Efficacy of Citrullus colocynthis seed extract on Earias vittella, Fabricius, (Lepidoptera: Noctuidae): environment sustainable approach

Abstract Earias vittellaFabricius, 1794 (Noctuidae: Lepidoptera) is deliberated to be one of the most destructive pests of cotton and okra vegetation in the world including Asia. The pest has established resistance to various synthetic insecticides. The use of bio-pesticide is one of the unconventional approaches to develop a vigorous ecosystem without harming non- target pests and beneficial natural insect fauna. In the present study, the toxicity levels of Citrullus colocynthis seed extract have been evaluated against the populations of E. vittellaunder standardized laboratory conditions. The toxic effects of C. colocynthis on development periods, protein contents and esterase activity of the life stages of E. vittella were also evaluated. The toxicity levels of methanol, ethanol, hexane, water and profenofos were evaluated on the 1st instar larvae of E. vittella. LC30 and LC80 concentrations exhibited the effectiveness of methanol-based C. colocynthis seed extract against 1st instar larvae of E. vitella. The enhanced larval and pupal periods were revealed in treated samples during the comparison with untreated samples. The intrinsic rate of increase, net reproductive rate in the LC30 and LC80 concentrations exposed larvae remained less than the control treatment. Fecundity, the esterase activity and protein contents were declined in LC30 and LC80 treated samples as compared to the control. The present findings suggest that C. colosynthis extracts based botanical insecticides are beneficial, ecosystem sustainable and can be integrated with insect management programs from environment safety perspective.

Resumo Earias vittella Fabricius, 1794 (Noctuidae: Lepidoptera) é considerada uma das pragas mais destrutivas de algodão e quiabo no mundo, incluindo a Ásia. Essa praga estabeleceu resistência a vários inseticidas sintéticos. O uso de biopesticidas é uma das abordagens não convencionais para desenvolver um ecossistema saudável sem prejudicar as pragas não alvo e a fauna natural benéfica de insetos. No presente estudo, os níveis de toxicidade do extrato de semente de Citrullus colocynthis foram avaliados nas populações de E. vittella em condições de laboratório padronizadas. Os efeitos tóxicos de C. colocynthis nos períodos de desenvolvimento, conteúdo de proteína e atividade esterase das fases de vida de E. vittella também foram avaliados. Os níveis de toxicidade de metanol, etanol, hexano, água e profenofós foram avaliados em larvas de 1º instar de E. vittella. As concentrações de LC30 e LC80 apresentaram eficácia do extrato de sementes de C. colocynthis à base de metanol contra larvas de 1º instar de E. vittella. Os períodos larval e pupal aumentados foram revelados nas amostras tratadas durante a comparação com as amostras não tratadas. A taxa intrínseca de aumento e a taxa reprodutiva líquida nas concentrações de larvas expostas LC30 e LC80 permaneceram menores do que o tratamento controle. A fecundidade, a atividade da esterase e o conteúdo de proteína diminuíram nas amostras tratadas com LC30 e LC80 em comparação com o controle. As presentes descobertas sugerem que os extratos de C. colocynthis à base de inseticidas botânicos são benéficos, sustentáveis para o ecossistema e podem ser integrados com programas de manejo de insetos do ponto de vista da segurança ambiental.

Efficacy of Citrullus colocynthis seed extract on Earias vittella, Fabricius, (Lepidoptera: Noctuidae): environment sustainable approach / Eficácia do extrato de semente de Citrullus colocynthis em Earias vittella Fabricius (Lepidoptera: Noctuidae): abordagem ambiental sustentável

