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Background: The phosphoisitol 3-kinase (PI3K) signaling pathway, which promotes cancer cell growth and metabolism, is the most frequently mutated pathway in breast cancer and is associated with chemoresistance and poor prognosis. In this study we present the first analysis in Panamanian and regional population, with precise antations of the PIK3CA mutation, clinicopathological characteristics and prognosis. Methods: Exploratory study, where tumors were prospectively collected from 74 patients with RH+/Her2- metastatic breast cancer from the Instituto Oncológico Nacional between 2022 and 2023. A real-time PCR assay for mutation analysis was performed on DNA extracted from formalin-fixed, paraffin-embedded tumor material to detect mutations in exons 1, 4, 7, 9 and 20 of the PIK3CA gene. Results: The median age of the patients studied was 59 years. The mutation in PIK3CA was found in 33.8% (25/74) of patients with breast cancer, among them 44% were mutations in exon 20, 38% in exon 9, 13% in exon 4 and 5% in exon 1. A significant correlation was observed between the mutation and having history of cancer in the family (P = 0.005), and in postmepausal patients (P = 0.045). We did not found association between the mutation and histologic type, grade, tumor size or axillary status at diagnosis. Median progression-free survival was t reached in both groups and did not show a significant difference. Conclusion: The prevalence of the mutation is relatively high compared to international settings, it may offer an advantage in choosing the best treatment options and should be routinely evaluated during clinical interventions. [ABSTRACT FROM AUTHOR]

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Copyright of Acta Médica Peruana is the property of Colegio Medico del Peru and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To examine the role of microRNAs (miRNAs), miR-331-5p, in gastric cancer (GC). Methods: The mRNA level of miR-331-5p and protein level of 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase-3 (PFKFB3) were determined using quantitative real-time reverse transcription- polymerase chain reaction (qRT-PCR) and western blotting, respectively. The cell viability and proliferation of the two GC cell lines (AGS and MKN45) were evaluated using Cell Counting Kit-8 (CCK- 8) and bromodeoxyuridine (BrdU) assays. Cell migration and invasion of AGS and MKN45 were evaluated using wound healing and invasion assays, respectively. Potential interactions between miR- 331-5p and PFKFB3 were assessed by luciferase activity assay, while the effects of the interactions on cell physiology and metabolism were investigated in cells overexpressing both miR-331-5p and PFKFB3. Results: MiR-331-5p overexpression inhibited cell proliferation, suppressed migration and invasion, and inhibited glycolysis in AGS and MKN45 cells. The mRNA for the glycolytic regulatory enzyme PFKFB3 was shown to be a direct target of miR-331-5p and modulated by miR-331-5p. In rescue experiments, PFKFB3 reversed the miR-331-5p-induced inhibition of proliferation, migration, invasion, and glycolysis in AGS cells. Conclusion: This work supports a role for miR-331-5p through the modulation of PFKFB3 activity in GC in vivo, thus providing insight into novel potential therapies for the treatment of GC. [ABSTRACT FROM AUTHOR]

Collagen based hydrogels are three dimensional (3D) networks with the capacity to absorb water and high biocompatibility for use in repairing damaged tissue. These materials have poor mechanical properties and rapid degradation rates, limiting their application to tissue engineering and biomedical strategies; for this reason, the incorporation of inorganic phases in the 3D matrix of collagen such as hydroxyapatite has contributed to improving its properties, increasing the efficiency of the hybrid hydrogels obtained. This work presents the most relevant contributions related to collagen-based hydrogel systems and hydroxyapatite particles dispersed within the collagen matrix, which shows that the combination of materials does not alter the typical biocompatibility and biodegradability of collagen, allowing adhesion, proliferation, cell growth and control of the metabolism of the cells involved in the processes of bone repair, presenting hydrogels as a strategy for their potential use in tissue engineering. [ABSTRACT FROM AUTHOR]

