Essential Oil of Piper Purusanum C.DC (Piperaceae) and Its Main Sesquiterpenes: Biodefensives Against Malaria and Dengue Vectors, Without Lethal Effect on Non-target Aquatic Fauna

The mosquitoes vectors of the genus Aedes and Anopheles present resistance to several commercial insecticides, which are also toxic to non-predators targets. On the other hand, essential oils are a promising source of insecticides. Thus, in this work, the essential oil from the leaves of Piper purusanum was characterized by gas chromatography based approaches and evaluated as biodefensive against malaria and dengue vectors. The main compounds of P. purusanum essential oil were β-caryophyllene (57.05%), α-humulene (14.50%) and germacrene D (8.20%). The essential oil inhibited egg hatching (7.6 ± 1.5 to 95.6 ± 4.5%) caused larval death (LC50 from 49.84 to 51.60 ppm) and inhibited the action of acetylcholinesterase (IC50 of 2.29 µg/mL), which can be related to the mechanisms of action. On the other hand, the biological activity of β-caryophyllene, α-humulene and germacrene D were higher than the essential oil. In addition, these sesquiterpenes and essential oil did not show a lethal effect on Toxorhynchites splendens, Anisops bouvieri, Gambusia affinis and Diplonychus indicus (LC50 from 2098.80 to 7707.13 ppm), although D. indicus is more sensible (SI/PSF from 48.56 to 252.02 ppm) to essential oil, representing a natural alternative against these relevant vectors.

ANABOLIC STEROID ABUSE AND CARDIOVASCULAR TOXICITY: CASE REPORT

Despite the development of tests for the detection of doping, Anabolic steroids, are still used to increase sports performance. Unfortunately, studies have clearly shown that overdose of anabolic steroids can induce serious cardiovascular complications that can be life-threatening. This implies the determining role of health professionals in informing the general population and athletes in particular about the lethal effect of these substances. We report the case of a young high-level athlete who consults for palpitations and in whom cardiac imaging reveals abnormalities related to chronic consumption of anabolic steroids.

Effect of S14161 Small Molecule and Glaucium Flavum Extract on A549 Cancer Cells

Background: Lung cancer is the fifth most common cancer in Iran. Due to the side effects of common cancer treatments, everyone has turned to herbal remedies and new treatments. This study aimed to compare the effect of S14161 small molecule and Glaucium flavum extract on the induction of apoptosis in A549 cancer cells. Materials and Methods: In this experimental study, the A549 cell line was treated with different concentrations of G. flavum and S14161 on days 1, 3, and 5. Also, half maximal inhibitory concentrations (IC 50) for both G. flavum and S14161 were measured. In addition, the quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to investigate the effects of S14161 and G. flavum extract on the expressions level of Bax, Bad, P53, and Bcl2 genes. Results: Results showed that both the combination of S14161 and G. flavum extract resulted in cell death and reduced cancer cell viability. Nevertheless, the viability rate was greater by S14161, and this small molecule significantly increased the expression of Bax, P53, and Bad apoptotic genes and decreased the expression of the Bcl2 gene, which shows the induced apoptotic death and lethal effect of S14161 in comparison with G. flavum extract. Conclusion: Our study showed that S14161 had fewer IC50 and caused cell death by inhibiting the PI3K/AKT pathway, and G. flavum caused cancer cell death due to its alkaloid compounds. Therefore, both compounds are recommended as drug candidates for the treatment of lung cancer.

Comparative Insecticidal Effects of Dry Ocimum Gratissium (Scent Leaves) and Rambo™ Paper on Mosquitoes in Jos, Nigeria

Insecticides are chemicals or biological substances that are used to kill or disable insects. Blood feeding mosquitoes are responsible for the intolerable biting nuisance and transmission of large number of diseases such as malaria, yellow fever, dengue fever, filarias is amongst others, causing serious health problems to humans and obstacles to socioeconomic development of developing nations like Nigeria. The insecticidal effect of scent leaves (Ocimum gratissum) and Rambo™ paper on mosquitoes was investigated. The study is aimed at comparing the insecticidal effects of Ocimum gratissimum and Rambo™ paper on mosquitoes in Jos. 100 mosquitoes were exposed to dried Ocimum gratissum and Rambo™ paper at different time intervals of 5, 10 and 12 min. Results obtained showed a time dependent insecticidal effect on mosquitoes, which was 54.2%, 54.0% and 55.6% total mortality of mosquitoes at respective time intervals on exposures to both Rambo™ paper insecticide and Osimum gratissum, indicating that there was a significant difference in the lethal effect of Rambo™ paper insecticide and scent leave on mosquitoes at (p<0.05). In comparing the lethal effect of Rambo™ paper insecticide and Ocimum grasstisimum on mosquitoes at differnt locations in Jos, at Dogon Karfe, after 10 min of treatment, Rambo™ paper had the highest lethal effect of 21 (84.0%) compared to scent leaves 6 (24.0%) and at Abattoir Jos, after 12 min of treatment, Rambo™ paper had the highest lethal effect of 17 (94.4%) compared to Ocimum grasstisimum 3 (16.7%). These comparisons were significant at p 0.05. This study provides evidence that Ocimum grasstisimum has a mosquitocidal effect. However, the Rambo™ paper gave a better mosquitocidal effect than Ocimum grasstisimum. There is a need to discover better additive or extract options that could give Ocimum grasstisimum a better effect as a natural product available in Africa towards the malaria eradication programme.

