Ángel Zarain-Herzberg

Connexin 36 (Cx36)-deficient mice exhibit deregulation of insulin secretion and glucose homeostasis. Mouse islet beta cells express Cx36 and connexin 30.2 (Cx30.2). Human beta cells express Cx36; however, it remains unknown whether they express Cx31.9 protein, the ortholog of Cx30.2. To address this question, sections of 23 human pancreatic autopsy samples from both sexes were analyzed by real-time qRT-PCR with oligonucleotides against Cx31.9 and by immunohistochemistry (IHC) with a specific antibody against this connexin. Mean levels of Cx31.9 mRNA were similar to those of Cx36 mRNA, used as a control gene, in all human samples analyzed (n = 7). IHC studies showed that Cx31.9-positive staining was localized to most islet cells in donor samples (15 of 16). The density of Cx31.9 staining per μm2 was calculated from 31 islet images from 10 donor samples. Pancreatic serial sections revealed that the spatial distribution of anti-Cx31.9-labeled cells is similar to that of anti-Cx36- and anti-insulin-positive cells. Moreover, anti-Cx31.9 staining was also localized in anti-CK19-positive epithelial ductal cells and in the endothelial cells of small, medium, and large-diameter vessels. Cx31.9 protein is expressed in endocrine islet beta cells as well as in exocrine ductal epithelial and vascular endothelial cells. In addition, there is a balance of Cx31.9 and Cx36 mRNA levels in the human pancreas.

Purpose: To determine the prevalence and types of secondary glaucoma in adult patients in a Mexican Tertiary Ophthalmology Hospital. Methods: Observational, cross-sectional, descriptive, and retrospective study in patients over 18 years of age diagnosed with secondary glaucoma in the period from January to June 2024. A non-probabilistic sampling was carried out within the established period, selecting patients with secondary glaucoma. The analysis included descriptive statistics of central tendency (mean, median, and mode) and dispersion (range, standard deviation) for numerical variables, as well as tables and/or graphs for categorical variables. Results: A total of 2390 records were analyzed, of which 987 corresponded to subsequent patients. A final sample of 1403 first-time patients was obtained, comprising 208 cases of secondary glaucoma (14.83%). The most frequent cause of secondary glaucoma was secondary to neovascularization (37.98%), in order of frequency, intraocular surgery (19.23%), corneal transplant (12.50%), ocular inflammation (10.10%), pseudoexfoliation syndrome (8.65%), ocular trauma (4.33%), pathologies associated with the lens (3.37%), other causes (1.44%), pigment dispersion syndrome and associated with corticosteroids (each 0.96%), finally associated with tumors (0.48%). The prevalence was 50% in women and 50% in men. Conclusion: Our results, although not representative of the entire population, offer valuable exploration for future research. Our database, as a national referral hospital for glaucoma cases, provides a robust and relevant source of data for understanding this condition. The findings of this study can be used to inform future research on secondary glaucoma and potentially improve diagnosis and treatment strategies for patients with this condition.

Breast cancer-associated deaths are related mainly to specific molecular subtypes and the presence of metastasis. The Epithelial-to-Mesenchymal Transition (EMT) and Ca²⁺ signaling pathways are involved in breast cancer metastasis, and they are regulated in part by epigenetic mechanisms. Moreover, activation of EMT modulates Ca²⁺ concentration and in turn, Ca²⁺ signaling regulates the expression of EMT markers. Also, activation of Ca²⁺ signaling genes with epigenetic inhibitors reverts the EMT. Thus, Ca²⁺ signaling might have an important role in breast cancer metastasis and EMT, particularly through the epigenetic regulation of genes involved in its signaling. However, little is known due to that an estimate of 1670 genes participate in the Ca²⁺ signaling and only a few genes have been studied. Here, we aimed to explore the expression of all genes involved in Ca²⁺ signaling in all breast cancer subtypes and EMT, and whether modulation of epigenetic mechanisms is related to their expression. Several genes of the Ca²⁺ signaling are altered in all breast cancer subtypes, being the cadherins and voltage channels the most frequent altered genes. Also, DNA methylation and histone posttranslational modifications showed a good correlation with their altered expression. The expression of the cadherins and voltage channels is also modulated during breast EMT, and ATAC-seq results suggest that chromatin rearrangement at their promoter is involved. In conclusion, the expression of the genes involved in Ca²⁺ signaling is altered in all breast cancer subtypes and during EMT, and epigenetic mechanisms are an attractive target to regulate their expression.

