Prevalencia de obesidad posCovid-19 en jóvenes universitarios de Tabasco.

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Niveles de procalcitonina y ferritina predicen la gravedad de Covid-19 en pacientes ingresados a la unidad de cuidados intensivos.

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Delta-lactoferrin induces cell death via the mitochondrial death signaling pathway by upregulating bax expression.

Delta-lactoferrin (∆Lf) is a transcription factor belonging to the lactoferrin family, the expression of which inhibits cell proliferation and leads to Skp1 and DcpS gene transactivation. In this study, we showed that ∆Lf expression also induces cell death via apoptosis in HEK 293 and MCF7 cells using a cell viability assay and DNA fragmentation. Western blot analyses showed that apoptosis was caspase-9, 7 and 8 dependent. Proteolytic cleavage of the endonuclease PARP was significantly increased. The levels of expression of Bcl family members were detected by immunochemistry and showed that the Bcl-xl/Bax and Bcl-2/Bax protein ratios were decreased. We determined that the pro-apoptotic effects of ∆Lf are mainly mediated by the activation of the mitochondria-dependent death-signaling pathway. Apoptosis induction by ∆Lf is concomitant with increased cellular levels of Bax protein. Analysis of the Bax promoter region detected a ∆Lf response element located at -155 bp from the transcription start site. Both luciferase reporter gene and chromatin immunoprecipitation assays confirmed that ∆Lf interacts in vitro and in vivo specifically with this sequence. Its deletion, realized using directed mutagenesis, totally abolished ∆Lf transcriptional activity, identifying it as a ∆Lf-responsive element. These results indicate that the Bax gene is a novel ∆Lf target. Moreover we also showed that the O-GlcNAc/P interplay, which controls ∆Lf transcriptional activity, modulates Bax transactivation.

Cocoa: a functional food that decreases insulin resistance and oxidative damage in young adults with class II obesity.

BACKGROUND/OBJECTIVES: Cocoa consumption is associated with health benefits due to its high content of polyphenols. However, the effects of short-term cocoa consumption remain unclear. We aimed to determine the effects generated by cocoa consumption (for 7 days) in young adults in normoweight and class II obesity. SUBJECTS/METHODS: Before-and-after study was carried out in normoweight (NW) (n = 15) and class II obesity (CIIO) (n = 15) young adults. The NW and CIIO participants consumed 25 and 39 g of cocoa, respectively, per day for 7 days. The effect of cocoa consumption was evaluated on the lipid profile, insulin resistance (IR), and inflammation. Oxidative damage was also examined by assessing the biomarkers of oxidative damage in plasma. In addition, recombinant human insulin was incubated with blood obtained from the participants, and the molecular damage to the hormone was analyzed. RESULTS: Cocoa consumption resulted in decreased low-density lipoprotein-cholesterol in both groups (P = 0.04), while the total cholesterol, high-density lipoprotein cholesterol, and triglycerides were maintained at the recommended levels. Initially, IR was detected in the CIIO group (homeostasis model assessment [HOMA] = 4.78 ± 0.4), which is associated with molecular damage to insulin. Interestingly, intervention with cocoa resulted in improved IR (HOMA = 3.14 ± 0.31) (P = 0.0018) as well as molecular damage to insulin. Finally, cocoa consumption significant decreased the arginase activity (P = 0.0249) in the CIIO group; this is a critical enzymatic activity in the inflammatory process associated with obesity. CONCLUSIONS: The short-term consumption of cocoa improves the lipid profile, exerts anti-inflammatory effects, and protects against oxidative damage. Results of this study indicate that cocoa consumption can potentially improve IR and restore a healthy redox status.

Comorbidities and laboratory parameters associated with SARS-CoV-2 infection severity in patients from the southeast of Mexico: a cross-sectional study.

Background. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic. Among the risk factors associated with the severity of this disease is the presence of several metabolic disorders. For this reason, the aim of this research was to identify the comorbidities and laboratory parameters among COVID-19 patients admitted to the intensive care unit (ICU), comparing the patients who required invasive mechanical ventilation (IMV) with those who did not require IMV, in order to determine the clinical characteristics associated with the COVID-19 severity. Methods. We carried out a cross-sectional study among 152 patients who were admitted to the ICU from April 1 st to July 31 st, 2021, in whom the comorbidities and laboratory parameters associated with the SARS-CoV-2 infection severity were identified. The data of these patients was grouped into two main groups: "patients who required IMV" and "patients who did not require IMV". The nonparametric Mann-Whitney U test for continuous data and the χ2 test for categorical data were used to compare the variables between both groups. Results. Of the 152 COVID-19 patients who were admitted to the ICU, 66 required IMV and 86 did not require IMV. Regarding the comorbidities found in these patients, a higher prevalence of type 2 diabetes mellitus (T2DM), hypertension and obesity was observed among patients who required IMV vs. those who did not require IMV ( p<0.05). Concerning laboratory parameters, only glucose, Interleukin 6 (IL-6), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were significantly higher among patients who required IMV than in those who did not require IMV ( p<0.05). Conclusion. This study performed in a Mexican population indicates that comorbidities such as: T2DM, hypertension and obesity, as well as elevated levels of glucose, IL-6, LDH and CRP are associated with the COVID-19 severity.

Atypical subunit composition of the chlorophycean mitochondrial F1FO-ATP synthase and role of Asa7 protein in stability and oligomycin resistance of the enzyme.

