Pentoxifylline and Norcantharidin Modify p62 Expression in 2D and 3D Cultures of B16F1 Cells.

Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.

Citalopram improves vasomotor syndrome and urogenital syndrome of menopause in Mexican women: a randomized clinical trial.

PURPOSE: This study aimed to determine the efficacy of non-hormonal therapy with citalopram vs fluoxetine for treating vasomotor syndrome (VMS) and urogenital syndrome of menopause (GSM) in Mexican women. METHODS: A parallel prospective randomized clinical trial was conducted in 91 postmenopausal women with a total score on the Menopause Rating Scale (MRS) ≥ 17 and with the clinical diagnosis of VSM and GSM. Patients were randomly assigned to receive citalopram (n = 49) or fluoxetine (n = 42). Follow-up was carried out at 3 and 6 months. RESULTS: The citalopram group experienced a significant improvement compared to the fluoxetine group in the MRS total score (p < 0.01), as well as in the psychological (p < 0.001) and somatic (p < 0.0001) domains at 3 and 6 months of follow-up. After 6 months of follow-up, the group that received citalopram decreased the relative risk (RR) to present VMS symptoms (RR = 0.30, CI 0.19-0.5, p = 0.0001), depressed mood (RR = 0.31, CI 0.15-0.6, p = 0.0002), irritability (RR = 0.40, CI 0.22-0.73, p = 0.002), anxiety (RR = 0.30, CI 0.13-0.69, p = 0.003), physical and mental exhaustion (RR = 0.35, CI 0.18-0.67, p = 0.001), sexual problems (RR = 0.18, CI 0.06-0.48, p = 0.0001), vaginal dryness (RR = 0.34, CI 0.14-0.80, p = 0.01), and urinary problems (RR = 0.36, CI 0.14-0.92, p = 0.043). CONCLUSION: We conclude that citalopram tends to improve VSM and GSM symptoms in postmenopausal Mexican women. Thus, we recommend the daily use of citalopram 20 mg. However, further studies will be required to support the results of the present work. These should include a larger number of patients and a placebo group. CLINICAL TRIAL REGISTRATION: This clinical trial was retrospectively registered by the United States National Library of Medicine in the www. CLINICALTRIALS: gov database on 04/20/2022. The given test Registration Number is NCT05346445.

A bioinformatic prediction of antigen presentation from SARS-CoV-2 spike protein revealed a theoretical correlation of HLA-DRB1*01 with COVID-19 fatality in Mexican population: An ecological approach.

SARS-CoV-2 infection is causing a pandemic disease that is reflected in challenging public health problems worldwide. Human leukocyte antigen (HLA)-based epitope prediction and its association with disease outcomes provide an important base for treatment design. A bioinformatic prediction of T cell epitopes and their restricted HLA Class I and II alleles was performed to obtain immunogenic epitopes and HLA alleles from the spike protein of the severe acute respiratory syndrome coronavirus 2 virus. Also, a correlation with the predicted fatality rate of hospitalized patients in 28 states of Mexico was done. Here, we describe a set of 10 highly immunogenic epitopes, together with different HLA alleles that can efficiently present these epitopes to T cells. Most of these epitopes are located within the S1 subunit of the spike protein, suggesting that this area is highly immunogenic. A statistical negative correlation was found between the frequency of HLA-DRB1*01 and the fatality rate in hospitalized patients in Mexico.