Abstract Earias vittellaFabricius, 1794 (Noctuidae: Lepidoptera) is deliberated to be one of the most destructive pests of cotton and okra vegetation in the world including Asia. The pest has established resistance to various synthetic insecticides. The use of bio-pesticide is one of the unconventional approaches to develop a vigorous ecosystem without harming non- target pests and beneficial natural insect fauna. In the present study, the toxicity levels of Citrullus colocynthis seed extract have been evaluated against the populations of E. vittellaunder standardized laboratory conditions. The toxic effects of C. colocynthis on development periods, protein contents and esterase activity of the life stages of E. vittella were also evaluated. The toxicity levels of methanol, ethanol, hexane, water and profenofos were evaluated on the 1st instar larvae of E. vittella. LC30 and LC80 concentrations exhibited the effectiveness of methanol-based C. colocynthis seed extract against 1st instar larvae of E. vitella. The enhanced larval and pupal periods were revealed in treated samples during the comparison with untreated samples. The intrinsic rate of increase, net reproductive rate in the LC30 and LC80 concentrations exposed larvae remained less than the control treatment. Fecundity, the esterase activity and protein contents were declined in LC30 and LC80 treated samples as compared to the control. The present findings suggest that C. colosynthis extracts based botanical insecticides are beneficial, ecosystem sustainable and can be integrated with insect management programs from environment safety perspective.

Resumo Earias vittella Fabricius, 1794 (Noctuidae: Lepidoptera) é considerada uma das pragas mais destrutivas de algodão e quiabo no mundo, incluindo a Ásia. Essa praga estabeleceu resistência a vários inseticidas sintéticos. O uso de biopesticidas é uma das abordagens não convencionais para desenvolver um ecossistema saudável sem prejudicar as pragas não alvo e a fauna natural benéfica de insetos. No presente estudo, os níveis de toxicidade do extrato de semente de Citrullus colocynthis foram avaliados nas populações de E. vittella em condições de laboratório padronizadas. Os efeitos tóxicos de C. colocynthis nos períodos de desenvolvimento, conteúdo de proteína e atividade esterase das fases de vida de E. vittella também foram avaliados. Os níveis de toxicidade de metanol, etanol, hexano, água e profenofós foram avaliados em larvas de 1º instar de E. vittella. As concentrações de LC30 e LC80 apresentaram eficácia do extrato de sementes de C. colocynthis à base de metanol contra larvas de 1º instar de E. vittella. Os períodos larval e pupal aumentados foram revelados nas amostras tratadas durante a comparação com as amostras não tratadas. A taxa intrínseca de aumento e a taxa reprodutiva líquida nas concentrações de larvas expostas LC30 e LC80 permaneceram menores do que o tratamento controle. A fecundidade, a atividade da esterase e o conteúdo de proteína diminuíram nas amostras tratadas com LC30 e LC80 em comparação com o controle. As presentes descobertas sugerem que os extratos de C. colocynthis à base de inseticidas botânicos são benéficos, sustentáveis ​​para o ecossistema e podem ser integrados com programas de manejo de insetos do ponto de vista da segurança ambiental.

Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease and an Incidental Thyroid Nodule.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare, immune-mediated demyelinating disease of the central nervous system (CNS) that has a predilection for children. Its association with malignancy or other autoimmune diseases is unclear. We present a case of MOGAD in a teenager with a coincidental thyroid malignancy and elevated intracranial pressure.

