Post-exposure Time Research Articles

Association of sulfur mustard toxicity with oxidant/antioxidant system in veterans: A meta-analysis of case-control studies.

Sulfur mustard (SM) is a chemical warfare agent that increases oxidative stress in veterans. The literature assessing oxidant/antioxidant parameters in SM-exposed veterans contains conflicting results. A total of 11 relevant studies were identified and screened. Data were extracted, and effect size and heterogeneity were assessed. The analysis revealed significant elevations in levels of malondialdehyde (MDA, an indicator of lipid peroxidation), catalase (CAT), and a reduction in glutathione (GSH) following SM exposure while superoxide dismutase (SOD) and total antioxidant levels did not change. The meta-analysis revealed that the MDA and CAT levels significantly increased in the two post-exposure sampling times (15-20 and 21-33years) except for theGSH level, which decreased only in the post-exposure sampling time of 21-33years. The subgroup meta-analysis of the type of analyzed samples indicated that SOD and CAT levels were only increased in the serum/plasma samples, while GSH was decreased. BALF/sputum and erythrocyte samples also revealed significant increases in MDA and SOD levels while GSH level was significantly decreased. This meta-analysis concluded that SM exposure affects the balance between oxidants and antioxidants, promoting oxidative stress that may persist long after exposure. This condition highlights the need for strategies to enhance antioxidant defenses in SM-exposed veterans.

Treatment of Mycobacterium tuberculosis infected macrophages with Rifabutin loaded β-glucan microparticles induces macroautophagy mediated bacillary killing

Tuberculosis (TB), attributable to Mycobacterium tuberculosis (M.tb.), constitutes a formidable global health challenge, particularly with the proliferation of multidrug-resistant (MDR-TB) strains. The efficacious clearance of M.tb. from host cells is imperative for mitigating infection and averting disease progression. Autophagy, an intricate cellular mechanism for degrading and recycling biomolecules, plays a pivotal role in the immune response to M.tb. by facilitating the degradation of intracellular pathogen through the formation of autophagosomes and their subsequent fusion with lysosomes. The present study elucidates the therapeutic efficacy of Rifabutin loaded YDGP (DYDGP) microparticles within M.tb.infected macrophage. Our results show that the administration of DYDGP improve the membrane integrity of macrophage infected with H37Rv as well as MDR strains, as compared to that of untreated controls at 30 min, 6 h and 24 h post-exposure time points. DCFHDA staining elucidated that DYDGP treatment significantly enhances intracellular reactive oxygen species (ROS) production compared to blank YDGP, even in the presence of NOX-2 inhibitors. Furthermore, DYDGP promotes the biogenesis of acidic vesicular organelles and phago-lysosomal maturation, as corroborated by acridine orange and Lysotracker Red staining. Immunofluorescence and dansylcadaverine dual staining data evidenced that DYDGP treatment enhances autophagosome formation, autophagy induction and LC3 puncta formation within M.tb. infected macrophage at both 30 min and 24 h post-exposure time points. Further, protein expression analyses demonstrated that DYDGP treatment enhances the expression levels of NOX-2 and LC3, thereby confirming autophagy induction within M.tb. infected macrophage. Antimycobacterial efficacy assessments revealed that DYDGP treatment engendered significant reductions in colony-forming units (CFUs) of H37Rv (64, 40, 19), MDR32420 (44, 35, 18), MDR32422 (44, 39, 21), and MDR32521 (38, 22, 18) after 30 min, 24 h, and 48 h, exposure respectively. These findings accentuate DYDGP's potential to substantially attenuate M.tb. burden, including the addressal of MDR strains, thereby positioning it as a promising adjunctive therapy for augmenting TB treatment.

Absence of genotoxicity following pulmonary exposure to metal oxides of copper, tin, aluminum, zinc, and titanium in mice.

