LncRNA H19 Impairs Chemo and Radiotherapy in Tumorigenesis Garcia-Padilla, Carlos; Lozano-Velasco, Estefanía; Muñoz-Gallardo, María del Mar ...
International journal of molecular sciences,
07/2022, Letnik:
23, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Various treatments based on drug administration and radiotherapy have been devoted to preventing, palliating, and defeating cancer, showing high efficiency against the progression of this disease. ...Recently, in this process, malignant cells have been found which are capable of triggering specific molecular mechanisms against current treatments, with negative consequences in the prognosis of the disease. It is therefore fundamental to understand the underlying mechanisms, including the genes—and their signaling pathway regulators—involved in the process, in order to fight tumor cells. Long non-coding RNAs, H19 in particular, have been revealed as powerful protective factors in various types of cancer. However, they have also evidenced their oncogenic role in multiple carcinomas, enhancing tumor cell proliferation, migration, and invasion. In this review, we analyze the role of lncRNA H19 impairing chemo and radiotherapy in tumorigenesis, including breast cancer, lung adenocarcinoma, glioma, and colorectal carcinoma.
There is scarce research assessing the productivity of scientific articles on forestry topics. The objective of this study was to analyze the scientific production on forestry topics that originated ...in Mexico and were published in Mexican journals from 1996 to 2019 and to identify the causes that determine the impact factor of such publications and the space-time evolution of forestry research in Mexico. In addition, to analyze whether researchers tend to publish in journals published by their affiliation institutions. The study considered 2384 scientific articles from seven journals belonging to category VI of Biotechnology and Agricultural Sciences listed in the Journals Classification System by the National Council of Science and Technology that publishes forestry topics. Bibliometric indicators were generated through text mining and analysis of co-authorship networks. It was found that forestry research in Mexico from 1996 to 2019 presented exponential growth in the number of publications. Forestry scientific production was concentrated in the center of the country. It was dominated by researchers from three of 122 institutions: Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (13.88%), Colegio de Postgraduados (12.50%), and Universidad Autonoma Chapingo (10.44%). The journals with the highest number of publications were: Revista Mexicana de Ciencias Forestales (26.51%), Revista Chapingo Serie Ciencias Forestales y del Ambiente (20.34%), and Madera y Bosques (18.88%). Results show that forestry researchers in Mexico published mostly in journals edited by their affiliation institutions, which restricts constructive criticism of peer review and increases academic endogamy. Also showed the need to generate more forestry research for the southeast of the country on topics such as climate change, carbon capture, forest biometry, and remote perception, which are relevant aspects when we consider that no published research evaluated the development of the forestry sector in Mexico.
Abstract Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV ( PADI4 ) gene has been associated with RA susceptibility ...in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_ 89∗G, PADI4 _90∗T and PADI4 _92∗G gene polymorphisms were associated with RA susceptibility (OR= 1.34, p =0.04; OR=1.35, p = 0.03; OR= 1.34, p =0.04; respectively). The GTG haplotype was also significantly associated with RA (OR=2.27 95%CI=1.18-4.41; p=0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.
Cardiovascular development is initiated soon after gastrulation as bilateral precardiac mesoderm is progressively symmetrically determined at both sides of the developing embryo. The precardiac ...mesoderm subsequently fused at the embryonic midline constituting an embryonic linear heart tube. As development progress, the embryonic heart displays the first sign of left-right asymmetric morphology by the invariably rightward looping of the initial heart tube and prospective embryonic ventricular and atrial chambers emerged. As cardiac development progresses, the atrial and ventricular chambers enlarged and distinct left and right compartments emerge as consequence of the formation of the interatrial and interventricular septa, respectively. The last steps of cardiac morphogenesis are represented by the completion of atrial and ventricular septation, resulting in the configuration of a double circuitry with distinct systemic and pulmonary chambers, each of them with distinct inlets and outlets connections. Over the last decade, our understanding of the contribution of multiple growth factor signaling cascades such as Tgf-beta, Bmp and Wnt signaling as well as of transcriptional regulators to cardiac morphogenesis have greatly enlarged. Recently, a novel layer of complexity has emerged with the discovery of non-coding RNAs, particularly microRNAs and lncRNAs. Herein, we provide a state-of-the-art review of the contribution of non-coding RNAs during cardiac development. microRNAs and lncRNAs have been reported to functional modulate all stages of cardiac morphogenesis, spanning from lateral plate mesoderm formation to outflow tract septation, by modulating major growth factor signaling pathways as well as those transcriptional regulators involved in cardiac development.
Inflammation is a key event that is closely associated with the pathophysiology of frailty. The relationship of genetic polymorphisms into inflammatory cytokines with frailty remains poorly ...understood. The aim of this study was to investigate the association between VNTR polymorphisms of the
IL
-
4
and
IL
-
1RN
genes with the risk of frailty. We included a sample of 630 community-dwelling elderly aged 70 and older. Both
IL
-
4
and
IL
-
1RN
VNTR polymorphisms were genotyped by the polymerase chain reaction (PCR) method. Mean age was 77.7 years (SD = 6.0) and 52.5 % were women. The participants classified as frail were more likely to be older, had lower MMSE score (
p
< 0.001), and had more disability for IADL (
p
< 0.001) and ADL (
p
< 0.001). Genotypic and allelic frequencies for the
IL
-
4
VNTR polymorphism did not show significant differences between study groups (
p
> 0.05). However, we just observed a significant difference in the allelic frequencies for the A2 allele of the
IL
-
1RN
VNTR polymorphism between frail and nonfrail groups (OR 1.84, 95 % CI 1.08–3.12,
p
= 0.02). In addition, we analyzed the combined effect of the
IL
-
4
and
IL
-
1RN
VNTR polymorphisms and their possible association with frailty, where the combined
IL
-
4
low
–
IL
-
1Ra
high
genotype was identified as a marker of risk to frailty syndrome (OR 7.86, 95 % CI 1.83–33.69,
p
= 0.006). Our results suggest that both A2 allele and the combined
IL
-
4
low
–
IL
-
1Ra
high
genotype might be genetic markers of susceptibility to frailty in Mexican elderly.