Cervical Cancer (CC) is the second cause of death in Mexico. Infection with the Human Papilloma Virus is a necessary condition during the carcinogenesis process. One of the characteristics of CC is that it presents an altered metabolism; cells tend to more efficiently capture glucose and increase glycolysis. Aberrant glycosylation is a hallmark of cancer, which reflects changes, such as the altered expression of glucosyltransferases and glucosidases. Therefore, the objective of the present work was to describe the expression pattern of CD43, pyruvate kinase II, and hexokinase II in healthy cervical tissue, tissue with CC and in CC cell lines. At this point, we find a higher expression of proteins when compared with healthy tissues. However, there would still be a lack of studies to show if they could be used as a prognostic factor for patients with epidermoid CaCu. [ABSTRACT FROM AUTHOR]

Mitochondria play an important role in energy metabolism within the cell. Also are known to be intimately involved in the processes that lead to cell death following reperfusion, in both necrotic and apoptotic forms of cell death, and so are potential targets for protective interventions. In this review, we consider several aspect of mitochondrial function that we believe to be possible targets for myocardial protection; namely, roles of the mitochondrial ion channels in the heart with particular emphasis on cardioprotection against ischemia/reperfusion injury, mitochondrial Ca2+ transport, the permeability transition pore, and improved mitochondrial substrate supply. These protective processes are activated by signaling pathways, which converge on mitochondria; these pathways can also be stimulated by pharmacological treatments like some anesthetics with cardioprotective effects. Finally, we describe how improved understanding of the aspects of mitochondrial function may lead to better protective strategies in the future. [ABSTRACT FROM AUTHOR]

Mathematical modeling of metabolism meets several important applications in the context of bioprocess engineering such as the interpretation of cell physiology. Metabolic flux analysis is a useful tool for mathematical modeling of cell metabolism. To applying this technique to describe the biosynthesis of recombinant human erythropoietin in CHO cells the matrix of stoichiometric numbers is built representing the major metabolic pathways that generates energy and essential precursors for product and biomass synthesis. It also includes the equations representing recombinant human erythropoietin biosynthesis and CHO cells growth, which provides advantages compared to other models reported before. The dimension of the matrix obtained is 47 x 44 with a rank equal to 44 and a condition number of 83; therefore, the model has a unique solution and it is not sensitive. The metabolic flux map obtained by the solution of the mathematical model using experimental data shows results consistent with the biochemistry of the CHO cells and coincides with other reports for these and other mammalian cells. The work shows the general steps of the methodology to build the proposed mathematical model. [ABSTRACT FROM AUTHOR]

Sprague Dawley rat livers were irradiated with 8 and 16 J/cm² daily doses during 15 days from the AsGA laser. equivalent to 904 rim. Liver samples were surgically removed from rats previously anesthetized, then processed for electronic microscopic transmission and subsequently studied and subjected to morphometric techniques using 8.500 X enlargements with special emphasis on quantifying cellular component volumetric fractions. The result analysis of the hepatocytes irradiated with 8 and 16J/cm² doses revealed that there were marked differences between the volumetric fractions of cellular components that determine cellular functionality and protein synthesis, a quantification that clearly demonstrates that with a dose of 8 J/cm² the optimum stimuli is achieved in order to obtain high functionality, while with a dose of 16 J/cm² a notable reduction of that functionality is noted, concluding that the effects of specific infrared radiation doses provoke a drastic transformation of its components in hepatocytes, and therefore its functionality, activating or inhibiting it, and representing the effect of these stimulations over this elevated metabolism cellular type. [ABSTRACT FROM AUTHOR]

Introduction: The brain is an extraordinarily dynamic structure specially its physiology in response to pathological events. This response include several mechanisms such as changes in cell metabolism, genes expression and possible modifications in cell phenotype and in connectivity that reflect activation of processes like neurogenesis, neuritogenesis and synaptogenesis. Several aspects related with neuroplasticity has been proposed as part of the pathophysiological bases to understand brain ischemia and its exofocal phenomena. Progress in understanding of the pathophysiology of brain lesion has required the use of experimental models to evaluate cellular events that occur immediately after the lesion or later, to associate this changes with clinical observations and to propose pharmacological neuroprotection therapies. Objective: The purpose of the present work is to compile the advances in understanding of plasticity after brain lesion, mainly related with exofocal areas to a core lesion. Discussion and conclusions: The present work shows recent advances in neuroplasticity based on experimental approaches, and preclinical findings related with the exofocal ischemic phenomena: changes in areas not completely ischemic, changes in no ischemic areas affected by chemical or electrical signals, changes in the pattern of connectivity and adaptative changes in remote areas to the ischemic core. Finally, we discuss clinical aspects associated with this changes, experimental strategies and clinical pharmacological interventions. [ABSTRACT FROM AUTHOR]

