Search

Tularemia is a disease caused primarily by 2 subspecies of Francisella tularensis: F. tularensis subsp. tularensis, which is restricted to North America; and F. tularensis subsp. holarctica, which is found [...]

Objective: Cancer is a leading cause of death worldwide, requires development of new effective, specific, and safe strategies that do not carry the disadvantages of traditional cancer treatment approaches. Hence, this study aimed to identify anticancer peptide candidates in fermented food microbiomes through an in silico investigation. Materials and Methods: One hundred eight shotgun metagenomic sequencing samples from six studies on fermented food microbiomes were downloaded from the NCBI and ENA databases and included in the study. Bioinformatic analyses including quality control of raw data, de novo assembly, prediction of protein sequences, anticancer peptide predictions by an integrated use of four different prediction tools, toxicity predictions and database comparisons were performed. Results: One hundred forty-two novel anticancer peptide candidates were identified. Liquor, coffee, kefir fermentation samples contained the greatest numbers of anticancer peptide candidates while sugar, dairy, coconut kefir and brine-type fermentations were dominant sources according to the substrate type. Conclusion: This study indicates the potential of fermented food microbiomes as a useful source for candidate anticancer peptide detection. In vitro and in vivo validations of detected peptides may lead to development of new candidate molecules for cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Advanced Research in Health Sciences (JARHS) / Sağlık Bilimlerinde İleri Araştırmalar Dergisi (SABİAD) is the property of Journal of Advanced Research in Health Sciences (JARHS) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Introduction: Hippocampal sclerosis is the most common lesion in patients with mesial temporal lobe epilepsy. Recently, there has been growing evidence on the involvement of mitochondria also in sporadic forms of epilepsy. In addition, it has been increasingly argued that mitochondrial dysfunction has an important role in epileptogenesis and seizure generation in temporal lobe epilepsy. Although mtDNA polymorphisms have been identified as potential risk factors for neurological diseases, the link between homoplasmy and heteroplasmy within tissues is not clear. We investigated whether mitochondrial DNA (mtDNA) polymorphisms are involved in a case report of a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS). Design: We report the whole genome mtDNA deep sequencing results and clinical features of a 36-year-old woman with MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial genome isolated from six different regions of her brain and blood. To assess the possible role of mitochondrial DNA variations in affected tissues, we compared all specimens from different regions of the hippocampus and blood. Results: In total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6 different regions of the hippocampus and in blood samples. While the samples did not display any difference in homoplasmic variations, it has been shown that hippocampus regions contain more heteroplasmic variations than blood. The number of heteroplasmic variations was highest in the CA2 region of the brain and accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the hippocampus had similar heteroplasmic variation profiles. Discussion: We present a new rare example of parallel mutation at 16223 position. Our case suggests that defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy. [Copyright &y& Elsevier]

Abstract: Introduction: Mitochondria have an essential role in neuronal excitability and neuronal survival. In addition to energy production, mitochondria also play a crucial role in the maintenance of intracellular calcium homeostasis, generation of reactive oxygen species and mechanisms of cell death. There is a relative paucity of data about the role of mitochondria in epilepsy. Mitochondrial genome analysis is rarely carried out in the investigation of some diseases. In mesial temporal lobe epilepsies (MTLE) cases, genome analysis has never been used previously. The aim of this study is to show mitochondrial dysfunctions using genome analysis in patients with MTLE-hippocampal sclerosis (HS). Methods: 44 patients with MTLE-HS and 86 matched healthy unrelated controls were included in this study. The patients were divided into four groups according to their clinical presentation as the following: Group 1 consists of patients with intractable epilepsy who refused operation; Group 2 of operated seizure free patients; Group 3 of operated patients with seizures; and Group 4 unoperated seizure free patients with or without antiepileptic drugs. Blood samples were used to isolate DNA. Parallel tagged sequencing was employed to allow pyrosequencing of 130 samples. Complete mtDNA is amplified in two overlapping fragments (11 and 9kb). The PCR amplicons were pooled in equimolar ratios. Titanium kits were used to produce shotgun libraries according to the manufacturer's protocol. Results: The average coverage in total was 130±30 and an average of 2365127 bases and 337bp fragment length was received from all samples. The mean mtDNA heteroplasmy in patients was 26.35±12.3 and in controls 25.03±9.34. Three mutations had prominently high significance in patient samples. The most significantly associated variation was located in the MT-ATP-8 gene (8502 A>T, Asn46Ile) whereas the other two were in the MT-ND4 (11994 C>T, Thr412Ile) and MT-ND5 (13231 A>C, Lys299Gln) genes. Conclusions: We have observed that three mutations were significantly related to the presence of epilepsy. These mutations were found at the 8502, 11994, and 13231bp of mtDNA, which resulted in amino acid changes at the MT-ATP-8, MT-ND4 and MT-ND5 genes. Finding mutations can lead us to knowing more about the pathophysiology of the MTLE disease. [Copyright &y& Elsevier]