Toxic Characteristics and Action Mode of the Mixotrophic Dinoflagellate Akashiwo sanguinea on Co-Occurring Phytoplankton and Zooplankton

The mixotrophic dinoflagellate Akashiwo sanguinea frequently forms harmful algal blooms around the world and has caused massive deaths of shellfish, finfish and birds, yet its toxic mechanism is still unclear. In this study, toxic effects of A. sanguinea on co-culturing phytoplankton and zooplankton were investigated. The results showed that sonicated cultures of A. sanguinea JX13 and JX14, isolated from the Pearl River Estuary, had a significant lethal effect on the rotifer Brachionus plicatilis, with the highest mortality rate of 80%. The highest inhibition rates of A. sanguinea cultures JX13 (90%) and JX14 (80%) on R. salina were much higher than that of AS2 (20%). Toxicity varied with the growth stage, during which A. sanguinea cells in the exponential stage showed the highest toxicity (40%), while A. sanguinea filtrate had the highest toxicity (10%) in the decline stage. The action mode of A. sanguinea toxicity on plankton was explored through an osmotic membrane culture device. It was found that A. sanguinea JX13 displayed an inhibitory effect on coexisting phytoplankton, whether they had contact or not, but the inhibition rate increased by 25% with contact. A lethal effect of A. sanguinea JX13 on rotifer Brachionus plicatilis was observed only in contact treatment. This study suggests that direct contact is the key action mode to trigger the release of toxins and induce toxic effects of A. sanguinea on co-occurring plankton.

Synergistic Effect of PARP Inhibitor and BRD4 Inhibitor in Multiple Models of Ovarian Cancer

Background: Ovarian cancer has the highest fatality rate among patients with gynaecological tumours. Current therapies including poly-ADP ribose polymerase (PARP) inhibitors have limitations due to the frequent recurrence of ovarian cancer after treatment and resistance to therapy.Methods: In this study, we used multiple models with different genetic backgrounds to investigate the potential synergism effect and mechanism between the bromodomain-containing protein 4 (BRD4) inhibitor AZD5153 and the PARP inhibitor Olaparib. The models were two-dimensional (2D) and 3D cell lines, patient-derived organoids (PDO) and patient-derived xenografts (PDX). Results: Cotreatment with Olaparib and AZD5153 exhibited marked synergistic effects, and significantly attenuated cell viability, whereas it increased DNA replication fork instability, chromosomal breakage and apoptosis compared to treatment with either drug alone. Mechanistically, the tumor upregulates PTEN after Olaparib treatment to make its DNA and chromosome more stable and therefore induces Olaparib resistance. AZD5153 can downregulate PTEN to reverse Olaparib resistance and thus increase joint lethal effect with Olaparib.Conclusion: This study reveals that AZD5153 can downregulate PTEN to reverse Olaparib resistance and thus increase joint lethal effect on DNA replication fork instability, chromosomal breakage, and apoptosis with Olaparib.

The effects of Pyrantel-Oxantel on the Dipylidium caninum tapeworm: An in vitro study

The present study aimed to evaluate, in vitro, the cestocidal effect of Pyrantel-Oxantel on the Dipylidium caninum tapeworm. Each intestine sample was obtained by means of a transversal incision of the abdominal area of each euthanized canine subject, individually dissected via longitudinal incision, and examined for the presence of D. caninum. An optical microscope was used to identify and verify proglottid morphology and viability based on its macroscopic appearance. The cestocidal effects of Pyrantel-Oxantel (75 mg pyrantel pamoate; 75 mg oxantel pamoate) were assessed in adult tapeworms (treated group, n= 21; control group, n= 21) placed on Petri dishes and incubated at 37 °C. One-hour post-incubation, the D. caninum cestodes treated with Pyrantel-Oxantel presented a 28 % decrease (P=0.001) in motility, which rose to a 52 % (P=0.0001) decrease by the end of the second hour. The control group (P=0.0001) presented 55.7 % motility for at least the first six hours of incubation and 4.2 % (P=0.001) motility by the end of the study, while 0 % motility was observed in the treated group by the end of the study. Pyrantel-Oxantel had a lethal effect (P=0.0001) on adult D. caninum, with 100 % mortality observed 6 h after in vitro post-incubation, while the control group presented 55.7 % viability after the same time period. In addition, Pyrantel-Oxantel reduced (P=0.001) tegument thickness by 42.5 % (10.24 ± 0.21 µm), while this was 17.81 ± 0.33 µm for the control group. The results of this study indicate that Pyrantel-Oxantel has a therapeutic effect on the presence of D. caninum, inducing both a reduction of the tegument thickness and increased mortality.

