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17 pages, 2039 KB  
Article
Long-Term Conservation Tillage Increases Soil Organic Carbon Stability by Modulating Microbial Nutrient Limitations and Aggregate Protection
by Zixuan Han, Xueping Wu, Huizhou Gao, Angyuan Jia and Qiqi Gao
Agronomy 2025, 15(7), 1571; https://doi.org/10.3390/agronomy15071571 - 27 Jun 2025
Cited by 1 | Viewed by 602
Abstract
Increasing soil organic carbon (SOC) storage is essential for improving soil fertility and mitigating climate change. The priming effect, which is regulated by physical, chemical and microbial interactions, plays a pivotal role in SOC turnover. However, the fate of both native and newly [...] Read more.
Increasing soil organic carbon (SOC) storage is essential for improving soil fertility and mitigating climate change. The priming effect, which is regulated by physical, chemical and microbial interactions, plays a pivotal role in SOC turnover. However, the fate of both native and newly added carbon under different tillage regimes remains unclear. To address this gap, a 13C-glucose labelling incubation experiment was conducted to assess SOC mineralization and priming effects under long-term tillage practices, including subsoiling with straw mulching (ST), no tillage with straw mulching (NT), and conventional tillage with straw removal (CT). The results demonstrated that conservation tillage (NT and ST) significantly reduced total SOC mineralization and glucose-derived CO2 release compared to CT. Notably, the priming effect under CT was 19.5% and 24.7% higher than under NT and ST, respectively. In the early incubation stage, positive priming was primarily driven by microbial co-metabolism, while during days 1–31, microbial stoichiometric decomposition dominated the process. In addition, NT and ST treatments significantly increased the proportion of >250 μm aggregates and their associated carbon and nitrogen contents, thereby enhancing aggregate stability and physical protection of SOC. The priming effect observed under conservation tillage was strongly negatively related to aggregate stability and aggregate associated carbon content, whereas it was positively related to the β-glucosidase/Peroxidase ratio (BG/PER) and the subtraction value between carbon/nitrogen (RC:N) and the carbon–nitrogen imbalance of the available resources (TERC:N). Overall, our findings highlight that conservation tillage enhances SOC stability not only by improving soil physical structure but also by alleviating microbial stoichiometric constraints, offering a synergistic pathway for carbon retention and climate-resilient soil management. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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14 pages, 1701 KB  
Article
A Perceived Dissociation Between Systemic Chronic Inflammation, Age, and the Telomere/Telomerase System in Type 2 Diabetes
by Mai S. Sater, Dhuha M. B. AlDehaini, Zainab H. A. Malalla, Muhalab E. Ali and Hayder A. Giha
Biomedicines 2025, 13(3), 531; https://doi.org/10.3390/biomedicines13030531 - 20 Feb 2025
Cited by 1 | Viewed by 846
Abstract
Background: Chronic inflammation is associated with leukocyte telomere length (LTL) shortening and type 2 diabetes (T2D). The latter is also associated with LTL shortening, while the three variables are associated with aging. Objective: It is tempting to test whether inflammation, age, or [...] Read more.
Background: Chronic inflammation is associated with leukocyte telomere length (LTL) shortening and type 2 diabetes (T2D). The latter is also associated with LTL shortening, while the three variables are associated with aging. Objective: It is tempting to test whether inflammation, age, or both are behind the telomere system aberrations in diabetic patients. Methods: In this cross-sectional observational study, blood samples collected from 118 T2D patients were analyzed via ELISA to estimate the plasma levels of four inflammatory markers, IL6, IL8, TREM1, and uPAR, and the telomerase enzyme (TE). Moreover, the extracted DNA was used for the LTL estimation via qPCR and for single nucleotide polymorphisms (SNP) genotyping of TE genes (TERT, TERC, and ACYP2) via rtPCR. Results: The results showed no correlation between the levels of all tested inflammatory markers and the LTL, TE level, and age. There were no significant differences between the marker levels in diabetic patients in the four quartiles of the LTL and TE levels. Moreover, there were no significant differences in the levels of the markers between carriers of the different TE genotypes. Conclusions: There were no associations between the tested inflammatory markers’ levels and the LTL, TE plasma levels, or age in T2D. Explanations for the dissociation between the above-known associations in T2D were proposed; however, the subject is worth further investigation. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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29 pages, 4449 KB  
Article
Techno-Economic Assessment of Molten Salt-Based Concentrated Solar Power: Case Study of Linear Fresnel Reflector with a Fossil Fuel Backup under Saudi Arabia’s Climate Conditions
by Ahmed Aljudaya, Stavros Michailos, Derek B. Ingham, Kevin J. Hughes, Lin Ma and Mohamed Pourkashanian
Energies 2024, 17(11), 2719; https://doi.org/10.3390/en17112719 - 3 Jun 2024
Cited by 1 | Viewed by 2245
Abstract
Concentrated solar power (CSP) has gained traction for generating electricity at high capacity and meeting base-load energy demands in the energy mix market in a cost-effective manner. The linear Fresnel reflector (LFR) is valued for its cost-effectiveness, reduced capital and operational expenses, and [...] Read more.