The small molecule Erk1/2 signaling pathway inhibitor PD98059 improves DNA repair in an experimental autoimmune encephalomyelitis SJL/J mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder in which the myelin sheath covering the central nervous system axons is damaged or lost, disrupting action potential conduction and leading to various neurological complications. The pathogenesis of MS remains unclear, and no effective therapies are currently available. MS is triggered by environmental factors in genetically susceptible individuals. DNA damage and DNA repair failure have been proposed as MS genetic risk factors; however, inconsistent evidence has been found in multiple studies. Therefore, more investigations are needed to ascertain whether DNA damage/repair is altered in this disorder. In this context, therapies that prevent DNA damage or enhance DNA repair could be effective strategies for MS treatment. The overactivation of the extracellular-signal-related kinase 1 and 2 (Erk1/2) pathway can lead to DNA damage and has been linked to MS pathogenesis. In our study, we observed substantially elevated oxidative DNA damage and slower DNA repair rates in an experimentally autoimmune encephalomyelitis animal model of MS (EAE). Moreover, statistical decreases in oxidative DNA strand breaks and faster repair rates were observed in EAE animals injected with the Erk1/2 inhibitor PD98059 (PD). Moreover, the expression of several genes associated with DNA strand breaks and repair changed in EAE mice at both the mRNA and protein levels, as revealed by the RT2 Profiler PCR array and verified by RT-PCR and protein analyses. The treatment with PD mitigated these changes and improved DNA repair gene expression. Our results demonstrate clear associations between Erk1/2 activation, DNA damage/repair, and MS pathology, and further suggest that PD therapy may be a promising adjuvant therapeutic strategy.

Splenomegaly and Splenic Pseudocyst in a Female Teenage Patient with Sickle Cell Anemia-A Case Report.

Splenomegaly is one of the complications of sickle cell disease (SCD) occurring in early childhood. This risk is reduced by the age of five years as the spleen undergoes auto splenectomy as a consequence of recurrent vasooclusion and splenic infarction. However, in some variants of SCD, the persistence of the spleen occurs. This can be complicated rarely by the formation of a splenic pseudocyst. We report a 17-year-old teenager with sickle cell anemia who presented with an 8-year history of gradually increasing left-sided abdominal swelling and a 2-month history of recurrent left upper abdominal pain. A computerized tomography scan revealed splenomegaly and multiple splenic cysts, not responsive to opioid analgesics which necessitated a total splenectomy. The histology report found an absence of epithelial lining confirming splenic pseudocysts. SCD patients with splenomegaly have underlying splenic infarction, which is a predisposition to splenic pseudocyst formation, though a rare occurrence. Many patients with splenic pseudocyst are usually asymptomatic and do not need intervention. However, the index patient developed serious symptoms indicating a need for a total splenectomy. A splenic pseudocyst is rare and found in <1% of splenectomies.

Efficacy of Citrullus colocynthis seed extract on Earias vittella, Fabricius, (Lepidoptera: Noctuidae): environment sustainable approach.

Earias vittellaFabricius, 1794 (Noctuidae: Lepidoptera) is deliberated to be one of the most destructive pests of cotton and okra vegetation in the world including Asia. The pest has established resistance to various synthetic insecticides. The use of bio-pesticide is one of the unconventional approaches to develop a vigorous ecosystem without harming non- target pests and beneficial natural insect fauna. In the present study, the toxicity levels of Citrullus colocynthis seed extract have been evaluated against the populations of E. vittellaunder standardized laboratory conditions. The toxic effects of C. colocynthis on development periods, protein contents and esterase activity of the life stages of E. vittella were also evaluated. The toxicity levels of methanol, ethanol, hexane, water and profenofos were evaluated on the 1st instar larvae of E. vittella. LC30 and LC80 concentrations exhibited the effectiveness of methanol-based C. colocynthis seed extract against 1st instar larvae of E. vitella. The enhanced larval and pupal periods were revealed in treated samples during the comparison with untreated samples. The intrinsic rate of increase, net reproductive rate in the LC30 and LC80 concentrations exposed larvae remained less than the control treatment. Fecundity, the esterase activity and protein contents were declined in LC30 and LC80 treated samples as compared to the control. The present findings suggest that C. colosynthis extracts based botanical insecticides are beneficial, ecosystem sustainable and can be integrated with insect management programs from environment safety perspective.

The effects of probiotic Lactobacillus acidophilus and/or prebiotic mannan oligosaccharides on growth performance, nutrient utilization, blood metabolites, faecal bacteria, and economics of crossbred calves.

