Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.

     

Expression of NLRP3 Inflammasomes in Neurogenic Niche Contributes to the Effect of Spatial Learning in Physiological Conditions but Not in Alzheimer’s Type Neurodegeneration

A common feature of neurodegenerative disorders, in particular Alzheimer's disease (AD), is a chronic neuroinflammation associated with aberrant neuroplasticity. Development of neuroinflammation affects efficacy of stem and progenitor cells proliferation, differentiation, migration, and integration of newborn cells into neural circuitry. However, precise mechanisms of neurogenesis alterations in neuroinflammation are not clear yet. It is well established that expression of NLRP3 inflammasomes in glial cells marks neuroinflammatory events, but less is known about contribution of NLRP3 to deregulation of neurogenesis within neurogenic niches and whether neural stem cells (NSCs), neural progenitor cells (NPCs) or immature neuroblasts may express inflammasomes in (patho)physiological conditions. Thus, we studied alterations of neurogenesis in rats with the AD model (intra-hippocampal injection of Aβ1-42). We found that in Aβ-affected brain, number of CD133+ cells was elevated after spatial training in the Morris water maze. The number of PSA-NCAM+ neuroblasts diminished by Aβ injection was completely restored by subsequent spatial learning. Spatial training leads to elevated expression of NLRP3 inflammasomes in the SGZ (subgranular zones): CD133+ and PSA-NCAM+ cells started to express NLRP3 in sham-operated, but not AD rats. Taken together, our data suggest that expression of NLRP3 inflammasomes in CD133+ and PSA-NCAM+ cells may contribute to stimulation of adult neurogenesis in physiological conditions, whereas Alzheimer’s type neurodegeneration abolishes stimuli-induced overexpression of NLRP3 within the SGZ neurogenic niche.

     

Bioconversion of Phenolic Monomers of Lignin and Lignin-Containing Substrates by the Basidiomycete <Emphasis Type="Italic">Lentinus tigrinus</Emphasis>

The bioconversion of phenolic monomers of lignin (veratrol, vanillin, and vanillyl alcohol), hydrolyzed lignin, and sodium lignosulfonate (a product of the chemical modification of native lignin) by the basidiomycete Lentinus tigrinus was studied. It was found that the growth of the fungi on lignin monomer compounds is suppressed. A noticeable growth of the fungal biomass was observed only on the technical substrate sodium lignosulfonate. A comprehensive physicochemical study of the products of microbial transformation of sodium lignosulfonate was performed. It was established that the main direction of lignin bioconversion is oxidative condensation to form humic substances. In this case, depolymerization of the phenolic skeleton of lignin to monomeric phenol derivatives did not occur. The aromatic carbon atoms of the phenolic skeleton, unlike the carbon atoms of polysaccharides, were not involved in the fungal biomass growth. The observed growth of the fungus on the technical substrate sodium lignosulfonate can be explained by the presence of admixtures of oligomeric polysaccharides hemicellulose and cellulose, which can be used by the fungus as a carbon source.     

Triterpenoids and Flavonoids from the Leaves of Astragalus membranaceus and Their Inhibitory Effects on Nitric Oxide Production

Four new cycloartane triterpenes, named huangqiyegenins V and VI and huangqiyenins K and L ( 1 – 4 , resp.), together with nine known triterpenoids, 5 – 13 , and eight flavonoids, 14 – 21 , were isolated from a 70%‐EtOH extract of Astragalus membranaceus leaves. The structures of the new compounds were elucidated by detailed spectroscopic analyses, and the compounds were identified as (9β,11α,16β,20R,24S)‐11,16,25‐trihydroxy‐20,24‐epoxy‐9,19‐cyclolanostane‐3,6‐dione ( 1 ), (9β,16β,24S)‐16,24,25‐trihydroxy‐9,19‐cyclolanostane‐3,6‐dione ( 2 ), (3β,6α,9β,16β,20R,24R)‐16,25‐dihydroxy‐3‐(β‐D ‐xylopyranosyloxy)‐20,24‐epoxy‐9,19‐cyclolanostan‐6‐yl acetate ( 3 ), and (3β,6α,9β,16β,24E)‐26‐(β‐D ‐glucopyranosyloxy)‐16‐hydroxy‐3‐(β‐D ‐xylopyranosyloxy)‐9,19‐cyclolanost‐24‐en‐6‐yl acetate ( 4 ). All isolated compounds were evaluated for their inhibitory activities against LPS‐induced NO production in RAW264.7 macrophage cells. Compounds 1 – 3, 14, 15 , and 18 exhibited strong inhibition on LPS‐induced NO release by macrophages with IC₅₀ values of 14.4–27.1 μM .     

