Leonwentworth9735

Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell-based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.

Diphyllin, an arylnaphthalene lignan lactone, isolated from many traditional medicinal plants, has been reported to possess anticancer and antiviral activities. Natural diphyllin and its glycosides were identified as potent vacuolar H+ -ATPase (V-ATPase) inhibitors.

The aim of this study was to design and synthesize a series of heterocyclic derivatives of diphyllin as novel anticancer agents.

The targeted heterocyclic derivatives of diphyllin were synthesized from diphyllin employing etherification reaction and N-substitution reaction. Cytotoxicity of these compounds on four cancer cells was assessed by MTT assay. The inhibitory activity of V-ATPase of compound 3n was measured on MGC-803 cells. Anti-migration and anti-invasion abilities were assessed by transwell invasion assay and scratch wound assay.

Most of these derivatives displayed potent cytotoxicity on four cancer cells at submicromolar concentrations. The most potent derivative 3n has been shown to inhibited V-ATPase activity, migration and invasion abilities on MGC-803 cells at 0.75 mM.

The collective results clearly indicate that heterocyclic derivatives of diphyllin inhibit the viability, V-ATPase activity, migration and invasion of the MGC803 cells. The current findings provide valuable insights for the future development of novel diphyllin derivatives as anticancer agents.

The collective results clearly indicate that heterocyclic derivatives of diphyllin inhibit the viability, V-ATPase activity, migration and invasion of the MGC803 cells. The current findings provide valuable insights for the future development of novel diphyllin derivatives as anticancer agents.Alzheimer's disease is one of the most common neurodegenerative disorder afflicting a large mass of population. BACE-1 (β-secretase) is an aspartyl protease of the amyloidogenic pathway considered responsible for Alzheimer's disease (AD). Since, it catalyzes the rate limiting step of Aβ-42 production from amyloid precursor protein (APP),its inhibition is considered a viable therapeutic strategy. We have reported the design of small molecular weight compounds supposed to be blood brain permeable as BACE-1 inhibitors. selleckchem The clue for the design of this series is drawn from the previously designed series from our research group.

Design and synthesis of 2,4,6-substituted pyrimidine derivatives has been reported. In vitro FRET based screening of synthesized derivatives was performed to evaluate the BACE-1 inhibition profile.

Based on the docking simulation studies, a library of derivatives was designed, synthesized and evaluated for BACE-1 inhibition in-vitro. The docking studies were performed on Glide (Schroding92µM. The series displayed a good correlation between docking score and BACE-1 inhibition profile.

Compounds substituted with m-benzyloxy on one aromatic ring and o,p-di-chloro on another aromatic ring displayed maximum BACE-1 inhibition. Compound 2.13A displayed high docking score and was found to be most potent with IC50 of 6.92µM. The series displayed a good correlation between docking score and BACE-1 inhibition profile.

Consolidation of current research findings as well as the most important concepts regarding neutrophil extracellular traps (NETs) in rheumatoid arthritis.

Relevant publications released from 2004 to 2018 were identified using PubMed, Web of Science, Scopus, and eLibrary databases. Primary search terms used were "neutrophil extracellular traps" or "NETs" in combination with "rheumatoid arthritis".

NETs are distinctive structures promoting capture and non-phagocytic cleavage of foreign substances. NETs usually consist of thin chromatin fibers decorated with various molecules of granular, cytosolic, and cytoskeletal origin. NETosis could develop in two ways either with neutrophil death or when the viability of the cell prolongs. ROS generation and pronounced protein citrullination are essential during the initial phase of NETs formation. NETosis is considered to have certain immunological consequences, including DAMPs-mediated signalling, proinflammatory cytokine secretion, and contact of extensively modified self and foreign epitopes with antigen presenting cells. There are several putative pathogenetic links between NETosis, citrullination, neoepitope formation, and production of anticitrulline autoantibodies that can strongly influence rheumatoid arthritis progression. NET-induced vascular injury in rheumatoid arthritis could arise both directly from NETs and indirectly through enhanced thrombosis and atherosclerosis.

NETs are currently estimated as a possible influential factor of rheumatoid arthritis initiation and/or progression, especially in the context of vascular involvement. NETs can also serve as a source of novel antigenic biomarkers for the diagnosis of rheumatoid arthritis.