In yeast, mammals, and land plants, mitochondrial F(1)F(O)-ATP synthase (complex V) is a remarkable enzymatic machinery that comprises about 15 conserved subunits. Peculiar among eukaryotes, complex V from Chlamydomonadales algae (order of chlorophycean class) has an atypical subunit composition of its peripheral stator and dimerization module, with nine subunits of unknown evolutionary origin (Asa subunits). In vitro, this enzyme exhibits an increased stability of its dimeric form, and in vivo, Chlamydomonas reinhardtii cells are insensitive to oligomycins, which are potent inhibitors of proton translocation through the F(O) moiety. In this work, we showed that the atypical features of the Chlamydomonadales complex V enzyme are shared by the other chlorophycean orders. By biochemical and in silico analyses, we detected several atypical Asa subunits in Scenedesmus obliquus (Sphaeropleales) and Chlorococcum ellipsoideum (Chlorococcales). In contrast, complex V has a canonical subunit composition in other classes of Chlorophytes (Trebouxiophyceae, Prasinophyceae, and Ulvophyceae) as well as in Streptophytes (land plants), and in Rhodophytes (red algae). Growth, respiration, and ATP levels in Chlorophyceae were also barely affected by oligomycin concentrations that affect representatives of the other classes of Chlorophytes. We finally studied the function of the Asa7 atypical subunit by using RNA interference in C. reinhardtii. Although the loss of Asa7 subunit has no impact on cell bioenergetics or mitochondrial structures, it destabilizes in vitro the enzyme dimeric form and renders growth, respiration, and ATP level sensitive to oligomycins. Altogether, our results suggest that the loss of canonical components of the complex V stator happened at the root of chlorophycean lineage and was accompanied by the recruitment of novel polypeptides. Such a massive modification of complex V stator features might have conferred novel properties, including the stabilization of the enzyme dimeric form and the shielding of the proton channel. In these respects, we discuss an evolutionary scenario for F(1)F(O)-ATP synthase in the whole green lineage (i.e., Chlorophyta and Streptophyta).

The polypeptides COX2A and COX2B are essential components of the mitochondrial cytochrome c oxidase of Toxoplasma gondii.

Two genes encoding cytochrome c oxidase subunits, Cox2a and Cox2b, are present in the nuclear genomes of apicomplexan parasites and show sequence similarity to corresponding genes in chlorophycean algae. We explored the presence of COX2A and COX2B subunits in the cytochrome c oxidase of Toxoplasma gondii. Antibodies were raised against a synthetic peptide containing a 14-residue fragment of the COX2A polypeptide and against a hexa-histidine-tagged recombinant COX2B protein. Two distinct immunochemical stainings localized the COX2A and COX2B proteins in the parasite's mitochondria. A mitochondria-enriched fraction exhibited cyanide-sensitive oxygen uptake in the presence of succinate. T. gondii mitochondria were solubilized and subjected to Blue Native Electrophoresis followed by second dimension electrophoresis. Selected protein spots from the 2D gels were subjected to mass spectrometry analysis and polypeptides of mitochondrial complexes III, IV and V were identified. Subunits COX2A and COX2B were detected immunochemically and found to co-migrate with complex IV; therefore, they are subunits of the parasite's cytochrome c oxidase. The apparent molecular mass of the T. gondii mature COX2A subunit differs from that of the chlorophycean alga Polytomella sp. The data suggest that during its biogenesis, the mitochondrial targeting sequence of the apicomplexan COX2A precursor protein may be processed differently than the one from its algal counterpart.

Modification by SUMOylation Controls Both the Transcriptional Activity and the Stability of Delta-Lactoferrin.

Delta-lactoferrin is a transcription factor, the expression of which is downregulated or silenced in case of breast cancer. It possesses antitumoral activities and when it is re-introduced in mammary epithelial cancer cell lines, provokes antiproliferative effects. It is posttranslationally modified and our earlier investigations showed that the O-GlcNAcylation/phosphorylation interplay plays a major role in the regulation of both its stability and transcriptional activity. Here, we report the covalent modification of delta-lactoferrin with the small ubiquitin-like modifier SUMO-1. Mutational and reporter gene analyses identified five different lysine residues at K13, K308, K361, K379 and K391 as SUMO acceptor sites. The SUMOylation deficient M5S mutant displayed enhanced transactivation capacity on a delta-lactoferrin responsive promoter, suggesting that SUMO-1 negatively regulates the transactivation function of delta-lactoferrin. K13, K308 and K379 are the main SUMO sites and among them, K308, which is located in a SUMOylation consensus motif of the NDSM-like type, is a key SUMO site involved in repression of delta-lactoferrin transcriptional activity. K13 and K379 are both targeted by other posttranslational modifications. We demonstrated that K13 is the main acetylation site and that favoring acetylation at K13 reduced SUMOylation and increased delta-lactoferrin transcriptional activity. K379, which is either ubiquitinated or SUMOylated, is a pivotal site for the control of delta-lactoferrin stability. We showed that SUMOylation competes with ubiquitination and protects delta-lactoferrin from degradation by positively regulating its stability. Collectively, our results indicate that multi-SUMOylation occurs on delta-lactoferrin to repress its transcriptional activity. Reciprocal occupancy of K13 by either SUMO-1 or an acetyl group may contribute to the establishment of finely regulated mechanisms to control delta-lactoferrin transcriptional activity. Moreover, competition between SUMOylation and ubiquitination at K379 coordinately regulates the stability of delta-lactoferrin toward proteolysis. Therefore SUMOylation of delta-lactoferrin is a novel mechanism controlling both its activity and stability.