- Spectroscopic and molecular modeling investigation on inhibition effect of nitroaromatic compounds on acetylcholinesterase activity. [Journal Article]
- CChemosphere 2019 Jul 13; 236:124365
- Nitroaromatic compounds (NACs) are widely distributed in the environment and are considered toxic or carcinogenic. However, little attention has been paid to the binding interactions between NACs and…
Nitroaromatic compounds (NACs) are widely distributed in the environment and are considered toxic or carcinogenic. However, little attention has been paid to the binding interactions between NACs and biomacromolecules (e.g., proteins). Here we investigated the effects of three model NACs, nitrobenzene (NB), 1,3-dinitrobenzene (DNB), and 1,3,5-trinitrobenzene (TNB), on the activity of acetylcholinesterase (AChE). The presence of NACs (up to 0.5 mM) effectively suppressed the AChE-catalyzed hydrolysis of acetylthiocholine iodide, with the suppression effect increasing with the nitro-group substitution (TNB > DNB > NB). Consistently, the UV absorption of AChE at 206 nm arising from the skeleton structure decreased by the addition NACs, and the decrease exhibited the same compound sequence, reflecting the perturbing interactions with the skeleton enzyme structure. However, no changes were made on the secondary structure of AChE, as evidenced by the circular dichroism analysis. The fluorescence quenching analysis of AChE demonstrated that NB and DNB interacted with both tryptophan (Trp) and tyrosine (Tyr) residues, whereas TNB interacted only with Trp. The UV absorption and fluorescence quenching analyses both reflected that the interactions with the non-skeleton aromatic amino acids were weak. 1H NMR analysis confirmed the strong π-π coupling interactions between TNB and model Trp. Molecular simulation indicated that the DNB or TNB molecule was sandwiched between Trp84 and Phe330 at the catalytic site via π-π coupling interactions. The findings highlight the importance of specific interactions of NACs with proteins to cause them to malfunction.
- Design, synthesis and antibacterial evaluation of novel 15-membered 11a-azahomoclarithromycin derivatives with the 1, 2, 3-triazole side chain. [Journal Article]
- EJEur J Med Chem 2019 Jul 11; 180:321-339
- Macrolides are widely prescribed in clinic to treat various respiratory tract infections. However, due to their inappropriate use, the prevalence of macrolide-resistant strains among clinical isolate…
Macrolides are widely prescribed in clinic to treat various respiratory tract infections. However, due to their inappropriate use, the prevalence of macrolide-resistant strains among clinical isolates has become a concern for public health. Therefore, novel macrolides skeleton structures against resistant pathogens are badly needed. Thus, three series of novel 15-membered 11a-azahomoclarithromycin derivatives (series A-C) with the 1, 2, 3-triazole side chain were designed and synthesized through creatively opening the ring of clarithromycin (CAM), expanding the ring properly and introducing a suitable side chain of 1, 2, 3-triazole at the C12 and C13 positions, and evaluated for their antibacterial activity. The antibacterial results indicated that compounds 38b, 38l and 38v possessed strong antibacterial activity against Staphylococcus aureus ATCC25923 (0.25 μg/mL) and Bacillus subtilis ATCC9372 (0.25 μg/mL). Furthermore, compounds 9e and 38g were found to exhibit promising potent activity (8 μg/mL) against Streptococcus pneumonia AB11 expressing the ermB and mefA genes. In addition, the determination of minimum bactericidal concentration (MBC) indicated that the most promising compounds 38b, 38l, 38v, 9e and 38g were excellent bacteriostatic agents. The bactericidal curve showed that 9e exhibited antibacterial activity through bacteriostatic mechanism. Finally, 38b, 38l and 38v were confirmed to be non-toxic to MCF-7 breast cancer cells up to a concentration of 32 μg/mL in preliminary cytotoxicity assay. In summary, 38b, 38l, 38v, 9e and 38g can be served as lead compounds to provide a new perspective for further structural optimization.
