Here, we assessed whether 41 SNPs within steroid hormone genes associated with erosive disease. The most relevant finding was the rheumatoid factor (RF)-specific effect of the CYP1B1, CYP2C9, ESR2, ...FcγR3A, and SHBG SNPs to modulate the risk of bone erosions (P = 0.004, 0.0007, 0.0002, 0.013 and 0.015) that was confirmed through meta-analysis of our data with those from the DREAM registry (P = 0.000081, 0.0022, 0.00074, 0.0067 and 0.0087, respectively). Mechanistically, we also found a gender-specific correlation of the CYP2C9
genotype with serum vitamin D3 levels (P = 0.00085) and a modest effect on IL1β levels after stimulation of PBMCs or blood with LPS and PHA (P = 0.0057 and P = 0.0058). An overall haplotype analysis also showed an association of 3 ESR1 haplotypes with a reduced risk of erosive arthritis (P = 0.009, P = 0.002, and P = 0.002). Furthermore, we observed that the ESR2, ESR1 and FcγR3A SNPs influenced the immune response after stimulation of PBMCs or macrophages with LPS or Pam3Cys (P = 0.002, 0.0008, 0.0011 and 1.97•10
). Finally, we found that a model built with steroid hormone-related SNPs significantly improved the prediction of erosive disease in seropositive patients (P
= 2.46•10
) whereas no prediction was detected in seronegative patients (P
= 0.36). Although the predictive ability of the model was substantially lower in the replication population (P
= 0.014), we could confirm that CYP1B1 and CYP2C9 SNPs help to predict erosive disease in seropositive patients. These results are the first to suggest a RF-specific association of steroid hormone-related polymorphisms with erosive disease.
Background
Alcoholic cirrhosis (AC) is a common cause of death among individuals abusing alcohol. In the last resort, liver transplantation (LT) is considered the only solution to save the patient's ...life, generating socioeconomic and public health problems. Clinical and sociodemographic characteristics, rejection frequency, and short‐ and long‐term graft survival are not well known in end‐term AC patients undergoing LT. The aim was to determine the sociodemographic and clinical characteristics, their incidence in LT, main pre‐ and posttransplant complications, and short‐ and long‐term post‐transplant graft survival in AC patients in southeastern Spain.
Methods
The medical records of 1,026 patients who underwent LT over the last 23 years were retrospectively reviewed, and demographic data and posttransplant survivals were analyzed and compared. Biochemical characteristics, major pre‐ and posttransplant complications and short‐ and long‐term survivals were analyzed in a total of 398 male patients with AC undergoing LT.
Results
AC and viral cirrhosis are the main indications for LT in our study. Mostly represented in our study are AC men without associated viral infections with a mean age of 53.06 years. Main pretransplant complications in AC patients are ascites (78.3%) and encephalopathy (43.5%), while acute graft rejection is the most common liver posttransplant complication (26.6%), nevertheless with low graft loss frequency (1.1%). AC and autoimmune cirrhosis show the best posttransplant survival in both the short and long term. Patients with AC included on the waiting list for LT were Child‐Pugh class B (52.1%) and Model for End‐Stage Liver Disease score of 10 to 19 (71.2%). The highest percentage of AC patient survival was observed at 1 year posttransplant (81.2%) and progressively decreased over time up to 10 years posttransplant (69.6%). Pretransplant complications such as ascites and encephalopathy did not have an influence on the percentage of posttransplant survivals, although better survival rates were observed in nonviral AC patients.
Conclusions
AC without viral infections is the main indication for LT in southeastern Spain although its frequency has decreased in last decade. AC is a good indication for LT for its high survival rate and few posttransplant complications. Despite having a high percentage of pretransplant complications (ascites and encephalopathy) but does not appear to influence survivals being observed posttransplant survival rates above those expected. Conversely, viral infections in the patient with AC decrease patient survivals. The main future goals are design new strategies to detect, treat, and reduce AC frequency in our population and know alcoholic recidivism rate posttransplant in our population.