Inhalation of nanosized metal oxides may occur at the workplace. Thus, information on potential hazardous effects is needed for risk assessment. We report an investigation of the genotoxic potential of different metal oxide nanomaterials. Acellular and intracellular reactive oxygen species (ROS) production were determined for all the studied nanomaterials. Moreover, mice were exposed by intratracheal instillation to copper oxide (CuO) at 2, 6, and 12 μg/mouse, tin oxide (SnO2) at 54 and 162 μg/mouse, aluminum oxide (Al2O3) at 18 and 54 μg/mouse, zinc oxide (ZnO) at 0.7 and 2 μg/mouse, titanium dioxide (TiO2) and the benchmark carbon black at 162 μg/mouse. The doses were selected based on pilot studies. Post-exposure time points were 1 or 28 days. Genotoxicity, assessed as DNA strand breaks by the comet assay, was measured in lung and liver tissue. The acellular and intracellular ROS measurements were fairly consistent. The CuO and the carbon black bench mark particle were potent ROS generators in both assays, followed by TiO2. Al2O3, ZnO, and SnO2 generated low levels of ROS. We detected no increased genotoxicity in this study using occupationally relevant dose levels of metal oxide nanomaterials after pulmonary exposure in mice, except for a slight increase in DNA damage in liver tissue at the highest dose of CuO. The present data add to the body of evidence for risk assessment of these metal oxides.

A comparative study of 589 and 532 nm low level laser irradiation effects on normal human peripheral blood mononuclear cells viability.

To assess how laser light affects blood lymphocyte viability in vitro. The comparative study was conducted from November 2021 to April 2022 at the Department of Medical Physics, Mustansiriyah University, Baghdad, Iraq, and comprised blood samples collected from healthy adults with no medical history of major illnesses or history of taking medications for major diseases.Low-level laser 589nm and 532nm was used at 30 J/cm², 50 J/cm² and 70J/cm² energy intensities and three different post-exposure time; immediately, 1h and 2h after radiation exposure. The viability of normal human lymphocytic cells of the blood was noted. Data was analysed using SPSS 24. The blood samples were drawn from 6 adult male voluteers. The percentage of cells that showed apoptosis post-exposure to 589nm laser was significantly lower than that following exposure to 532nm laser (p<0.05). However, the proportion of apoptotic cells was significantly higher following irradiation with 532nm at varying doses than after irradiation with 589nm (p<0.05). A low-level laser could promote and prevent apoptosis in human peripheral blood cells in a dose- and time-dependent manner.

ARGONAUTE2 Localizes to Sites of Sporocysts in the Schistosome-Infected Snail, Biomphalaria glabrata.

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression in various biological processes, including normal development, immune responses, reproduction, and stress adaptation. In this study, we aimed to establishment the requirement of the miRNA pathway as part of the molecular response of exposure of Biomphalaria glabrata (snail host) to Schistosoma mansoni (trematode parasite). Initially, the core pieces of miRNA pathway protein machinery, i.e., Drosha, DGCR8, Exportin-5, Ran, and Dicer, together with the central RNA-induced silencing complex (RISC) effector protein Argonaute2 (Ago2) were elucidated from the B. glabrata genome. Following exposure of B. glabrata to S. mansoni miracidia, we identified significant expression up-regulation of all identified pieces of miRNA pathway protein machinery, except for Exportin-5, at 16 h post exposure. For Ago2, we went on to show that the Bgl-Ago2 protein was localized to regions surrounding the sporocysts in the digestive gland of infected snails 20 days post parasite exposure. In addition to documenting elevated miRNA pathway protein machinery expression at the early post-exposure time point, a total of 13 known B. glabrata miRNAs were significantly differentially expressed. Of these thirteen B. glabrata miRNAs responsive to S. mansoni miracidia exposure, five were significantly reduced in their abundance, and correspondingly, these five miRNAs were determined to putatively target six genes with significantly elevated expression and that have been previously associated with immune responses in other animal species, including humans. In conclusion, this study demonstrates the central importance of a functional miRNA pathway in snails, which potentially forms a critical component of the immune response of snails to parasite exposure. Further, the data reported in this study provide additional evidence of the complexity of the molecular response of B. glabrata to S. mansoni infection: a molecular response that could be targeted in the future to overcome parasite infection and, in turn, human schistosomiasis.