- Walnut core-like hollow carbon micro/nanospheres supported SnOx@C composite for high performance lithium-ion battery anode. [Journal Article]
- JCJ Colloid Interface Sci 2019 Jul 12; 554:424-432
- Herein, to cope with the volume variation problem of SnO2 anodes for lithium-ion batteries, individual walnut core-like hollow carbon micro/nanospheres (WCSs) have been prepared to be used as a suppo…
Herein, to cope with the volume variation problem of SnO2 anodes for lithium-ion batteries, individual walnut core-like hollow carbon micro/nanospheres (WCSs) have been prepared to be used as a supporting skeleton to form WCSs@SnOx@C composite. In WCSs@SnOx@C the SnOx (SnO2 with relatively small amounts of SnO) nanoparticles are well sandwiched between inner WCSs supporting skeleton and outmost glucose derived carbon anchoring coating. It is suggested that the characteristic composite construction has three key contributions to the electrochemical performance of WCSs@SnOx@C composite: firstly, with structural characteristics such as network filled cavities and porous shells, the WCSs has stronger stress tolerance, and therefore can be better able to withstand structural deformation of SnOx nanoparticles; secondly, the outmost glucose derived carbon, as an anchoring coating, can not only prevent SnOx nanoparticles from aggregating but also pulverization; finally, the ultrafine SnOx nanoparticles have low absolute volume change and shortened ions and electrons transfer distances, and therefore possess improved electrochemical performance. As a result, with the combined effect of WCSs, ultrafine SnOx nanoparticles and outmost carbon coating, the as-constructed WCSs@SnOx@C exhibits outstanding electrochemical performances such as high capacity (853 mAh g-1 at 200 mA g-1 after 400 cycles) and ultra-long lifespan (417 mAh g-1 at 1000 mA g-1 after even 1000 cycles).
- Enhanced interrogation of degraded DNA from human skeletal remains: Increased genetic data recovery using the expanded CODIS loci, multiple sex determination markers, and consensus testing. [Journal Article]
- AAAnthropol Anz 2019 Jul 19
- Skeletal remains are among the most difficult types of samples encountered in forensic DNA casework and historical investigations due to prolonged exposure to environmental insults. DNA extracted fro…
Skeletal remains are among the most difficult types of samples encountered in forensic DNA casework and historical investigations due to prolonged exposure to environmental insults. DNA extracted from bone often is degraded, in low quantities, and contains co-purified inhibitors from the surrounding soil and/or burial vault material. When sexually dimorphic skeletal elements are not recovered, determining the sex of a decedent can be challenging. With unidentified human skeletal remains, genetic data often are evaluated in concert with anthropological analyses, as well as other types of metadata, to improve confidence in making associations or for positive identifications. This study evaluated a multi-faceted molecular genetic approach to increasing the amount of data that can be recovered from degraded skeletal remains. Results demonstrate that using a newer-generation multiplex (GlobalFiler™) with an expanded set of highly discriminatory DNA markers - combined with co-amplification of three different sex-determining loci, one additional PCR cycle, and testing multiple cuttings from the same bone or multiple regions within a skeleton - can improve reliability and accuracy in skeletal remains identifications by providing data concordance.
- The Role of Obesity in Pediatric Orthopedics. [Journal Article]
- JAJ Am Acad Orthop Surg Glob Res Rev 2019; 3(5):e036
- Pediatric obesity has become a worldwide epidemic and leads to notable effects on the developing skeleton that can have lifelong implications. Obesity in the pediatric population alters bone metaboli…
Pediatric obesity has become a worldwide epidemic and leads to notable effects on the developing skeleton that can have lifelong implications. Obesity in the pediatric population alters bone metabolism, increasing the risk for fracture. It can alter the presentation of common pediatric orthopaedic conditions such as scoliosis. Obesity also leads to changes in the patterns and severity of pediatric fractures as well as alters conservative fracture treatment due to increased displacement risk. Obese pediatric trauma patients place a high burden on the nationwide hospital system in a variety of ways including the increased risk of perioperative complications. Obesity is modifiable, and addressing the issue can improve the orthopaedic and overall health of children.
- Ciliary Proteins: Filling the Gaps. Recent Advances in Deciphering the Protein Composition of Motile Ciliary Complexes. [Review]
- CCells 2019 Jul 17; 8(7)
- Cilia are highly evolutionarily conserved, microtubule-based cell protrusions present in eukaryotic organisms from protists to humans, with the exception of fungi and higher plants. Cilia can be broa…
Cilia are highly evolutionarily conserved, microtubule-based cell protrusions present in eukaryotic organisms from protists to humans, with the exception of fungi and higher plants. Cilia can be broadly divided into non-motile sensory cilia, called primary cilia, and motile cilia, which are locomotory organelles. The skeleton (axoneme) of primary cilia is formed by nine outer doublet microtubules distributed on the cilium circumference. In contrast, the skeleton of motile cilia is more complex: in addition to outer doublets, it is composed of two central microtubules and several diverse multi-protein complexes that are distributed periodically along both types of microtubules. For many years, researchers have endeavored to fully characterize the protein composition of ciliary macro-complexes and the molecular basis of signal transduction between these complexes. Genetic and biochemical analyses have suggested that several hundreds of proteins could be involved in the assembly and function of motile cilia. Within the last several years, the combined efforts of researchers using cryo-electron tomography, genetic and biochemical approaches, and diverse model organisms have significantly advanced our knowledge of the ciliary structure and protein composition. Here, we summarize the recent progress in the identification of the subunits of ciliary complexes, their precise intraciliary localization determined by cryo-electron tomography data, and the role of newly identified proteins in cilia.