This figure shows Kaplan–Meier patient's survival curves according to the main indications for liver transplant in south‐eastern Spain in the short‐ and long‐term over 10 years. A comparative table showing statistically significant differences between the survival of alcoholic cirrhosis patients (with and without associated viral infections) and other liver transplant indications is also shown: total number of patients included in each group considered; NS, not significant.
Employees’ health is being affected not only by the possibility of contracting COVID-19, but by all the negative consequences that this pandemic has brought, such as confinement, social distancing, ...and self-isolation. In recent decades, more companies have opted for corporate well-being programmes in their workplaces, improving the health and quality of life of their employees. The effects generated by the current COVID-19 pandemic require these programmes to adapt to this new situation. The objective of this case study is to analyse the corporate well-being programme, in times of COVID-19, of Mahou San Miguel, a benchmark company in corporate well-being in Spain. A mixed method approach to data collection was used. The findings show the benefits achieved in its adaptation to this new physical-virtual environment. This paper could help other companies around the world to adapt their corporate well-being programmes to the new reality brought about by COVID-19.
Transcriptomic Changes in Cisplatin-Resistant MCF-7 Cells Ruiz-Silvestre, Araceli; Garcia-Venzor, Alfredo; Ceballos-Cancino, Gisela ...
International journal of molecular sciences,
04/2024, Letnik:
25, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Breast cancer is a leading cause of cancer-related deaths among women. Cisplatin is used for treatment, but the development of resistance in cancer cells is a significant concern. This study aimed to ...investigate changes in the transcriptomes of cisplatin-resistant MCF7 cells. We conducted RNA sequencing of cisplatin-resistant MCF7 cells, followed by differential expression analysis and bioinformatic investigations to identify changes in gene expression and modified signal transduction pathways. We examined the size and quantity of extracellular vesicles. A total of 724 genes exhibited differential expression, predominantly consisting of protein-coding RNAs. Notably, two long non-coding RNAs (lncRNAs), NEAT1 and MALAT, were found to be dysregulated. Bioinformatic analysis unveiled dysregulation in processes related to DNA synthesis and repair, cell cycle regulation, immune response, and cellular communication. Additionally, modifications were observed in events associated with extracellular vesicles. Conditioned media from resistant cells conferred resistance to wild-type cells in vitro. Furthermore, there was an increase in the number of vesicles in cisplatin-resistant cells. Cisplatin-resistant MCF7 cells displayed differential RNA expression, including the dysregulation of NEAT1 and MALAT long non-coding RNAs. Key processes related to DNA and extracellular vesicles were found to be altered. The increased number of extracellular vesicles in resistant cells may contribute to acquired resistance in wild-type cells.
AbstractBackground and aims. Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver in which the immunological mechanisms involved in tissue destruction and/or repair are still ...unclear. Different pro-inflammatory cytokines have been shown to play a determinant role in AIH pathogenesis. Here, we aim to compare the circulating levels of pro-and anti-inflammatory cytokines such as IL-6, TNF-α, IL-17A/F, IL-21, IL-22, IL-23, and IL-10 in patients with type 2 AIH compared to patients with type 1 AIH and healthy controls (HC). Fourty-six Mexican patients with AIH were recruited in our study. Patients were classified as type 1 or 2 AIH based on immune serological markers. Fourty-four serum samples from healthy individuals were included as controls. Serum cytokine levels were determined by ELISA technique. Results. Compared to healthy controls, serum levels of IL-17F, IL-21, IL-23, IL-10, IL-6, and TNF-α, but not IL-17A and IL-22, were significantly increased in AIH patients. When patients were grouped by aminotransferase activity, a biomarker of active disease, a positive correlation between serum IL-17F and alanine transaminase (rs: 0.4739; P = 0.0009) and aspartate transaminase (rs: 0.4984; P = 0.0004) levels was found. A cytokine signature profile associated with type 2 AIH was characterized by high serum IL-21 (type 1 AIH: 0.66 pg/mL; type 2 AIH: 331.1 pg/mL; P = 0.0042) and IL-22 (type 1 AIH: 0.1 pg/mL; type 2 AIH: 55.26 pg/mL; P = 0.0028) levels. Conclusions. We show for the first time, differential regulation of certain pro-inflammatory cytokines associated with disease progression and AIH type in Mexican patients.