Background: The ban on antibiotics as growth promoters paved the way for probiotics and prebiotics as growth promoters in animal production. Aims: The present study was conducted to evaluate the effect of probiotic Lactobacillus acidophilus and/or prebiotic Mannan oligosaccharides on growth performance, blood biochemical variables, and faecal bacterial count in crossbred calves. Methods: Fifteen-day-old crossbred calves (n=24) were divided into four groups, each consisting of six calves, and subjected to different experimental diets. The control group (T0) received a basal diet without any additives. The T1 and T2 groups received the basal diet and the probiotic (L. acidophilus, 2 × 1010 cfu/g) @ 1 g/calf per day and prebiotic (Mannan oligosaccharide) @ 4 g/calf per day, respectively. Calves of the T3 group were offered a basal diet and synbiotic (L. acidophilus, 0.5 g + Mannan oligosaccharide, 2 g/calf per day). The feed additives were mixed in milk. Results: The results of 90 days feeding trial showed that calves of the T3 and T1 groups had higher (P<0.05) body weight (BW) gain and dry matter digestibility than the control. Feeding the probiotic showed a positive effect (P<0.05) on body length at the first, second, and third months, compared to the control. The blood serum total protein and globulin concentrations in the T1 group, on days 30 and 90, and T3 group, on day 90, were higher (P<0.05) than those of the control. All the treatment groups (T1, T2, and T3) showed a reduction (P<0.05) in faecal coliform and E. coli count, compared to the control, on the 15th and 30th days of the study. Additionally, the T2 group showed a significant coliform count reduction on days 45 and 60 of the study. Conclusion: The dietary addition of L. acidophilus, 2 × 1010 cfu/g @ 1 g/calf per day and the combination of L. acidophilus, 0.5 g + Mannan oligosaccharide, 2 g/calf per day improved growth performance, serum biochemical values, and favourable gut microbiota.

A Study of Methylcellulose Based Polymer Electrolyte Impregnated with Potassium Ion Conducting Carrier: Impedance, EEC Modeling, FTIR, Dielectric, and Device Characteristics.

In this research, a biopolymer-based electrolyte system involving methylcellulose (MC) as a host polymeric material and potassium iodide (KI) salt as the ionic source was prepared by solution cast technique. The electrolyte with the highest conductivity was used for device application of electrochemical double-layer capacitor (EDLC) with high specific capacitance. The electrical, structural, and electrochemical characteristics of the electrolyte systems were investigated using various techniques. According to electrochemical impedance spectroscopy (EIS), the bulk resistance (Rb) decreased from 3.3 × 105 to 8 × 102 Ω with the increase of salt concentration from 10 wt % to 40 wt % and the ionic conductivity was found to be 1.93 ×10-5 S/cm. The dielectric analysis further verified the conductivity trends. Low-frequency regions showed high dielectric constant, ε' and loss, ε″ values. The polymer-salt complexation between (MC) and (KI) was shown through a Fourier transformed infrared spectroscopy (FTIR) studies. The analysis of transference number measurement (TNM) supported ions were predominantly responsible for the transport process in the MC-KI electrolyte. The highest conducting sample was observed to be electrochemically constant as the potential was swept linearly up to 1.8 V using linear sweep voltammetry (LSV). The cyclic voltammetry (CV) profile reveals the absence of a redox peak, indicating the presence of a charge double-layer between the surface of activated carbon electrodes and electrolytes. The maximum specific capacitance, Cs value was obtained as 118.4 F/g at the sweep rate of 10 mV/s.

A Polymer Blend Electrolyte Based on CS with Enhanced Ion Transport and Electrochemical Properties for Electrical Double Layer Capacitor Applications.