Tumor necrosis factor-α (TNF-α) plays a central role in inflammation, and it has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). TNF-α activity is mediated through TNFRI ...and TNFRII cell surface receptors, which act as physiological attenuators of TNF-α activity. We recruited 190 RA patients and 190 healthy subjects (HS) in order to associate the −383A>C
TNFRI
polymorphism with sTNFRI levels and DAS28 score in RA. In results, sTNFRI levels were higher in RA patients than HS (
P
= 0.04). The −383A>C
TNFRI
polymorphism did not show significant differences in both studied groups. However, in the RA group the sTNFRI levels were significantly elevated (
P
= 0.004) in A/A genotype carriers. In addition, the A/A genotype carriers had the higher DAS28 score than A/C genotype (
P
= 0.02). These data suggest that −383A>C
TNFRI
polymorphism is not a susceptibility marker in RA, whereas the increased levels of sTNFRI could reflect the clinical activity in RA patients.
Congenital factor XI (FXI) deficiency is a probably underestimated coagulopathy that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the ...identification of single-nucleotide variants and small insertion/deletions because they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described.
To identify and characterize the SVs affecting F11.
The study was performed in 93 unrelated subjects with FXI deficiency recruited in Spanish hospitals over a period of 25 years (1997-2022). F11 was analyzed by next-generation sequencing, multiplex ligand probe amplification, and long-read sequencing.
Our study identified 30 different genetic variants. Interestingly, we found 3 SVs, all heterozygous: a complex duplication affecting exons 8 and 9, a tandem duplication of exon 14, and a large deletion affecting the whole gene. Nucleotide resolution obtained by long-read sequencing revealed Alu repetitive elements involved in all breakpoints. The large deletion was probably generated de novo in the paternal allele during gametogenesis, and despite affecting 30 additional genes, no syndromic features were described.
SVs may account for a high proportion of F11 genetic defects implicated in the molecular pathology of congenital FXI deficiency. These SVs, likely caused by a nonallelic homologous recombination involving repetitive elements, are heterogeneous in both type and length and may be de novo. These data support the inclusion of methods to detect SVs in this disorder, with long-read–based methods being the most appropriate because they detect all SVs and achieve adequate nucleotide resolution.
•Only 3 genetic structural variants (SVs) associated with factor XI (FXI) deficiency have been described so far.•We aimed to identify and characterize SVs in F11 causing FXI deficiency by long-read sequencing.•Three SVs, a de novo whole F11 deletion, and 2 partial duplications were identified in 93 patients.•Our data support the screening and characterization of SVs in FXI deficiency by long-read sequencing.
Objectives
Information on the recently COVID‐19‐associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus ...disease 2019 (COVID‐19), and review the published literature from Western countries.
Methods
Prospective study (March to May, 2020) that included all COVID‐19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used.
Results
COVID‐19‐associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non‐immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA‐related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all‐cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%.
Conclusions
COVID‐19‐associated pulmonary aspergillosis must be considered a serious and potentially life‐threatening complication in patients with severe COVID‐19 receiving immunosuppressive treatment.
Dyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aimed to describe the baseline LDL-c levels of patients presenting to cardiovascular ...clinics and evaluate the proportion who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines.
The REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP.
A total of 5443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid-lowering treatment at entry, while 12.4% were receiving high-intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9 ± 40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70–55 mg/dL and 19.3% were achieving LDL-c levels <55 mg/dL. In diabetic patients at very high risk, only 25.7% achieved their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals.
An important number of patients were not receiving any lipid-lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimization of lipid-lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk.
•Largest registry evaluating the lipid-lowering therapy in a Mexican cohort.•In patients with atherosclerotic cardiovascular disease 14.1% achieved LDL-c goals.•An important number of patients were not receiving any lipid-lowering therapy.
Asthma Control Questionnaire (ACQ) is a validated tool to measure asthma control. Cut-off points that best discriminate "well-controlled" or "not well-controlled" asthma have been suggested from the ...analysis of a large randomized clinical trial but they may not be adequate for daily clinical practice.
To establish cut-off points of the ACQ that best discriminate the level of control according to Global Initiative for Asthma (GINA) 2006 guidelines in patients with asthma managed at Allergology and Pulmonology Departments as well as Primary Care Centers in Spain.
An epidemiological descriptive study, with prospective data collection. Asthma control following GINA-2006 classification and 7-item ACQ was assessed. The study population was split in two parts: 2/3 for finding the cut-off points (development population) and 1/3 for validating the results (validation population).
A total of 1,363 stable asthmatic patients were included (mean age 38 ± 14 years, 60.3% women; 69.1% non-smokers). Patient classification according to GINA-defined asthma control was: controlled 13.6%, partially controlled 34.2%, and uncontrolled 52.3%. The ACQ cut-off points that better agreed with GINA-defined asthma control categories were calculated using receiver operating curves (ROC). The analysis showed that ACQ < 0.5 was the optimal cut-off point for "controlled asthma" (sensitivity 74.1%, specificity 77.5%) and 1.00 for "uncontrolled asthma" (sensitivity 73%, specificity 88.2%). Kappa index between GINA categories and ACQ was 0.62 (p < 0.001).
The ACQ cut-off points associated with GINA-defined asthma control in a real-life setting were <0.5 for controlled asthma and ≥1 for uncontrolled asthma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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