Comparative Chemical and Bioactivity Studies of Intra- and Extracellular Metabolites of Endophytic Bacteria,Bacillus subtilis NCIB 3610

International Journal of Peptide Research and Therapeutics - Endophytic bacteria are able to produce unique bioactive compounds for various biotechnological applications. The intracellular and...     

Could vagus nerve stimulation influence bone remodeling?

Objectives:To investigate the effect of vagus nerve stimulation (VNS) on the bone mineral density (BMD) in epileptic patients.Methods:A prospective cohort study was conducted on individuals with refractory seizures who underwent VNS surgery between January 2012 and December 2018. BMD was measured preoperatively and between 6 months and one year after surgery.Results:Twenty-one patients (mean age (±SD)=23.6±12.3 years) were recruited for the implantation of a VNS device. The mean absolute increase in lumbar BMD in the 21 patients was 0.04±0.04 g/cm² resulting in an overall percent increase from baseline of 4.7±6.1%. BMD increased by an amount ≥ the least significant change (LSC) for the lumbar spine in 13 patients (61.9%). The lumbar Z score also increased in these patients from -1.22±1.15 to -0.88±1.22, P=0.006). Pre and Post VNA femoral BMD was measured in only 11 patients and, of those 3 showed a significant increase in BMD, 1 a significant decrease and 7 no change.Conclusion:The implantation of a VNS was associated with an increase in lumbar BMD. This study could lead to a new application for VNS in the treatment of osteoporosis.     

The powerful synergistic effect of spiramycin/propolis loaded chitosan/alginate nanoparticles on acute murine toxoplasmosis

The novel formula of spiramycin/propolis loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) was assessed for Toxoplasma gondii (T. gondii) treatment in comparison with the commercially available spiramycin regarding tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally by 2500 tachyzoites of the virulent T. gondii RH strain. The experimental groups were treated with oral spiramycin, propolis, CS/Alg NPs, spiramycin loaded CS/Alg NPs, propolis loaded CS/Alg NPs, and spiramycin/propolis loaded CS/Alg NPs. The results demonstrated that spiramycin/propolis loaded CS/Alg NPs exerted the longest survival time with no mortality on the sacrifice day (8^th) in addition to representing the highest significant parasite percent reduction of (≥96% reduction) in liver, spleen and brain designating successful tissue penetration and BBB passage. Tachyzoites treated with spiramycin/propolis loaded CS/Alg NPs demonstrated the most disfigured rapturing organism via scanning electron microscope examination along with representing an overall remarkable improvement of the histopathological pictures of liver, spleen and brain. In conclusion, spiramycin/propolis loaded CS/Alg NPs showed the uppermost efficacy in the treatment of acute murine toxoplasmosis. The safe nature and the anti-parasitic effect of each of CS, Alg, spiramycin and propolis encourage the synergistic use of spiramycin/propolis loaded CS/Alg NPs as a potent treatment for human toxoplasmosis.     

Actions of avermectin B1a on the γ-aminobutyric AcidA receptor and chloride channels in rat brain

The interaction of avermectin B_1a (AVM) with the γ-aminobutyric acid (GABA) receptor of rat brain was studied using radioactive ligand binding and tracer ion flux assays. Avermectin potentiated the binding of [³H]flunitrazepam and inhibited the binding of both [³H]muscimol and [³⁵S]t-butylbicyclo-phosphorothionate to the GABA_A receptor. Inhibition of muscimol binding by AVM suggested competitive displacement. Two kinds of ³⁶chloride (Cl) flux were studied. The ³⁶Cl efflux from preloaded microsacs was potentiated by AVM and was highly inhibited by the Cl-channel blocker 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS). However, it was not potentiated by GABA nor was it sensitive to the convulsants picrotoxin or bicuculline. On the other hand, ³⁶Cl-influx measurement in a different microsac preparation of rat brain was very sensitive to GABA and other GABA-ergic drugs. Avermectin induced ³⁶Cl influx into these microsacs in a dose–dependent manner, but to only 35% of the maximal influx induced by GABA. The AVM-induced ³⁶Cl influx was totally blocked by bicuculline. It is suggested that AVM opens the GABA_A-receptor Cl channel by binding to the GABA recognition site and acting as a partial receptor agonist, and also opens a voltage–dependent Cl channel which is totally insensitive to GABA but is very sensitive to DIDS.     