Semicontinuous cultures are a powerful tool for cell characterization. However , it is hard to be established at small scale due to the far more complex experimental configuration required. In this work, the use of semicontinuous culture in spinner flasks was explored with daily feeds and extractions, considering that metabolic and growth rates are lower in animal cells under continuous culture regimes. Relatively stabilized conditions were established, characterized by small fluctuations in the concentration of the different metabolic species (glucose, lactate, etc.) at the dilution rates evaluated, and the kinetic parameters (m, qp, qGlu) were calculated as a function of the dilution rate for each phase. Results obtained were equivalent to those expected for a continuous culture, the semicontinuous operation mode being a much simpler variant. Up to now there are only scarce reports on using semicontinuous cultures as a feasible alternative to simulate the kinetic behavior at stationary states. Finally, the antibody production pattern was confirmed as growth independent, with glutamine as the limiting substrate in the medium. The results were validated by an statistical homogeneity of variance test (ANOVA) and with normally distributed data as evidenced by a Student's t test. [ABSTRACT FROM AUTHOR]

The transfusion of globular package can represent a risk for the patient that receives it since the metabolism of the erythrocyte during its storage substances that can be responsible for diverse reactions in the organism can take place. In the erythrocytes the nitric oxide can react with hemoglobin to form meta-hemoglobin and nitrates. Both substances contained in the globular package can produce alterations in the human that receives it. Objective: Our objective was to determine if globular packages preserved under normal conditions in a Blood Bank present alterations in the concentration of nitric oxide and meta-hemoglobin along the time. Material and methods: Twelve globular packages were chosen following the routine procedures of the Blood Bank of our institution. Samples of each package were obtained daily for five days and every five days until 30 days. Concentration of total nitrates (as an index of the presence of the nitric oxide) and meta-hemoglobin were determined. Results: An important increment was show in the concentration of total nitrates and meta-hemoglobin along the time in the erythrocytes from globular packages. Conclusions: The increment in the concentration of nitric oxide and meta-hemoglobin in the globular packages it can be a factor that produces adverse reactions in the patient that receives a blood transfusion. [ABSTRACT FROM AUTHOR]

In addition to their role in cellular metabolism, nucleo tides can be released from the cell to act as chemical transmitters in diverse cellular systems. In particular, adenosine triphosphate or ATP, once outside the cell, is degraded by ecto-ATPases, forming ADP, AMP and adenosine. All of these molecules, including ATP, exert physiological actions through the stimulation of P-type receptors. These proteins are divided into the P1 and P2 receptors, which are activated mainly by adenosine and ATP, respectively. In general, P1 subtype receptors are coupled to G proteins, and members of this group participate in cellular phenomena such as: anti-inflammatory processes, decrease of the neuronal activity, and the inhibition of muscular contraction. On the other hand, the P2 subtype is subdivided into P2Y and P2X subtypes. The P2Y receptors are also coupled to G proteins and are involved in processes such as: cellular proliferation and differentiation, the release of macromolecules, coagulation, and cellular permeability. The P2X receptors are cationic channels which are operated directly byATP binding, and their activation is related to several processes, for example: transmission of sensorial information, smooth muscle contraction, the inflammatory response, and apoptosis. A comprehensive understanding of the relationship between the structure and function of the different elements involved in purinergic communication, and particularly that of P receptors, would allow their physiological role to be defined, and in some cases, would facilitate the design of specific drugs to treat associated pathologies. [ABSTRACT FROM AUTHOR]