Revista De Investigacion Clinica-Clinical and Translational Investigation最新文献

Unassigned: Background: Obesity and aging are risk factors for chronic degenerative diseases that favor neuroinflammation leading to cognitive and motor impairment. Mexico ranks second in obesity worldwide, being more prevalent in the female population. Objectives: To determine whether serum biomarkers of obesity, inflammation, oxidative stress, and brain damage vary according to age, sex, and ethnicity, we studied Mexican elderly women with obesity since this population has been historically neglected. Methods: A total of 156 women over 60 years of age (89 obese and 67 non-obese) were selected from the FraDySMex-2019 Cohort study samples. Serum markers of inflammation (Interleukin [IL]-6, tumor necrosis factor-α, IL-10, adiponectin, and peroxisome proliferator-activated receptor gamma [PPAR-γ]), and neurodegeneration (glial fibrillary acidic protein, brain-derived neurotrophic factor, and S100B), redox status (GSH/GSSG ratio), and protein oxidative damage were assessed. A biochemical profile was obtained and used for a factor analysis including their morphometric data. Results: The data from the participating elderly women clustered in relation to their obesity characteristics. The markers that were higher in obese women were GSSG, protein carbonylation, IL-6, and S100B, along with lower levels of adiponectin and PPAR-γ, suggesting they could be interesting biomarkers of neuroinflammation in obese Mexican women. Conclusion: Further case-control studies must be implemented to validate their prognosis value in elderly obese Mexican women with cognitive impairment. (Rev Invest Clin. 2025;77(1):13-25).

Unassigned: Background: In severe aplastic anemia (AA) sibling haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from the peripheral blood (PB) is an alternative when an HLA-identical donor is unavailable. Objective: To document the results of haplo-HSCT in high-risk severe AA. Methods: Twelve patients with severe AA who failed medical therapy and received a haploidentical PB unmanipulated HSCT from a sibling at an academic medical center were analyzed. Overall (OS) and event-free survival (EFS) were determined by Kaplan-Meier analyses. Results: The median between AA diagnosis and haplo-HSCT was 6.5 months (2-19). Median of age was 25.5 (range, 4-54) years; 9 (75%) recipients were males, and all suffered multiple treatment failures. Anti-thymocyte globulin-based conditioning regimens were given to 6 (50%) patients. Five (41.7%) HSCT were ambulatory. Infections developed in all patients and graft failure in 9 (75%). 2-year OS was 52% and EFS 25%. High transfusion burden, treatment failure, and donors > 30 years had no effect on OS (p = 0.518, p = 0.984, p = 0.321) or EFS (p = 0.113, p = 0.692, p = 0.199). Patient's age > 40 was not significant for survival (p = 0.395). Three of five evaluable patients developed acute graft-versus-host disease that progressed to chronic disease. Conclusions: Delayed PB haplo-HSCT for severe AA offered poor outcomes. Rapid referral for HSCT is critically required. (Rev Invest Clin. 2025;77(1):26-33).

Unassigned: Background: Osmotic demyelination syndrome is a rare neurological disorder caused by damage to the myelin sheath of oligodendrocytes, typically due to a rapid increase in serum osmolarity. Objective: The objective of the study was to investigate the factors associated with the development of pontine or extrapontine myelinolysis. Methods: A retrospective, observational study which included patients with magnetic resonance imaging-confirmed diagnosis of pontine and extrapontine myelinolysis from 1990 to 2024 at a referral hospital in Mexico City. Results: Fourteen patients were included; the median age was 49 years, and 35.7% were men. Regarding comorbidities, diabetes was the most frequent (35.7%), followed by liver cirrhosis, malnutrition, and chronic alcoholism. Significantly, hyponatremia was found in 11 patients (78.5%), being severe in 42.8% of the patients. Other frequent biochemical abnormalities were hypokalemia (42.8%) and hypomagnesemia in 5 (35.7%). Sodium overcorrection occurred in 50% of patients, and the 90-day mortality rate was 28.5%. Conclusions: Electrolyte disturbances, particularly hyponatremia, were common in this population, along with the comorbidities traditionally associated with this condition. Although neurological sequelae and mortality have decreased over time, they remain present in 64% and 28.5% of patients, respectively. (Rev Invest Clin. 2025;77(1):1-5).

