implantation, fetal growth, and healthy birth are applied, fewer embryos will be excluded, and more live births will be achieved. Our review aims to discuss the recent literature on the transfer of mosaic preimplantation embryos. It also highlights controversies as far as the clinical utilization of preimplantation embryos concerns. Finally, it provides the appropriate background to elucidate and highlight cellular and genetic aspects of this novel direction.

6.
In Vivo ; 34(5): 2269-2276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871749

RESUMO

BACKGROUND/AIM: The expression of reverse transcriptase (RT) in ovaries, testes, gametes and embryos highlights its critical role in cell growth and differentiation. We sought to investigate the effects of the potent RT inhibitor lamivudine in gametogenesis and mouse embryo preimplantation development. MATERIALS AND METHODS: Male and female FVB/N mice were treated with the reverse transcriptase inhibitor Lamivudine for seven consecutive weeks. Following treatment, mouse sperm parameters, testicular and ovarian morphology as well as post-IVF embryo development were evaluated. RESULTS: Lamivudine impaired the sperm parameters and the testicular structure in male mice, the number of primordial germ cells and primary oocytes in ovaries of female mice, and the embryos' morphology and development up to the blastocyst stage during in vitro culture. CONCLUSION: The administration of lamivudine affected the processes of spermatogenesis and oogenesis as well as the in vitro preimplantation development of mouse embryos.


Assuntos
Oócitos , DNA Polimerase Dirigida por RNA , Animais , Blastocisto , Desenvolvimento Embrionário , Feminino , Masculino , Camundongos , Oogênese , DNA Polimerase Dirigida por RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
Clin Endocrinol (Oxf) ; 81(1): 38-44, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24621381

RESUMO

UNLABELLED: Aromatase is encoded by the CYP19 gene and catalyses the conversion of androgens to oestrogens, which in turn regulate skeletal homeostasis. CYP19 gene polymorphisms have been studied for their association with bone mineral density (BMD) in the general population with mixed results. OBJECTIVE: To explore the influence of the CYP19 (TTTA)n repeat polymorphism on BMD and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κΒ ligand (RANKL), and bone metabolic markers in a Greek female population. DESIGN: Cross-sectional study. PARTICIPANTS AND MEASUREMENTS: Two hundred and seventeen peri- and postmenopausal women aged 42-63 years were enrolled. All participants underwent spinal BMD evaluation by dual-energy X-ray absorptiometry (DXA). Genotyping of the (TTTA)n repeat polymorphism was performed by polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured. RESULTS: Genotype analysis revealed alleles having 7-12 TTTA repeats. Women carrying the (TTTA)11 and/or (TTTA)12 alleles had significantly higher spinal BMD than women not carrying these alleles in the total study population as well as in the subgroup of women with osteoporosis (P = 0·042 and P = 0·006, respectively). The aforementioned associations remained significant after adjustment for age, years since menopause, smoking and body mass index (P = 0·048 and P = 0·023, respectively, by multivariate analysis). Moreover, the urinary calcium to creatinine ratio was associated with the (TTTA)n polymorphism. No association of the (TTTA)n polymorphism with circulating levels of OPG, sRANKL was observed. CONCLUSIONS: The (TTTA)n polymorphism of the CYP19 gene is associated with spinal BMD in peri- and postmenopausal Greek women.


Assuntos
Aromatase/genética , Densidade Óssea/genética , Pós-Menopausa/genética , Adulto , Estudos Transversais , Feminino , Genótipo , Grécia , Humanos , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Ligante RANK/sangue , População Branca
8.
J Assist Reprod Genet ; 29(11): 1185-91, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22915343

RESUMO

PURPOSE: Follicle stimulating hormone, sex hormone-binding globulin and cytochrome P450 aromatase play crucial roles in the regulation of mammalian reproduction. The synergistic effect of FSHR 307(T/A)/FSHR 680(N/S), SHBG(TAAAA) ( n ) and CYP19(TTTA) ( n ) genotypes on ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction (IVF/ICSI) was explored. METHODS: The study population consisted of 300 women under IVF/ICSI treatment and 300 women with at least with at least one successful child birth as controls. The polymorphisms were genotyped while the follicular size, the follicle and oocyte numbers were recorded during oocyte retrieval. RESULTS: The genotype analysis, excluding heterozygotes for each particular polymorphism, revealed eight combined homozygotic FSHR/SHBG/CYP19 genotypes. A gradual reduction in the number of follicles and oocytes from FSHR 307Thr/680Asn allele/long SHBG allele/long CYP19 allele homozygotes to FSHR 307Ala/680Ser allele/short SHBG allele/short CYP19 allele homozygotes was observed (20.36 ± 6.74 vs. 8.05 ± 2.47, p < 0.008 and 13 ± 4.63 vs. 6.1 ± 2.32, p < 0.02, respectively). CONCLUSIONS: FSHR/SHBG/CYP19 combined genotypes are associated with ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction.


Assuntos
Aromatase/genética , Gonadotropinas/farmacologia , Indução da Ovulação , Polimorfismo Genético , Receptores do FSH/genética , Globulina de Ligação a Hormônio Sexual/genética , Adulto , Aromatase/metabolismo , Feminino , Fertilização in vitro , Genótipo , Gonadotropinas/administração & dosagem , Humanos , Recuperação de Oócitos , Folículo Ovariano , Ovário/metabolismo , Indução da Ovulação/métodos , Receptores do FSH/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , Injeções de Esperma Intracitoplásmicas
9.
Gynecol Endocrinol ; 27(1): 27-32, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20540673

RESUMO

OBJECTIVE: Sex hormone-binding globulin (SHBG) is the main transport protein of sex steroids. Recently, it has been found to be produced by granulosa lutein cells, suggesting a local role of SHBG in the ovary. The aim of this study was to investigate whether serum and follicular fluid SHBG levels and SHBG (TAAAA)(n) polymorphism are related to follicle size and pregnancy rate in women undergoing in vitro fertilisation. METHODS: The study population consisted of 154 women with tubal and/or male-factor infertility undergoing IVF/ICSI and follicular fluid with oocytes from small (diameter ≤12 mm) and large (diameter ≥18 mm) follicles were studied. Genotyping of SHBG (TAAAA)(n) polymorphism was performed in peripheral blood samples. Serum and follicular fluids were used for hormones determination. RESULTS: Women with short allele genotypes (with less than 8 TAAAA repeats) had higher number of small follicles compared to women with long allele genotypes (5.6 ± 3.9 vs. 3.5 ± 3.2 small follicles, p < 0.003). Follicular fluid SHBG levels correlated positively with serum SHBG levels (p < 0.001) and with the total number of follicles (p < 0.02). Furthermore, small follicles had higher follicular fluid SHBG concentration compared to large follicles (102.9 ± 35.0 nmol/l vs. 85.85 ± 34.88 nmol/l, p < 0.028). CONCLUSION: SHBG levels and the SHBG (TAAAA)(n) polymorphism are associated with follicle size.


Assuntos
Líquido Folicular/química , Folículo Ovariano/anatomia & histologia , Indução da Ovulação , Polimorfismo Genético/genética , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/genética , Adulto , Alelos , Feminino , Fertilização in vitro , Genótipo , Humanos , Infertilidade/terapia , Gravidez , Injeções de Esperma Intracitoplásmicas
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