Slight vapor deficit accelerates graft union healing of tomato plug seedling

The application of grafting in tomato production has substantially improved tomato quality and yields. It has been demonstrated that humidity plays an important role in the graft healing of seedlings. This study focuses on the optimum relative humidity (RH) conditions for scion and rootstock healing of grafted tomato (Solanum lycopersicum L.) seedlings. Two tomato cultivars, ‘Super Sunload’ and ‘Super Dotaerang’, grafted onto ‘B-Blocking’ rootstock were subjected to one of three RH regimens: 70–80, 80–90, or 90–100%. The results showed that the scions of both cultivars showed apparent wilting under the 70–80 and 80–90% RH treatments. On this basis, the 90–100% RH treatment was subdivided into 95–96, 97–98, and 99–100% RH treatments, which were then applied. Among these subdivided RH treatments, the fresh weights of the scions and rootstocks significantly increased in response to the treatments of 97–98 and 99–100% RH, and the graft union connection of both cultivars was also enhanced after two days of healing. Furthermore, lower levels of endogenous H₂O₂ and less activity of antioxidant enzymes were observed in both cultivars in response to treatment with 95–96 or 97–98% RH, which indicated that less oxidative stress occurred. Overall, it is suggested that 97–98% is the optimal RH level for the graft healing of tomato seedlings.     

High prevalence of serum folate receptor autoantibodies in children with autism spectrum disorders

Abstract

Background: Supplementation of folic acid by pregnant mothers is thought to lower the risk of autism spectrum disorders (ASDs) in the offspring. Folic acid is taken up by cells via receptors with high affinity for folate and reduced folic acid derivatives. However, this is blocked by the presence of folate receptor autoantibodies (FRAA). Cerebral FRAA have been detected with high frequency in children with ASDs, suggesting the existence of a link between folic acid uptake and disease aetiology.

Methods: We investigated the frequency of FRAA in serum samples from 40 children with ASDs and 42 gender- and age-matched children with typical development (TD). Serum FRAA concentrations were measured by enzyme-linked immunosorbent assay.

Results: We found a significant difference in the frequency of serum FRAA in the two study cohorts. Serum FRAA were present in 77.5% (31/40) of children with ASDs compared with 54.8% (23/42) of TD children (p?=?0.03746, Fischer’s exact test). Thus, serum FRAA are more prevalent in children with ASDs than in TD children.

Conclusions: Our data suggest that children with ASDs may have defects in folic acid absorption that play a role in the onset of ASDs.     

HDAC6 controls autophagosome maturation essential for ubiquitin‐selective quality‐control autophagy

Autophagy is primarily considered a non‐selective degradation process induced by starvation. Nutrient‐independent basal autophagy, in contrast, imposes intracellular QC by selective disposal of aberrant protein aggregates and damaged organelles, a process critical for suppressing neurodegenerative diseases. The molecular mechanism that distinguishes these two fundamental autophagic responses, however, remains mysterious. Here, we identify the ubiquitin‐binding deacetylase, histone deacetylase‐6 (HDAC6), as a central component of basal autophagy that targets protein aggregates and damaged mitochondria. Surprisingly, HDAC6 is not required for autophagy activation; rather, it controls the fusion of autophagosomes to lysosomes. HDAC6 promotes autophagy by recruiting a cortactin‐dependent, actin‐remodelling machinery, which in turn assembles an F‐actin network that stimulates autophagosome–lysosome fusion and substrate degradation. Indeed, HDAC6 deficiency leads to autophagosome maturation failure, protein aggregate build‐up, and neurodegeneration. Remarkably, HDAC6 and F‐actin assembly are completely dispensable for starvation‐induced autophagy, uncovering the fundamental difference of these autophagic modes. Our study identifies HDAC6 and the actin cytoskeleton as critical components that define QC autophagy and uncovers a novel regulation of autophagy at the level of autophagosome–lysosome fusion.