New Synthetic Lethality Re-Sensitizing Platinum-Refractory Cancer Cells to Cisplatin In Vitro: The Rationale to Co-Use PARP and ATM Inhibitors

The pro-apoptotic tumor suppressor BIN1 inhibits the activities of the neoplastic transcription factor MYC, poly (ADP-ribose) polymerase-1 (PARP1), and ATM Ser/Thr kinase (ATM) by separate mechanisms. Although BIN1 deficits increase cancer-cell resistance to DNA-damaging chemotherapeutics, such as cisplatin, it is not fully understood when BIN1 deficiency occurs and how it provokes cisplatin resistance. Here, we report that the coordinated actions of MYC, PARP1, and ATM assist cancer cells in acquiring cisplatin resistance by BIN1 deficits. Forced BIN1 depletion compromised cisplatin sensitivity irrespective of Ser15-phosphorylated, pro-apoptotic TP53 tumor suppressor. The BIN1 deficit facilitated ATM to phosphorylate the DNA-damage-response (DDR) effectors, including MDC1. Consequently, another DDR protein, RNF8, bound to ATM-phosphorylated MDC1 and protected MDC1 from caspase-3-dependent proteolytic cleavage to hinder cisplatin sensitivity. Of note, long-term and repeated exposure to cisplatin naturally recapitulated the BIN1 loss and accompanying RNF8-dependent cisplatin resistance. Simultaneously, endogenous MYC was remarkably activated by PARP1, thereby repressing the BIN1 promoter, whereas PARP inhibition abolished the hyperactivated MYC-dependent BIN1 suppression and restored cisplatin sensitivity. Since the BIN1 gene rarely mutates in human cancers, our results suggest that simultaneous inhibition of PARP1 and ATM provokes a new BRCAness-independent synthetic lethal effect and ultimately re-establishes cisplatin sensitivity even in platinum-refractory cancer cells.

On the Synergism of Biogenic Gold Nanoparticles and Hydroxyaluminum Phthalocyanines in the Photoeradication of Staphylococcus aureus

Due to the unusual properties of gold nanoparticles, these structures are widely used in medicine and biology. This paper describes for the first time the synthesis of colloidal gold nanoparticles by the cell-free filtrate obtained from the Coriolus versicolor biomass and the use of these biogenic nanostructures to increase the photosensitizing efficiency of di- (AlPcS2) and tetrasulfonated (AlPcS4) hydroxyaluminum phthalocyanines in antibacterial photodynamic therapy. The obtained monodisperse particles were extremely stable, and this remarkable stability was due to the presence of phosphoprotein as a capping agent. The studied gold nanoparticles had a spherical shape, were uniformly distributed, and were characterized by a single plasmon band at wavelength of 514–517 nm. Almost 60% of the gold particles were found to be in the range of 13 to 15 nm. In accordance with the regulations of the American Microbiological Society, indicating that any antimicrobial technique must kill at least 3 log CFU (99.9%) to be accepted as “antimicrobial”, this mortality of Staphylococcus aureus was shown to be achieved in the presence of AlPcS4 + AuNPs mixture and 4.8 J cm−2 light dose compared to AlPcS4 alone, which required a light dose of 24 J cm−2. The best effect of increasing the effectiveness of combating this pathogen was observed in the case of AlPcS2 + AuNPs as a photosensitizing mixture. The light dose of 24 J cm−2 caused a lethal effect of the studied coccus in the planktonic culture.

Transcriptional responses of Daphnis nerii larval midgut to oral infection by Daphnis nerii cypovirus-23

Background Daphnis nerii cypovirus-23 (DnCPV-23) is a new type of cypovirus and has a lethal effect on the oleander hawk moth, Daphnis nerii which feeds on leave of Oleander and Catharanthus et al. After DnCPV-23 infection, the change of Daphnis nerii responses has not been reported. Methods To better understand the pathogenic mechanism of DnCPV-23 infection, 3rd-instar Daphnis nerii larvae were orally infected with DnCPV-23 occlusion bodies and the transcriptional responses of the Daphnis nerii midgut were analyzed 72 h post-infection using RNA-seq. Results The results showed that 1979 differentially expressed Daphnis nerii transcripts in the infected midgut had been identified. KEGG analysis showed that protein digestion and absorption, Toll and Imd signaling pathway were down-regulated. Based on the result, we speculated that food digestion and absorption in insect midgut might be impaired after virus infection. In addition, the down-regulation of the immune response may make D. nerii more susceptible to bacterial infections. Glycerophospholipid metabolism and xenobiotics metabolism were up-regulated. These two types of pathways may affect the viral replication and xenobiotic detoxification of insect, respectively. Conclusion These results may facilitate a better understanding of the changes in Daphnis nerii metabolism during cypovirus infection and serve as a basis for future research on the molecular mechanism of DnCPV-23 invasion.