Background: There is currently no prognostic scale for patients with Guillain-Barré syndrome (GBS) in the Mexican population.

Objective: The objective of the study was to examine the factors associated with functional prognosis by proposing short-term and long-term prognostic scales.

Methods: Prospective cohort of patients with GBS at an academic medical center, with neuroconduction study and 6-month follow-up. Through logistic regression, we evaluated clinical and paraclinical variables, and the results are expressed as odds ratios 95% confidence intervals [CIs]). We used a scale to predict poor functional prognosis. The performance of the scale was assessed using the area under the curve (AUC).

Results: A total of 259 patients (age 46.1 +- 16.1 years) were included in the study; 38.6% had a history of diarrhea, and 42.8% had an axonal variant. The rates of poor functional prognosis were 36.6% and 22.7% at 3 and 6 months of follow-up, respectively. The following variables were included in the univariate logistic regression: age >- 70 years, history of diarrhea, axonal variant, and Medical Research Council score. We performed a prognostic scale (0-9 points), with AUC of 0.81 (95% CI: 0.75-0.86) at 3 months, and 0.82 (95% CI: 0.76-0.87) at 6 months, which was higher than the modified Erasmus Guillain-Barré Outcome Score scale at admission (AUC: 0.75. 95% CI: 0.69-0.81 and AUC: 0.78. 95% CI: 0.72-0.83).

Conclusion: The proposed prognostic scale performs well in discerning poor functional prognosis in short- and long-term frames among Mexican patients.

Background: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer (BC), characterized by a dismal prognosis. Dysregulated long non-coding RNA LINC01614 might be a potential biomarker for BC as previously reported. Nevertheless, its functions and mechanism in TNBC cells are unclear.

Objectives: The study aimed to study the effects of LINC01614 on TNBC cell migration, invasion, and epithelial-mesenchymal transition (EMT) process as well as the related mechanism.

Methods: Reverse transcription quantitative polymerase chain reaction was performed to detect the expression of LINC01614 and SP1 in TNBC cells and tissues. The cellular localization of LINC01614 was determined by subcellular fraction assays. Cell counting kit-8 and Transwell invasion assays were conducted for measurement of TNBC cell viability and invasive ability. Cell migration was performed using wound healing assays and Transwell migration assays. Chromatin immunoprecipitation assays and luciferase reporter assays were used to explore the interaction between SP1 and LINC01614. Western blotting was used to assess protein levels of factors involved in EMT process and Wnt/ß-catenin signaling in TNBC cells.

Results: LINC01614 expression was elevated in TNBC tissues and cells. LINC01614 knockdown inhibited cell viability as well as migratory and invasive abilities of TNBC cells. LINC01614 knockdown also obstructed EMT process, as shown by E-cadherin upregulation and vimentin downregulation in TNBC cells. SP1 directly bound to the promoter of LINC01614 and activated LINC01614 expression. SP1 overexpression reversed the suppressive effect of LINC01614 knockdown on TNBC cell migration, invasion, and EMT process. Protein levels of Wnt and ß-catenin were diminished by LINC01614 knockdown, and the trend was partially rescued by SP1 overexpression.

Conclusion: SP1-induced LINC01614 promoted malignant behavior of TNBC cells by activating the Wnt/ß-catenin signaling pathway.

Background: The leading cause of spontaneous intracerebral hemorrhage (ICH) is hypertensive arteriolopathy. In addition to age and hypertension history, patients usually present other comorbidities that potentially increase morbimortality. Ancillary studies other than non-contrast computerized tomography (NCCT) may help clarify the diagnosis and increase the detection of potentially modifiable vascular risk factors. Unfortunately, their use is not routinely performed.