Inhibition of myostatin in adult mice increases skeletal muscle mass and strength

A human therapeutic that specifically modulates skeletal muscle growth would potentially provide a benefit for a variety of conditions including sarcopenia, cachexia, and muscular dystrophy. Myostatin, a member of the TGF-beta family of growth factors, is a known negative regulator of muscle mass, as mice lacking the myostatin gene have increased muscle mass. Thus, an inhibitor of myostatin may be useful therapeutically as an anabolic agent for muscle. However, since myostatin is expressed in both developing and adult muscles, it is not clear whether it regulates muscle mass during development or in adults. In order to test the hypothesis that myostatin regulates muscle mass in adults, we generated an inhibitory antibody to myostatin and administered it to adult mice. Here we show that mice treated pharmacologically with an antibody to myostatin have increased skeletal muscle mass and increased grip strength. These data show for the first time that myostatin acts postnatally as a negative regulator of skeletal muscle growth and suggest that myostatin inhibitors could provide a therapeutic benefit in diseases for which muscle mass is limiting.     

Towards using of new and safety material against tomato leafminer,Tuta absoluta (Mayrick)

New silica formulations offer expanded possibilities for use in horticultural crops. However, many crop pests are found on the leaf underside, and this is especially challenging when using silica because the substance must have direct contact with the insect to be effective. Silica a new and safety material was used against the second instar larvae of tomato leafminer, Tuta absoluta (Mayrick) alone and combined with other pesticides (chlorfenapyr, spinetoram and chlorantraniliprole). The results showed that when silica was used alone, the percents of mortalities were 51.7, 26.7 and 13.3%. The results showed also chlorantraniliprole was the most toxic compared with the other compounds. The per cents of mortalities were 90, 65 and 30% with the first, second and third concentrations, respectively. When silica was used in a combination with the tested pesticides, the mixture of silica and chlorfenapyr was the most toxic against the second instar larvae of T. absoluta, the percents of mortalities were 100, 76.7 and 60% with the first, second and third concentrations, respectively. The results recommended that silica was moderate toxic to the second instar larvae of T. absoluta when it used alone, so it can be used when this pest under the economic threshold or with integrated pest management programme. Silica has an activation action on the tested pesticides. Although silica was combined with one-fifth of the field rate of the tested pesticides, the toxicity of these pesticides was increased.     

Upregulation of the Glutaminase II Pathway Contributes to Glutamate Production upon Glutaminase 1 Inhibition in Pancreatic Cancer

The targeting of glutamine metabolism specifically via pharmacological inhibition of glutaminase 1 (GLS1) has been translated into clinical trials as a novel therapy for several cancers. The results, though encouraging, show room for improvement in terms of tumor reduction. In this study, the glutaminase II pathway is found to be upregulated for glutamate production upon GLS1 inhibition in pancreatic tumors. Moreover, genetic suppression of glutamine transaminase K (GTK), a key enzyme of the glutaminase II pathway, leads to the complete inhibition of pancreatic tumorigenesis in vivo unveiling GTK as a new metabolic target for cancer therapy. These results suggest that current trials using GLS1 inhibition as a therapeutic approach targeting glutamine metabolism in cancer should take into account the upregulation of other metabolic pathways that can lead to glutamate production; one such pathway is the glutaminase II pathway via GTK.     

Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms might influence the cancer risk due to their antiproliferative, antiangiogenic, and apoptotic effects. The aim of this study was to explore the genetic association of VDR polymorphisms with lung cancer risk in Tunisian population. The genotype and haplotype frequencies of four VDR polymorphisms, FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were studied using polymerase chain reaction and restriction fragment length polymorphism analysis in 240 patients with lung cancer and 280 healthy controls. The distribution of genotype frequencies differed significantly between lung cancer subjects and controls (FokI P _adj  = 0.002; ApaI P _adj  = 0.013). Haplotype analyses revealed a significant association between G-A-C and A-C-T haplotypes and lung cancer risk (P _corr  = 0.0128, P _corr  = 0.008). When patients were stratified according to gender, age, and smoking, significant associations were detected with FokI and TaqI polymorphisms. We found a lack of association between BsmI, TaqI polymorphisms and lung cancer risk (P > 0.05). Only, the attributable proportion due to interaction and the synergic index for interaction between ApaI polymorphism and smoking were statistically significant (P _adj  = 0.74, 95 % CI = 0.38–1.20) and (P _adj  = 0.63, 95 % CI = 0.05–1.21), respectively. Both the additive interaction measures suggested the existence of a biological interaction between SNP ApaI, but not FokI, and smoking. The multiplicative interaction measure was not statistically significant (P > 0.05). This is the first study in Tunisia, which suggested that VDR FokI and ApaI polymorphisms might be risk factors for lung cancer development.