Assessment of the herpes zoster risk among renal transplant recipients administered the influenza vaccine

BackgroundReactivation of the latent varicella-zoster virus can cause herpes zoster (HZ) infection, and renal transplant recipients undergoing immunosuppressive therapy are particularly susceptible to this condition. This study aims to evaluate the potential increase in HZ incidence following influenza vaccination among this specific patient population. MethodsThis study was a population-based, retrospective, self-controlled case series. Data were retrieved from Taiwan’s National Health Insurance Research Database spanning the years 2008 to 2017. Patients diagnosed with HZ within a 6-month period before and after receiving the influenza vaccine were eligible for inclusion. Two distinct time intervals were defined for analysis: the initial 15 days and 30 days following vaccination were categorized as risk intervals, while all other periods served as control intervals. Incidence rate ratios (IRRs) were computed to compare HZ incidence during the risk intervals with that during the control intervals. ResultsThis study encompassed a cohort of 4,222 renal transplant recipients who had received the influenza vaccine. Among this group, 67 recipients were subsequently diagnosed with HZ. The IRR during both the initial 15 days (IRR = 0.63; 95 % CI, 0.23–1.89) and the first 30 days (IRR = 1.50; 95 % CI, 0.71–3.16) following influenza vaccination did not demonstrate a statistically significant increase when compared to the post-exposure observation times. Comparable results were also observed when comparing these IRR values to the pre-exposure observation times. The subgroup analysis, stratified by age, sex, and underlying medical conditions (including cancer and autoimmune diseases), revealed that the IRRs did not exhibit statistically significant differences. ConclusionsNo significant association between the influenza vaccine and an elevated risk of HZ was detected. The administration of annual influenza vaccines appears to be a reasonable practice for renal transplant recipients.

The impact of surface functionalization of cellulose following simulated digestion and gastrointestinal cell-based model exposure

Surface-functionalized cellulose materials are developed for various purposes, including food additives and food contact materials. A new biologically relevant testing strategy has been developed based on guidance from the European Food Safety Authority to demonstrate the safety of several next-generation surface-functionalized cellulose materials. This strategy involves a complex three-stage simulated digestion to compare the health effects of thirteen novel different types of cellulose. The physical and chemical properties of surface-functionalized fibrillated celluloses differed depending on the type, amount, and location of functional groups such as sulfonate, TEMPO-oxidized carboxy, and periodate-chlorite oxidized dicarboxylic acid celluloses. Despite exposure to gastrointestinal fluids, the celluloses maintained their physicochemical properties, such as negative surface charges and high length-to-width/thickness aspect ratios. An established intestinal co-culture model was used to measure cytotoxicity, barrier integrity, oxidative stress, and pro-inflammatory response to create a toxicological profile for these unique materials. We conclude that the C6 carboxylated cellulose nanofibrils by TEMPO-oxidation induced the most toxicity in the biological model used in this study and that the observed effects were most prominent at the 4-hour post-exposure time point.

In vitro study of radiosensitivity in colorectal cancer cell lines associated with Lynch syndrome.

Lynch syndrome patients have an inherited predisposition to cancer due to a deficiency in DNA mismatch repair (MMR) genes which could lead to a higher risk of developing cancer if exposed to ionizing radiation. This pilot study aims to reveal the association between MMR deficiency and radiosensitivity at both a CT relevant low dose (20 mGy) and a therapeutic higher dose (2 Gy). Human colorectal cancer cell lines with (dMMR) or without MMR deficiency (pMMR) were analyzed before and after exposure to radiation using cellular and cytogenetic analyses i.e., clonogenic assay to determine cell reproductive death; sister chromatid exchange (SCE) assay to detect the exchange of DNA between sister chromatids; γH2AX assay to analyze DNA damage repair; and apoptosis analysis to compare cell death response. The advantages and limitations of these assays were assessed in vitro, and their applicability and feasibility investigated for their potential to be used for further studies using clinical samples. Results from the clonogenic assay indicated that the pMMR cell line (HT29) was significantly more radio-resistant than the dMMR cell lines (HCT116, SW48, and LoVo) after 2 Gy X-irradiation. Both cell type and radiation dose had a significant effect on the yield of SCEs/chromosome. When the yield of SCEs/chromosome for the irradiated samples (2 Gy) was normalized against the controls, no significant difference was observed between the cell lines. For the γH2AX assay, 0, 20 mGy and 2 Gy were examined at post-exposure time points of 30 min (min), 4 and 24 h (h). Statistical analysis revealed that HT29 was only significantly more radio-resistant than the MLH1-deficient cells lines, but not the MSH2-deficient cell line. Apoptosis analysis (4 Gy) revealed that HT29 was significantly more radio-resistant than HCT116 albeit with very few apoptotic cells observed. Overall, this study showed radio-resistance of the MMR proficient cell line in some assays, but not in the others. All methods used within this study have been validated; however, due to the limitations associated with cancer cell lines, the next step will be to use these assays in clinical samples in an effort to understand the biological and mechanistic effects of radiation in Lynch patients as well as the health implications.