- [Morphological characteristics of paravertebral muscles in patients with scoliosis caused by primaryprogressive muscular dystrophies]. [Journal Article]
- APArkh Patol 2019; 81(3):45-50
- CONCLUSIONS: The identified morphopathological characteristics of muscle tissue in patients with progressive muscular dystrophy are very similar. However, Duchenne muscular dystrophy is the most severe pathology, in which fatty degeneration and sclerotization of muscle tissue and perimysial vessels are most pronounced. To solve this problem, there is a need for the integration of geneticists, biochemists, molecular biologists, pharmacologists, and histologists.
- New Advances in the Study of Bone Tumors: A Lesson From the 3D Environment. [Journal Article]
- FPFront Physiol 2019; 10:814
- Bone primary tumors, such as osteosarcoma, are highly aggressive pediatric tumors that in 30% of the cases develop lung metastasis and are characterized by poor prognosis. Bone is also the third most…
Bone primary tumors, such as osteosarcoma, are highly aggressive pediatric tumors that in 30% of the cases develop lung metastasis and are characterized by poor prognosis. Bone is also the third most common metastatic site in patients with advanced cancer and once tumor cells become homed to the skeleton, the disease is usually considered incurable, and treatment is only palliative. Bone sarcoma and bone metastasis share the same tissue microenvironment and niches. 3D cultures represent a new promising approach for the study of interactions between tumor cells and other cellular or acellular components of the tumor microenvironment (i.e., fibroblasts, mesenchymal stem cells, bone ECM). Indeed, 3D models can mimic physiological interactions that are crucial to modulate response to soluble paracrine factors, tumor drug resistance and aggressiveness and, in all, these innovative models might be able of bypassing the use of animal-based preclinical cancer models. To date, both static and dynamic 3D cell culture models have been shown to be particularly suited for screening of anticancer agents and might provide accurate information, translating in vitro cell cultures into precision medicine. In this mini-review, we will summarize the current state-of-the-art in the field of bone tumors, both primary and metastatic, illustrating the different methods and techniques employed to realize 3D cell culture systems and new results achieved in a field that paves the way toward personalized medicine.
- Tubulin in Platelets: When the Shape Matters. [Review]
- IJInt J Mol Sci 2019 Jul 16; 20(14)
- Platelets are anuclear cells with a short lifespan that play an essential role in many pathophysiological processes, including haemostasis, inflammation, infection, vascular integrity, and metastasis…
Platelets are anuclear cells with a short lifespan that play an essential role in many pathophysiological processes, including haemostasis, inflammation, infection, vascular integrity, and metastasis. Billions of platelets are produced daily from megakaryocytes (platelet precursors). Despite this high production, the number of circulating platelets is stable and, under resting conditions, they maintain their typical discoid shape thanks to cytoskeleton proteins. The activation of platelets is associated with dynamic and rapid changes in the cytoskeleton. Two cytoskeletal polymer systems exist in megakaryocytes and platelets: actin filaments and microtubules, based on actin, and α- and β-tubulin heterodimers, respectively. Herein, we will focus on platelet-specific tubulins and their alterations and role of the microtubules skeleton in platelet formation (thrombopoiesis). During this process, microtubules mediate elongation of the megakaryocyte extensions (proplatelet) and granule trafficking from megakaryocytes to nascent platelets. In platelets, microtubules form a subcortical ring, the so-called marginal band, which confers the typical platelet discoid shape and is also responsible for changes in platelet morphology upon activation. Molecular alterations in the gene encoding β1 tubulin and microtubules post-translational modifications may result in quantitative or qualitative changes in tubulin, leading to altered cytoskeleton reorganization that may induce changes in the platelet number (thrombocytopenia), morphology or function. Consequently, β1-tubulin modifications may participate in pathological and physiological processes, such as development.
New Search Next
- Stickler syndrome: exploring prophylaxis for retinal detachment. [Journal Article]
- COCurr Opin Ophthalmol 2019 Jul 10
- CONCLUSIONS: Stickler syndrome is a systemic collagenopathy affecting multiple organ systems including the eye, ear, and skeleton. Stickler syndrome is probably the most common cause of genetically determined pediatric rhegmatogenous retinal detachment. Congenital developmental anomalies constitute over half rhegmatogenous detachments (RRD) in patients less than 10 years. The majority are caused by hereditary vitreoretinopathies associated with Stickler syndrome. Sixty percent of patients with Stickler syndrome develop RRD's over their lifetime with possible severe visual loss and subsequent lifelong morbidity. In view of these complications, some have emphasized the importance of prophylactic laser treatment to the retina of patients with Stickler syndrome to reduce the occurrence of and/or prevent future rhegmatogenous retinal detachment, but there appears to be insufficient data to support the absolute benefit of such prophylactic treatment. Guidelines regarding the age at prophylactic treatment as well as type and frequency of intervention are scarce and would benefit from additional clinical investigations.