The fabrication of energy storage EDLC in this work is achieved with the implementation of a conducting chitosan-methylcellulose-NH4NO3-glycerol polymer electrolyte system. The simple solution cast method has been used to prepare the electrolyte. The impedance of the samples was fitted with equivalent circuits to design the circuit diagram. The parameters associated with ion transport are well studied at various plasticizer concentrations. The FTIR investigation has been done on the films to detect the interaction that occurs among plasticizer and polymer electrolyte. To get more insights into ion transport parameters, the FTIR was deconvoluted. The transport properties achieved from both impedance and FTIR are discussed in detail. It was discovered that the transport parameter findings are in good agreement with both impedance and FTIR studies. A sample with high transport properties was characterized for ion dominancy and stability through the TNM and LSV investigations. The dominancy of ions in the electrolyte verified as the tion of the electrolyte is established to be 0.933 whereas it is potentially stable up to 1.87 V. The rechargeability of the EDLC is steady up to 500 cycles. The internal resistance, energy density, and power density of the EDLC at the 1st cycle are 53 ohms, 6.97 Wh/kg, and 1941 W/kg, respectively.

Structural, Electrical and Electrochemical Properties of Glycerolized Biopolymers Based on Chitosan (CS): Methylcellulose (MC) for Energy Storage Application.

In this work, a pair of biopolymer materials has been used to prepare high ion-conducting electrolytes for energy storage application (ESA). The chitosan:methylcellulose (CS:MC) blend was selected as a host for the ammonium thiocyanate NH4SCN dopant salt. Three different concentrations of glycerol was successfully incorporated as a plasticizer into the CS-MC-NH4SCN electrolyte system. The structural, electrical, and ion transport properties were investigated. The highest conductivity of 2.29 × 10-4 S cm-1 is recorded for the electrolyte incorporated 42 wt.% of plasticizer. The complexation and interaction of polymer electrolyte components are studied using the FTIR spectra. The deconvolution (DVN) of FTIR peaks as a sensitive method was used to calculate ion transport parameters. The percentage of free ions is found to influence the transport parameters of number density (n), ionic mobility (µ), and diffusion coefficient (D). All electrolytes in this work obey the non-Debye behavior. The highest conductivity electrolyte exhibits the dominancy of ions, where the ionic transference number, tion value of (0.976) is near to infinity with a voltage of breakdown of 2.11 V. The fabricated electrochemical double-layer capacitor (EDLC) achieves the highest specific capacitance, Cs of 98.08 F/g at 10 mV/s by using the cyclic voltammetry (CV) technique.

The Study of Plasticized Sodium Ion Conducting Polymer Blend Electrolyte Membranes Based on Chitosan/Dextran Biopolymers: Ion Transport, Structural, Morphological and Potential Stability.

The polymer electrolyte system of chitosan/dextran-NaTf with various glycerol concentrations is prepared in this study. The electrical impedance spectroscopy (EIS) study shows that the addition of glycerol increases the ionic conductivity of the electrolyte at room temperature. The highest conducting plasticized electrolyte shows the maximum DC ionic conductivity of 6.10 × 10-5 S/cm. Field emission scanning electron microscopy (FESEM) is used to investigate the effect of plasticizer on film morphology. The interaction between the electrolyte components is confirmed from the existence of the O-H, C-H, carboxamide, and amine groups. The XRD study is used to determine the degree of crystallinity. The transport parameters of number density (n), ionic mobility (µ), and diffusion coefficient (D) of ions are determined using the percentage of free ions, due to the asymmetric vibration (υas(SO3)) and symmetric vibration (υs(SO3)) bands. The dielectric property and relaxation time are proved the non-Debye behavior of the electrolyte system. This behavior model is further verified by the existence of the incomplete semicircle arc from the Argand plot. Transference numbers of ion (tion) and electron (te) for the highest conducting plasticized electrolyte are identified to be 0.988 and 0.012, respectively, confirming that the ions are the dominant charge carriers. The tion value are used to further examine the contribution of ions in the values of the diffusion coefficient and mobility of ions. Linear sweep voltammetry (LSV) shows the potential window for the electrolyte is 2.55 V, indicating it to be a promising electrolyte for application in electrochemical energy storage devices.