Rapid heat stress causes increased delta spectral power 24 h post-exposure and altered reaction time in firefighters by its dynamic ability to generate heat storage

This experiment determined the duration that rapid heat stress (RHS) impacts neural function and reaction time. Previous research has discovered that RHS results in neural function changes immediately post-exposure. No studies have evaluated the duration that these variables are impacted. Additionally, research has not assessed the impact of RHS on reaction time. We hypothesized that RHS would lead to sustained electroencephalography (EEG) spectral power and reaction time changes. Twenty participants performed a treadmill protocol in an environmental chamber (35 °C; 45% humidity) in firefighter personal protective equipment until reaching a core temperature of 39 °C. The subjects performed a Go/No-Go (response inhibition) task (pre-, post-, 24, and 48 h post-RHS) while EEG and reaction time were recorded. Results from the Go/No-Go task revealed a difference between pre-RHS and post-RHS delta spectral power. These differences support previous literature. The first novel finding of this study is that delta power is still perturbed 24 h post-RHS exposure. The second novel finding is that reaction time is altered post-RHS, 24 h, and 48 h post-RHS. These cognitive changes could result in compounded consequences if two bouts of RHS occur in 24 h (e.g., two fires or other hyperthermic events), which could jeopardize critical life-saving missions.

Bioactive potential of L. camara and O. gratissimum extracts in the control of mosquito larvae: An ecologically friendly approach

In the present study, the larvicidal efficacy of the extracts of the weeds Lantana camara Linn (L. camara) and Ocimum gratissimum Linn (O. gratissimum) was evaluated against the larvae of the malaria vectors A. aegypti, An. subpictus, and C. quinquefasciatus. The ethanol, n-hexane and diethyl ether crude leaf extracts were evaluated in a preliminary screening for larvicidal activity at 20,40,80,160,320 and 640 mg/l concentrations. 20 larvae of each species were introduced in different sterile Petri dishes in aqueous media under a controlled environment to assess biological activity. The larvicidal activity of both extracts was evaluated at 6 and 12-h post-exposure time points by observing the movement of each larva. The obtained data were subjected to probit analysis to determine the lethal concentrations that kill 50% and 90% (LC50 and LC90) of the treated larvae. The results revealed a noticeable larvicidal activity following 12 h of exposure. The extract of L. camara leaves exhibited an LC50 range between 18.66 and 51.35 mg/l and an LC90 range between 87.78 and 312.21 mg/l. Moreover, for the extract of O. gratissimum leaves, the LC50 range was 52.26 to 59.09 mg/l and the LC90 range was 260.22 to 348.23 mg/l. Taken together, the results indicate that the extracts of L. camara and O. gratissimum leaves may be useful as effective, economical, and eco-friendly larvicidal agents. However, additional studies are needed to explore the bioactive components of the weeds that exhibit larvicidal activity along with their mode of action.

Ultrastructure of noise-induced cochlear synaptopathy

Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has been extensively studied by confocal microscopy, however, understanding the nature and sequence of damage requires ultrastructural analysis. Here, we used focused ion-beam scanning electron microscopy to mill, image, segment and reconstruct ANF terminals in mice, 1 day and 1 week after synaptopathic exposure (8–16 kHz, 98 dB SPL). At both survivals, ANF terminals were normal in number, but 62% and 53%, respectively, lacked normal synaptic specializations. Most non-synapsing fibers (57% and 48% at 1 day and 1 week) remained in contact with an IHC and contained healthy-looking organelles. ANFs showed a transient increase in mitochondrial content (51%) and efferent innervation (34%) at 1 day. Fibers maintaining synaptic connections showed hypertrophy of pre-synaptic ribbons at both 1 day and 1 week. Non-synaptic fibers were lower in mitochondrial content and typically on the modiolar side of the IHC, where ANFs with high-thresholds and low spontaneous rates are normally found. Even 1 week post-exposure, many ANF terminals remained in IHC contact despite loss of synaptic specializations, thus, regeneration efforts at early post-exposure times should concentrate on synaptogenesis rather than neurite extension.

