Immunomodulatory Expression of Cathelicidins Peptides in Pulp Inflammation and Regeneration: An Update

The role of inflammatory mediators in dental pulp is unique. The local environment of pulp responds to any changes in the physiology that are highly fundamental, like odontoblast cell differentiation and other secretory activity. The aim of this review is to assess the role of cathelicidins based on their capacity to heal wounds, their immunomodulatory potential, and their ability to stimulate cytokine production and stimulate immune-inflammatory response in pulp and periapex. Accessible electronic databases were searched to find studies reporting the role of cathelicidins in pulpal inflammation and regeneration published between September 2010 and September 2020. The search was performed using the following databases: Medline, Scopus, Web of Science, SciELO and PubMed. The electronic search was performed using the combination of keywords “cathelicidins” and “dental pulp inflammation”. On the basis of previous studies, it can be inferred that LL-37 plays an important role in odontoblastic cell differentiation and stimulation of antimicrobial peptides. Furthermore, based on these outcomes, it can be concluded that LL-37 plays an important role in reparative dentin formation and provides signaling for defense by activating the innate immune system.     

Effect of Triphala on oxidative stress and on cell-mediated immune response against noise stress in rats

Stress is one of the basic factors in the etiology of number of diseases. The present study was aimed to investigate the effect of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) on noise-stress induced alterations in the antioxidant status and on the cell-mediated immune response in Wistar strain male albino rats. Noise-stress employed in this study was 100 dB for 4 h/d/15 days and Triphala was used at a dose of 1 g/kg/b.w/48 days. Eight different groups of rats namely, non-immunized: control, Triphala, noise-stress, Triphala with noise-stress, and corresponding immunized groups were used. Sheep red blood cells (5×10⁹ cells/ml) were used to immunize the animals. Biochemical indicators of oxidative stress namely lipid peroxidation, antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), ascorbic acid in plasma and tissues (thymus and spleen) and SOD, GPx and corticosterone level in plasma were estimated. Cell-mediated immune response namely foot pad thickness (FPT) and leukocyte migration inhibition (LMI) test were performed only in immunized groups. Results showed that noise-stress significantly increased the lipid peroxidation and corticosterone level with concomitant depletion of antioxidants in plasma and tissues of both non-immunized and immunized rats. Noise-stress significantly suppressed the cell-mediated immune response by decreased FPT with an enhanced LMI test. The supplementation with Triphala prevents the noise-stress induced changes in the antioxidant as well as cell-mediated immune response in rats. This study concludes that Triphala restores the noise-stress induced changes may be due to its antioxidant properties.     

Phosphorylation of Enoyl-Acyl Carrier Protein Reductase InhA Impacts Mycobacterial Growth and Survival

InhA, the primary target for the first line anti-tuberculosis drug isoniazid, is a key enzyme of the fatty-acid synthase II system involved in mycolic acid biosynthesis in Mycobacterium tuberculosis. In this study, we show that InhA is a substrate for mycobacterial serine/threonine protein kinases. Using a novel approach to validate phosphorylation of a substrate by multiple kinases in a surrogate host (Escherichia coli), we have demonstrated efficient phosphorylation of InhA by PknA, PknB, and PknH, and to a lower extent by PknF. Additionally, the sites targeted by PknA/PknB have been identified and shown to be predominantly located at the C terminus of InhA. Results demonstrate in vivo phosphorylation of InhA in mycobacteria and validate Thr-266 as one of the key sites of phosphorylation. Significantly, our studies reveal that the phosphorylation of InhA by kinases modulates its biochemical activity, with phosphorylation resulting in decreased enzymatic activity. Co-expression of kinase and InhA alters the growth dynamics of Mycobacterium smegmatis, suggesting that InhA phosphorylation in vivo is an important event in regulating its activity. An InhA-T266E mutant, which mimics constitutive phosphorylation, is unable to rescue an M. smegmatis conditional inhA gene replacement mutant, emphasizing the critical role of Thr-266 in mediating post-translational regulation of InhA activity. The involvement of various serine/threonine kinases in modulating the activity of a number of enzymes of the mycolic acid synthesis pathway, including InhA, accentuates the intricacies of mycobacterial signaling networks in parallel with the changing environment.     

Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants

Dietary phenolic compounds are known to elicite vital cellular responses such as cell cycle arrest, apoptosis and differentiation by activating a cascade of molecular events. As there is an increasing interest to improve the efficacy of these compounds for use as potential chemopreventive agents, we wanted to understand the impact of phenolic compounds on target genes in prostate cancer. In this study we used human cDNA microarrays with 2400 clones consisting of 17 prosite motifs to characterize alterations in gene expression pattern in response to the phenolic antioxidants ellagic acid (EA) and resveratrol (RE). Over a 48-hr exposure of androgen - sensitive LNCaP cells to EA and RE, a total of 593 and 555 genes respectively, showed more than a two fold difference in expression. A distinct set of genes in both EA-and RE-treated cells may represent the signature profile of phenolic antioxidant-induced gene expression in LNCaP cells. Although extensive similarity was found between effects of EA - and RE - responsive genes in prostate cancer cells, out of 246 genes with overlapping responses, 25 genes showed an opposite effect. Quantitative RT-PCR was used to verify and validate the differential expression of selected genes identified from cDNA microarrays. In-depth analysis of the data from this study provided insight into the alterations in the p53 - responsive genes, p300, Apaf-1, NF-kBp50 and p65 and PPAR families of genes, suggesting the activation of multiple signaling pathways that leads to growth inhibition of LNCaP cells. This is a first study to look for changes in a large number of human genes in response to dietary compounds.     