Solid-State EDLC Device Based on Magnesium Ion-Conducting Biopolymer Composite Membrane Electrolytes: Impedance, Circuit Modeling, Dielectric Properties and Electrochemical Characteristics.

The polymer electrolyte based on Dx:Cs:Mg(CH3COO)2:Ni with three different glycerol concentrations have been prepared. The impedance study has verified that the electrolyte with 42 wt.% of glycerol (A3) has the highest ionic conductivity of 7.71 × 10-6 S cm-1 at room temperature. The ionic conductivity is found to be influenced by the transport parameters. From the dielectric analysis, it was shown that the electrolytes in this system obeyed the non-Debye behavior. The A3 electrolyte exhibited a dominancy of ions (tion > te) with a breakdown voltage of 2.08 V. The fabricated electrochemical double layer capacitor (EDLC) achieved the specific capacitance values of 24.46 F/g and 39.68 F/g via the cyclic voltammetry (CV) curve and the charge-discharge profile, respectively. The other significant parameters to evaluate the performance of EDLC have been determined, such as internal resistance (186.80 to 202.27 Ω) energy density (4.46 Wh/kg), power density (500.58 to 558.57 W/kg) and efficiency (92.88%).

The Study of Plasticized Solid Polymer Blend Electrolytes Based on Natural Polymers and Their Application for Energy Storage EDLC Devices.

In this work, plasticized magnesium ion-conducting polymer blend electrolytes based on chitosan:methylcellulose (CS:MC) were prepared using a solution cast technique. Magnesium acetate [Mg(CH3COO)2] was used as a source of the ions. Nickel metal-complex [Ni(II)-complex)] was employed to expand the amorphous phase. For the ions dissociation enhancement, glycerol plasticizer was also engaged. Incorporating 42 wt% of the glycerol into the electrolyte system has been shown to improve the conductivity to 1.02 × 10-4 S cm-1. X-ray diffraction (XRD) analysis showed that the electrolyte with the highest conductivity has a minimum crystallinity degree. The ionic transference number was estimated to be more than the electronic transference number. It is concluded that in CS:MC:Mg(CH3COO)2:Ni(II)-complex:glycerol, ions are the primary charge carriers. Results from linear sweep voltammetry (LSV) showed electrochemical stability to be 2.48 V. An electric double-layer capacitor (EDLC) based on activated carbon electrode and a prepared solid polymer electrolyte was constructed. The EDLC cell was then analyzed by cyclic voltammetry (CV) and galvanostatic charge-discharge methods. The CV test disclosed rectangular shapes with slight distortion, and there was no appearance of any redox currents on both anodic and cathodic parts, signifying a typical behavior of EDLC. The EDLC cell indicated a good cyclability of about (95%) for throughout of 200 cycles with a specific capacitance of 47.4 F/g.

Blending and Characteristics of Electrochemical Double-Layer Capacitor Device Assembled from Plasticized Proton Ion Conducting Chitosan:Dextran:NH4PF6 Polymer Electrolytes.

This research paper investigates the electrochemical performance of chitosan (CS): dextran (DX) polymer-blend electrolytes (PBEs), which have been developed successfully with the incorporation of ammonium hexafluorophosphate (NH4PF6). X-ray diffraction (XRD) analysis indicates that the plasticized electrolyte system with the highest value of direct current (DC) ionic conductivity is the most amorphous system. The glycerol addition increased the amorphous phase and improved the ionic dissociation, which contributed to the enhancement of the fabricated device's performance. Transference number analysis (TNM) has shown that the charge transport process is mainly by ions rather than electrons, as tion = 0.957. The CS:DX:NH4PF6 system was found to decompose as the voltage goes beyond 1.5 V. Linear sweep voltammetry (LSV) revealed that the potential window for the most plasticized system is 1.5 V. The fabricated electrochemical double-layer capacitor (EDLC) was analyzed with cyclic voltammetry (CV) and charge-discharge analysis. The results from CV verify that the EDLC in this work holds the characteristics of a capacitor. The imperative parameters of the fabricated EDLC such as specific capacitance and internal resistance were found to be 102.9 F/g and 30 Ω, respectively. The energy stored and power delivered by the EDLC were 11.6 Wh/kg and 2741.2 W/kg, respectively.