Thermal effects on the time build-up patterns of a weather resistant radiophotoluminescence glass (SAPANS)

A recently developed weather-resistant radiophotoluminscence (RPL) glass, named “SAPANS”, has a feature of slow time build-up of RPL. This feature could be utilized for the estimation of post-exposure elapsed time in a radiological accident accompanied with an unnoticed radiation exposure. In the present study, thermal effects on the time build-up patterns of RPL from SAPANS (“SAPANS RPL” hereafter) were examined. Small SAPANS samples were irradiated with 160 kV X-rays at 1 Gy(H2O) and the time changes of RPL were observed under six different temperatures: 45 °C, 36 °C, 20 °C, 15 °C, 5.5 °C and −18 °C. It was found that the time build-up of SAPANS RPL was notably accelerated by heating. While the ratio of measured RPL to that after preheating (at 160 °C for 1 h) gradually increased to about 35% at 20 °C in 24 h, it reached nearly 80% at 45 °C, and hardly increased at −18 °C. To investigate the thermal effects on the accuracy of the previously proposed method for estimating a post-exposure elapsed time, samples were placed outdoor for nearly two weeks and the observed time build-up of SAPANS RPL was compared to the estimation based on the temperature change measured at 30-min intervals. A good agreement was seen between the measured and estimated RPL data, which indicates that more precise estimation of the post-exposure elapsed time could be achieved with SAPANS based on the information of thermal history. These findings would be useful to broaden the applicability of SAPANS to retrospective dosimetry as part of nuclear/radiological emergency preparedness.

Metabolomics for identifying pathways involved in vesicating agent lewisite-induced corneal injury

Lewisite (LEW) is an arsenical vesicant that can be a potentially dangerous chemical warfare agent (CWA). Eyes are particularly susceptible to vesicant induced injuries and ocular LEW exposure can act swiftly, causing burning of eyes, edema, inflammation, cell death and even blindness. In our previous studies, we developed a LEW exposure-induced corneal injury model in rabbit and showed increased inflammation, neovascularization, cell death, and structural damage to rabbit corneas upon LEW exposure. In the present study, we further assessed the metabolomic changes to delineate the possible mechanisms underlying the LEW-induced corneal injuries. This information is vital and could help in the development of effective targeted therapies against ocular LEW injuries. Thus, the metabolomic changes associated with LEW exposures in rabbit corneas were assessed as a function of time, to delineate pathways from molecular perturbations at the genomic and proteomic levels. New Zealand white rabbit corneas (n = 3–6) were exposed to LEW vapor (0.2 mg/L; flow rate: 300 ml/min) for 2.5 min (short exposure; low dose) or 7.5 min (long-exposure; high dose) and then collected at 1, 3, 7, or 14 days post LEW exposure. Samples were prepared using the automated MicroLab STAR® system, and proteins precipitated to recover the chemically diverse metabolites. Metabolomic analysis was carried out by reverse phase UPLC-MS/MS and gas chromatography (GC)-MS. The data obtained were analyzed using Metabolon's software. The results showed that LEW exposures at high doses were more toxic, particularly at the day 7 post exposure time point. LEW exposure was shown to dysregulate metabolites associated with all the integral functions of the cornea and cause increased inflammation and immune response, as well as generate oxidative stress. Additionally, all important metabolic functions of the cells were also affected: lipid and nucleotide metabolism, and energetics. The high dose LEW exposures were more toxic, particularly at day 7 post LEW exposure (>10-fold increased levels of histamine, quinolinate, N-acetyl-β-alanine, GMP, and UPM). LEW exposure dysregulated integral functions of the cornea, caused inflammation and heightened immune response, and generated oxidative stress. Lipid and nucleotide metabolism, and energetics were also affected. The novel information about altered metabolic profile of rabbit cornea following LEW exposure could assist in delineating complex molecular events; thus, aid in identifying therapeutic targets to effectively ameliorate ocular trauma.

