After the metabolic syndrome and its components, thyroid disorders represent the most common endo... more After the metabolic syndrome and its components, thyroid disorders represent the most common endocrine disorders, with increasing prevalence in the last two decades. Thyroid dysfunctions are distinguished by hyperthyroidism, hypothyroidism, or inflammation (thyroiditis) of the thyroid gland, in addition to the presence of thyroid nodules that can be benign or malignant. Thyroid cancer is typically detected via an ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) and cytological examination of the specimen. This approach has significant limitations due to the small sample size and inability to characterize follicular lesions adequately. Due to the rapid advancement of high-throughput molecular biology techniques, it is now possible to identify new biomarkers for thyroid neoplasms that can supplement traditional imaging modalities in postoperative surveillance and aid in the preoperative cytology examination of indeterminate or follicular lesions. Here, we review current kno...
Does Alzheimer Disease show a decline in cognitive functions that relate to the awareness of exte... more Does Alzheimer Disease show a decline in cognitive functions that relate to the awareness of external reality? In this paper, we will propose a perspective that patients with increasing symptoms of AD show a change in the awareness of subjective versus objective representative axis of reality thus consequently move to a more internal like perception of reality. This paradigm shift suggests that new insights into the dynamicity of the conscious representation of reality in the AD brain may give us new clues to the very early signs of memory and self-awareness impairment that originates from, in our view the microtubules. Dialog between Adso and William, in Umberto Eco’s The Name of the Rose, Third Day: Vespers. “But how does it happen,” I said with admiration, “that you were able to solve the mystery of the library looking at it from the outside, and you were unable to solve it when you were inside?” “Thus, God knows the world, because He conceived it in His mind, as if it was from t...
Inhibition of Na/K-ATPase by selected Au(iii) and Pt(ii) complexes is induced by binding these co... more Inhibition of Na/K-ATPase by selected Au(iii) and Pt(ii) complexes is induced by binding these complexes between the M2 and M4 helices at the intracellular side of pump.
The distinguishing property of Sm/LSm protein assemblies is their high stability. In order to bet... more The distinguishing property of Sm/LSm protein assemblies is their high stability. In order to better understand the nature of Sm/LSm protein oligomers in this study we have analyzed the contribution of non-canonical interactions to the stability of assemblies. The predominant types of non-canonical interactions at Sm/LSm protein interfaces are CH⋅⋅⋅O, and CH⋅⋅⋅N interactions represented at interfaces. Our results show low percentages of XH-π and non-canonical interactions involving sulfur atoms, while the backbone groups were less frequently involved. The data show a high percentage of non-canonical interactions in interfaces formed by charged residues with Lys and Arg, these being the major charged donors. The main chain non-canonical interactions might be slightly more linear than the side chain interactions, and they have somewhat shorter median distances. Comparing the stabilizing amino acid residues with amino acids which build non-canonical interactions at interfaces shows that certain amino acids like Phe, Pro, His and Tyr are involved with a high percentage. The high conservation score of amino acids that are involved in non-canonical interactions in protein interfaces is an additional strong argument for their importance in the stabilization of Sm/LSm protein assemblies.
Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through ... more Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA2) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA2 are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA2 and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA2 by 1.5-fold ( p < 0.01), which was blocked by the cPLA2 inhibitor MAFP (10 microM; 15 min). Similarly, the PI3K inhibitor LY294002 (10 microM; 15 min) and ERK1/2 inhibitor PD98059 (20 microM; 15 min) abolished the INS-mediated increase in cPLA2 phosphorylation by 59% (p < 0.001), and by 75% ( p < 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% ( p < 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% ( p < 0.001). The effect of INS on VSMCs proliferation was significantly ( p < 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA2 and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA2 activity.
In this study we have described the noncanonical interactions between the porphyrin ring and the ... more In this study we have described the noncanonical interactions between the porphyrin ring and the protein part of porphyrin-containing proteins to better understand their stabilizing role. The analysis reported in this study shows that the predominant type of non-canonical interactions at porphyrins are CH····O and CH····N interactions, with a small percentage of CH···π and noncanonical interactions involving sulfur atoms. The majority of non-canonical interactions are formed from side-chains of charged and polar amino acids, whereas backbone groups are not frequently involved. The main-chain noncanonical interactions might be slightly more linear than the side-chain interactions, and they have somewhat shorter median distances. The analysis, performed in this study, shows that about 44% of the total interactions in the dataset are involved in the formation of multiple (furcated) noncanonical interactions. The high number of porphyrin-water interactions show importance of the inclusion of solvent in protein-ligand interaction studies. Furthermore, in the present study we have observed that stabilization centers are composed predominantly from nonpolar amino acid residues. Amino acids deployed in the environment of porphyrin rings are deposited in helices and coils. The results from this study might be used for structure-based porphyrin protein prediction and as scaffolds for future porphyrin-containing protein design.
Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of ... more Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting.