Metal Complex as a Novel Approach to Enhance the Amorphous Phase and Improve the EDLC Performance of Plasticized Proton Conducting Chitosan-Based Polymer Electrolyte.

This work indicates that glycerolized chitosan-NH4F polymer electrolytes incorporated with zinc metal complexes are crucial for EDLC application. The ionic conductivity of the plasticized system was improved drastically from 9.52 × 10-4 S/cm to 1.71 × 10-3 S/cm with the addition of a zinc metal complex. The XRD results demonstrated that the amorphous phase was enhanced for the system containing the zinc metal complex. The transference number of ions (tion) and electrons (te) were measured for two of the highest conducting electrolyte systems. It confirmed that the ions were the dominant charge carriers in both systems as tion values for CSNHG4 and CSNHG5 electrolytes were 0.976 and 0.966, respectively. From the examination of LSV, zinc improved the electrolyte electrochemical stability to 2.25 V. The achieved specific capacitance from the CV plot reveals the role of the metal complex on storage properties. The charge-discharge profile was obtained for the system incorporated with the metal complex. The obtained specific capacitance ranged from 69.7 to 77.6 F/g. The energy and power densities became stable from 7.8 to 8.5 Wh/kg and 1041.7 to 248.2 W/kg, respectively, as the EDLC finalized the cycles.

Assessment of DNA repair efficiency in the inbred BTBR T+tf/J autism spectrum disorder mouse model exposed to gamma rays and treated with JNJ7777120.

Information regarding DNA repair in autism is limited to a few studies, which have reported inconsistent results. Therefore, we designed a study to determine whether DNA repair efficiency is altered in autism and to investigate whether the H4 ligand JNJ7777120 can enhance DNA repair efficiency in BTBR T+tf/J (BTBR) mice; we also attempted to elucidate the mechanism(s) underlying this amelioration. Evaluation of DNA damage using the comet assay on bone marrow cells showed increased levels of DNA damage in BTBR mice compared with age-matched control C57BL/6J mice. Conversely, BTBR animals pretreated with 20 mg/kg JNJ7777120 for five days exhibited significant decreases in DNA damage compared with that of control BTBR mice. Our results also indicated higher sensitivity of BTBR mice exposed to gamma rays to DNA damage generation. A marked difference was observed between BTBR and C57BL/6J mice at different sampling times after irradiation, with BTBR mice showing a higher percentage of DNA damage and slower repair rate than that of C57BL/6J mice. JNJ7777120 led to enhanced repair of the DNA damage induced by radiation when administered to BTBR mice five days prior to radiation. Additionally, oxidative stress in BTBR mice was significantly elevated with a reduced GSH/GSSG ratio; significant amelioration was subsequently observed in JNJ7777120-pretreated BTBR mice. Furthermore, repetitive behaviors were also attenuated in BTBR mice by JNJ7777120 treatment without altering locomotor activity. Our results suggest that JNJ7777120 can be developed for use as a therapeutic agent to enhance DNA repair efficiency in autism spectrum disorder.

Investigation of belinostat-induced genomic instability by molecular cytogenetic analysis and pathway-focused gene expression profiling.

Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study. Our data showed that the exposure of mice to belinostat at the recommended human doses induced chromosome breakage, whole-chromosome lagging, and oxidative DNA damage in bone marrow cells in a dose-dependent manner. The expression levels of 84 genes involved in the DNA damage signaling pathway were evaluated by using an RT2 Profiler PCR array. Belinostat exposure altered the expression of 25 genes, with statistically significant changes observed in 17 genes. The array results were supported by RT-PCR and western blotting experiments. Collectively, our results showed that belinostat exposure caused oxidative DNA damage and downregulated the expression of genes involved in DNA damage repair, which may be responsible for belinostat-induced genomic instability. Thus, the clinical usage of this drug should be weighed against the hazards of carcinogenesis, and the observed genotoxicity profile of belinostat may support further development of efficient HDAC inhibitors with weaker genotoxicity.

Glucose-6-phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase-derived reactive oxygen species.

Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary oedema and pulmonary inflammation. The most common direct aetiological factor for ALI is usually parenchymal lung infection or haemorrhage. Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose-6-phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through the supply of NADPH. However, how G6PD modulation affects NOX2-mediated ROS in the airway epithelial cells (AECs) during acute lung injury has not been explored previously. Therefore, we investigated the effect of G6PD inhibitor, 6-aminonicotinamide on G6PD activity, NOX2 expression, ROS production and enzymatic anti-oxidants in AECs in a mouse model of ALI induced by lipopolysaccharide (LPS). ALI led to increased G6PD activity in the AECs with concomitant elevation of NOX2, ROS, SOD1 and nitrotyrosine. G6PD inhibitor led to reduction of LPS-induced airway inflammation, bronchoalveolar lavage fluid protein concentration as well as NOX2-derived ROS and subsequent oxidative stress. Conversely, ALI led to decreased glutathione reductase activity in AECs, which was normalized by G6PD inhibitor. These data show that activation of G6PD is associated with enhancement of oxidative inflammation in during ALI. Therefore, inhibition of G6PD might be a beneficial strategy during ALI to limit oxidative damage and ameliorate airway inflammation.

The role of TGF-ß in the pathophysiology of peritoneal endometriosis.

BACKGROUND: Endometriosis is estimated to affect 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea and subfertility. It is currently managed surgically or medically but symptoms recur in up to 75% of cases and available medical treatments have undesirable side effects. Endometriosis is defined as the presence of endometrial tissue outside the uterus with lesions typically found on the peritoneum. The aetiology of endometriosis is uncertain but there is increasing evidence that transforming growth factor (TGF)-ß plays a major role. OBJECTIVE AND RATIONALE: A descriptive review was undertaken of the published literature on the expression pattern of TGF-ß ligands and signalling molecules in women with and without endometriosis, and on the potential roles of TGF-ß signalling in the development and progression of peritoneal endometriosis. The current understanding of the TGF-ß signalling pathway is summarized. SEARCH METHODS: We searched the Pubmed database using the terms 'transforming growth factor beta' and 'endometriosis' for studies published between 1995 and 2016. The initial search identified 99 studies and these were used as the basic material for this review. We also extended our remit for important older publications. In addition, we searched the reference lists of studies used in this review for additional studies we judged as relevant. Studies which were included in the review focused on peritoneal endometriosis only as increasing evidence suggests that ovarian and deep endometriosis may have a differing pathophysiology. Thus, a final 95 studies were included in the review. OUTCOMES: TGF-ß1 is reported to be increased in the peritoneal fluid, serum, ectopic endometrium and peritoneum of women with endometriosis compared to women without endometriosis, and TGF-ß1-null mice have reduced endometriosis lesion growth when compared to their wild-type controls. Studies in mice and women have indicated that increasing levels of TGF-ß ligands are associated with decreased immune cell activity within the peritoneum, together with an increase in ectopic endometrial cell survival, attachment, invasion and proliferation, during endometriosis lesion development. TGF-ß1 has been associated with changes in ectopic endometrial and peritoneal cell metabolism and the initiation of neoangiogenesis, further fuelling endometriosis lesion development. WIDER IMPLICATIONS: Together these studies suggest that TGF-ß1 plays a major role in the development of peritoneal endometriosis lesions and that targeting this pathway may be of therapeutic potential.