Cellular and bioenergetic effects of polystyrene microplastic in function of cell type, differentiation status and post-exposure time

The ubiquity of microplastics (MPs) in food sources and personal care products increasingly raises concerns on human health. However, little is known about the duration of the effects of MPs and whether effects depend on cellular differentiation status. Herein, cellular and bioenergetic effects of MPs in different exposure scenarios on four types of human cell lines derived from lung (A549 and BEAS-2B), colon (Caco-2) and liver (HepG2) were investigated. These cell lines are models for the major exposure routes in the body (inhalation, ingestion and physiological transport through the liver by the portal vein). To this aim, different scenarios were implemented by exposing undifferentiated and differentiated cells to single dosing of 2-μm polystyrene (PS) (102-105 particles/mL) for 48 h and 12 days. The undifferentiated Caco-2 cells with short exposure (48 h) showed the highest uptake rate of PS yet without significant cellular and mitochondrial responses. The biological effects, with the exception of ROS production, were not influenced by differentiation states of A549 and Caco-2 cells although differentiated cells showed much weaker ability to internalize PS. However, PS had significantly long-term impacts on cellular and mitochondrial functions even after the initial exposure period. In particular, Caco-2 cells that were post-exposed for 12 days after single PS dosing suffered higher oxidative stress and exhibited mitochondrial dysfunction than that for short exposure. Correspondingly, we observed that PS particles still remained in cell membrane and even in nuclei with high retention rate by 14-d post exposure during which metabolism and exchange of internalization and release occurred in cells. This indicates PS could induce chronic stress and even harmful effects on human cells after single intake that persists for a long time. This study paves the way for assessing the influence of PS on human health at low particle concentrations and with multiple exposure scenarios.

An efficient UV-C device for photoinactivation of human Corona and Influenza virus: Solution for small-scale reuse of personal protective equipment (PPE)

The world has recently witnessed a significant surge in the use of non-recyclable items such as Personal Protective Equipment (PPE) due to the COVID-19 pandemic. This has increased environmental pollution and caused a massive burden on the global waste management system. Hence, an effective strategy to address the demand-supply disparity and provide road map for sustainable management of used PPE are the need of the hour. In the present work, we aimed to develop a cost-effective, convenient, and effective strategy to safely reuse PPE by engineering an in-house UV-C-based Sanitization Device (UVSD) and systematically evaluating its potential to disinfect virus-contaminated PPE. To this end, we tested the capacity of the UVSD to disinfect single-use PPE and N95 face masks, experimentally soiled with the human Influenza (A/PR/8/1934/H1N1) and human Coronavirus (HCoV-OC43). For this, the UV-C-based photoinactivation of both viruses was assessed by in vitro cell protection, quantification of viral gene transcript, and residual viral load by plaque-forming assay. Further, Indirect immunofluorescence and viral hemagglutination assays were also performed to visualize and quantify the viral titers at different post-exposure (UV-C) time points. Our results demonstrate that 15 min exposure to the virus-contaminated simple or complex PPE within the UVSD cabinet could effectively inactivate both the H1N1 and HCoV-OC43 viruses.

Larvicidal activity of green synthesized iron oxide nanoparticles using Grevillea robusta Cunn. leaf extract against vector mosquitoes and their characterization

