Schisandrin Protects against Norepinephrine-Induced Myocardial Hypertrophic Injury by Inhibiting the JAK2/STAT3 Signaling Pathway

Aims. Heart failure is closely associated with norepinephrine-(NE-) induced cardiomyocyte hypertrophy. Schisandrin is derived from the traditional Chinese medicine Schisandra; it has a variety of pharmacological activities, and the mechanism of schisandrin-mediated protection of the cardiovascular system is not clear. Main Methods. NE was used to establish a cardiomyocyte hypertrophy model to explore the mechanism of action of schisandrin. An MTT assay was used for cell viability; Hoechst fluorescence staining was used to observe the cell morphology and calculate the apoptosis rate. The cell surface area was measured and the protein to DNA ratio was calculated, changes in mitochondrial membrane potential were detected, and the degree of hypertrophic cell damage was evaluated. WB, QRT-PCR, and immunofluorescence were used to qualitatively, quantitatively, and quantitatively detect apoptotic proteins in the JAK2/STAT3 signaling pathway. Key Findings. In the NE-induced model, schisandrin treatment reduced the apoptosis rate of cardiomyocytes, increased the ratio of the cell surface area to cardiomyocyte protein/DNA, and also, increased the membrane potential of the mitochondria. The expression of both JAK2 and STAT3 was downregulated, and the BAX/Bcl-2 ratio was significantly reduced. In conclusion, schisandrin may protect against NE-induced cardiomyocyte hypertrophy by inhibiting the JAK2/STAT3 signaling pathway and reducing cardiomyocyte apoptosis.

Corneal endothelial cells changes in different stages of Keratoconus: a multi-Centre clinical study

Purpose To assess the corneal endothelial cells morphology and count in keratoconus patients and their correlation with different stages of keratoconus. Methods Prospective non randomized multi-centric clinical study included 150 eyes of 150 keratoconus patients. Four centers in Egypt participated in this study included: Departments of Ophthalmology in Alexandria University, Tanta University and Port Said University and Alex I-Care hospital. Pentacam (Wavelight Oculyzer II) and specular microscopy (Tomey EM-3000) were done to all eyes. Keratoconic eyes were classified according to Amsler classification into stage 1, 2 and 3. Stage 1 included 99 eyes, stage 2 included 32 eyes & stage 3 included 19 eyes. Results The mean age of keratoconus patients was 24.07 ± 6.154 years. Forty five cases were males (30%) and 105 cases were females (70%). There was statistically significant difference in endothelial cell density (p < 0.001) and coefficient of variation (p = 0.012) between different stages of keratoconus eyes. Regarding cell surface area, there was statistically significant difference in cell surface area between different stages of keratoconus eyes (p < 0.001). In addition, for cell morphology, there was statistically significant difference between different stages of keratoconus eyes (p < 0.001). Conclusions Qualitative and quantitative structural changes were seen in endothelial cells of keratoconus eyes by using specular microscopy. For stages 1 and 2, keratoconus may not affect the corneal endothelim significantly. The endothelium in stage 3 shows significant changes regarding polymegathism and pleomorphism.

A ‘Dynamic Adder Model’ For Cell Size Homeostasis in Dictyostelium Cells

After a cell divides into two daughter cells, the total cell surface area of the daughtercells should increase to the original size to maintain cell size homeostasis in a single cellcycle. Previously, three models have been proposed to explain the regulation of cell sizehomeostasis: sizer, timer, and adder models. Here, we precisely measured the total cellsurface area of Dictyostelium cells in a whole cell cycle by using the agar-overlaymethod, which eliminated the influence of surface membrane reservoirs, such asmicrovilli and membrane winkles. The total cell surface area linearly increased duringinterphase, slightly decreased at the metaphase, and then increased by approximately20% during cytokinesis. From the analysis of the added surface area, we concluded thatthe cell size was regulated by the near-adder model in interphase and by the timer modelin the mitotic phase. The adder model in the interphase is not caused by a simple cellmembrane addition, but is more dynamic due to the rapid cell membrane turnover. Wepropose a ‘dynamic adder model’ to explain cell size homeostasis in the interphase.

MiR-26a-5p inhibits GSK3β expression and promotes cardiac hypertrophy in vitro

Background The role of miR-26a-5p expression in cardiac hypertrophy remains unclear. Herein, the effect of miR-26a-5p on cardiac hypertrophy was investigated using phenylephrine (PE)-induced cardiac hypertrophy in vitro and in a rat model of hypertension-induced hypertrophy in vivo. Methods The PE-induced cardiac hypertrophy models in vitro and vivo were established. To investigate the effect of miR-26a-5p activation on autophagy, the protein expression of autophagosome marker (LC3) and p62 was detected by western blot analysis. To explore the effect of miR-26a-5p activation on cardiac hypertrophy, the relative mRNA expression of cardiac hypertrophy related mark GSK3β was detected by qRT-PCR in vitro and vivo. In addition, immunofluorescence staining was used to detect cardiac hypertrophy related mark α-actinin. The cell surface area was measured by immunofluorescence staining. The direct target relationship between miR-26a-5p and GSK3β was confirmed by dual luciferase report. Results MiR-26a-5p was highly expressed in PE-induced cardiac hypertrophy. MiR-26a-5p promoted LC3II and decreased p62 expression in PE-induced cardiac hypertrophy in the presence or absence of lysosomal inhibitor. Furthermore, miR-26a-5p significantly inhibited GSK3β expression in vitro and in vivo. Dual luciferase report results confirmed that miR-26a-5p could directly target GSK3β. GSK3β overexpression significantly reversed the expression of cardiac hypertrophy-related markers including ANP, ACTA1 and MYH7. Immunofluorescence staining results demonstrated that miR-26a-5p promoted cardiac hypertrophy related protein α-actinin expression, and increased cell surface area in vitro and in vivo. Conclusion Our study revealed that miR-26a-5p promotes myocardial cell autophagy activation and cardiac hypertrophy by regulating GSK3β, which needs further research.