Concentrated solar power (CSP) has gained traction for generating electricity at high capacity and meeting base-load energy demands in the energy mix market in a cost-effective manner. The linear Fresnel reflector (LFR) is valued for its cost-effectiveness, reduced capital and operational expenses, and limited land impact compared to alternatives such as the parabolic trough collector (PTC). To this end, the aim of this study is to optimize the operational parameters, such as the solar multiple (SM), thermal energy storage (TES), and fossil fuel (FF) backup system, in LFR power plants using molten salt as a heat transfer fluid (HTF). A 50 MW LFR power plant in Duba, Saudi Arabia, serves as a case study, with a Direct Normal Irradiance (DNI) above 2500 kWh/m2. About 600 SM-TES configurations are analyzed with the aim of minimizing the levelized cost of electricity (LCOE). The analysis shows that a solar-only plant can achieve a low LCOE of 11.92 ¢/kWh with a capacity factor (CF) up to 36%, generating around 131 GWh/y. By utilizing a TES system, the SM of 3.5 and a 15 h duration TES provides the optimum integration by increasing the annual energy generation (AEG) to 337 GWh, lowering the LCOE to 9.24 ¢/kWh, and boosting the CF to 86%. The techno-economic optimization reveals the superiority of the LFR with substantial TES over solar-only systems, exhibiting a 300% increase in annual energy output and a 20% reduction in LCOE. Additionally, employing the FF backup system at 64% of the turbine’s rated capacity boosts AEG by 17%, accompanied by a 5% LCOE reduction. However, this enhancement comes with a trade-off, involving burning a substantial amount of natural gas (503,429 MMBtu), leading to greenhouse gas emissions totaling 14,185 tonnes CO₂ eq. This comprehensive analysis is a first-of-a-kind study and provides insights into the optimal designs of LFR power plants and addresses thermal, economic, and environmental considerations of utilizing molten salt with a large TES system as well as employing natural gas backup. The outcomes of the research address a wide audience including academics, operators, and policy makers. Full article
(This article belongs to the Collection Renewable Energy and Energy Storage Systems)
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17 pages, 683 KB  
Article
Association of HOTAIR, MIR155HG, TERC, miR-155, -196a2, and -146a Genes Polymorphisms with Papillary Thyroid Cancer Susceptibility and Prognosis
by Jelena Karajovic, Bozidar Kovacevic, Bojana Uzelac, Debora Stefik, Bojana Jovanovic, Petar Ristic, Snezana Cerovic and Gordana Supic
Cancers 2024, 16(3), 485; https://doi.org/10.3390/cancers16030485 - 23 Jan 2024
Cited by 4 | Viewed by 2074
Abstract
Polymorphisms in long non-coding RNA and microRNA genes may play a significant role in the susceptibility and progression of papillary thyroid carcinoma (PTC). The current study investigates the polymorphisms HOTAIR rs920778, MIR155HG rs1893650, TERC rs10936599, miR-155 rs767649, miR-196a2 rs11614913 and miR-146a rs2910164 in [...] Read more.