Extensive fumigation of synthetic pesticides to control the mosquito vector during each post-monsoon season in Pakistan significantly enhanced the environmental contamination and extinction of beneficial insects from the urban ecosystems. In this context, the present study examined the larvicidal efficacy of green synthesized iron nanoparticles (IONPs), using an aqueous leaf extract of Grevillea robusta against the early 2nd and 4th instar larvae of Aedes aegypti and Anopheles stephensi in Pakistan. The prepared IONPs were characterized by UV–Vis spectrum, FTIR, X-ray diffraction, scanning electron microscopy, and energy-dispersive diffraction. Larvicidal bioassay was conducted at various concentrations (80, 160, 240, 320, and 400 ppm) of IONPs prepared from leaf extract of G. robusta, and readings were taken-every 12 h for two consecutive days. In vitro, larvicidal assay, G. robusta leaf extract IONPs exhibited high mortalities of 64–96% (LC50 = 259.07 ppm; LC90 = 443.92 ppm) for the second instar and 65–98% (LC50 = 238.05 ppm; LC90 = 433.93 ppm) for the fourth instar of Ae. aegypti, while in the case of An. stephensi 56–84% (LC50 = 297.96 ppm; LC90 = 528.69 ppm) for the second and 56–88% (LC50 = 292.72 ppm; LC90 = 514.00 ppm) mortality for fourth larvae at 12–48 h post-exposure times were observed respectively. Significant (p < 0.05) dose-dependent and exposure time-dependent trends were observed among the 2nd and 4th larvalinstar of An. stephensi and Ae. aegypti. However, both species showed similar response and observed no significant (p > 0.05) difference in percentage mortality between the vector mosquitoes An. stephensi and Ae. aegypti. Overall, this study demonstrates that the larvicidal efficacy of green synthesized IONPs at low concentrations can be an ideal eco-friendly and cost-effective biocontrol of vector mosquitoes' larvae of An. stephensi and Ae. aegypti.

Identification of a Gene Signature Predicting (Nano)Particle-Induced Adverse Lung Outcome in Rats.

Nanoparticles are extensively used in industrial products or as food additives. However, despite their contribution to improving our quality of life, concerns have been raised regarding their potential impact on occupational and public health. To speed up research assessing nanoparticle-related hazards, this study was undertaken to identify early markers of harmful effects on the lungs. Female Sprague Dawley rats were either exposed to crystalline silica DQ-12 with instillation, or to titanium dioxide P25, carbon black Printex-90, or multi-walled carbon nanotube Mitsui-7 with nose-only inhalation. Tissues were collected at three post-exposure time points to assess short- and long-term effects. All particles induced lung inflammation. Histopathological and biochemical analyses revealed phospholipid accumulation, lipoproteinosis, and interstitial thickening with collagen deposition after exposure to DQ-12. Exposure to the highest dose of Printex-90 and Mitsui-7, but not P25, induced some phospholipid accumulation. Comparable histopathological changes were observed following exposure to P25, Printex-90, and Mitsui-7. Comparison of overall gene expression profiles identified 15 potential early markers of adverse lung outcomes induced by spherical particles. With Mitsui-7, a distinct gene expression signature was observed, suggesting that carbon nanotubes trigger different toxicity mechanisms to spherical particles.

Biological effects of inhaled crude oil vapor. III. Pulmonary inflammation, cytotoxicity, and gene expression profile

Objective Workers may be exposed to vapors emitted from crude oil in upstream operations in the oil and gas industry. Although the toxicity of crude oil constituents has been studied, there are very few in vivo investigations designed to mimic crude oil vapor (COV) exposures that occur in these operations. The goal of the current investigation was to examine lung injury, inflammation, oxidant generation, and effects on the lung global gene expression profile following a whole-body acute or sub-chronic inhalation exposure to COV. Materials and Methods To conduct this investigation, rats were subjected to either a whole-body acute (6 hr) or a sub-chronic (28 d) inhalation exposure (6 hr/d × 4 d/wk × 4 wk) to COV (300 ppm; Macondo well surrogate oil). Control rats were exposed to filtered air. One and 28 d after acute exposure, and 1, 28, and 90 d following sub-chronic exposure, bronchoalveolar lavage was performed on the left lung to collect cells and fluid for analyses, the apical right lobe was preserved for histopathology, and the right cardiac and diaphragmatic lobes were processed for gene expression analyses. Results No exposure-related changes were identified in histopathology, cytotoxicity, or lavage cell profiles. Changes in lavage fluid cytokines indicative of inflammation, immune function, and endothelial function after sub-chronic exposure were limited and varied over time. Minimal gene expression changes were detected only at the 28 d post-exposure time interval in both the exposure groups. Conclusion Taken together, the results from this exposure paradigm, including concentration, duration, and exposure chamber parameters, did not indicate significant and toxicologically relevant changes in markers of injury, oxidant generation, inflammation, and gene expression profile in the lung.