Calcium (Ca²⁺) signaling has a major role in regulating a wide range of cellular mechanisms, including gene expression, proliferation, metabolism, cell death, muscle contraction, among others. Recent evidence suggests that ~ 1600 genes are related to the Ca²⁺ signaling. Some of these genes’ expression is altered in several pathological conditions, including different cancer types, and epigenetic mechanisms are involved. However, their expression and regulation in hepatocellular carcinoma (HCC) and the liver are barely known. Here, we aimed to explore the expression of genes involved in the Ca²⁺-signaling in HCC, liver regeneration, and hepatocyte differentiation, and whether their expression is regulated by epigenetic mechanisms such as DNA methylation and histone posttranslational modifications (HPM). Results show that several Ca²⁺-signaling genes’ expression is altered in HCC samples; among these, a subset of twenty-two correlate with patients’ survival. DNA methylation correlates with eight of these genes’ expression, and Guadecitabine, a hypomethylating agent, regulates the expression of seven down-regulated and three up-regulated genes in HepG2 cells. The down-regulated genes displayed a marked decrease of euchromatin histone marks, whereas up-regulated genes displayed gain in these marks. Additionally, the expression of these genes is modulated during liver regeneration and showed similar profiles between in vitro differentiated hepatocytes and liver-derived hepatocytes. In conclusion, some components of the Ca²⁺-signaling are altered in HCC and displayed a correlation with patients’ survival. DNA methylation and HMP are an attractive target for future investigations to regulate their expression. Ca²⁺-signaling could be an important regulator of cell proliferation and differentiation in the liver.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vessel remodeling; however, its severity and impact on survival depend on right ventricular (RV) failure. Resveratrol (RES), a polyphenol found in red wine, exhibits cardioprotective effects on RV dysfunction in PAH. However, most literature has focused on RES protective effect on lung vasculature; recent finding indicates that RES has a cardioprotective effect independent of pulmonary arterial pressure on RV dysfunction, although the underlying mechanism in RV has not been determined. Therefore, this study is aimed at evaluating sirtuin‐3 (SIRT3) modulation by RES in RV using a monocrotaline‐ (MC‐) induced PAH rat model. Myocyte function was evaluated by confocal microscopy as cell contractility, calcium signaling, and mitochondrial membrane potential (ΔΨm); cell energetics was assessed by high‐resolution respirometry, and western blot and immunoprecipitation evaluated posttranslational modifications. PAH significantly affects mitochondrial function in RV; PAH is prone to mitochondrial permeability transition pore (mPTP) opening, thus decreasing the mitochondrial membrane potential. The compromised cellular energetics affects cardiomyocyte function by decreasing sarco‐endoplasmic reticulum Ca²⁺‐ATPase (SERCA) activity and delaying myofilament unbinding, disrupting cell relaxation. RES partially protects mitochondrial integrity by deacetylating cyclophilin‐D, a critical component of the mPTP, increasing SIRT3 expression and activity and preventing mPTP opening. The preserved energetic capability rescues cell relaxation by maintaining SERCA activity. Avoiding Ca²⁺ transient and cell contractility mismatch by preserving mitochondrial function describes, for the first time, impairment in excitation‐contraction‐energetics coupling in RV failure. These results highlight the importance of mitochondrial energetics and mPTP in PAH.