Polymorphisms in long non-coding RNA and microRNA genes may play a significant role in the susceptibility and progression of papillary thyroid carcinoma (PTC). The current study investigates the polymorphisms HOTAIR rs920778, MIR155HG rs1893650, TERC rs10936599, miR-155 rs767649, miR-196a2 rs11614913 and miR-146a rs2910164 in 102 PTC patients and 106 age- and sex-matched controls of the Caucasian Serbian population, using real-time PCR. We observed differences in genotype distributions of the HOTAIR rs920778 (p = 0.016) and MIR155HG rs1893650 (p = 0.0002) polymorphisms between PTC patients and controls. HOTAIR rs920778 was associated with increased PTC susceptibility (adjusted OR = 1.497, p = 0.021), with the TT variant genotype increasing the risk compared to the CC genotype (OR = 2.466, p = 0.012) and C allele carriers (CC + CT) (OR = 1.585, p = 0.006). The HOTAIR rs920778 TT genotype was associated with lymph node metastasis (p = 0.022), tumor recurrence (p = 0.016), and progression-free survival (p = 0.010) compared to C allele carriers. Multivariate Cox regression revealed that ATA risk (HR = 14.210, p = 0.000004) and HOTAIR rs920778 (HR = 2.811, p = 0.010) emerged as independent prognostic factors in PTC. A novel polymorphism, MIR155HG rs1893650, was negatively correlated with susceptibility to PTC, with TC heterozygotes exerting a protective effect (OR = 0.268, p = 0.0001). These results suggest that the polymorphisms HOTAIR rs920778 and MIR155HG rs1893650 could be potential prognostic and risk biomarkers in papillary thyroid carcinomas. Full article
(This article belongs to the Special Issue Thyroid Cancer: New Advances from Diagnosis to Therapy)
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8 pages, 583 KB  
Communication
Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study
by Inmaculada Rodriguez-Martin, Gonzalo Villanueva-Martin, Alfredo Guillen-Del-Castillo, Norberto Ortego-Centeno, José L. Callejas, Carmen P. Simeón-Aznar, Javier Martin and Marialbert Acosta-Herrera
Int. J. Mol. Sci. 2023, 24(21), 15589; https://doi.org/10.3390/ijms242115589 - 25 Oct 2023
Cited by 5 | Viewed by 2665
Abstract
Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using [...] Read more.
Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528–0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563–0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc. Full article
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16 pages, 334 KB  
Article
Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+)
by Maja Šetinc, Matea Zajc Petranović, Goran Slivšek, Sandra Mijač, Željka Celinščak, Anita Stojanović Marković, Vesna Bišof, Marijana Peričić Salihović and Tatjana Škarić-Jurić
Genes 2023, 14(9), 1806; https://doi.org/10.3390/genes14091806 - 15 Sep 2023
Viewed by 2301
Abstract
Some sources report a connection of cellular senescence with chronic pathological conditions; however, the association between particular cellular processes and general health is rarely examined. This study aims to test the relationship of general health with DNA damage pathways that play a crucial [...] Read more.
Some sources report a connection of cellular senescence with chronic pathological conditions; however, the association between particular cellular processes and general health is rarely examined. This study aims to test the relationship of general health with DNA damage pathways that play a crucial role in senescence. The association of ten selected SNPs with subjective and objective general health and functional ability indicators has been tested in 314 oldest-old people from Croatia. Multivariate logistic regression was employed to simultaneously test the impact of variables potentially influencing targeted health and functional ability variables. The best model, explaining 37.1% of the variance, has six independent significant predictors of functional ability scores: rs16847897 in TERC, rs533984 in MRE11A, and rs4977756 in CDKN2B, chronic disease count, Mini-Mental State Examination scores, and age at surveying. In conclusion, the examined ten loci involved in DNA damage repair pathways showed a more significant association with self-rated health and functional ability than with the number of disease or prescribed medicaments. The more frequent, longevity-related homozygote (GG) in rs16847897 was associated with all three aspects of self-assessments—health, mobility, and independence—indicating that this TERC locus might have a true impact on the overall vitality of the oldest-old persons. Full article
(This article belongs to the Special Issue Genetic Variants in Human Population and Diseases)
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17 pages, 299 KB  
Article
The Influence of TEP1 and TERC Genetic Variants on the Susceptibility to Multiple Sclerosis
by Gintarė Rumšaitė, Greta Gedvilaitė, Renata Balnytė, Loresa Kriaučiūnienė and Rasa Liutkevičienė
J. Clin. Med. 2023, 12(18), 5863; https://doi.org/10.3390/jcm12185863 - 9 Sep 2023
Viewed by 1711
Abstract
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: Our aim was to determine the associations of [...] Read more.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: Our aim was to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. Methods: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. The obtained data were analysed using the program “IBM SPSS Statistics 29.0”. Haplotype analysis was performed using the online program “SNPStats”. Results: The TERC rs12696304 G allele of this SNP is associated with 1.4-fold lower odds of developing MS (p = 0.035). TERC rs35073794 is associated with approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G—rs1713418-A haplotype is statistically significantly associated with 1.75-fold increased odds of developing MS (p = 0.006). The rs12696304-C–rs35073794-A haplotype is statistically significantly associated with twofold decreased odds of developing MS (p = 0.008). In addition, the rs12696304-G—rs35073794-A haplotype was found to be statistically significantly associated with 5.3-fold decreased odds of developing MS (p < 0.001). Conclusion: The current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Multiple Sclerosis)
18 pages, 7464 KB  
Article
In Silico Bioinformatics Analysis on the Role of Long Non-Coding RNAs as Drivers and Gatekeepers of Androgen-Independent Prostate Cancer Using LNCaP and PC-3 Cells
by Mandisa Mbeje, Jeyalakshmi Kandhavelu, Clement Penny, Mmamoletla Kgoebane-Maseko, Zodwa Dlamini and Rahaba Marima
Curr. Issues Mol. Biol. 2023, 45(9), 7257-7274; https://doi.org/10.3390/cimb45090459 - 1 Sep 2023
Viewed by 2359
Abstract
Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer “hallmarks”. Androgen signaling plays an important role in PCa progression. [...] Read more.
Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer “hallmarks”. Androgen signaling plays an important role in PCa progression. This study aimed to profile the aberrantly expressed lncRNAs in androgen-dependent (LNCaP) PCa compared to androgen-independent (PC-3) PCa cells. This was achieved by using a 384-well plate of PCa lncRNA gene panel. Differential expression of ±2 up or downregulation was determined using the CFX Maestro software v2.1. LncSEA and DIANA-miRPath were used to identify the enriched pathways. Telomerase RNA component (TERC) lncRNA was illustrated to participate in various tumourigenic classes by in silico bioinformatics analysis and was thus selected for validation using RT-qPCR. Further bioinformatics analysis revealed the involvement of differentially expressed lncRNAs in oncogenic pathways. Some lncRNAs undergo hypermethylation, others are encapsulated by exosomes, while others interact with several microRNAs (miRNAs), favouring tumourigenic pathways. Notably, TERC lncRNA was shown to interact with tumour-suppressor miRNAs hsa-miR-4429 and hsa-miR-320b. This interaction in turn activates TGF-β-signaling and ECM-receptor interaction pathways, favouring the progression of PCa. Understanding lncRNAs as competitive endogenous RNA molecules and their interactions with miRNAs may aid in the identification of novel prognostic PCa biomarkers and therapeutic targets. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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13 pages, 1065 KB  
Review
Emerging Therapies for Antibody-Mediated Rejection in Kidney Transplantation
by Farah Abuazzam, Casey Dubrawka, Tarek Abdulhadi, Gwendolyn Amurao, Louai Alrata, Dema Yaseen Alsabbagh, Omar Alomar and Tarek Alhamad
J. Clin. Med. 2023, 12(15), 4916; https://doi.org/10.3390/jcm12154916 - 26 Jul 2023
Cited by 5 | Viewed by 5819
Abstract
Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, [...] Read more.
Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing both active and chronic active AMR and highlight the ongoing clinical trials. Full article
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8 pages, 1082 KB  
Opinion
Extending Validity of the Bacterial Cell Cycle Model through Thymine Limitation: A Personal View
by Arieh Zaritsky
Life 2023, 13(4), 906; https://doi.org/10.3390/life13040906 - 29 Mar 2023
Cited by 1 | Viewed by 1784
Abstract
The contemporary view of bacterial physiology was established in 1958 at the “Copenhagen School”, culminating a decade later in a detailed description of the cell cycle based on four parameters. This model has been subsequently supported by numerous studies, nicknamed BCD (The Bacterial [...] Read more.