Changes in the Cytomorphometric Indices in Epitheliocytes of the Oral Mucosa of Patients with Generalized Periodontitis

For the study of some mechanisms of the pathogenesis of generalized periodontitis, there were examined 64 patients who were divided into the following groups: Group I – 12 healthy people (6 men and 6 women); Group ІІ – 40 patients with grade I generalized periodontitis (20 men and 20 women) and Group ІІІ – 12 patients with grade II-III generalized periodontitis (6 men and 6 women). On the cytological preparations of buccal epitheliocytes of the oral mucosa stained with aceto-orcein, 100 nucleus-containing epitheliocytes were examined with the help of microscope “Axioskop”, a company Zeizz, with a 1000×magnification. Cytomorphometric characteristics were studied: the perimeter and the cell surface area, the perimeter and the surface area of ​​the nucleus, and the ratio of the surface area of the nucleus to the cell surface area. In all the patients with generalized periodontitis, the perimeter and cell area and the perimeter and epithelial cell nuclei area (p<0.05 – p<0.001) as well as the nuclear-cytoplasmic correlation reduced significantly, especially in men, that could be regarded as compensatory changes at the cellular level. According to the parameters of cells of epitheliocytes, and especially their nuclei, in both healthy people and patients with generalized periodontitis, gender differences were identified, especially in Group ІІІ. Thus, it could be argued that the measurement of the perimeter and the area of ​​cells of buccal epitheliocytes and their nuclei reflects the functional activity of the hereditary apparatus in the patients with generalized periodontitis.

Coccolith arrangement follows Eulerian mathematics in the coccolithophore Emiliania huxleyi

Background The globally abundant coccolithophore, Emiliania huxleyi, plays an important ecological role in oceanic carbon biogeochemistry by forming a cellular covering of plate-like CaCO3 crystals (coccoliths) and fixing CO2. It is unknown how the cells arrange different-sized coccoliths to maintain full coverage, as the cell surface area of the cell changes during daily cycle. Methods We used Euler’s polyhedron formula and CaGe simulation software, validated with the geometries of coccoliths, to analyze and simulate the coccolith topology of the coccosphere and to explore the arrangement mechanisms. Results There were only small variations in the geometries of coccoliths, even when the cells were cultured under variable light conditions. Because of geometric limits, small coccoliths tended to interlock with fewer and larger coccoliths, and vice versa. Consequently, to sustain a full coverage on the surface of cell, each coccolith was arranged to interlock with four to six others, which in turn led to each coccosphere contains at least six coccoliths. Conclusion The number of coccoliths per coccosphere must keep pace with changes on the cell surface area as a result of photosynthesis, respiration and cell division. This study is an example of natural selection following Euler’s polyhedral formula, in response to the challenge of maintaining a CaCO3 covering on coccolithophore cells as cell size changes.

Coccolith arrangement follows Eulerianmathematics in the coccolithophore Emiliania huxleyi

Background. The globally abundant coccolithophore, Emiliania huxleyi, plays an importantecological role in oceanic carbon biogeochemistry by forming a cellularcovering of plate-like CaCO 3 crystals (coccoliths) and fixing CO 2 .It is unknown how the cells arrange different-size of coccoliths to maintainfull coverage, as the cell surface area of the cell changes during daily cycle. Methods. We used Euler’s polyhedron formula and CaGe simulationsoftware, validated with the geometries of coccoliths, to analze and simulatethe coccolith topology of the coccosphere and to explore the arrangementmechanisms. Results. There were only small variations in the geometries ofcoccoliths, even when the cells were cultured under variable light conditions.Because of geometric limits, small coccoliths tended to interlock with fewerand larger coccoliths, and vice versa. Consequently, to sustain a full coverageon the surface of cell, each coccolith was arranged to interlock with four tosix others, which in turn led to each coccosphere contains at least 6coccoliths. Conclusions. The number of coccoliths per coccosphere must keep pacewith changes on the cell surface area as a result of photosynthesis,respiration and cell division. This study is an example of natural selectionfollowing Euler’s polyhedral formula, in response to the challenge ofmaintaining a CaCO 3 covering on coccolithophore cells as cell sizechanges.

Coccolith arrangement follows Eulerianmathematics in the coccolithophore Emiliania huxleyi

Background. The globally abundant coccolithophore, Emiliania huxleyi, plays an importantecological role in oceanic carbon biogeochemistry by forming a cellularcovering of plate-like CaCO 3 crystals (coccoliths) and fixing CO 2 .It is unknown how the cells arrange different-size of coccoliths to maintainfull coverage, as the cell surface area of the cell changes during daily cycle. Methods. We used Euler’s polyhedron formula and CaGe simulationsoftware, validated with the geometries of coccoliths, to analze and simulatethe coccolith topology of the coccosphere and to explore the arrangementmechanisms. Results. There were only small variations in the geometries ofcoccoliths, even when the cells were cultured under variable light conditions.Because of geometric limits, small coccoliths tended to interlock with fewerand larger coccoliths, and vice versa. Consequently, to sustain a full coverageon the surface of cell, each coccolith was arranged to interlock with four tosix others, which in turn led to each coccosphere contains at least 6coccoliths. Conclusions. The number of coccoliths per coccosphere must keep pacewith changes on the cell surface area as a result of photosynthesis,respiration and cell division. This study is an example of natural selectionfollowing Euler’s polyhedral formula, in response to the challenge ofmaintaining a CaCO 3 covering on coccolithophore cells as cell sizechanges.