Evidence shows that objectives for detecting and controlling dyslipidemia are not being effectively met, and outcomes differ between men and women. This study aimed to assess gender-related ...differences in diagnostic inertia around dyslipidemia. This ambispective, epidemiological, cohort registry study included adults who presented to public primary health care centers in a Spanish region from 2008 to 2012, with dyslipidemia and without cardiovascular disease. Diagnostic inertia was defined as the registry of abnormal diagnostic parameters-but no diagnosis-on the person's health record in a window of six months from inclusion. A total of 58,970 patients were included (53.7% women) with a mean age of 58.4 years in women and 57.9 years in men. The 6358 (20.1%) women and 4312 (15.8%) men presenting diagnostic inertia had a similar profile, although in women the magnitude of the association with younger age was larger. Hypertension showed a larger association with diagnostic inertia in women than in men (prevalence ratio 1.81 vs. 1.56). The overall prevalence of diagnostic inertia in dyslipidemia is high, especially in women. Both men and women have a higher risk of cardiovascular morbidity and mortality.
Evidence shows that objectives for detecting and controlling cardiovascular risk factors are not being effectively met, and moreover, outcomes differ between men and women. This study will assess the ...gender-related differences in diagnostic inertia around the three most prevalent cardiovascular risk factors: dyslipidemia, arterial hypertension, and diabetes mellitus, and to evaluate the consequences on cardiovascular disease incidence. This is an epidemiological and cohort study. Eligible patients will be adults who presented to public primary health care centers in a Spanish region from 2008 to 2011, with hypertension, dyslipidemia, or/and diabetes and without cardiovascular disease. Participants' electronic health records will be used to collect the study variables in a window of six months from inclusion. Diagnostic inertia of hypertension, dyslipidemia, and/or diabetes is defined as the registry of abnormal diagnostic parameters-but no diagnosis-on the person's health record. The cohort will be followed from the date of inclusion until the end of 2019. Outcomes will be cardiovascular events, defined as hospital admission due to ischemic cardiopathy, stroke, and death from any cause. The results of this study could inform actions to rectify the structure, organization and training of health care teams in order to correct the inequality.
This research aimed to study the salivary flow and other autonomic reactions -heart rate (HR) and skin conductance response (SCR)- in blood-injection-injury (BII) phobia and snake phobia ...participants, under the assumption that exposure to blood-related pictures in BII phobia will provoke an increase in parasympathetic activity that, in turn, will lead to a greater saliva production than other affective contents.
We selected 18 BII phobia and 14 snake phobia participants along with 22 non-phobia individuals. All participants were exposed to 3 blocks of pictures (12 pictures per block) depicting either mutilations, snakes or neutral, household objects. Saliva samples were taken in the 2-min interval before and after each block.
In comparison to other contents, blood-related pictures provoked an increase in salivary flow in BII phobia participants, as well as an increase in the number of SCRs. In the snake phobia group, snake pictures provoked HR acceleration, but the SCRs they elicited did not differ from the SCRs provoked by the blood-related pictures.
BII phobia individuals react to their phobic object with a series of physiological changes resulting from a sympathetic-parasympathetic co-activation. This is in contrast with other specific phobias (e.g., small animal phobias) that usually show a sympathetically mediated, defensive reactivity when exposed to their disorder-relevant stimuli. These data support the use of therapeutic interventions in BII phobia that may differ in some respect from those used in other specific phobias.
•Blood-related pictures, unlike other contents, increase salivary flow in blood phobia.•Phobia-related pictures increase skin responses in blood phobia and snake phobia.•Snake pictures provoke heart rate acceleration in snake phobia.•Blood phobia participants show a sympathetic-parasympathetic co-activation.
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