Objective: The study aimed to determine the frequency of ancillary studies performed in patients with hypertensive ICH.

Methods: We performed a retrospective analysis of three Latin American cerebrovascular registries from academic medical centers, analyzing the results with descriptive statistics focusing on diagnosis and short-term outcomes.

Results: We analyzed a total of 1,324 patients (mean age 64 years). Hypertension and obesity were the most prevalent risk factors. Only 14% underwent MRI, 10.3% extracranial ultrasonography, and 6.7% echocardiography. Among the three registries, the Latin America Stroke Registry performed more ancillary studies. Most of the patients presented a poor clinical outcome and in-hospital death.

Conclusions: The use of ancillary studies in the diagnostic workup of ICH was poor in the three registries, and mortality was high. The lack of ancillary studies performed may negatively impact outcomes.

Background: Several models have been developed to assess bleeding risk in patients with venous thromboembolism, such as HAS-BLED, but their external validity has not been adequately assessed.

Objective: The objective of the study was to evaluate the discriminative ability and calibration of the HAS-BLED scale for predicting 1-month bleeding risk in patient's anticoagulated for venous thromboembolism.

Materials and methods: External validation study of a prediction model based on a retrospective cohort of patients with venous thromboembolism treated between November 2019 and January 2022. Calibration of the HAS-BLED scale was evaluated using the Hosmer-Lemeshow test and the ratio of observed to expect events within each risk category. Discriminatory ability was assessed using the area under the curve (AUC) of a receiver operating characteristic curve.

Results: We included 735 patients (median age 64 years, female sex 55.2%), pulmonary embolism was diagnosed in most patients (60.7%), and 4.9% presented bleeding events. Regarding calibration, the HAS-BLED scale systematically underestimates the risk both in the general population (ROE 3.76, p < 0.001) and in cancer patients (ROE 4.16). The Hosmer-Lemeshow test rejected the hypothesis of adequate calibration (p < 0.001). Discriminatory ability was limited both in the general population (AUC = 0.57, 95% confidence interval [CI]: 0.48-0.66) and in the subgroup with active cancer (AUC = 0.53, 95% CI: 0.36-0.69).

Conclusion: The HAS-BLED scale in patients with venous thromboembolism underestimates the risk of bleeding at 1 month and has a low ability to discriminate high-risk patients. Cautious interpretation of the scale is recommended until additional evidence is available.

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. Curzerene is a sesquiterpene and component of Curcuma rhizomes and has anti-tumor and anti-inflammatory properties.

Objective: The study aimed to investigate the effects of curzerene on the malignant phenotypes and tumor growth in HCC.

Methods: Various concentrations of curzerene were used to treat human HCC cells (Huh7 and HCCLM3). Cell viability, apoptosis, cell cycle, invasion, and migration were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, Transwell, and wound healing assays. Cell cycle-, apoptosis-, and signaling pathway-related proteins were analyzed by Western blot analysis. A mouse xenograft model was established to analyze the anti-tumor effects of curzerene in vivo.

Results: Curzerene repressed the proliferation, invasion, and migration of Huh7 and HCCLM3 cells. Curzerene also induced G2/M cycle arrest and cell apoptosis. Curzerene downregulated the CDK1, cyclin B1, PCNA, Bcl-2, matrix metallopeptidases (MMP)2, and MMP9 protein expression and upregulated the Bax, cleaved caspase3, and cleaved poly ADPribose polymerase protein expression in HCC cells. Curzerene restrained the phosphorylation of PI3K, AKT, and the Mammalian target of rapamycin (mTOR) in Huh7 and HCCLM3 cells. The in vivo data revealed that curzerene inhibited HCC tumor growth and decreased the expression of phosphorylated mTOR in xenograft mouse models.

Conclusion: Curzerene inhibited cell malignancy in vitro and tumor growth in vivo in HCC, suggesting that curzerene may be a candidate agent for anti-HCC therapy.