NETs are currently estimated as a possible influential factor of rheumatoid arthritis initiation and/or progression, especially in the context of vascular involvement. NETs can also serve as a source of novel antigenic biomarkers for the diagnosis of rheumatoid arthritis.

To analyze the association between serum levels of osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and the annual percent change (Δ%) in bone mineral density (BMD) in patients with tightly controlled rheumatoid arthritis (RA).

Observational mixed-study. RA patients followed-up with a tight-control strategy were included. Bone densitometries were performed at baseline (T0) and follow-up (T1) and serum levels of OPG and DKK-1 were measured by ELISA also in T0 and T1; additional clinical variables included disease activity measures, and treatment for RA and osteoporosis. Descriptive bivariate and multivariate analyses, stratified by gender, were performed.

We included 97 RA patients (70% female, with a mean age of 53 years, and 76% with low activity by DAS28); 95% were treated with DMARDs and 37% with anti-osteoporotic drugs. Mean time between T0 and T1 was 2.7 years. Most patients had their BMD improved. The mean Δ%BMD was +0.42% for lumbar spine, +0.15% for femoral neck and +0.91% for total femur. In men, baseline OPG was significantly associated with higher BMD loss (β coefficient -0.64) at the femoral neck. In women, DKK-1 was associated with higher BMD loss at the femoral neck (β coefficient -0.09), and total femur (β coefficient -0.11); however, DKK-1 was associated with lower BMD loss at the lumbar spine (β coefficient 0.06).

In tightly controlled RA patients, we have found no evidence of bone loss. The role of DKK1 and OPG seems small and might be related to sex and location.

In tightly controlled RA patients, we have found no evidence of bone loss. The role of DKK1 and OPG seems small and might be related to sex and location.

Malaria, a devastating infectious parasitic disease, has been recognized by the World Health organization (WHO) as a major public health problem worldwide. It is one of the leading causes of morbidity and mortality in the developing countries. There are fewer number of the antimalarial drugs available in the market to combat this deadly disease. The situation is further worsened due to the emergence of resistant strains of Plasmodium falciparum, which warrants the search for novel antimalarial drugs capable of acting at multiple targets to expand the current antimalarial drug arsenal for better therapeutic outcome.

This review aimed to provide the reader with the recent advances and progress made in the development of chemotherapeutic agents for malaria.

Literature review data on chemistry and antimalarial activity of natural and synthetic heterocyclic compounds published in the last ten years were compiled by referring various peer reviewed journal websites and medical search engines.

This review is covers the recent advances and progress made in the treatment strategies, patent granted, synthetic approaches, mechanism of action with more emphasis on structure activity relationship (SAR) of potential chemotherapeutic agents as antimalarial agents which could pave the way for the development of more effective and potent antimalarial agents. This review might interest the fellow researchers working on the development of novel antimalarial drug candidates with better therapeutic index.

Based on the literature covered in the current review article and seeing the recent trends, authors are of the opinion that the multi target conjugated hybrid approach is the best strategy to discover and develop the effective antimalarial agents.

Based on the literature covered in the current review article and seeing the recent trends, authors are of the opinion that the multi target conjugated hybrid approach is the best strategy to discover and develop the effective antimalarial agents.

Incoherent use of antibiotics has led toward resistance in MRSA, which is becoming multidrugresistant with high rate of virulence in the community and hospital settings.

Synergistic anti-MRSA activity was investigated in this study for hybrid material composite spheres of amoxicillin, Ag nanoparticles and chitosan which were prepared by one-step synthesis method and various characterizations were performed.

Antimicrobial-susceptibility assay on MRSA was achieved by disc diffusion and agar dilution techniques while agar well diffusion was used for hybrid composite spheres. The in vitro and cytotoxicity studies was done by skin abrasion mouse model and MTT assay on RD cell respectively.

All isolates were resistant with the tested antibiotics except vancomycin. MIC against MRSA showed high resistance with amoxicillin from 4 to 128 mg L-1. The mean diameter of chitosan spheres and Ag nanoparticles was 02 mm and 277 nm respectively. Morphology of spheres was uneven, varied, porous and irregular in SEM and Ag nanoparticles presence and formation was also seen in micrograph.