Abstract: One application of next-generation sequencing (NGS) is the targeted resequencing of interested genes which has not been used in viral integration site analysis of gene therapy applications. Here, we combined targeted sequence capture array and next generation sequencing to address the whole genome profiling of viral integration sites. Human 293T and K562 cells were transduced with a HIV-1 derived vector. A custom made DNA probe sets targeted pLVTHM vector used to capture lentiviral vector/human genome junctions. The captured DNA was sequenced using GS FLX platform. Seven thousand four hundred and eighty four human genome sequences flanking the long terminal repeats (LTR) of pLVTHM fragment sequences matched with an identity of at least 98% and minimum 50bp criteria in both cells. In total, 203 unique integration sites were identified. The integrations in both cell lines were totally distant from the CpG islands and from the transcription start sites and preferentially located in introns. A comparison between the two cell lines showed that the lentiviral-transduced DNA does not have the same preferred regions in the two different cell lines. [Copyright &y& Elsevier]

Background: In recent years, omics technologies have offered an exceptional chance to gain a deeper insight into the structural and functional characteristics of microbial communities. As a result, there is a growing demand for user-friendly, reproducible, and versatile bioinformatic tools that can effectively harness multi-omics data to provide a holistic understanding of microbiomes. Previously, we introduced gNOMO, a bioinformatic pipeline tailored to analyze microbiome multi-omics data in an integrative manner. In response to the evolving demands within the microbiome field and the growing necessity for integrated multi-omics data analysis, we have implemented substantial enhancements to the gNOMO pipeline., Results: Here, we present gNOMO2, a comprehensive and modular pipeline that can seamlessly manage various omics combinations, ranging from 2 to 4 distinct omics data types, including 16S ribosomal RNA (rRNA) gene amplicon sequencing, metagenomics, metatranscriptomics, and metaproteomics. Furthermore, gNOMO2 features a specialized module for processing 16S rRNA gene amplicon sequencing data to create a protein database suitable for metaproteomics investigations. Moreover, it incorporates new differential abundance, integration, and visualization approaches, enhancing the toolkit for a more insightful analysis of microbiomes. The functionality of these new features is showcased through the use of 4 microbiome multi-omics datasets encompassing various ecosystems and omics combinations. gNOMO2 not only replicated most of the primary findings from these studies but also offered further valuable perspectives., Conclusions: gNOMO2 enables the thorough integration of taxonomic and functional analyses in microbiome multi-omics data, offering novel insights in both host-associated and free-living microbiome research. gNOMO2 is available freely at https://github.com/muzafferarikan/gNOMO2., (© The Author(s) 2024. Published by Oxford University Press GigaScience.)

Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability, which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction, which has been associated with CI. Because the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that the axillary microbiota of PD patients shifts in association with CI progression, and thus can be used as a proxy for classification of CI stages in PD. We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia [PDD] and 48 PD patients with mild cognitive impairment [PD-MCI]) and 26 cognitively normal healthy controls (HC). We found that axillary microbiota profiles differentiate HC, PD-MCI, and PDD groups based on differential ranking analysis, and detected an increasing trend in the log ratio of Corynebacterium to Anaerococcus in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of the Anaerococcus, Peptoniphilus , and W5053 genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increases in myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity, in parallel to increasing CI. Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota has the potential to be exploited as a noninvasive tool in the development of novel strategies. IMPORTANCE Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients. The emergence and progression of cognitive impairment shows high variability among PD patients, and thus requires better diagnostic and monitoring strategies. Recent findings indicate a close link between autonomic dysfunction and cognitive impairment. Since thermoregulatory dysfunction and skin changes are among the main manifestations of autonomic dysfunction in PD, we hypothesized that alterations in the axillary microbiota may be useful for tracking cognitive impairment stages in PD. To our knowledge, this the first study characterizing the axillary microbiota of PD patients and exploring its association with cognitive impairment stages in PD. Future studies should include larger cohorts and multicenter studies to validate our results and investigate potential biological mechanisms.

Epstein-Barr virus (EBV) is associated with several B and epithelial cell cancers. EBV-encoded latent membrane protein 2A (LMP2A) contributes to cellular transformation by mimicking B cell receptor signaling. LMP2A/MYC double transgenic mice develop splenomegaly and B cell lymphoma much faster than MYC transgenic mice do. In this study, we explored the potential therapeutic efficacy of a novel spleen tyrosine kinase (SYK) and FLT3 inhibitor TAK-659 for development of a treatment option for EBV-associated malignancies. In our transgenic model, TAK-659 treatment totally abrogated splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments. TAK-659 treatment killed tumor cells, but not host cells within the spleen and tumors. Furthermore, TAK-659 treatment abrogated metastasis of tumor cells into bone marrow. Our data also show that TAK-659 inhibits SYK phosphorylation and induces apoptosis in LMP2A/MYC tumor cells at low nanomolar concentrations. Therefore, TAK-659 may provide an effective therapeutic option for treatment of LMP2A-positive EBV-associated malignancies and should be explored further in clinical trials. IMPORTANCE The novel SYK and FLT3 inhibitor TAK-659 prevents the enlargement of spleen and tumor development in a mouse model of EBV-associated lymphoma by counteracting the activation of cellular kinase SYK through the viral LMP2A gene by inducing cell death in tumor cells but not in nontumor cells. These findings indicate that TAK-659 may be a very effective nontoxic therapeutic molecule especially for EBV-positive hematologic malignancies., (Copyright © 2018 Cen et al.)

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.