The contemporary view of bacterial physiology was established in 1958 at the “Copenhagen School”, culminating a decade later in a detailed description of the cell cycle based on four parameters. This model has been subsequently supported by numerous studies, nicknamed BCD (The Bacterial Cell-Cycle Dogma). It readily explains, quantitatively, the coupling between chromosome replication and cell division, size and DNA content. An important derivative is the number of replication positions n, the ratio between the time C to complete a round of replication and the cell mass doubling time τ; the former is constant at any temperature and the latter is determined by the medium composition. Changes in cell width W are highly correlated to n through the equation for so-called nucleoid complexity NC (=(2n − 1)/(ln2 × n)), the amount of DNA per terC (i.e., chromosome) in genome equivalents. The narrow range of potential n can be dramatically extended using the method of thymine limitation of thymine-requiring mutants, which allows a more rigorous testing of the hypothesis that the nucleoid structure is the primary source of the signal that determines W during cell division. How this putative signal is relayed from the nucleoid to the divisome is still highly enigmatic. The aim of this Opinion article is to suggest the possibility of a new signaling function for nucleoid DNA. Full article
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6 pages, 1390 KB  
Proceeding Paper
Experimental Identification of Aberrantly Expressed Long Non-Coding RNAs in Breast Cancer
by Irina Pronina, Svetlana Lukina, Vitaly Loginov, Aleksey Burdennyy, Tatiana Kazubskaya, Eleonora Braga and Elena Filippova
Med. Sci. Forum 2023, 21(1), 7; https://doi.org/10.3390/ECB2023-14083 - 1 Mar 2023
Viewed by 1082
Abstract
Breast cancer (BC) remains one of the leading causes of cancer deaths among women worldwide. Recently, studies of long non-coding RNAs (lncRNAs) involved in the regulation of various signaling pathways in cells have become increasingly important, since they demonstrate great prognostic potential in [...] Read more.
Breast cancer (BC) remains one of the leading causes of cancer deaths among women worldwide. Recently, studies of long non-coding RNAs (lncRNAs) involved in the regulation of various signaling pathways in cells have become increasingly important, since they demonstrate great prognostic potential in cancer. The aim of our work was to identify new aberrantly expressed lncRNAs in BC. We identified 30 aberrantly expressed lncRNAs in BC. For most lncRNAs, a decrease in the expression level by 2.34–13.2 times (p < 0.05) was noted, and only for lncRNA TERC, an increase in the expression level by 2.24 times (p = 0.034) was noted. Of greatest interest are the data obtained for the lncRNAs ADAMTS9-AS2, EMX2OS, HOTAIRM1 and MEG3, as they are consistent with the data of the bioinformatic analysis. Full article
(This article belongs to the Proceedings of The 2nd International Electronic Conference on Biomedicines)
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16 pages, 3923 KB  
Article
High-Molecular-Weight Plasmids Carrying Carbapenemase Genes blaNDM-1, blaKPC-2, and blaOXA-48 Coexisting in Clinical Klebsiella pneumoniae Strains of ST39
by Ekaterina S. Kuzina, Angelina A. Kislichkina, Angelika A. Sizova, Yury P. Skryabin, Tatiana S. Novikova, Olga N. Ershova, Ivan A. Savin, Olga E. Khokhlova, Alexander G. Bogun and Nadezhda K. Fursova
Microorganisms 2023, 11(2), 459; https://doi.org/10.3390/microorganisms11020459 - 11 Feb 2023
Cited by 15 | Viewed by 3157
Abstract
Background: Klebsiella pneumoniae, a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids. Methods: Four clinical K. pneumoniae isolates were collected [...] Read more.
Background: Klebsiella pneumoniae, a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids. Methods: Four clinical K. pneumoniae isolates were collected from four patients of a neuro-intensive care unit in Moscow, Russia, during the point prevalence survey. The AMR phenotype was estimated using the Vitec-2 instrument, and whole genome sequencing (WGS) was done using Illumina and Nanopore technologies. Results: All strains were resistant to beta-lactams, nitrofurans, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines. WGS analysis revealed that all strains were closely related to K. pneumoniae ST39, capsular type K-23, with 99.99% chromosome identity. The novelty of the study is the description of the strains carrying simultaneously three large plasmids of the IncHI1B, IncC, and IncFIB groups carrying the carbapenemase genes of three types, blaOXA-48, blaNDM-1, and blaKPC-2, respectively. The first of them, highly identical in all strains, was a hybrid plasmid that combined two regions of the resistance genes (blaOXA-48 and blaTEM-1 + blaCTX-M-15 + blaOXA-1 + catB + qnrS1 + int1) and a region of the virulence genes (iucABCD, iutA, terC, and rmpA2::IS110). Conclusion: The spread of K. pneumoniae strains carrying multiple plasmids conferring resistance even to last-resort antibiotics is of great clinical concern. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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9 pages, 615 KB  
Communication
Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer
by Abel Martel-Martel, Luis A. Corchete, Marc Martí, Rosario Vidal-Tocino, Elena Hurtado, Edurne Álvaro, Fernando Jiménez, Marta Jiménez-Toscano, Francesc Balaguer, Gonzalo Sanz, Irene López, Sergio Hernández-Villafranca, Araceli Ballestero, Alfredo Vivas, Sirio Melone, Carlos Pastor, Lorena Brandáriz, Manuel A. Gómez-Marcos, Juan J. Cruz-Hernández, José Perea and Rogelio González-Sarmientoadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(4), 3526; https://doi.org/10.3390/ijms24043526 - 9 Feb 2023
Cited by 8 | Viewed by 3864
Abstract
Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere [...] Read more.
Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC. Full article
(This article belongs to the Special Issue Cellular Mechanism and Immune Response of Colorectal Cancer)
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20 pages, 1133 KB  
Review
The Genetic and Epigenetic Footprint in Idiopathic Pulmonary Fibrosis and Familial Pulmonary Fibrosis: A State-of-the-Art Review
by Claudio Tirelli, Chiara Pesenti, Monica Miozzo, Michele Mondoni, Laura Fontana and Stefano Centanni
Diagnostics 2022, 12(12), 3107; https://doi.org/10.3390/diagnostics12123107 - 9 Dec 2022
Cited by 35 | Viewed by 5135
Abstract
Idiopathic pulmonary fibrosis (IPF) is a rare disease of the lung with a largely unknown etiology and a poor prognosis. Intriguingly, forms of familial pulmonary fibrosis (FPF) have long been known and linked to specific genetic mutations. There is little evidence of the [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a rare disease of the lung with a largely unknown etiology and a poor prognosis. Intriguingly, forms of familial pulmonary fibrosis (FPF) have long been known and linked to specific genetic mutations. There is little evidence of the possible role of genetics in the etiology of sporadic IPF. We carried out a non-systematic, narrative literature review aimed at describing the main known genetic and epigenetic mechanisms that are involved in the pathogenesis and prognosis of IPF and FPF. In this review, we highlighted the mutations in classical genes associated with FPF, including those encoding for telomerases (TERT, TERC, PARN, RTEL1), which are also found in about 10–20% of cases of sporadic IPF. In addition to the Mendelian forms, mutations in the genes encoding for the surfactant proteins (SFTPC, SFTPA1, SFTPA2, ABCA3) and polymorphisms of genes for the mucin MUC5B and the Toll-interacting protein TOLLIP are other pathways favoring the fibrogenesis that have been thoroughly explored. Moreover, great attention has been paid to the main epigenetic alterations (DNA methylation, histone modification and non-coding RNA gene silencing) that are emerging to play a role in fibrogenesis. Finally, a gaze on the shared mechanisms between cancer and fibrogenesis, and future perspectives on the genetics of pulmonary fibrosis have been analyzed. Full article
(This article belongs to the Special Issue Molecular Diagnosis of Interstitial Lung Disease)
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35 pages, 3865 KB  
Review
Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies
by Ion Udroiu, Jessica Marinaccio and Antonella Sgura
Int. J. Mol. Sci. 2022, 23(23), 15189; https://doi.org/10.3390/ijms232315189 - 2 Dec 2022
Cited by 12 | Viewed by 6983
Abstract
A growing number of studies have evidenced non-telomeric functions of “telomerase”. Almost all of them, however, investigated the non-canonical effects of the catalytic subunit TERT, and not the telomerase ribonucleoprotein holoenzyme. These functions mainly comprise signal transduction, gene regulation and the increase of [...] Read more.
A growing number of studies have evidenced non-telomeric functions of “telomerase”. Almost all of them, however, investigated the non-canonical effects of the catalytic subunit TERT, and not the telomerase ribonucleoprotein holoenzyme. These functions mainly comprise signal transduction, gene regulation and the increase of anti-oxidative systems. Although less studied, TERC (the RNA component of telomerase) has also been shown to be involved in gene regulation, as well as other functions. All this has led to the publication of many reviews on the subject, which, however, are often disseminating personal interpretations of experimental studies of other researchers as original proofs. Indeed, while some functions such as gene regulation seem ascertained, especially because mechanistic findings have been provided, other ones remain dubious and/or are contradicted by other direct or indirect evidence (e.g., telomerase activity at double-strand break site, RNA polymerase activity of TERT, translation of TERC, mitochondrion-processed TERC). In a critical study of the primary evidence so far obtained, we show those functions for which there is consensus, those showing contradictory results and those needing confirmation. The resulting picture, together with some usually neglected aspects, seems to indicate a link between TERT and TERC functions and cellular stemness and gives possible directions for future research. Full article
(This article belongs to the Section Molecular Biology)
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