Entomopoxvirus of cotton bollworm,Helicoverpa armigera (Hbn.)

Occurrence of an Entomopoxvirus (EPV) from a lepidopteran insect viz;. cotton bollworm, H. armigera (HaEPV) along with gross pathological symptoms is reported for the first time in India. Histopathological study revealed that the fat body being the most favoured site of infection followed by haemocytes and gut epithelium. HaEPV was found to be not cross infective to six of the agricultural lepidopteran insect pests except for the potato black cutworm, Agrotis segetum registering 100% mortality showing typical symptom. Further, safety of HaEPV was shown against beneficial insect like mulberry silkworm, Bombyx mori and an useful insect general predator, Chrysoperla carnea.     

Ascorbic acid and alpha-tocopherol as potent modulators on arsenic induced toxicity in mitochondria

Arsenic exists ubiquitously in our environment and various forms of arsenic circulate in air, water, soil and living organisms. Since arsenic compounds have shown to exert their toxicity chiefly by generating reactive oxygen species, we have evaluated the effect of antioxidants ascorbic acid and alpha-tocopherol on lipid peroxidation, antioxidants and mitochondrial enzymes in liver and kidney of arsenic exposed rats. A significant increase in the level of lipid peroxidation and decrease in the levels of antioxidants and in the activities of mitochondrial enzymes were observed in arsenic intoxicated rats. Co-administration of arsenic treated rats with ascorbic acid and alpha-tocopherol showed significant reduction in the level of lipid peroxidation and elevation in the levels of ascorbic acid, alpha-tocopherol, glutathione and total sulfhydryls and in the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, NADH-dehydrogenase and cytochrome c oxidase. From our results, we conclude that ascorbic acid and alpha-tocopherol alleviate arsenic- induced alterations in mitochondria.     

New purine derivatives for efficient preparation of nucleoside analogs via alkylation

New diazabicycloundecenium and phosphazenium derivatives of purines are introduced for mild and efficient preparation of nucleoside analogs via in situ alkylation. Diazabicycloundecenium salts of purines were obtained directly as a result of an unusual reaction between two corresponding amino compounds.     

Effect of AMPA on Cerebral Cortical Oxygen Balance of Ischemic Rat Brain

We tested the hypothesis that the excitatory neurotransmitter receptor agonist, alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), would worsen cerebral cortical oxygen supply/consumption balance during focal ischemia. In this study, we compared regional cerebral blood flow, arterial and venous O₂ saturation, O₂ extraction and oxygen consumption of ischemic and AMPA treated ischemic and control regions of rat brain. Ischemia was induced by middle cerebral artery (MCA) occlusion in isoflurane (1.4%) anesthetized Wistar rats. Twenty minutes after MCA occlusion, 10^–5 M AMPA was applied to the ischemic cortex (IC) for a period of 40 min; the fluid was changed every 10 min. After 1 hr of ischemia, animals were sacrificed and regional cerebral blood flow (rCBF) was determined using the C¹⁴-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined microspectrophotometrically. In control, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 46 ± 20 vs. 81 ± 39 ml/min/100g, O₂ consumption: 2.8 ± 1.4 vs. 3.6 ± 1.4 ml O₂/min/100g). 10^–5 M AMPA did not significantly alter regional cerebral blood flow and oxygen consumption of the IC, but did decrease the average venous O₂ saturation of the IC from 50.2 ± 3.9% to 46.7 ± 1.6%. AMPA also significantly increased the frequency of small veins with less than 45% O₂ saturation in the IC (8 out of 56 veins in IC vs. 18 out of 56 veins in AMPA treated IC). Thus, topical application of 10^–5 M AMPA to the ischemic area worsens cerebral O₂ balance and suggests that excitatory amino acids contribute to the degree of cerebral ischemia.     

The Small GTPase RhoA Is Required for Proper Locomotor Circuit Assembly

The assembly of neuronal circuits during development requires the precise navigation of axons, which is controlled by attractive and repulsive guidance cues. In the developing spinal cord, ephrinB3 functions as a short-range repulsive cue that prevents EphA4 receptor-expressing corticospinal tract and spinal interneuron axons from crossing the midline, ensuring proper formation of locomotor circuits. Here we report that the small GTPase RhoA, a key regulator of cytoskeletal dynamics, is also required for ephrinB3/EphA4-dependent locomotor circuit formation. Deletion of RhoA from neural progenitor cells results in mice that exhibit a rabbit-like hopping gait, which phenocopies mice lacking ephrinB3 or EphA4. Consistent with this locomotor defect, we found that corticospinal tract axons and spinal interneuron projections from RhoA-deficient mice aberrantly cross the spinal cord midline. Furthermore, we determined that loss of RhoA blocks ephrinB3-induced growth cone collapse of cortical axons and disrupts ephrinB3 expression at the spinal cord midline. Collectively, our results demonstrate that RhoA is essential for the ephrinB3/EphA4-dependent assembly of cortical and spinal motor circuits that control normal locomotor behavior.