Synthesis and characterization of three covalently linked porphyrin-phthalocyanine pentamers with nucleophilic substitution

In this paper the synthetic methods of three covalently linked porphyrin-phthalocyanine heteropentamers, containing four units of porphyrin linked to a central phthalocyanine (Mpor-LPc; M = 2H, Fe, L = Zn, Fe), are described. The synthetic strategy is on the basis of nucleophilic substitution reactions between [1,8,15,22-tetra nitro phthalocyanines] and [5-(4-hydroxy phenyl)-10,15,20-triphenyl porphyrins] as the phenolic alcohols. Porphyrins are linked with oxygen as spacer through meso position of phenyl group to phthalocyanines. These macromolecules were characterized by ¹H NMR, UV-Vis, IR, fluorescence and mass spectroscopy. The electronic absorption spectrums of the hetero-dyad systems changed significantly upon coupling and showed a great red shift in the phthalocyanine Q-bands. These changes confirm the electron-donating effects of the porphyrin units and the extension of conjugated п-systems. The emission spectra of the products supports intramolecular energy and charge transfer between the sub-units.     

The Interplay between Chondrocyte Redifferentiation Pellet Size and Oxygen Concentration

Chondrocytes dedifferentiate during ex vivo expansion on 2-dimensional surfaces. Aggregation of the expanded cells into 3-dimensional pellets, in the presence of induction factors, facilitates their redifferentiation and restoration of the chondrogenic phenotype. Typically 1×10⁵–5×10⁵ chondrocytes are aggregated, resulting in “macro” pellets having diameters ranging from 1–2 mm. These macropellets are commonly used to study redifferentiation, and recently macropellets of autologous chondrocytes have been implanted directly into articular cartilage defects to facilitate their repair. However, diffusion of metabolites over the 1–2 mm pellet length-scales is inefficient, resulting in radial tissue heterogeneity. Herein we demonstrate that the aggregation of 2×10⁵ human chondrocytes into micropellets of 166 cells each, rather than into larger single macropellets, enhances chondrogenic redifferentiation. In this study, we describe the development of a cost effective fabrication strategy to manufacture a microwell surface for the large-scale production of micropellets. The thousands of micropellets were manufactured using the microwell platform, which is an array of 360×360 µm microwells cast into polydimethylsiloxane (PDMS), that has been surface modified with an electrostatic multilayer of hyaluronic acid and chitosan to enhance micropellet formation. Such surface modification was essential to prevent chondrocyte spreading on the PDMS. Sulfated glycosaminoglycan (sGAG) production and collagen II gene expression in chondrocyte micropellets increased significantly relative to macropellet controls, and redifferentiation was enhanced in both macro and micropellets with the provision of a hypoxic atmosphere (2% O₂). Once micropellet formation had been optimized, we demonstrated that micropellets could be assembled into larger cartilage tissues. Our results indicate that micropellet amalgamation efficiency is inversely related to the time cultured as discreet microtissues. In summary, we describe a micropellet production platform that represents an efficient tool for studying chondrocyte redifferentiation and demonstrate that the micropellets could be assembled into larger tissues, potentially useful in cartilage defect repair.     

Reviewing the role of cardiac exosomes in myocardial repair at a glance

Exosome-based therapy is an emerging novel approach for myocardial infarction (MI) treatment. Exosomes are identified as extracellular vesicles that are produced within multivesicular bodies in the cells' cytosols and then are secreted from the cells. Exosomes are 30–100 nm in diameter that are released from viable cells and are different from other secreted vesicles such as apoptotic bodies and microvesicles in their origin and contents such as RNAs, proteins, and nucleic acid. The recent advances in exosome research have demonstrated the role of these bionanovesicles in the physiological, pathological, and molecular aspects of the heart. The results of in vitro and preclinical models have shown that exosomes from different cardiac cells can improve cardiac function following MI. For example, mesenchymal stem cells (MSCs) and cardiac progenitor cells (CPCs) containing exosomes can affect the proliferation, survival, and differentiation of cardiac fibroblasts and cardiomyocytes. Moreover, MSCs- and CPCs-derived exosomes can enhance the migration of endothelial cells. Exosome-based therapy approaches augment the cardiac function by multiple means, such as reducing fibrosis, stimulation of vascular angiogenesis, and proliferation of cardiomyocytes that result in replacing damaged heart tissue with newly generated functional myocytes. This review article aims to briefly discuss the recent advancements in the role of secreted exosomes in myocardial repair by focusing on cardiac cells-derived exosomes.     