Biosynthesized silver nanoparticles (Ag NPs) from isolated actinomycetes strains and their impact on the black cutworm, Agrotis ipsilon

Nanomaterials have been produced with the use of bio-nanotechnology, which is a low-cost approach. Currently, research is being conducted to determine whether actinomycetes isolated from Egyptian soil can biosynthesize Ag nanoparticles (Ag NPs) and characterized by using the following techniques: Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Fourier transforms infrared (FT-IR), Energy-dispersive X-ray spectroscopy (EDX), UV–Vis spectroscopy and X-ray diffraction (XRD). The most promising actinomycetes isolate were identified, morphologically, biochemically, and molecularly. Streptomyces avermitilis Azhar A.4 was found to be able to reduce silver metal nanoparticles from silver nitrate in nine isolates collected from Egyptian soil. Toxicity of biosynthesized against 2nd and 4th larval instar of Agrotis ipsilon (Hufn.) (Lepidoptera: Noctuidae) was estimated. In addition, activity of certain vital antioxidant and detoxifying enzymes as well as midgut histology of treated larvae were also investigated. The results showed appositive correlations between larval mortality percentage (y) and bio-AgNPs concentrations (x) with excellent (R2). The 4th larval instar was more susceptible than 2nd larval instar with LC50 (with 95% confirmed limits) =8.61 (2.76–13.89) and 26.44(13.25–35.58) ppml−1, respectively of 5 days from treatment. The initial stages of biosynthesized AgNps exposure showed significant increases in carboxylesterase (CarE) and peroxidases (PODs) activity followed by significant suppression after 5 days pos-exposure. While protease activity was significantly decreased by increasing time post-exposure. Midgut histology showed abnormality and progressive damage by increasing time post exposure leading to complete destruction of midgut cells after 5 days from exposure. These results make biosynthesized AgNPs an appropriate alternative to chemical insecticide in A. ipsilon management.

Effects of low doses of gamma-radiation on the development of cardiac pathologies and heart rhythm disorders in male C57Bl/6J mice

Epidemiological studies have revealed a potential of low doses (< 500mGy) of gamma-radiation to induce cardiac pathologies, such as circulatory disease and ischemia. Involvement of Arrythmias in this pathological context is less clear. Indeed the development of arrythmia is reported in some but not all epidemiological studies (internal 137-Cesium (137Cs) exposure). The controversies can be attributed to the lack of understanding of the underlying mechanisms involved. Arrhythmias may be caused by an imbalance between stimulation of the sympathetic nervous system and inhibition by the parasympathetic. The objective of this project is to identify the signalling pathways involved in cardiac pathologies after exposure and over time. The study hypothesis would be that exposure to low doses of gamma-radiation induces tissue and nerve remodelling in the heart. We exposed C57Bl/6J male mice to whole-body single external doses ranging from 50 to 2000mGy from a 137Cs gamma-radiation source. Two post-exposure time points were studied (4 hours and 3 months). The heart function was monitored by Doppler ultrasound examination. Signalling pathways were examined by measuring levels of proteins involved in various cardiac functions by Western blotting and Sirius red staining of histological sections. In all, 4 hours after exposure, Western blot analysis showed a significant decrease in the expression of proteins involved in the conduction of cardiac nerve influx (Connexins 43 at 100 and 250mGy; P-value < 0.05) and in the synthesis of catecholamines (Tyrosine Hydroxylase at 50 and 250mGy; P-value < 0.05). These decreases may be responsible for heart contraction problems. Conversely, at 3 months post-exposure, we observed a significant increase in the levels of these same proteins of interest (Connexins 43 and Synapsin at 500 and 2000mGy; P-value < 0.05) which could induce long-term arrhythmia. These protein expression changes were observed only in the atrium and right ventricle. In addition, we observed interstitial fibrosis in the hearts of the mice exposed to the same doses (P-value < 0.05). Lastly, we observed a significant increase in the percentage of muscularized pulmonary arterioles (at 500mGy; P-value < 0.05), indicating the development of pulmonary hypertension. In summary, our results suggest that a single external exposure to a low dose of gamma rays can induce long-term functional alteration in the heart and that a potential dose threshold for such effect is below 500mGy.