After the metabolic syndrome and its components, thyroid disorders represent the most common endo... more After the metabolic syndrome and its components, thyroid disorders represent the most common endocrine disorders, with increasing prevalence in the last two decades. Thyroid dysfunctions are distinguished by hyperthyroidism, hypothyroidism, or inflammation (thyroiditis) of the thyroid gland, in addition to the presence of thyroid nodules that can be benign or malignant. Thyroid cancer is typically detected via an ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) and cytological examination of the specimen. This approach has significant limitations due to the small sample size and inability to characterize follicular lesions adequately. Due to the rapid advancement of high-throughput molecular biology techniques, it is now possible to identify new biomarkers for thyroid neoplasms that can supplement traditional imaging modalities in postoperative surveillance and aid in the preoperative cytology examination of indeterminate or follicular lesions. Here, we review current kno...
Does Alzheimer Disease show a decline in cognitive functions that relate to the awareness of exte... more Does Alzheimer Disease show a decline in cognitive functions that relate to the awareness of external reality? In this paper, we will propose a perspective that patients with increasing symptoms of AD show a change in the awareness of subjective versus objective representative axis of reality thus consequently move to a more internal like perception of reality. This paradigm shift suggests that new insights into the dynamicity of the conscious representation of reality in the AD brain may give us new clues to the very early signs of memory and self-awareness impairment that originates from, in our view the microtubules. Dialog between Adso and William, in Umberto Eco’s The Name of the Rose, Third Day: Vespers. “But how does it happen,” I said with admiration, “that you were able to solve the mystery of the library looking at it from the outside, and you were unable to solve it when you were inside?” “Thus, God knows the world, because He conceived it in His mind, as if it was from t...
Inhibition of Na/K-ATPase by selected Au(iii) and Pt(ii) complexes is induced by binding these co... more Inhibition of Na/K-ATPase by selected Au(iii) and Pt(ii) complexes is induced by binding these complexes between the M2 and M4 helices at the intracellular side of pump.
The distinguishing property of Sm/LSm protein assemblies is their high stability. In order to bet... more The distinguishing property of Sm/LSm protein assemblies is their high stability. In order to better understand the nature of Sm/LSm protein oligomers in this study we have analyzed the contribution of non-canonical interactions to the stability of assemblies. The predominant types of non-canonical interactions at Sm/LSm protein interfaces are CH⋅⋅⋅O, and CH⋅⋅⋅N interactions represented at interfaces. Our results show low percentages of XH-π and non-canonical interactions involving sulfur atoms, while the backbone groups were less frequently involved. The data show a high percentage of non-canonical interactions in interfaces formed by charged residues with Lys and Arg, these being the major charged donors. The main chain non-canonical interactions might be slightly more linear than the side chain interactions, and they have somewhat shorter median distances. Comparing the stabilizing amino acid residues with amino acids which build non-canonical interactions at interfaces shows that certain amino acids like Phe, Pro, His and Tyr are involved with a high percentage. The high conservation score of amino acids that are involved in non-canonical interactions in protein interfaces is an additional strong argument for their importance in the stabilization of Sm/LSm protein assemblies.
Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through ... more Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA2) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA2 are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA2 and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA2 by 1.5-fold ( p < 0.01), which was blocked by the cPLA2 inhibitor MAFP (10 microM; 15 min). Similarly, the PI3K inhibitor LY294002 (10 microM; 15 min) and ERK1/2 inhibitor PD98059 (20 microM; 15 min) abolished the INS-mediated increase in cPLA2 phosphorylation by 59% (p < 0.001), and by 75% ( p < 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% ( p < 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% ( p < 0.001). The effect of INS on VSMCs proliferation was significantly ( p < 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA2 and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA2 activity.
In this study we have described the noncanonical interactions between the porphyrin ring and the ... more In this study we have described the noncanonical interactions between the porphyrin ring and the protein part of porphyrin-containing proteins to better understand their stabilizing role. The analysis reported in this study shows that the predominant type of non-canonical interactions at porphyrins are CH····O and CH····N interactions, with a small percentage of CH···π and noncanonical interactions involving sulfur atoms. The majority of non-canonical interactions are formed from side-chains of charged and polar amino acids, whereas backbone groups are not frequently involved. The main-chain noncanonical interactions might be slightly more linear than the side-chain interactions, and they have somewhat shorter median distances. The analysis, performed in this study, shows that about 44% of the total interactions in the dataset are involved in the formation of multiple (furcated) noncanonical interactions. The high number of porphyrin-water interactions show importance of the inclusion of solvent in protein-ligand interaction studies. Furthermore, in the present study we have observed that stabilization centers are composed predominantly from nonpolar amino acid residues. Amino acids deployed in the environment of porphyrin rings are deposited in helices and coils. The results from this study might be used for structure-based porphyrin protein prediction and as scaffolds for future porphyrin-containing protein design.
Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of ... more Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting.
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Papers by Bozidarka Zaric