Esophageal cancer alters the expression of nuclear pore complex binding protein Hsc70 and eIF5A-1

Nuclear pore complex (NPC) is the only corridor for macromolecules exchange between nucleus and cytoplasm. NPC and its components, nucleoporins, play important role in the diverse physiological processes including macromolecule exchange, chromosome segregation, apoptosis and gene expression. Recent reports also suggest involvement of nucleoporins in carcinogenesis. Applying proteomics, we analyzed expression pattern of the NPC components in a newly established esophageal cancer cell line from Persia (Iran), the high-risk region for esophageal cancer. Our results indicate overexpression of Hsc70 and downregulation of subunit alpha type-3 of proteasome, calpain small subunit 1, and eIF5A-1. Among these proteins, Hsc70 and eIF5A-1 are in direct interaction with NPC and involved in the nucleocytoplasmic exchange. Hsc70 plays a critical role as a chaperone in the formation of a cargo–receptor complex in nucleocytoplasmic transport. On the other hand, it is an NPC-associated protein that binds to nucleoporins and contributes in recycling of the nucleocytoplasmic transport receptors in mammals and affects transport of proteins between nucleus and cytoplasm. The other nuclear pore interacting protein: eIF5A-1 binds to the several nucleoporins and participates in nucleocytoplasmic transport. Altered expression of Hsc70 and eIF5A-1 may cause defects in nucleocytoplasmic transport and play a role in esophageal carcinogenesis.     

Fatal Invasive Pulmonary Aspergillosis in COVID-19 Patient with Acute Myeloid Leukemia in Iran

Mycopathologia - Although patients with severe immunodeficiency and hematological malignancies has been considered at highest risk for invasive fungal infection, patients with severe pneumonia due...     

A comparison study of the interaction between β-lactoglobulin and retinol at two different conditions: spectroscopic and molecular modeling approaches

The interaction between bovin β-Lactoglobulin (β-LG) and retinol at two different pH values was investigated by multispectroscopic, zeta potential, molecular modeling, and conductometry measurements. The steady state and polarization fluorescence spectroscopy revealed that complex formation at two different pH values could occur through a remarkable static quenching. According to fluorescence quenching, one set of binding site at pH 2 and two sets of binding sites at pH 7 were introduced for binding of retinol to β-LG that show the enhancement of saturation score of β-LG to retinol in dimmer condition. The polarization fluorescence analysis represented that there is more affinity between β-LG and retinol at pH 7 rather than at pH 2. The effect of retinol on β-LG was studied by UV-visible, circular dichroism (CD), and synchronous fluorescence, which indicated that retinol induced more structural changes on β-LG at pH 7. β-LG–retinol complex formation at two different pH values was recorded via applying resonance light scattering (RLS) and zeta potential. Conductometry and RLS showed two different behaviors of interaction between β-LG and retinol at two different pH values; therefore, dimmer formation played important roles in different behaviors of interaction between β-LG and retinol. The zeta potential was the implied combination of electrostatic and hydrophobic forces which are involved in β-LG–retinol complex at two different pH values, and the hydrophobic interactions play a dominant role in complex formation. Molecular modeling was approved by all experimental results. The acquired results suggested that monomer and dimmer states of β-LG can be induced by retinol with different behaviors.     

Ex Vivo Modeling of Chemical Synergy in Prenatal Kidney Cystogenesis

Cyclic adenosine monophosphate (cAMP) drives genetic polycystic kidney disease (PKD) cystogenesis. Yet within certain PKD families, striking differences in disease severity exist between affected individuals, and genomic and/or environmental modifying factors have been evoked to explain these observations. We hypothesized that PKD cystogenesis is accentuated by an aberrant fetal milieu, specifically by glucocorticoids. The extent and nature of cystogenesis was assessed in explanted wild-type mouse embryonic metanephroi, using 8-Br-cAMP as a chemical to mimic genetic PKD and the glucocorticoid dexamethasone as the environmental modulator. Cysts and glomeruli were quantified by an observer blinded to culture conditions, and tubules were phenotyped using specific markers. Dexamethasone or 8-Br-cAMP applied on their own produced cysts predominantly arising in proximal tubules and descending limbs of loops of Henle. When applied together, however, dexamethasone over a wide concentration range synergized with 8-Br-cAMP to generate a more severe, glomerulocystic, phenotype; we note that prominent glomerular cysts have been reported in autosomal dominant PKD fetal kidneys. Our data support the idea that an adverse antenatal environment exacerbates renal cystogenesis.     

Cobalt separation by <Emphasis Type="Italic">Alphaproteobacterium</Emphasis> MTB-KTN90: magnetotactic bacteria in bioremediation

Bioremediation of toxic metals by magnetotactic bacteria and magnetic separation of metal-loaded magnetotactic bacteria are of great interest. This bioprocess technique is rapid, efficient, economical, and environmentally friendly. In this study, cobalt removal potential of a novel isolated magnetotactic bacterium (Alphaproteobacterium MTB-KTN90) as a new biosorbent was investigated. The effects of various environmental parameters in the cobalt removal and the technique of magnetic separation of cobalt-loaded bacterial cells were studied. Cobalt removal by MTB-KTN90 was very sensitive to pH solution; higher biosorption capacity was observed around pH 6.5–7.0. When biomass concentration increased from 0.009 to 0.09 g/l, the biosorption efficiency increased from 13.87 % to 19.22 %. The sorption of cobalt by MTB-KTN90 was rapid during the first 15 min (859.17 mg/g dry weight). With the increasing of cobalt concentrations from 1 to 225 mg/l, the specific cobalt uptake increased. Maximum cobalt removal (1160.51 ± 15.42 mg/g dry weight) took place at optimum conditions; pH 7.0 with initial cobalt concentration of 115 mg/l at 60 min by 0.015 g/l of dry biomass. The results showed maximum values for constants of Langmuir and Freundlich models so far. The biosorption mechanisms were studied with FTIR, PIXE, and FESEM analysis. Cobalt-loaded MTB-KTN90 had ability to separate from solution by a simple magnetic separator. Magnetic response in MTB-KTN90 is due to the presence of unique intracellular magnetic nanoparticles (magnetosomes). The orientation magnetic separation results indicated that 88.55 % of cobalt was removed from solution. Consequently, Alphaproteobacterium MTB-KTN90 as a new biosorbent opens up good opportunities for the magnetic removal of cobalt from the polluted aquatic environments.     

Evaluation of the binding effect and cytotoxicity assay of 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione on calf thymus DNA: spectroscopic,calorimetric, and molecular dynamics approaches

With advances in new drug therapies, it is essential to understand the interactions between drugs and target molecules. In this study, we applied multiple spectroscopic techniques including absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, calorimetric, and molecular dynamics (MD) simulation to study the interaction between 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione (PPF) and calf thymus DNA (ct DNA) in the absence or presence of histone H1. PPF exhibits a high binding affinity towards ct DNA in binary and ternary systems. In addition, the result for the binding constant was observed within the range 10⁴ M⁻¹ achieved through fluorescence quenching data, while the values for enthalpy and entropy changes for ct DNA–PPF and (ct DNA–H1) PPF complexes were measured to be −72.54 kJ.mol⁻¹, −161.14 J.mol⁻¹ K⁻¹, −85.34 kJ.mol⁻¹, and −19.023 J.mol⁻¹ K⁻¹, respectively. Furthermore, in accordance with circular dichroism spectra, the inducement of ct DNA structural changes was observed during binding of PPF and H1 in binary and ternary system forms. The essential roles of hydrogen bonding and van der Waals forces throughout the interaction were suggested using thermodynamic parameters. According to the obtained data, the interaction mode of ct DNA–PPF and (ct DNA–H1) PPF complexes was intercalation binding. Suggested by the MD simulation study, the ct DNA–H1 complex caused a reduction in the stability of the DNA structure in the presence or absence of ligand, which demonstrated that PPF as an intercalating agent can further distort the structure. The information achieved from this study will be very helpful in understanding the effects of PPF on the conformational state of ct DNA in the absence or presence of the H1 molecule, which seems to be quite significant for clarifying the mechanisms of action and its pharmacokinetics.     

Survivin a pivotal antiapoptotic protein in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease, pathologically characterized by lymphocyte infiltration of the synovial membrane that leads to chronic inflammation and progressive joint damage. RA develops as a result of increased cell infiltration and cell proliferation as well as impaired cell death. Activated cells in joints including lymphocytes and fibroblast-like synoviocytes (FLS) survive for a long time as a consequence of compromised apoptosis, but the mechanism underlying cell survival in synovium remains to be firmly established. Inhibition of apoptosis by survivin, as a critical antiapoptotic protein, contributes to both the persistence of autoreactive T lymphocytes and tumor-like phenotype of FLS in RA. In addition to the antiapoptotic role, survivin also has prognostic relevance in RA prodromal phase. Hence, this review provides an overview of the current knowledge regarding the involvement of survivin protein in the pathogenesis of RA.